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Does vitamin B12 improve hair growth? Supplement companies say yes, but scientific studies reveal a much murkier (and nuanced) relationship between vitamin B12, hair loss, and hair growth… one you’ll want to understand before you start supplementing.

In this article, we’ll dive into the arguments for and against a connection between vitamin B12 and hair growth. We’ll explore methylation, vitamin B12’s role in the hair cycle, and B12’s connection to different hair loss disorders. Then, we’ll reveal when vitamin B12 might (and might not) help our hair.

Finally, we’ll outline some potential best-practices for those who want to supplement with vitamin B12 for hair growth. After all, too little (and too much) of this vitamin may be counterproductive to both our hair and overall health.

What is vitamin B12?

Vitamin B12 is a singular vitamin apart of the greater B complex family. Like many B vitamins, vitamin B12 acts as an enzymatic cofactor for essential functions of the body (1). Specifically, vitamin B12 helps us metabolize food, produce red blood cells, and “methylate” DNA (more on this later). It also plays a protective role in cardiovascular health, as it helps to reduce excess amounts of a protein called homocysteine – which, at high levels, is inflammatory.

Vitamin B12 Supplement Mockup

Given its importance in so many bodily functions, it’s natural to wonder: does vitamin B12 also help fight hair loss? After all, it seems to be a staple ingredient in most hair health nutritional supplements. So, what does the evidence show?

The case for a vitamin B12-hair loss connection

From a scientific perspective, vitamin B12 might support hair growth in many ways.

1. Vitamin B12 help support the production of DNA – which is necessary to maintain the rapid cell division that drives hair growth (2). Without cell division, not only can hair not grow… but human life cannot sustain itself, either. In this respect, technically anything that supports human survival – even water – supports hair growth.
2. Vitamin B12 helps us produce hemoglobin – a molecule inside our red blood cells that carries oxygen and iron into our tissues (3). When someone has low hemoglobin, they often have an iron deficiency (i.e., anemia). Interestingly, anemia is highly correlated with hair loss – particularly in women ages 14-40 – and vitamin B12 supplementation can help improve hemoglobin product and thereby iron levels for those who are deficient.

But there’s also another reason that vitamin B12 might support hair growth – and it happens to do with one of the biggest buzzwords surrounding this vitamin: methylation.

In the simplest terms, methylation is a way in which our bodies can “turn on” or “turn off” certain genes. In other words, methylation helps change our gene expression – and thereby influences our ability to prevent cancer, reduce inflammation, and everything in between.

Here are just a few roles that methylation – and our methylation cycle – regulates inside our bodies:

• Production of methionine and cysteine. These are two sulfur-based amino acids that play integral roles in muscle building, inflammation regulation, and antioxidant production.
• Glutathione production. Sulfur amino acids are a major precursor for glutathione, the body’s master antioxidant.
• Homocysteine reduction. High levels of homocysteine in the blood are linked to a variety of inflammatory diseases.
• Production of SAMe. This protein is believed to support mental health, among many other things (4).

So, how does methylation relate to B12 and hair loss?

In one study on rabbits, researchers found methionine to be a promoter of hair growth. The mechanism behind this? An increase in the activity of the Wnt/β-catenin signaling pathway (5).

The Wnt/β-catenin pathway is important to this discussion for a few reasons:

1. This pathway helps promote the creation of stem cells, which are required for hair growth and hair follicle function (6).
2. In androgenic alopecia (AGA) – the most common form of hair loss in adult men – male hormones interfere with Wnt/β-catenin signaling. Specifically, this signaling pathway is dampened, also known as downregulated. As a result, hair follicle stem cell activity is impaired, which prevents proper hair cycling. This shortens the growth stage of a hair follicle, causing it to prematurely shed. Over time, this hinders hair growth and may even accelerate hair follicle miniaturization – a defining hallmark of male and female pattern hair loss (7).

Here’s where vitamin B12 might come into play:

Vitamin B-12 is a cofactor in the methylation cycle, meaning that it helps to activate methylation. Interestingly, vitamin B-12 deficiencies are believed to be a major driver of a dysfunctional methylation cycle – as evidenced by an association between homocysteine levels and vitamin B-12 deficiency (8). This suggests that the methylation cycle is “backed up”, preventing homocysteine from being converted to cysteine and methionine.

Thus, B-12 deficiency may impair methionine synthesis from the methylation cycle. Because we know that methionine contributes to Wnt/β-catenin signaling, it’s possible that a reduction in methionine may lead to reduced Wnt/β-catenin activity. And therefore, it’s possible that a vitamin B12 deficiency in scalp tissues might play a role for people dealing with androgenic alopecia.

Summary (so far): how vitamin B12 might help fight hair loss

There are a variety of ways that vitamin B12 might be connected to hair loss in humans:

• Vitamin B12 helps support DNA synthesis. Without DNA synthesis, we would die. We can’t grow much hair if we’re dead.
• Vitamin B12 helps normalize hemoglobin production (and thereby iron levels). For females with both hair loss and an iron deficiency, vitamin B12 might be a great way to improve iron status and encourage hair growth.
• Vitamin B12 helps support methylation. This might have ramifications for one of the world’s most common hair loss disorders – male pattern hair loss (AGA. In AGA-affected hair follicles, the Wnt / β-catenin signaling pathway is dampened, which leads to shorter-growing hair, premature hair shedding, and potentially even hair follicle miniaturization. If this happens to be the direct result of a deficit in localized methylation in scalp tissues, then vitamin B12 might help improve methylation and thereby improve Wnt / β-catenin signaling, which would allow for hairs to grow longer, shed less prematurely, and (hopefully) not miniaturize as quickly.

But it’s important to stress: these suspected mechanism are all hypothetical. Yes, vitamin B12 is connected to each mechanism. Yes, these mechanisms are linked to hair loss (and hair growth). But there’s a difference between association and causation. And this difference, unfortunately, is consistently forgotten by companies trying to sell you B12 supplements. Thus, to prove a strong association or causation, the real questions we should be asking are:

1. Are vitamin B12 deficiencies (in skin tissues or throughout the body) observed more frequently in people who are balding?
2. Does vitamin B12 – through supplementation or topical application – actually improve hair loss outcomes?

In answering these questions, we can actually discern whether or not it makes sense for most people to spend money on vitamin B12 supplements to try and regrow their hair.

And as you can guess, these questions happen to lead us to our next section: the case against a vitamin B12-hair loss connection.

The case against a vitamin B12-hair loss connection

While there is hypothetical evidence linking vitamin B12 to hair loss and hair growth, this argument begins falls apart when we zoom out and start looking at the broader evidence.

Specifically, we’re going to talk about the following:

1. Misconceptions about methylation, B12, Wnt/β-catenin pathways, and hair loss
2. Vitamin B12 levels of hair loss patients
3. Observations in birth control-induced vitamin B12 deficiencies, and what this does (or doesn’t do) to hair

Methylation misconceptions

Earlier we discussed how, in balding hair follicles, a deficiency in the methylation cycle might interfere with Wnt/β-catenin signaling pathways, which might accelerate hair loss. We argued that because vitamin B12 supports methylation, this vitamin might also help reverse this methylation deficiency, and thereby help fight hair loss from androgenic alopecia.

But it’s important to note: vitamin B12 is just one (of many) vitamins and nutrients that support methylation. For instance, many other B-vitamins also support methylation, and these B-vitamins are found in abundance in foods like beef, eggs, and poultry.

This means that even if you do have a vitamin B12 deficiency, your body will likely be able to compensate for this – at least from a methylation perspective – via your dietary choices. Therefore, in balding hair follicles, even if Wnt / β-catenin downregulation were exclusively due to a methylation issue (it isn’t), your body would still have many “fallback” vitamins to address that methylation issue. So, in androgenic alopecia, changes to a hair follicle’s gene expression cannot be significantly attributed to a vitamin B12 deficiency.

Therefore, it also shouldn’t be surprising to find out that there aren’t any differences in vitamin B12 levels between those with and without hair loss.

Looking at B12 levels in the blood of hair loss patients

When we zoom out beyond the actual hair follicle and look at studies on people with common hair loss disorders like AGA, telogen effluvium (TE), or alopecia areata (AA) – the data are consistently clear: there is no difference in blood measurements of vitamin B12 between people with and without hair loss (9). In other words, people who are losing their hair and who have full heads of hair appear to have the same vitamin B12 levels.

Even more compelling, recent literature reviews have found no evidence to support the use of vitamin B12 for hair loss of any type (9). That means that not only are vitamin B12 levels the same across those with and without hair loss, but that for those with hair loss, vitamin B12 supplementation generally doesn’t improve hair loss outcomes.

What about women with hair loss due to an iron deficiency? Doesn’t vitamin B12 help improve iron stores, and have some therapeutic benefit here?

Yes and no.

Earlier, we argued a connection between hemoblogin, iron, vitamin B12, and hair loss. As a refresher, hemoglobin is a molecule found in red blood cells. Hemoglobin carries oxygen and iron, and in general, when someone has low hemogloblin levels, they also have low iron (10). Low iron levels are often found in women ages 14-40 with hair loss. Vitamin B12 is a key cofactor in hemoglobin formulation. Therefore, you might be able boost hemoglobin production with vitamin B12, and therefore potentially normalize low iron levels. If someone is dealing with hair loss as a direct result of low iron levels, then vitamin B12 supplementation might help to normalize these levels and maybe regrow some hair.

So, in a situation where someone’s hair loss is due to poor iron status, and their poor iron status is a direct result of low vitamin B12, then it absolutely makes sense to supplement with vitamin B12. In doing so, you’d improve hemoglobin production, oxygen and iron transport, and (very likely) hair loss outcomes. This is why a lot of popular hair loss supplements – like Nutrafol – contain B12.

At the same time, a vitamin B12 deficiency is only one possible contributor toward an iron deficiency. A more likely contributor? A deficiency in iron itself (11). So, while vitamin B12 is probably therapeutically useful in some circumstances of iron deficiency-related hair loss, it’s not the only reason – or even the biggest reason – for why the iron deficiency arises.

Therefore, B12 is likely useful for a much smaller percentage of women than advertisements for these hair health supplements might lead you to believe.

Observations in birth control-induced B12 deficiency

This argument is further strengthened by another observation researchers have made: women with vitamin B12 deficiencies caused by hormonal birth control don’t experience hair loss or adverse changes to hair growth (9). As such, even when a deficiency is present, it doesn’t seem to negatively impact hair growth. In fact, many women on hormonal contraceptives report the opposite effect – hair regrowth – which is why some contraceptives are also used off-label as a hair loss treatment.

The good news? Vitamin B12 might help reverse premature hair graying

In regard to hair health, there is one way that vitamin B12 might positively impact hair health outcomes. It might help to prevent, or even reverse, premature graying.

To be clear, the majority of research doesn’t indicate B12 deficiency is a cause of hair loss. But, there are several reports supporting an association between inadequate B12 levels and premature hair graying, which is grey hair that onsets before the ages of 20-30 (depending on the demographic) (12).

For instance, one small study demonstrated that individuals with premature hair graying had lower vitamin B12, folate, and biotin levels than control subjects without premature gray hair (13). Additionally, some studies report a higher incidence of premature graying in pernicious anemia, a blood condition sometimes caused by B12 deficiency (14).

There are also three case reports of patients reversing their premature gray hair with B12 supplementation (15-17). Needless to say, there seems to be evidence of both an association of low B12 and early greying, and a reversal of early greying following B12 supplementation.

The association between B12 deficiency and premature graying isn’t fully established, and there are absolutely other factors that can lead to premature hair graying. Moreover, B12 supplementation is really only relevant to reversing graying hair in the context of B12 deficiency.

That being said, a vitamin B12 deficiency may be worth investigating for anyone experiencing premature hair graying – regardless of whether you’re losing your hair.

The verdict: in most situation, vitamin B12 likely has no effect on hair loss (and hair regrowth), but vitamin B12 might reverse premature hair graying in the presence of B12 deficiency

Although hypothetical evidence suggests an absence of B12 activity could negatively impact hair growth, in vivo human studies indicate that either (1) there is no relationship between vitamin B12 deficiency and hair loss and/or (2) there is an overriding factor (like methionine provision outside of the methylation cycle) that prevents B12 deficiency from causing hair loss.

The exception to this is if someone has iron deficiency-related hair loss, and if their iron deficiency is exclusively the result of poor hemoglobin production due to a vitamin B12 deficiency. In this case, vitamin B12 supplementation can address the deficiency, improve hemoglobin production, and thereby drastically improve iron transport (and, ultimately, hair growth). But it goes without mentioning that this is a very specific scenario that is not faced by the majority of hair loss sufferers in the developed world.

In any case, it’s clear that supplementing with B12 is probably not the best solution for improving hair growth – at least as a standalone therapy.

That being said, it’s important to note that having adequate B12 is essential for optimal health. Even if it doesn’t cause hair loss, B12 deficiency can still lead to anxiety, fatigue, neuropathy, and cardiovascular issues, among other health issues. Moreover, B12 deficiency appears to be one potential cause of premature hair graying.

As such, even if it doesn’t improve hair loss, some may still find it necessary to supplement with vitamin B12. So, in these cases, what’s the best approach for supplementation?

Things to keep in mind when supplementing with vitamin B12

Vitamin B12 supplements are available in three forms: cyanocobalamin, methylcobalamin, and adenosylcobalamin. Methyl- and adenosylcobalamin are naturally-occurring forms of B12 whereas cyanocobalamin is synthetic.

Though synthetic is not always subpar to naturally-occurring forms of B12, in this case, supplementing with methyl- and adenosylcobalamin B12s is much more efficient. The reason for this is they are already in their active forms, ready to be used by the body. Cyanocobalamin, on the other hand, requires enzymatic processing before it can be utilized. On top of this, cells don’t seem to retain cyanocobalamin as well as some of the other forms (18).

Additionally, some researchers have raised concerns with long term cyanocobalamin supplementation, due to the cyanide present in the compound (18). Even though these concerns aren’t yet substantiated, an abundance of caution may be warranted here.

The bottom line? If your diet isn’t providing you with enough vitamin B12 and you choose to supplement, consider opting for a B-complex or multivitamin formulated with methyl- or adenosylcobalamin.

Summary

Vitamin B12 deficiency isn’t likely to be a cause for hair loss. As such, claims that supplementing with B12 will improve hair growth are largely unfounded. This is despite some pretty compelling theoretical evidence – like B12’s role in hemoglobin formation, nucleic acid synthesis, and the methylation cycle that produces growth-supporting methionine.

It just goes to show how important it is that we don’t rely on studies of isolated nutrients in cell cultures. Moreover, we shouldn’t have high hopes for products marketed on these premises when it comes to regrowing our hair.

That being said, vitamin B12 deficiency can still cause real problems and, in some cases, may be an underlying factor in premature hair graying. So, for those who are dealing with early-onset gray hair, it may be worth checking your B12 levels. And if you are deficient? Restoring your B12 levels may just reverse the condition.

So, if supplementing is warranted in your case, opt for a methyl- or adenosylcobalamin-containing supplement over one containing cyanocobalamin. They’re more bioavailable and may be safer in the long-term.

But, for the overwhelming majority? You’re likely to get all the vitamin B12 you need from food — more than enough to rule it out as a plausible factor in hair loss.

Have any questions about vitamin B12? Leave them below.

Alopecia areata is an autoimmune form of hair loss that affects 2% of people worldwide. If you’re dealing with alopecia areata, the burden of hair loss often feels overwhelming – as the condition can progress rapidly, inexplicably, and without regard.

Fortunately, alopecia areata is treatable. In many cases, it’s also reversible. The first step toward making progress? Understanding alopecia areata, its myriad triggers, and how these factors relate to your unique hair loss situation.

In this article, we’ll uncover the characteristics of alopecia areata: its clinical presentations, histological features, and more. We’ll also dive into alopecia areata’s causes: what we know, what we don’t, and what this type of hair loss can tell us about our health.

Finally, we’ll outline treatments for alopecia areata (both conventional and natural): the research supporting them, the expectations for regrowth, and who might be the best candidates for each intervention.

What is alopecia areata?

Alopecia areata (AA) is a form of hair loss driven by autoimmunity. To put it simply, alopecia areata occurs when our bodies mistakenly recognize our hair follicles as foreign invaders, and then begin to attack our hair follicles. This leads to the dysfunction of hair follicle stem cells, and eventually, hair loss.

What does alopecia areata look like?

You might know alopecia areata (AA) from its “patchy” presentation, whereby slick-bald patches begin to form in a non-uniform fashion. But AA can also vary in appearance – and even mask the look of many other common hair loss disorders.

Types of alopecia areata
Alopecia areata focalis or “patchy” alopecia areata	Hair loss in patches, can extend beyond just the scalp. The most common form of alopecia areata. It may or may not progress into alopecia totalis or alopecia universalis.
Alopecia areata totalis	Loss of all hair on the scalp including eyelashes and eyebrows.
Alopecia areata universalis	Hair loss of the scalp, eyelashes, eyebrows, and whole body, including all body hair.
Ophiasis or alopecia areata marginata	Hair loss around the circumference of the head in a band-like fashion. It is most commonly seen behind the ears and the nape of the neck, but can occur in the frontal hairline and extend throughout the scalp in severe cases, as well.
Ophiasis inversus	Hair loss that begins in the center of the scalp and progresses into the surrounding regions.
Alopecia areata incognita	Diffuse hair loss whereby no specific bald “patches”, normally characteristic of alopecia areata, can be distinguished.

What’s the histology of alopecia areata?

Histology is a term used to describe a close-up view of a tissue’s structure. In the world of hair loss, histology refers to the microscopic view of a hair follicle (i.e., what a hair follicle looks like when biopsied).

When doctors are uncertain about someone’s hair loss diagnosis, they’ll often take a biopsy of their patient’s scalp so that they can get a look of the histological features of the affected hair follicles. Then, they’ll compare what they see against the histological hallmarks of certain hair loss disorders.

It might sound invasive, but these scalp biopsies are perhaps the most effective way for dermatologists to definitively diagnose someone’s hair loss. And when it comes to alopecia areata, this type of hair loss has a lot of interesting features:

• Inflammation. Specifically, the infiltration of lymphocytes near hair follicle stem cell bulges. Lymphocytes are immune cells; the bodies uses them as part of an inflammatory response. Where there are high lymphocytes, there are usually high amounts of inflammation. One study found that 84% of alopecia areata subjects presented with this kind of inflammation.
• Dysfunctional hair follicle stem cell bulges. Hair follicle stem cells contain the blueprints to make new hair follicles. When too many lymphocytes collect near these stem cells, they generate inflammation, and that inflammation interferes with the ability for these stem cells to function. This leads to stem cell dysfunction and an inability to form new hair.
• Hair follicle miniaturization. This is a decrease in hair strand diameter, which leads to thinner-looking hair. One study observed that 90% of alopecia areata subjects had hair follicle miniaturization. Conversely, this study only found miniaturization in 25% of subjects. This study found that the presence of miniaturization is likely dependent on the nature of the hair loss – for example, early stages of AA likely do not present with miniaturization. It is most commonly often found in recurrent and chronic forms of AA.
• Increased number of catagen hairs. This study found that 93% of patients presented with an abnormally high number of hair follicles in the catagen phase – the phase in the hair cycle whereby nutrient supply is cut off and the hair prepares to shed. In healthy scalps, only 1% of hair follicles are typically in catagen. With AA, that percent can skyrocket.

Isn’t inflammation & hair follicle miniaturization part of androgenic alopecia (AGA)?

Yes.

Pattern hair loss, also known as androgenic alopecia (AGA), is also often defined by the presence of inflammation, hair follicle miniaturization, and even an increased number of catagen and telogen hairs. This begs the question: how can we distinguish between AGA and alopecia areata… especially in cases where alopecia areata is diffuse?

Well, there are some additional factors that can help us identify if we’re dealing with alopecia areata (AA) or androgenic alopecia (AGA).

What makes alopecia areata (AA) unique from androgenic alopecia (AGA)?

1. The patterning of AA. In most AA cases, hair loss begins in a “patchy” fashion — a patterning that is exclusive to AA. In contrast, AGA occurs in a very different, yet still distinct manner. For men, it’s temple recession and crown thinning. For women, it’s most often a widening of the part while their hairline stays intact (also known as a “Christmas tree” pattern).
2. Exclamation-point hairs in AA. Exclamation point hairs, pictured below, are a phenomenon only observed in AA. These hairs remain thick along the shaft but are noticeably thinner towards the opening of the follicle, creating an appearance akin to that of an exclamation mark ( ! ). This is only a defining factor if hair is still present.

   1. Exclamation mark (!) hair
      

3. Pigment casts in AA. Melanin is a substance produced by cells to create pigment for our skin and hair. Interestingly, in cases of AA, there are often “clumps” of melanin deposits throughout the follicular unit. This can appear like a small, dark tattoo where there should be a hair follicle. The incidence of pigment casts varies from study to study from 44% to 72%. Having said that, pigment casts by themselves aren’t a good indicator of AA – mostly because they’re often observed at similar rates in other hair loss disorders like trichotillomania (i.e., a “hair-pulling disorder”).

What causes alopecia areata?

To reiterate from earlier, inflammation seems to initiate of AA. The process looks like this:

1. Inflammatory cells infiltrate the area surrounding a hair follicle stem cell bulge.
2. This inflammation disrupts stem cell functionality, leading to stem cell dysfunction.
3. These dysfunctional stem cells stop producing normal-looking hair follicles.

This leads to:

• Rapid hair follicle miniaturization (i.e., exclamation hairs).
• A loss of visible hair (i.e., slick-bald patches in alopecia areata focalis).
• Weaker, brittler hair that breaks off soon after growing out of the skin surface.

This begs the question… when it comes alopecia areata, what causes the inflammation that kickstarts the whole process?

What causes the inflammation in alopecia areata?

While the exact origin of inflammation isn’t known, researchers have a good idea of three contributing factors: genetics, environmental triggers, and loss of immune privilege in the follicle.

And though we don’t know the exact nature of these contributing factors, researchers have begun to uncover some of the details:

• Genetics. Studies have shown that AA is common among family members, affirming the role of a genetic component in certain cases. Specific genes affected include those that code for immune cell receptors, cell death coordination, immune-regulating cells, other proteins that regulate cellular communication.
• Environmental factors. Much like genetics, environmental elements faced by AA-affected families might also explain why this condition tends to appear multiple times within the same family. These environmental factors include
  • Stress
  • Infections
  • Hormone fluctuations
  • Dysbiosis of the gut flora
  • Oxidative stress
  • Soy consumption (implicated in animal studies, though not yet confirmed in human studies)
  • Nutrient deficiencies (specifically, vitamin A and/or vitamin D deficiency.
• Loss of immune privilege. Under normal circumstances, a hair follicle produces its own “shield” from our own immune system. This shield is comprised of many immune-suppressing molecules. This is known as immune privilege, and it’s what make hair follicles incredibly unique mini-organs. However, in AA, researchers believe this immune privilege collapses – preventing the hair follicle from protecting itself against a damaging attack by the immune system. This would lead to inflammation and, thereby, the destruction of the hair follicle stem cell bulge. How this occurs is unknown, but researchers believe it is a result of proteins secreted by skin cells that the body forms an “antibody” to, leading to an immune attack.

What are the available treatments?

Currently, there are a variety of drug and non-drug treatments for AA. But before we reveal them, there are two things worth mentioning:

1. Because we don’t fully understand why AA occurs, the most well-studied treatments primarily focus on suppressing the signals that lead to AA (as opposed to treating its root cause). More recent research has explored treatments that try to target some of these potential root causes. These studies show promise, but they’re also a little “out there” in terms of peoples’ comfortabilities. So, as you read on, keep this in mind.
2. When it comes to reversing alopecia areata, 34-50% of cases resolve spontaneously. This makes it hard to know which treatments work, and which treatments just happened to coincide with spontaneous reversals. This is why control groups are so important in AA studies. Moreover, the likelihood of spontaneous reversal depends highly on the progression of the disease: as AA progresses, the likelihood of spontaneous resolution declines.

Regardless of these factors, it seems like treating AA in earlier stages leads to better outcomes and decreases the risk of future treatment resistance. So, if you’re facing AA right now, it’s best not to place your bets on a spontaneous reversal; rather, hedge those bets with the treatment options at your disposal (or at least the ones you’re comfortable trying).

The following sections detail many conventional and alternative treatments: the evidence, best practices, mechanisms of action, and more.

Drug-based treatments

Topical, intralesional, and systemic steroids (first line of treatment)

• Best candidates: Patchy AA may be controlled with topical or intralesional steroids. More severe or resistant cases (alopecia totalis, alopecia universalis, ophiasis) may require systemic steroid treatment or combination therapy (steroids + other treatments).
• Mechanisms of action: Reduction of inflammation.
• Dosages: For topical steroids, concentrations vary from 0.05% to 0.25%; for intralesional steroids, most commonly-used agent is triamcinolone acetonide, at concentrations of 2.5 mg/mL to 10 mg/mL; for systemic steroids, varying doses given as pulse doses, a.k.a large bolus doses for a specific period of time, administered in intervals.
• Outcomes: Results vary between methods of administration. Topical steroids are best suited to earlier stages of AA, with about 57% of these patients demonstrating complete regrowth. Intralesional steroids have a slight advantage over topicals, with 63% of patients achieving complete growth in one study. Systemic steroid treatment is primarily relegated to resistant cases.
• Problems: With topical and intralesional treatment, the main side effect is cutaneous atrophy or thinning of the skin. Systemic steroids come with a higher risk of side effects, and these risks may outweigh the benefits of hair growth. The relapse rate after steroid treatment ranges between 33% and 75%.

Janus kinase (JAK) inhibitors (oral and topical)

• Best candidates: Men, women, and children with patchy AA, alopecia universalis, alopecia totalis, according to preliminary evidence.
• Mechanisms of action: Blocks inflammatory signaling.
• Dosages: 5mg twice per day.
• Outcomes: Efficacy is similar in patchy alopecia areata, alopecia universalis, and alopecia totalis as well as in both men vs. women and adults vs. children. Oral administration is more likely to produce a good response when compared to the use of topical applications. Studies show initial hair growth occurs as soon as 2 months, with full regrowth occurring in an average of 6 months.
• Problems: Evidence is limited and primarily in the form of case reports. As such, though JAK inhibitors show promise, we don’t know a lot about the safety or efficacy of these medications in AA, yet. Drugs in this class have been linked to an increased risk of upper respiratory issues, latent virus reactivation, and cancer. The exact risk of these adverse effects in the treatment of AA is unknown, however, upper respiratory infection was the most common among available case studies. Like other therapies in AA, there is a high rate of relapse after cessation of the drug.

Immunotherapy (dinitrochlorobenzene, squaric acid dibutylester and diphenylcyclopropenone, with diphenylcyclopropenone)

• Best candidates: Mild to moderate patchy alopecia areata.
• Mechanisms of action: Immunogenic compound “distracts” the immune system with a more stimulating antigen than the self-antigen the mediates the autoimmune reaction.
• Dosages: Concentration sufficient enough to induce an allergic response.
• Outcomes: Response rates as reported in the literature range widely, from about 9% to 87%. About 20% to 30% of patients are able to achieve significant hair growth, such that they are able to manage their hair loss without a wig. This specific therapy may require longer treatment times, as evidenced by over a two-fold increase in response rate at 32 months versus 6 months. So, ask your doctor about whether a longer treatment period might be right for you. In over 30 years of use, long-term side effects have not been reported with immunotherapy, however, some side effects can occur during therapy. The most common side effect is cervical and occipital lymphadenopathy and severe dermatitis, however, these only last for the duration of the therapy. Moreover, dermatitis can be avoided by using the proper concentration of the antigenic compounds. Vitiligo and itching have also been reported but are considered rare. Overall, the treatment appears to be well-tolerated and effective.
• Problems: As with most treatments, relapse rates are high at around 62%. Response rates are somewhat low when administered for the same treatment periods as other treatments. In other words, immunotherapy takes longer to work than other treatments.

Minoxidil

• Best candidates: Mild patchy AA, AA patients tapering off of steroid therapy
• Mechanisms of action: Not fully known, but is believed to stimulate the “anagen” growth phase of the hair cycle, thereby promoting regrowth of lost hairs.
• Dosages: 2% or 5% minoxidil, two to three times daily.
• Outcomes: In one study, 85% of patients using 5% minoxidil alone experienced regrowth, however, this regrowth wasn’t cosmetically significant. Another study demonstrated that the application of 2% minoxidil, when applied three times daily, helped retain hair regrowth after tapering off of steroid treatment.
• Problems: Minoxidil doesn’t seem to be that effective outside of post-steroid hair retention.

Methotrexate

• Best candidates: Moderate to severe AA, including universalis, diffuse, and totalis phenotypes.
• Mechanisms of action: Suppression of the immune system.
• Dosage: 10-25mg per week + folate/folic acid supplements (methotrexate depletes folic acid).
• Outcomes: One study reported that 44.4% of subjects taking methotrexate were able to regain 50% or more of their hair as observed in a follow-up period ranging from 3 to 51 months. The best responders were males, those with multifocal patchy AA (followed by totalis, then universalis, and, lastly, diffuse), and those who used a cumulative dose of 1,000 to 1,500mg. When corticosteroids were used alongside methotrexate, the number of patients regrowing at least 50% of their hair increased to 77.3%.
• Problems: Methotrexate isn’t well-studied for AA — the evidence is primarily made up of case studies. 3-24% of patients can expect to experience side effects like mild to moderate leukopenia, thrombocytopenia, and megaloblastic anemia. There is also the risk of liver fibrosis, with an incidence ranging from 7% to 71.8%. Such a wide range makes the true risk hard to quantify. Myelosuppression is also a dangerous side effect and its risk associated with methotrexate use is unpredictable. Relapse rates vary from 33% to 80%, with some studies suggesting the rate is associated with how much hair is gained during treatment — more hair regrowth during treatment is associated with a lower risk of relapse after treatment.

Non-drug based treatments

Fecal microbiota transplant (FMT)

Fecal microbiota transplant (FMT) is a procedure whereby gut bacteria are isolated from a donor’s feces, purified, and then transplanted into an FMT candidate. This is the only procedure in which bacterial strains that have been lost from the gut can be reinoculated.

Currently, the procedure is elective in Europe (anyone can elect to have it performed). But in the U.S., it’s only available for chronic C. difficile infections. In the U.K., Taymount Clinic is one of the most popular worldwide-serving clinics for elective FMT.

• Best candidates: Evidence is limited but FMT has been used to treat patchy AA and alopecia universalis. May also be effective in treatment-resistant cases.
• Mechanisms of action: Unknown, but probably a normalization of the gut flora, leading to reduced autoimmune activity.
• Dosage: N/A; donor transplant is performed in one procedure, although people often elect for multiple procedures (depending on the delivery method).
• Outcomes: There are currently three case studies (studies here and here) investigating the efficacy of FMT in AA: two in alopecia universalis and one in patchy AA. Of the 3 case studies, all patients showed marked improvement following FMT — with two cases of almost full regrowth (one in universalis alopecia and one in patchy AA) and one case of partial regrowth. In all cases, this hair regrowth was sustained for at least 1.5 to 3 years. Considering the relapse of AA for most treatments is high, this sustained regrowth is promising. However, whether or not this regrowth was sustained beyond the follow-up period is unknown.
• Problems: FMT is still considered an investigative treatment in the U.S. and is, therefore, not elective for individuals with AA, unless a patient is also dealing with chronic C. difficile infection. As such, US residents wanting to explore the treatment must travel for the procedure and pay for it out-of-pocket — these costs can rack up (but may be worth it in the long run).

FMT before & after photos

Case #1: (A) 1 month, (B) 4 months, (C) 1.5 years after FMT in patchy AA

Case #2: (A) The patient’s scalp when his AA first began (B) a few months, (C) 1.5 years after FMT in alopecia universalis

Case #3: The beginning of hair regrowth after FMT in a case of long-standing alopecia universalis

Essential oils

• Best candidates: Evidence is limited, however, efficacy has been demonstrated for general AA in one study. In this specific study, the authors did not specify which kind of AA patients were dealing with.
• Mechanisms of action: Unknown, but probably a reduction in inflammation.
• Dosage: 2 drops thyme essential oil (EO), 3 drops lavender EO, 3 drops rosemary EO, 2 drops cedarwood EO diluted in 3mL jojoba oil and 20mL grapeseed oil.
• Outcomes: In this study, 54% of AA patients in the active group experienced hair regrowth over 7 months while 46% experienced no change (however, hair loss also did not get worse). A majority of these patients achieved hair regrowth in the 10-30% range, followed by 81-100%. In contrast, 78% of the placebo group did not improve, suggesting the essential oil mixture did, indeed, have an effect. It’s likely that the remaining 22% were experiencing spontaneous remission. Neither group experienced adverse side effects.
• Problems: It’s not clear just how many patients may benefit from EO application given that spontaneous resolution is a common occurrence. We see evidence of this in the placebo group, which may be a confounding factor in the measurement of treatment efficacy (since we don’t know how many in the active group would have resolved without intervention). Taking this into account, the response rate, when compared to other treatments for AA, is relatively low. Another issue is the fact that the study did not have a designated follow-up period to measure the rate of relapse. Therefore, we can’t be sure of just how effective this treatment is in the long run. Moreover, the treatment period was quite long in comparison to what is normally employed with other therapies. Given that AA can become more treatment-resistant as time goes on, using topical EOs may delay appropriate treatment and, as a result, require more aggressive therapies in the future.

Onion juice

• Best candidates: Men and women with patchy AA.
• Mechanisms of action: Unknown, but researchers believe it could work similarly to immunotherapy.
• Dosage: Application sufficient to cover the affected area(s) twice daily.
• Outcomes: This study found that patients with patchy AA were able to see hair regrowth as early as 2 weeks into the study period. Full hair regrowth was seen in 86.9% of patients after 8 weeks. Contrastingly, hair regrowth was only observed in 13% of the control group, making the findings of this study statistically significant.
• Problems: This study, unfortunately, had no follow-up period. As such, we don’t know how many patients experienced a relapse after cessation of treatment. Moreover, the smell of onion juice may make this treatment hard to adhere to long-term.

Garlic gel

• Best candidates: Men and women with mild patchy AA.
• Mechanisms of action: Unknown, but researchers believe it could work similarly to immunotherapy.
• Dosage: 5% garlic gel with 0.1% betamethasone valerate gel, twice daily.
• Outcomes: This study found that garlic was able to enhance the hair growth-promoting effects of a corticosteroid, betamethasone valerate. After 3 months, the active group was able to achieve a significant reduction of hair loss patches — more so than the corticosteroid topical alone.
• Problems: Like the onion juice study, this study (1) did not measure the rate of relapse after cessation of therapy and (2) fails to account for the smell, which may make the treatment difficult to adhere to in real-world settings.

Capsaicin

• Best candidates: Patients with patchy AA and, possibly, alopecia totalis.
• Mechanisms of action: Unknown, but researchers suspect neuroimmunological modulation in the hair follicle.
• Dosage: 0.075% capsaicin topical applied daily.
• Outcomes: Studies employing the use of capsaicin have show varying results. Some studies report the regrowth of vellus hairs, but no appreciable regrowth sufficient to justify its use over other treatments, while others report hair growth in just 3 weeks.
• Problems: Evidence suggests capsaicin may promote some degree of regrowth, but not enough to justify its use over other treatments — especially considering that AA becomes increasingly treatment-resistant over time. Thus, capsaicin use may delay appropriate treatment and, thus, increase the risk of refractory AA in the long-run.

Vitamin D repletion

• Best candidates: Patients with patchy AA and vitamin D deficiency and/or genetically reduced vitamin D receptor expression.
• Mechanisms of action: Likely a modulation of autoimmune activity in the follicle, due to vitamin D’s widespread effects on balancing the immune system.
• Dosage: For oral vitamin D use, the dosage will vary depending on the severity of vitamin D deficiency and whether your practitioner decides to opt for weekly bolus or daily doses. For topical vitamin D therapy, topical applications range from 0.005% calcipotriol twice daily to 50 micrograms/mL calcipotriol once daily.
• Outcomes: Evidence from meta-analyses show that AA patients are more likely to be vitamin D deficient than healthy controls. This would suggest that vitamin D could be beneficial to AA patients, however, no studies have been conducted to assess clinical benefit. The topical application of vitamin D-like, conversely, has been investigated as a treatment avenue. These studies show that twice daily application of various concentrations results that vary from 50% regrowth all the way to clinical remission (full hair regrowth). One study found that efficacy was associated with lower vitamin D levels at the beginning of the study, suggesting that lower vitamin D levels may be a marker of a good candidate. Additionally, one case report demonstrated full clinical remission in a patient with AA and reduced vitamin D receptor expression. Thus, AA patients with low vitamin D levels or reduced vitamin D receptor expression may have the best response to treatment. Studies also show minimal risk of adverse side effects.
• Problems: Studies do not currently show benefit in more severe cases of AA, like alopecia totalis or alopecia universalis. There is limited evidence investigating the therapeutic potential of oral supplements.

Zinc

• Best candidates: Patients with mild AA and zinc deficiency.
• Mechanisms of action: Unknown, but could be attributed to antioxidant regulation and anti-inflammatory activity.
• Dosage: Dosage depends on the severity of the deficiency, however, doses between 50 and 220mg have been used in the literature.
• Outcomes: Studies suggest AA patients have lower zinc levels compared to healthy controls. Interestingly, evidence also suggests a correlation between zinc levels and treatment resistance, meaning zinc deficiency may have an emerging role in refractory AA. However, some studies have failed to find a relationship between zinc and AA. Moreover, some studies show no benefit with zinc supplementation while others suggest zinc therapy may be beneficial in the context of mild AA with zinc levels below 70 μg/dL. Overall, the role of zinc therapy in AA is unclear other than zinc deficiency is more common among AA patients. Nonetheless, zinc repletion may confer health benefits in the presence of deficiency, even if clinical regrowth is not achieved.
• Problems: Research is mixed, with some studies suggesting benefit and others suggest a net zero effect. Thus, there is no conclusive evidence to support the use of zinc in AA.

Azelaic acid

• Best candidates: Patients with patchy AA.
• Mechanisms of action: Unknown, but preliminary evidence suggests it may act similarly to that of immunotherapy.
• Dosage: 20% azelaic acid topical applied twice daily.
• Outcomes: Evidence supporting the use of azelaic acid in patients with AA is lacking. However, one pilot study demonstrates efficacy on par with anthralin, a medication used to treat psoriasis (another autoimmune disease that affects the skin). Just over half of the patients tested achieved complete regrowth with both treatments with no report of adverse events.
• Problems: Research is limited and, as such, the true efficacy of azelaic acid is not known. Moreover, the aforementioned study did not employ a follow-up period, which is necessary to estimate the rate of relapse.

Platelet-rich plasma (PRP)

• Best candidates: Patients with ophiasis-pattern AA resistant to steroid treatment or AA patients who develop side effects with steroid treatment.
• Mechanisms of action: Unknown, possibly immunomodulatory effects.
• Dosage: 9 mL injection.
• Outcomes: In one case study of steroid-resistant ophiasis AA, a form of AA which is generally hard to treat, the patient was able to achieve regrowth by month 1 with significant regrowth by month 3. The patient reported no side effects. Another study demonstrated the superiority of PRP over steroid injections for patchy AA.
• Problems: Unfortunately, there is limited evidence available. The rate of relapse is unknown. The procedure is also costly.

Case study: ophiasis-type AA before and 3 months after PRP treatment.

Brotzu Lotion

Brotzu lotion is a topical formulated by Dr. Brotzu. It contains three main compounds: dihomo-gamma-linoleic acid, S-Equol, and propionyl-L-carnitine — ingredients designed to target inflammation and decreased blood flow in follicles.

There is currently no clinical evidence to support the efficacy of Brotzu lotion in AA. Nonetheless, some initial case studies do show promise. Take, for example, these two before-and-afters:

Brotzu Lotion: a child with alopecia universalis

And here’s a case of near-complete recovery of patchy AA in just 16 months from Dr. Brotzu’s presentation at this conference — start at 10:30):

Brotzu Lotion: alopecia areata recovery

While these are the only case studies we have pictures of, Dr. Brotzu’s patent cites more case studies. This is encouraging for AA patients — especially given it seems confer benefit even in more severe cases, of which are generally more likely to be resistant to treatment.

But it bears repeating: even Dr. Brotzu has claimed it’s difficult to know just how effective the lotion is for AA – mainly because of the spontaneous recoveries.

Helminthic therapy

Helminths, better known as hookworms, are tiny parasites that embed themselves in the small intestines of their hosts.

Helminths are unique in that they have a novel survival mechanism — one that might actually to a broader, modulatory effect on the whole immune system!

The specifics? Helminths “mute” the activity of T-cells, protecting them from destruction by the host’s immune system. This is accomplished through the stimulation of Tregs, a group of cells that reduce the inflammatory potential of the immune system.

As such, in theory, T-cell activity is modulated as a whole, reducing our reactivity to other reactive compounds — including our own tissue. Because auto-reactivity to our own tissue is what mediated autoimmunity (including in AA) reduced T-cell activity may also mean a reduced risk of autoimmunity.

And though research on helminth therapy is still in its infancy, preliminary studies suggest that this evidence might just translate to real-world efficacy. In fact, the therapy has shown promise for a variety of disorders, ranging from inflammatory bowel disorders to allergy all the way to mouse models of multiple sclerosis, an autoimmune disorder.

Considering this evidence, it’s not surprising that Moises Velasquez-Manoff, a male with alopecia totalis, reported hair growth for the first time in years following his experimentation with helminth therapy. He details his experience with helminth self-infection, alongside a historical perspective of helminth eradication, in his book: An Epidemic of Absence.

While this evidence alone is certainly not enough to warrant self-experimentation with helminth self-infection, this emerging research is compelling and underscores the growing importance of the symbiotic relationship of humans and microbes.

Success rates

As seen in the outcomes of the different studies, the likelihood of significant (or complete) recovery is relatively high. And, again, a large proportion of AA patients (34-50%) will spontaneously recover within one year.

This is great news! But, it also makes it difficult to effectively estimate the true success rate of treatments. So, is there any way that someone with AA might be able to gauge their likelihood of recovery (or lack thereof)?

Yes. In clinical practices, there are criteria for AA known as “poor prognostic factors” – i.e., things that might make you less likely to experience full hair recovery. According to the literature, these include:

1. Bald patches that persist for longer than 1 year.
2. Onset of hair loss before puberty.
3. A family history of AA.
4. Ophiasis pattern of AA.
5. Associated nail changes, a.k.a when nail changes occur alongside AA.
6. Atopy, a.k.a a propensity to developing allergic diseases like eczema, asthma, and allergic rhinitis.

So, if you fit into these categories, chances are your AA might be more treatment-resistant. That being said, it doesn’t mean you can’t recover your hair; it just means that you may need to explore more treatment avenues (or combination therapies) to find what works for your hair loss specifically. Your practitioner can help guide you through identifying these treatment avenues.

With that, you’ll also want to consult your doctor early into the process – as treatment resistance can increase as the condition progresses. As such, it’s better to forego experimental / home remedies and begin a treatment plan right away.

This isn’t to say natural therapies might not be an option for you, but, rather that you should discuss the evidence of those treatments with your doctor and, if suited to you, explore the therapy under their supervision.

This will help avoid treatment resistance that may result from delayed treatment, which would partly mitigate a major poor prognostic factor that is within your control.

Summary

Alopecia areata (AA) is a form of autoimmune hair loss characterized by inflammation, exclamation mark hairs, patchy hair loss (in early stages), and hair follicle miniaturization (in later stages). The condition can progress to alopecia totalis (loss of eyebrow and eyelash hairs) or alopecia universalis (loss of hair all over the body). But in many cases, it spontaneously reverses.

An autoimmune attack near the hair follicle stem cell bulge is what triggers AA-related hair loss. This results in inflammation, stem cell dysfunction, a malformed hair follicle, and thereby thiner, brittler hair that is prone to breakage. Eventually, hair cycling also becomes dysfunctional, leading to continued hair growth dysfunction and premature hair fall.

Thankfully, a large proportion of AA cases will spontaneously resolve within a year of onset. Having said that, it’s not a guarantee. So, while “waiting it out” may mean you need no treatment at all, it also poses a risk of progression. The further AA progresses, the higher the likelihood of treatment resistance.

So, it’s important that talk to your doctor when you first notice the hair loss. The earlier you catch it, the better your chances of regrowth. This is especially true if:

• Your hair loss began before puberty
• You have a family history of AA.
• Your hair loss is in the “ophiasis” pattern.
• Your hair loss is associated with nail changes.
• You have concurrent atopy (eczema, asthma, allergic rhintis).

Nevertheless, a wide array of treatment options do exist — both drug-based and non-drug-based – for manageable and refractory cases alike. Generally, corticosteroids are one of the first-line treatments. When corticosteroids aren’t effective, immunotherapy, methotrexate, JAK inhibitors, and alternative treatments (aromatherapy, vitamins/minerals, microbial modulation, and more) are usually explored.

Overall, the prognosis for most AA patients is good. Having said that, the risk of relapse is still high. This is mainly attributed to the fact that most treatments are confined to suppressing the signaling that leads to AA hair loss, as opposed to mitigating the root cause of AA. We just don’t know enough about the origin of AA to target these causes (yet).

The one exception to this rule might be fecal microbiota transplants (FMT) — a treatment that has shown major hair recoveries for long-standing AA patients (who typically don’t respond well to treatment), and no signs of relapse for those responders (at least within study windows of 1.5 to 3 years). However, evidence on FMT is incredibly limited. Moreover, the treatment is currently not readily accessible in the US (unless you have AA and you’re seeking treatment for a chronic C. difficile infection).

Overall, hair regrowth is absolutely possible for most AA patients — whether through natural or conventional means. Just make sure to get in touch with a doctor as soon as you notice your hair loss, so that they can help direct a treatment plan that’s going to be best suited to your condition.

If you have any questions, please feel free to leave them in the comments!

Scarring alopecias make up about 7% of patients seen in hair loss clinics. This means almost 1 in 10 hair loss cases are attributed to scarring alopecia.

In this article, we’ll outline what scarring alopecias are, what makes them unique, and why they might develop. Then we’ll uncover why this classification of hair loss – scarring vs. non-scarring – might be a bit outdated.

Finally, we’ll reveal new research that’s changing the way we think about scarring forms of hair loss. Historically, scarring alopecias have been considered irreversible. But new case reports are showing just the opposite: that some people with scarring alopecias can achieve significant – and sometimes complete – hair regrowth.

We’ll dive into why this is important, how this may impact treatment avenues, and what you can do to start combatting the progression of scarring alopecias today, both naturally and conventionally.

What are scarring alopecias?

Scarring alopecias are an umbrella term for hair loss from the rapid destruction and scarring of hair follicles.

There are several types of scarring alopecias (1), and each type varies by its presentation and causes:

• Central centrifugal cicatricial alopecia (CCCA). A type of hair loss that occurs predominantly in African American women. Characterized by a progressive thinning that begins in the center of the scalp and gradually expands to the peripheral regions. The only feature that distinguishes it from female pattern hair loss is the lack of visible follicles in the affected areas and a shiny, smooth scalp. It was once believed to be caused by hair styling techniques; however, recent data (2) has refuted that claim.
• Frontal fibrosing alopecia. This type of scarring alopecia occurs in a band-like distribution in the front of the hair and may also be present in the eyebrows. It mostly affects postmenopausal women. It predominantly affects the hairline, leading to uniform recession as if the hairline marched backward.
• Lichen planopilaris. Patchy hair loss with itchiness, scaling, and visible redness in affected areas. It might also affect non-scalp areas. It sometimes presents as diffuse thinning.
• Chronic cutaneous lupus erythematosus. Patchy, scarring hair loss as a result of an autoimmune disorder: lupus. Onset of this type of scarring alopecia may result from UV exposure, though research hasn’t yet confirmed this.
• Pseudopelade of Brocq. Small and/or large irregular patches of hair loss with no signs of inflammation.
• Folliculitis decalvans. A single patch of hair loss that progressively expands. Typically found on the peripheral regions of the scalp. Affected areas may have pustules, honey-colored crusting, and tufting.
• Dissecting cellulitis of the scalp. Multiple, red, inflamed, and interconnected nodules that erupt from various scalp regions in somewhat of a web-like pattern. It may also be associated with acne conglobota.

How do scarring alopecias happen?

No one is quite sure. However, many researchers believe scarring alopecias are caused by an interaction between inflammation, our immune systems, and (potentially) our hormones.

Similar to other hair loss disorders, the step-process for developing a scarring alopecia seems to be:

Inflammation >> scarring >> hair loss

You might see this step-process and think it looks a lot similar to other hair loss disorders, like androgenic alopecia (AGA). At face-value, you’re right. But there are a few differences that make scarring alopecias unique.

1. In scarring alopecias, the location of inflammation is in the hair follicle stem cell bulge; in androgenic alopecia, it’s in the infundibulum (upper third of the hair follicle) and likely deeper below the hair follicles, but above the galea aponeurotica.
2. In scarring alopecias, the nature of inflammation in unknown and/or autoimmune-related; in androgenic alopecia, the inflammation is likely related to scalp tension, pathogenic microorganisms, and accelerated hair cycling.

It might seem absurd to distinguish scarring alopecias from androgenic alopecia by the nature and location of inflammation. After all, our hair follicles are already tiny “mini-organs”. What difference does it make if one hair loss disorder’s source of inflammation is just a couple of nanometers away from another’s?

Apparently, a lot. And this is because across hair loss disorders, the location of inflammation predicts where scarring will occur, which predicts what these hair loss disorders will end up looking like.

This is why, in the later stages, androgenic alopecia and scarring alopecias look so different:

With scarring alopecias, the inflammation is far more widespread, so the scarring ends up wiping out the entire hair follicle – the stem cell bulges, sebaceous glands, arrector pili muscles, and hair shaft.

In androgenic alopecia, the scarring remains clustered around the hair follicle. Subsequently, the scarring doesn’t wipe out these other components of our hair follicles until many years into AGA’s progression.

In scarring alopecias, why do a hair follicle’s stem cell bulges become inflamed?

No one is quite sure. While researchers have identified dozens of potential triggers (3) across patients with scarring alopecias…

• Sebaceous gland dysfunction
• Substance P transmission (a neuropeptide released during stress)
• Deficiency in PPAR signaling
• Collapse of hair follicle immune privilege (the hair follicle is generally resistant against to damage by the immune system)
• Bacterial infection
• Abnormal cellular changes
• Genetic factors
• Hairstyling
• Certain drugs (anticonvulsants, hepatitis B vaccine, cyclosporin)
• Autoimmunity
• Sunscreen use on the forehead

…It’s still unclear which causes might apply to each case, why our hair follicle’s stem cell bulges become inflamed, and why this inflammation becomes persistent in the first place.

It all seems to begin with a miscommunication between an inflammatory stimulant, our immune systems, and our hair.

The miscommunication: inflammatory stimulants, myofibroblasts, and beyond

During a normal inflammatory process, the body encounters some sort of inflammatory stimulus – a wound, a virus, or even an environmental irritant. This stimulus is identified by the immune system as foreign, at which point our immune system recruits cells to “attack” the foreign invader. This leads to inflammation (i.e., tissue swelling), which in many cases, is enough to kill off the foreign invader. Once the threat is gone, the immune system signals these cells to stop attacking, and the inflammation dissipates, leaving us the same as we were prior to the attack.

In scarring alopecias, this process does not go according to plan.

During scarring alopecias, our immune system picks up on a foreign threat and sends a group of cells called myofibroblasts to start attacking. These myofibroblasts have a number of roles in the body – three of which are (1) enhancing the inflammatory response, (2) supporting the healing process, and (3) producing proteins like collagen (which, if produced in a disorganized fashion, form the building blocks of scar tissue).

Under normal settings, myofibroblasts would help enhance the inflammatory response until the foreign threat is destroyed, at which point the myofibroblasts would no longer be needed. At this point, the myofibroblasts would then help to repair the damage caused by inflammation by laying down new collagen fibers (i.e., skin tissues). Then, these myofibroblasts would die off.

However, in the case of scarring alopecias, myofibroblasts fail to die off. To put it simply, there’s a disruption in the normal cell signaling that tells our myofibroblasts that they’re no longer needed. As a result, they continue to lay down collagen, which becomes excessive and disorganized, which then turns to scar tissue.

Subsequently, functional tissue begins to be replaced by poorly-functioning scar tissue. As the fibrosis continues, the affected organs continue to lose functionality. We see this in conditions like cirrhosis, scleroderma, and pulmonary fibrosis (fibrosis of the lungs) – for example, where fibrosis makes it difficult for the liver, skin, and lungs to do their job.

This is exactly what happens in the hair follicle during scarring alopecia.

Infection and sustained inflammation begin to severely damage the hair follicle. And unfortunately, this scarring process ends up destroying our hair follicle stem cell bulges. This stem cell bulge is incredibly important; it contains the “blueprints” – or the building blocks – of each hair follicle. And without a hair follicle stem cell bulge, our hair follicles have no blueprints to follow for replication.

This leads to the complete destruction of the hair follicle… and the scarring of its surrounding skin. And as you can imagine, this is not a position most hair loss sufferers want to be in.

Are scarring alopecias reversible?

Traditionally, researchers have generally held the stance that scarring alopecias aren’t reversible.

This is because of the fact that scarring alopecias (1) lead to widespread scarring of an entire skin region, and thereby (2) wipe out the hair follicle stem cell bulges. For these reasons, many researchers have held onto the belief that scarring alopecias are irreversible – and that the best we can do is slow or stop their progression.

Encouragingly, this belief is now changing. Why? Because new evidence is showing that scarring alopecias are not only theoretically reversible, but that we actually have case studies of this happening. It’s all a matter of unlocking how to do it on a consistent basis.

Here’s why we believe this is possible.

#1: AGA, which also leads to scarring, is reversible even in its latest stages.

To reiterate from earlier, end-stage AGA closely resembles that of end-stage scarring alopecias. In both conditions, we see so much fibrosis (scarring), that there’s a total loss of follicular integrity.

Having said that, even in late stages of androgenic alopecia, we’ve seen pretty significant hair regrowth. This is obvious with examples from a few of our case studies from our membership community – like Mike and Raul – who used natural methods to see regrowth beyond what is typically observed with conventional treatments.

Mike’s Regrowth

Raul’s Regrowth

But perhaps the most impressive example of hair regrowth from advanced AGA happened entirely by accident.

In 1986, a 78-year man who’d been bald for 30+ years fell asleep in his rocking chair. Inadvertently, he slumped over, landed head-first onto hot coals, and received second degree burns across much of his scalp.

He refused to be treated at the hospital and was eventually sent home as an outpatient. Four months later, he returned for a checkup. During that time from the injury, he’d accidentally regrown his entire juvenile hairline (4).

Remember: in advanced cases of AGA, a hair follicle’s stem cell bulges appear either scarred or completely depleted. This implies an inability for hair recovery. Yet here, we see a case of complete hair recovery… just the opposite of what we’d expect.

And as we dig deeper into the research on scarring alopecias, we can find plenty of cases where recoveries happen, too.

#2: scarring alopecias have been reversed before!

There are several case studies of people with scarring alopecias regrowing significant amounts of hair. In some cases, the hair recovers completely.

In some cases, this has happened with interventions as simple as stopping the use of facial sunscreen (5). In other cases, significant regrowth came after using topical metformin (6). In one case of lupus-related scarring alopecia, complete hair regrowth was observed within three months following the use of hydroxychloroquine (7). And in cases of frontal fibrosing alopecia, oral finasteride led to near-complete hairline regrowth after just 12 months (8).

In light of these findings, there are really only two explanations:

1. In scarring alopecias, stem cell bulges aren’t totally lost. Therefore, the hair is still recoverable. Or…
2. Our understanding of hair follicle stem cell bulges needs to be revised. Maybe hair follicles can regenerate in the absence of stem cells, and through not-yet-discussed processes, like that of follicle-to-follicle communication.

Let’s explore that second idea for a second, as it may shape the next decade of hair loss research.

What do we know about follicle-to-follicle communication?

Follicle-to-follicle communication is a phenomenon that was originally observed in one fascinating study (9) – the findings of which we described in this article. To summarize:

In 2015, researchers wanted to see if hair follicles could communicate with each other to coordinate behaviors – like making new hair follicles. So they set up a test…

They plucked 200 hairs from the backs of mice… but did so while controlling for the diameter of a plucking region. In some cases, 200 hairs were plucked in a 2.4mm region. In other cases, 200 hairs were plucked from an 8mm region. The smaller the region, the higher-density the plucking – and vice-versa.

The goal: to see if hair follicle behavior changed on how closely hairs were plucked from one another. So they measured hair growth over the next several weeks.

The results were fascinating.

With low-density plucking, hair follicles either didn’t grow back at all… or grew back to their normal pre-plucking densities. That’s what we would expect to happen.

But with higher-density plucking, additional hair follicles were created… to the tune of a five-fold increase.

What’s more interesting is why this happened. The researchers theorized that higher-density plucking created more inflammatory signaling, which led to more cross-communication between hair follicles directly next to each other, which signaled to hair follicles to start regenerating – regardless of whether they’d been plucked.

The end-result: a huge increase in hair.

The implications? That nearby hair follicles can communicate with one another (!), and that these communications must include signaling for hair follicle regeneration. Based on this study, it’s clear that healthy hair follicles can coordinate regeneration with damaged hair follicles.

So, how does this relate to scarring alopecia?

Considering hair loss from scarring alopecia is a result of complete hair follicle destruction, and considering that this destruction has puzzlingly reversed itself across many case studies…

We can presume that follicle-to-follicle communication is playing a role here, and that understanding this role (and harnessing this cellular crosstalk) is probably one way people with scarring alopecias can unlock huge hair recoveries.

So, how do we do this?

We don’t yet know! Research is still emerging, and as it continues to evolve, we’ll update this article.

In the meantime, there’s plenty we can do to stop the progression of scarring alopecias – and potentially even see major recoveries.

What are the current treatments for scarring alopecias?

Step 1: connect with a dermatologist

The first step is always making an appointment with a dermatologist. By understanding what kind of scarring alopecia you have, you can better target your treatment regimens to save yourself time, effort, and money.

Step 2: identify and remove any potential inflammatory “triggers”

Once you’ve scheduled your appointment, one of the most critical next steps is to make your best effort to identify and remove some of the most common triggers of scarring alopecias. This will be highly individual and dependent, again, on the type of scarring alopecia with which you’re diagnosed.

Here are a few of the common inflammatory stimulants suspected in scarring alopecias:

• Sunscreen use: there is a weak link between sunscreen use and frontal fibrosing alopecia (FFA) (5). Some researchers hypothesize this could be due to decreased sebum production during the time in which a woman is most likely to be affected by FFA, menopause. This results in an inability to clear topical products, like sunscreen, from the follicle, potentially leading to an autoimmune reaction. Other researchers have proposed an alternate view: with the anti-inflammatory, immunomodulatory effects of UV light, blocking UV light (using sunscreen) may actually encourage autoimmunity in the follicle. Cessation of sunscreen use has been shown to produce noticeable regrowth in as little as 6 months with an almost full recovery in 36+ months.
• Hairstyling: While studies have failed to establish hairstyling as the sole cause of CCCA, certain hairstyling techniques may contribute to at least some cases of scarring alopecia. If you find yourself dealing with a potential case of scarring alopecia and you regularly receive hair relaxant treatments, employ hot combing, or style your hair in braids, cornrows, or using other traction styling methods (10) – it might be best to avoid these treatments and/or stylings (or at least reduce their frequency) until you can rule out their potential involvement.
• Environmental toxins as inducers of autoimmunity: Autoimmunity is one of the purported causes underpinning the development of scarring alopecia. This is due to the fact that the stem cell bulge of the follicle is normally a site of immune privilege, meaning it is usually protected from the action of the immune system. However, autoimmune processes can actually cause this immune privilege to be lost. Interestingly, environmental toxins have the ability to induce autoimmunity. For this reason, avoidance of environmental triggers linked to autoimmunity, like rancid vegetable oils, mineral oils, and sources of heavy metals, is a good precautionary measure (11).
• UV exposure: Some causes of scarring alopecia, like chronic cutaneous lupus erythematosus, are exacerbated by UV exposure. Use of sunscreen or UV-blocking clothing/hats may be needed to prevent the worsening of lesions that contribute to hair loss.

Step 3: settle on a treatment approach

There are two ways we can approach this: drug-based treatments and non-drug treatments.

We’ve divided these interventions into their respective sections and described who these treatments might be best for, which dosages are used in the literature (where applicable), the outcomes of the research, and what potential issues might arise with each given treatment.

Drug-based treatments

Topical, intralesional, and oral corticosteroids:

• Best candidates: Most forms of scarring alopecia, patients with CCCA not related to traumatic hair styling.
• Dosages: 10mg/mL for intralesional injections every 6-8 weeks; 25-40mg per day for 2-4 months with oral corticosteroids (1).
• Outcomes: Corticosteroid treatment, in any form of administration is mostly limited to halting the progression of disease as it doesn’t address the scarring that impedes hair follicle regeneration. Can promote regrowth in some patients with dissecting cellulitis (12).
• Problems: Oral corticosteroids are limited to severe/rapidly progressing disease; topical corticosteroid treatment can result in skin atrophy, a.k.a thinning of the skin.

Hydroxychloroquine:

• Best candidates: Patients with frontal fibrosing alopecia, lichen planopilaris, and chronic cutaneous lupus erythematosus.
• Dosages: Below 7.5/mg/kg for lichen planopilaris and frontal fibrosing alopecia, 400mg daily during summer months with chronic cutaneous lupus erythematosus and smaller doses during winter (1).
• Outcomes: Effective at decreasing signs and symptoms of lichen planopilaris and frontal fibrosing alopecia and preventing further hair loss, effectively resolve lesions related to chronic cutaneous lupus erythematosus (13), full hair regrowth has been observed with hydroxychloroquine in at least one case of lupus-related alopecia (7).
• Problems: Studies are often too short to estimate the true incidence of retinopathy at dosages used for these conditions.

Antibiotics (Minocycline, rifampicin, fusidic acid):

• Best candidates: Patients with folliculitis decalvans.
• Dosages: 300mg rifampicin 2x daily (should not be used as a monotherapy, which can promote antibiotic resistance), combination of 300mg rifampicin, 300mg clindamycin, and fusidic acid along with topical corticosteroid lotion for 3 months has been used with success, topical clindamycin or benzoyl peroxide can control mild cases, oral antibiotics are needed for more severe cases (1).
• Outcomes: Effective at addressing the infection that leads to folliculitis decalvans, but not restoring the hair lost.
• Problems: Rifampicin is the preferred antibiotic because it is highly lipid-soluble (the scalp environment is very lipidic) and accumulates in high quantities in the hair follicle, however, antibiotic resistance is a major issue with its use.

Topical metformin:

• Best candidates: Who topical metformin might be best for is still unclear, as research is preliminary, but case studies have demonstrated success in CCCA patients (6).
• Dosages: 10% topical metformin with the potential for higher concentrations if the patient responds well to the treatment.
• Outcomes: Although research is preliminary, there have been two cases of partial regrowth in CCCA – traditionally believed to be irreversible (and notoriously difficult to treat) (6).
• Problems: Preliminary research suggests there is little to no systemic side effects. Instead, side effects are usually superficial and limited to scalp dryness and irritation.

Oral Isotretinoin (Accutane®):

• Best candidates: Patients with dissecting cellulitis and cases of chronic cutaneous lupus erythematosus resistant to antimalarial therapies like hydroxychloroquine.
• Dosages: 0.5-1mg/kg daily for dissecting cellulitis (1).
• Outcomes: Usually produces rapid results in chronic cutaneous lupus erythematosus, treatment for 6-11 months in dissecting cellulitis shrinks lesions and can even induce periods of long remission.
• Problems: Oral isotretinoin can cause large quantities of hair follicles to prematurely enter the telogen phase, which can lead to diffuse shedding (1). The risk of disease progression should be weighed carefully against the potential risk of increased shedding.

Finasteride:

• Best candidates: Patients with frontal fibrosing alopecia.
• Dosages: 2.5mg daily (14).
• Outcomes: Some studies suggest finasteride is the most effective therapy for treating frontal fibrosing alopecia. Patients with this condition can expect a response rate of about 50% with finasteride alone (14). At least one case report demonstrated marked regrowth and a reversal of skin atrophy (i.e., skin thinning) (8).
• Problems: In women with already low or normal androgen levels, finasteride could produce sexual/mental side effects.

Non-drug treatments

Microneedling + platelet-rich plasma:

• Best candidates: Unknown.
• Methods: 20 sessions spaced 2 weeks apart.
• Outcomes: Clinical improvement in one case of general scarring alopecia – the details of this clinical improvement aren’t specified (i.e., improvement of inflammatory lesions vs. actual hair regrowth)
• Problems: Likely cannot be used to treat some forms of scarring alopecia like folliculitus decalvans, at least in their active infection phase, due to the bacterial nature of the condition.

Low level light/laser therapy (LLLT):

• Best candidates: Patients with lichen planopilaris.
• Methods: 272 pulsed laser diode cap with 1360 mW total output
• Outcomes: Case reports suggest lichen planopilaris patients may be able to achieve hair regrowth with the use of LLLT (15).

Excimer laser (UV-B light)

• Best candidates: Patients with lichen planopilaris and some cases of frontal fibrosing alopecia.
• Methods: Sessions as frequent as twice weekly with an average of 10 sessions reported in the literature.
• Outcomes: Studies have demonstrated a decrease in inflammation, as well as some instances of hair regrowth (16).

Hair Transplants

We know from the literature that there are some cases of scarring alopecia that are reversible. But, what if your hair doesn’t grow all the way back, even with the best-of-the-best treatment?

This is where hair transplants might be useful.

Hair transplants in scarring alopecias are different than hair transplants for non-scarring hair loss disorders. While grafts in non-scarring alopecias have a 90% survival rate, scarring alopecias may only have an average 50% survival rate.

But, transplants don’t have to be a stab in the dark. We can usually predict whether or not a transplant is going to be successful by (1) understanding what kind of scarring alopecia you have, and (2) performing a pre-surgery transplant test.

We’ve compiled the types of scarring alopecias that are more likely to see success from a transplant vs. those that might not:

Scarring alopecias more likely to receive transplants successfully	Scarring alopecias where hair transplants are less likely to survive
Central centrifugal cicatrial alopecia (CCCA)	Lichen planopilaris
Discoid lupus erythematosus	Frontal fibrosing alopecia
Pseudopelade brocq
Folliculitis decalvans

However, the safest way to estimate your individual tolerance to a hair transplant is to have a dermatologist perform a pre-surgery transplant test.

But, what if your chances of hair transplant survival end up being low? Or what if hair transplants are too expensive? Or too invasive? What are the options, then?

In these cases, there is one additional option.

Artificial hair integrations

For treatment-resistant and/or transplant-intolerant cases or for those who aren’t comfortable with the price or the procedure, the next best option is artificial hair integrations.

The good news is that these are inexpensive and readily accessible – and something you can begin to use right away. But, you’ll want to be absolutely sure that these integrations aren’t putting any additional strain on existing hair, as this can do more harm than good. In some cases, it may trigger a case of traction alopecia or, worse, a new case of scarring alopecia.

So, to recap, here’s a sequential approach you should consider for treatment:

1. Make a dermatologist appointment to identify what kind of scarring alopecia you might have (if any).
2. Identify and remove any potential triggers.
3. Based on what type of scarring alopecia you have, explore some treatment avenues provided and discuss them with your dermatologist.
4. If you aren’t able to achieve full recovery, explore hair transplants. Performing a pre-surgery transplant test can help you gauge whether or not a transplant will survive on your scalp.
5. If you are intolerant to transplants and/or aren’t comfortable with the price or the procedure itself, artificial hair integrations are relatively inexpensive and very accessible.

Summary

Scarring alopecias are relatively uncommon; they constitute just 7% of hair loss diagnoses in hair loss clinics. Having said that, they’re characterized by aggressive scarring. This scarring leads to the destruction of skin tissue surrounding hair follicles, as well as the destruction of stem cell bulges which make hair follicles and the hair follicles themselves. Consequently, many researchers have historically considered that scarring alopecias are irreversible.

This is no longer the case. Case reports of full hair recoveries from scarring alopecias, alongside evidence that healthy hair follicles and unhealthy hair follicles can actually communicate with each other, now leads researchers to believe that scarring alopecias are reversible… we just don’t know how to do it consistently (yet).

Because scarring alopecias are less common, there are still many questions researchers have yet to answer:

• Why are some cases of scarring alopecias reversible, if all scarring alopecias are believed to result in a loss of the stem cell bulge?
• If there are at least some scarring alopecias that happen to retain stem cells, could there be an overlap in treatments with AGA? In other words, could some scarring alopecia patients benefit from AGA treatments that address fibrosis?
• If stem cells aren’t retained, is there some other regenerative process, like follicle-to-follicle communication, at play?

As researchers attempt to answer these questions, there are still some great treatments out there for scarring alopecia patients – both drug-based and drug-free, that have shown clear benefit. While most are limited to improving symptoms and slowing or halting the progression of hair loss, some patients are seeing partial and/or full recoveries.

For those who find their hair loss is treatment-resistant or want to restore hair lost to scarring alopecia, hair transplants are a decent option. However, they can be a hit or miss, being that the transplant survival rate is around 50% (vs. 90% for other hair loss types). You can maximize your chances of survival by identifying what kind of scarring alopecia you’re dealing with as well as performing a pre-surgery transplant test.

Artificial hair integrations are also a great option — and one much cheaper and more accessible than hair transplants. However, it is of the utmost importance that these are applied correctly to avoid undue strain on healthy hair (which may trigger the onset of new hair loss).

Have any questions about the new treatments for or emerging research on scarring alopecia? Please let us know in the comments section below.

Oral minoxidil for women with hair loss: an underutilized treatment?

Although topical minoxidil seems to get most of the attention as a hair loss treatment, its oral counterpart is also effective at promoting hair regrowth in both males and females.

Generally, higher dosing means better efficacy, but with a higher risk profile. As it relates to oral minoxidil, this means limb swelling, low blood pressure, and, potentially, heart palpitations. But, there’s one side effect that may be more concerning for women taking oral minoxidil than men: excessive body hair growth.

Considering this is something most women want to avoid or may also struggle with alongside their hair loss (in cases of female androgenic alopecia), this side effect could be of significant concern.

So, is there a way we can harness the hair-growing effects of oral minoxidil without the side effects?

Yes. This Quick Win dives into the research: the clinical evidence, the best dosages, and the best ways to avoid excessive body hair growth while taking this medication.

Note: Quick Wins are short articles focused on answering one question about hair loss. Given their specificity, these articles are written in a more scientific tone. If you’re new to hair loss education, start with these articles.

Oral minoxidil: research at a glance

What is oral minoxidil?

Oral minoxidil was initially developed as a treatment for ulcers, but later rebranded as a medication that might potentially lower blood pressure. During clinical trials, a lot of participants started reporting unexpected hair growth. This led researchers to reformulate minoxidil as a topical for hair loss, which eventually became FDA-approved in 1988.

Minoxidil’s structure

While no one is quite sure how minoxidil works to regrow hair, researchers suspect that it has something to do with minoxidil’s ability to (1) improves blood flow, and (2) increase prostaglandin E2 synthesis – a fatty acid derivative that likely plays a role in hair cycle maintenance.

Is oral minoxidil better than topical minoxidil?

Potentially. Both oral and topical minoxidil need to interact with an enzyme called sulfotransferase before becoming active and eliciting any effects on our hair follicles. Unfortunately, many men and women who are losing their hair also lack enough sulfotransferase in the scalp skin for topical minoxidil to do its job. This likely explains why for 30-40% of people, topical minoxidil doesn’t work at all (myself included).

Enter oral minoxidil. This drug is metabolized is activated in the liver – where there is plenty of sulfotransferase to go around – and then rapidly distributed to tissues throughout the body. This is why, when it comes to regrowing hair, oral minoxidil has a much higher response rate – typically 90-100%.

Unfortunately, with the rapid tissue distribution of oral minoxidil, we can also experience its hair-growing effects elsewhere in the body: namely, across our chests and faces.

This isn’t such a problem for men (in fact, many men enjoy the increased body and facial hair growth). But for women, this can be a dealbreaker – with the fear of unwanted body hair growth relegating them topical minoxidil or other treatment options.

So, for females, is there a way to mitigate any unwanted side effects of oral minoxidil while still maximizing its hair-promoting effects?

Yes.

Clinical studies

Unlike the research on topical minoxidil, oral minoxidil research is sparse (especially in women). Nevertheless, there do seem to be certain dosages of oral minoxidil – and combination therapies – that greatly reduce the risk of unwanted hair growth in women.

Here’s a table of the studies conducted on women taking oral minoxidil for hair loss.

Daily Dose (duration)	Type of Hair Loss	Results	Side Effects
1mg daily (6 months) (1)	Female Pattern Hair Loss	12% increase in hair count	Limb Swelling: 4% Hypotension: 0% Excess Hair Growth Outside the Scalp: 27%
0.25mg + 25mg spironolactone daily (12 months) (2)	Female Pattern Hair Loss	72% improvement in hair loss severity	Limb Swelling: Not reported Hypotension: 2% Hives: 2% Excess Hair Growth Outside the Scalp: 4%
0.25mg-2.5mg with most patients taking 1mg (12 months) (3)	Chronic Telogen Effluvium	45% improvement in hair loss severity	Limb Swelling: Not reported Hypotension: 5% Excess Hair Growth Outside the Scalp: 38%

Looking at the results, we see that all doses of oral minoxidil are effective at promoting hair growth: 1.5-2 mg by itself, and 0.25 mg of oral minoxidil in combination with 25 mg of spironolactone (an anti-androgen drug).

When analyzing side effects, serious adverse events – like hypotension and limb swelling – are uncommon, even with doses as high as 1-2.5mg. But at these dosages, there are quite a few women (27-38%) reporting unwanted hair growth elsewhere on the body… which is exactly what we’d like to avoid.

But there’s an inflection point: a dosage that we can minimize the risk of unwanted hair growth (hypertrichosis) while maximizing oral minoxidil’s pro-hair effects on the scalp.

It’s with 0.25mg of oral minoxidil + 25mg of spironolactone daily.

With this daily dosage of oral minoxidil + oral spironolactone,  only 4% of women report excess hair growth… while the majority of females in the study saw significant improvements to their scalp hair loss.

What this means: this combination therapy of low-dose minoxidil + low-dose spironolactone (an anti-androgen drug) is sort of the oral minoxidil “sweet spot” – at least in terms of lowering your risk of body hair growth, and raising your likelihood of scalp hair growth.

Low-dose oral minoxidil + low-dose oral spironolactone is a winning formula for female hair loss sufferers

But, what if you’re sensitive to spironolactone?

Although 0.25 mg of oral minoxidil alongside 25 mg of spironolactone daily might be a viable option for many women with hair loss, spironolactone can cause mild allergic reactions in sensitive individuals. (4, 5) While these effects are rare, we have had some members of our community echo these concerns and even report adverse reactions of their own.

So, maybe you’ve found that you’re sensitive to spironolactone and that combining low dose spironolactone + oral minoxidil isn’t an option for you. What’s the next best option?

At this point, it really depends on what your tolerance for higher dosages of oral minoxidil (and their potential for side effects). Higher doses of 1mg to 2.5mg will likely provide results, but also increase your risk of body/facial hair growth.

If you have milder hair loss or really aren’t comfortable with increased body/facial hair (or don’t want to manage it with other therapies), you can always start with 0.25mg of minoxidil on its own. If it still isn’t providing the results you’re looking for, you can always look into alternative oral or topical therapies to bolster your results. As always, discuss your options with your doctor before doing anything.

You may also decide to implement totally different therapies. After all, many females have seen success treating hair loss outside of the drug model, and with therapies like:

• Platelet-rich plasma
• Massaging
• Microneedling
• Low-level laser therapy

…and more. So, before you jump on any treatment, make sure that you have a firm understanding of 1) the drivers of your hair loss, and 2) your treatment options. Then, make an action plan for hair recovery that’s tailored to your needs and preferences.

What’s the bottom line?

If you’re a female with pattern hair loss, and your goal is to maximize the hair-promoting properties of oral minoxidil while minimizing your risks of hypertrichosis, research shows that combining 0.25mg of oral minoxidil with 2.5mg of spironolactone is likely your best option. At these dosages, you’re positioning yourself for scalp hair growth while minimizing the risk of body hair growth.

If spironolactone isn’t an option for you, that’s okay. Higher doses of oral minoxidil (1-2.5mg) don’t present with any increased risk of hypotension or limb swelling, but at these dosages, 27-38% of women do report excess body/facial hair growth in clinical studies. If this is a concern for you, consider combining low-dose oral minoxidil with alternative therapies or opting for another treatment altogether.

Lastly, oral minoxidil is a prescription medication. So be sure to consult your doctor before doing anything.

Question? Comments? Please reach out in the comments section.

Saw palmetto for hair growth: does it stack up to finasteride?

Saw palmetto is often touted as nature’s finasteride. This herbal extract reduces levels of the hormone dihydrotestosterone (DHT). For this reason, it’s clinically demonstrated to improve hair growth in men with androgenic alopecia (AGA).

But is saw palmetto as effective as finasteride?

Not quite. In fact, a closer look into the research on saw palmetto reveals that taking this supplement also comes with risks.

That’s not to say that saw palmetto is ineffective. But if you’re going to opt for saw palmetto over finasteride, you’re going to want to weigh its benefits and risks. Specifically, you’re going to want to know how saw palmetto compares to finasteride in terms of its (1) ability to reduce DHT, (2) ability to regrow hair, and (3) reported side effects.

This Quick Win dives into the details (and answers). The bottom line: saw palmetto isn’t as powerful as finasteride, but it also comes with some upsides that may make it a better option, at leaast for certain hair loss sufferers.

Note: Quick Wins are short articles focused on answering one question about hair loss. Given their specificity, these articles are written in a more scientific tone. If you’re new to hair loss research, start with our long-form articles.

What is saw palmetto?

Saw palmetto is a palm plant native to warm humid climates (Florida).

Saw palmetto plant

Thirty years ago, researchers discovered that certain polyphenol and lipid extracts of saw palmetto could reduce the activity of type II 5-alpha reductase – an enzyme our bodies use to make the hormone dihydrotestosterone (DHT).

DHT is the main hormone implicated in pattern hair loss, also called androgenic alopecia (AGA). And interestingly, the popular hair loss drug finasteride (Propecia®) reduces that same enzyme – type II 5-alpha reductase – to lower DHT levels and improve pattern hair loss outcomes in ~80% of men trying the drug.

Unfortunately, finasteride use is also associated with sexual side effects. This scares a lot of men away from trying the drug. It also leads many of them to wonder…

“If I use saw palmetto instead of finasteride, can I still regrow hair while also reducing my risk of side effects? After all, saw palmetto is natural, and natural often means safer.”

For starters, anything branded as “natural” isn’t always safer. Many natural supplements sold through Amazon and tested by third parties have been found to contain dangerous levels of heavy metals. Moreover, many popular natural extracts – i.e., green tea extract – have been associated with hepatic failure due to the metabolic demands these extracts can place on our livers. (For more information, see my master class).

In any case, if we’re to answer the question, “Is saw palmetto as effective as finasteride?”, we’ll need to evaluate saw palmetto versus finasteride in terms of its (1) expected hair regrowth, and (2) risk of side effects.

The rest of this Quick Win does just this.

Saw palmetto vs finasteride: hair regrowth

“Hair regrowth” is a non-specific term, and most clinical studies on pattern hair loss define this term differently:

• Reductions to hair shedding
• Improvements to anagen:telogen ratios
• Increases in non-vellus hair counts
• Global photography assessments

…the list goes on.

That’s why, whenever we’re diving in studies on hair loss, we standardize the term “hair regrowth” into two categories:

1. Response Rate. This is the percentage of people receiving treatment who see a slowing, stopping, or reversal in their hair loss. After all, simply slowing down the progression of AGA is a win for most hair loss sufferers.
2. Regrowth Rate. This is the percent change in terminal (i.e., non-vellus) hair counts before and after treatment. We use this metric because it’s best out there in terms of translation to visual improvements. Increases to vellus hair counts (i.e., small, wispy, white hairs) just don’t show up in photographs, so we don’t count those.

So, if we summarize the data on saw palmetto versus finasteride, how do these two interventions compare? (1) (2)

	Saw Palmetto (320mg)	Finasteride (1mg)
Response Rate	60%; dependent on the dose and delivery (supplement or topical)	80-90%
Regrowth Rate	0-10%; potentially higher if used alongside other therapies	10%, alongside thickening of miniaturizing hair

The key takeaway: compared to finasteride, saw palmetto has a lower response rate and regrowth rate. And when we look at the individual studies that constitute these aggregated estimations, things look a little bleak.

To date, there’s only one clinical study directly comparing saw palmetto versus finasteride for the treatment of androgenic alopecia. The investigation team randomized 100 men with androgenic alopecia into two groups. They gave one group 320mg of saw palmetto and the other group 1mg of finasteride – every day, for two years. (3)

The results? After 24 months, 68% of finasteride users saw hair regrowth, while only 38% of men taking saw palmetto saw hair regrowth. Moreover, investigators noted that in the saw palmetto group, hair regrowth only occurred in the crown (i.e., vertex), and that the magnitude of regrowth was significantly less than finasteride.

In other words, saw palmetto achieves half the response rate of finasteride, and that if regrowth does occur, it’s not nearly as impressive as what finasteride achieves.

Having said that, it’s not all bad news. That same study also demonstrated that 45/50 men in the saw palmetto group saw a stop in hair loss over the two years that they took it. So, in this one study, saw palmetto showed a response rate of 90%.

This means it’s not a complete stretch to say that most men taking 320mg of saw palmetto daily should see an improvement in their pattern hair loss. It’s just that this improvement won’t be anywhere near on-par what is achievable with finasteride.

Why isn’t saw palmetto as effective as finasteride?

This likely has to do with the ways in which saw palmetto reduces DHT, and the amount of DHT that saw palmetto reduces.

Finasteride is a synthetic azosteroid. It reduces DHT by competing with (and binding to) a coenzyme that our bodies use to make type II 5-alpha reductase – the enzyme that converts free testosterone into DHT.

Conversely, saw palmetto competitively and non-competitively inhibiting type II 5-alpha reductase, reducing the binding of DHT to androgen receptors, and increasing the conversion of DHT to a weaker metabolite called androstanediol (4).

The long-story short is that these factors, along with differences in the half lives of both finasteride and saw palmetto, lead to differences in their abilities to lower DHT.

For reference, see this graph on the DHT-reducing capabilities of both saw palmetto and finasteride, as organized by different tissue sites.

The bottom line: saw palmetto is about half as effective as finasteride because it just doesn’t reduce as much DHT.

What about side effects?

At this point, we’ve really only evaluated half of the question: is saw palmetto as effective as finasteride?

In terms of response rates and regrowth rates, the answer is no. But can saw palmetto make up for its lower efficacy by being a safer long-term supplement for hair loss sufferers?

Maybe.

Saw palmetto: risk of adverse events

Long-term clinical studies show that saw palmetto’s overall rate of side effects is just 2%. Moreover, if side effects do occur, they’re relegated more so to gastrointestinal distress than to sexual dysfunction. Even better, many studies on saw palmetto show no change in libido; some studies show improvement to sexual health (at least for men with enlarged prostates). (5) (6) (7)

Finasteride: risk of adverse events

The “Yelp effect” is a phenomenon where patrons of a business are far more likely to leave a review if their experience was negative rather than positive. Finasteride is a drug that suffers from the Yelp effect, meaning that its sexual side effects are often overstated and amplified online.

Having said that, side effects do occur. Moreover, the self-assessment questionnaires filled out by participants in large-scale clinical trials for finasteride were worded in such a way where under-reporting certain side effects were more likely than not (but that’s for another article).

In any case, finasteride use does come with a heightened risk of side effects. Depending on which study you cite, between 1% and 25% of finasteride users will report issues ranging from brain fog to depression to sexual dysfunction. (8) (9) Moreover, when side effects are reported, they seem to be of higher magnitude versus saw palmetto.

The bottom line:

• Finasteride’s side effects are likely overstated online and understated in the literature
• Compared to saw palmetto, finasteride likely leads to side effects that are (1) of higher incidence, and (2) more severe

Saw palmetto or finasteride: which one is right for you?

It depends on your risk tolerance for side effects, and whether you plan on combining saw palmetto with other treatments, therapies, or procedures to make up for its lower response rates and regrowth rates.

There’s evidence that supplemental + topical saw palmetto, alongside other ingredients, might lead to better hair loss outcomes than just supplemental saw palmetto. Moreover, combining saw palmetto with massaging, microneedling, platelet-rich plasma therapy, or other interventions might help mitigate its lower efficacy.

Having said that, making these choices will depend entirely on someone’s needs, preferences, and unique hair loss situation.

Anything else to know?

Unlike finasteride, saw palmetto isn’t standardized. Serenoa repens growing conditions, extraction methods, and manufacturing practices can all impact the composition, bioavailability, and absorption of each saw palmetto supplement. In fact, these differences might explain the variances in response rates and regrowth rates seen across saw palmetto studies.

So, if you’re looking for a more comprehensive guide on how to use saw palmetto – including recommendations for dosages, extraction practices, and combinations therapies – see our saw palmetto ultimate guide here.

The bottom line

In order to evaluate whether saw palmetto is as effective as finasteride, we need to understand how the supplement compares in terms of (1) response rates, (2) regrowth rates, and (3) risk of side effects.

Saw palmetto isn’t as effective as finasteride in terms of its response rates or regrowth rates, but it also seems to cause fewer (and less severe) side effects. Because of this, making the choice to use saw palmetto over finasteride depends entirely on someone’s risk tolerance for side effects, as well as whether they plan on combining the supplement with other treatments, therapies, or procedures to make up for its less-impressive efficacy.

	Saw Palmetto (320 mg)	Finasteride (1 mg)
Response Rate	60%; dependent on the dose and delivery (supplement or topical)	80-90%
Regrowth Rate	0-10%; potentially higher if used alongside other therapies	10%, alongside thickening of miniaturizing hair
Side Effects	2%; more relegated to gastrointestinal distress than sexual side effects	1-25%; partly psychosomatic, but more severe than saw palmetto

Otherwise, if you have any questions, please feel free to leave them in the comments section.

 

Ketoconazole shampoo is an anti-fungal, anti-inflammatory shampoo that is sometimes used to treat androgenic alopecia (AGA).

There are two formulations of ketoconazole shampoo: 1% and 2%. While 1% ketoconazole is sold over-the-counter as an ingredient in many hair loss shampoos, only 2% ketoconazole is clinically shown to improve pattern hair loss. And unfortunately, 2% ketoconazole requires a prescription from your doctor.

This leads a lot of pattern hair loss sufferers to opt for 1% ketoconazole shampoo, and mainly out of convenience. But if you’re opting for 1% ketoconazole instead of 2%, are you selling yourself short any potential hair gains?

More specifically, when it comes to 1% versus 2% ketoconazole for hair loss, does one percentage point really matter?

This Quick Win dives into the studies on ketoconazole to answer this question.

Note: Quick Wins are short articles focused on answering one question about hair loss. Given their specificity, these articles are written in a more scientific tone. If you’re new to hair loss education, start with these articles.

Is 2% ketoconazole better than 1% ketoconazole?

Currently, there are no studies directly comparing 1% to ketoconazole to 2% ketoconazole in their ability to promote hair growth.

However, we can look at some different studies that use either formulation and compare how each one performs in its respective studies. Then, we can compare the results of each study to get a feel for which one is more effective.

First, let’s look at 2% ketoconazole. This study investigated 2% ketoconazole’s ability to increase hair counts in AGA patients. They found that, after 6 months (and 3x per week of use), participants experienced an average 18% increase in hair count.

Now, let’s evaluate 1% ketoconazole. This study looked at the effectiveness of 1% ketoconazole for AGA. After 6 months of use 3x per week, 1% ketoconazole didn’t increase hair count, but it did decrease hair shedding. In other words, 1% ketoconazole is effective enough to slow or stop shedding, but not to promote hair regrowth.

Both studies employed the same frequency for the same amount of time and on subjects with the same condition. Because of this, we can assume that ketoconazole at a 2% concentration is likely more effective than at 1%.

An additional study also compared 1% versus 2% ketoconazole in their ability to combat the scalp yeast Malassezia and the condition seborrheic dermatitis. Malassezia overgrowths and seborrheic dermatitis are often observed alongside pattern hair loss. These conditions lead to excessive sebum production and scalp flaking (i.e., dandruff), and thereby may accelerate AGA by increasing overall scalp inflammation. Moreover, there’s also research suggesting that resolving Malassezia overgrowths and seborhheic dermatitis may enhance hair regrowth. Long-story short: if we’re going to use a ketoconazole formulation for hair loss, it only benefits us if that formulation also improves these conditions.

The findings from that research team? When it came to decreasing Malassezia load and scalp flakiness from seborrheic dermatitis, 2% ketoconazole outperformed 1% ketoconazole in both categories. Moreover, 2% ketoconazole led to fewer relapses of either condition.

“During follow-up [ketoconazole] 2% showed a trend to fewer relapses than [ketoconazole] 1%. [Ketoconazole] 2% had superior efficacy compared to [ketoconazole] 1% in the treatment of severe dandruff and scalp seborrhoeic dermatitis”

So, in summary: yes, there is evidence to suggest that when it comes to improving pattern hair loss, 2% ketoconazole is more effective over a six-month period versus 1% ketoconazole. The one percentage point difference does matter.

The questions then becomes: why?

Why is 2% ketoconazole better than 1% ketoconazole?

Ketoconazole is suspected to work in three ways to slow/stop hair loss and promote hair regrowth. The drug:

1. Reduces inflammation related to microbial activity on the scalp.
2. Reduces levels of dihydrotestosterone, the most powerful male hormone and the culprit behind AGA.
3. Prolongs the anagen phase (i.e., growing phase) of the hair cycle, thereby reducing excessive shedding.

We don’t exactly know why 2% ketoconazole is better than 1% ketoconazole. But, chances are that the 2% dilution simply accomplishes these things more effectively and (maybe) more rapidly, meaning that it:

1. Kills off more Malassezia, resulting in a more dramatic reduction in inflammation.
2. Reduces scalp DHT more effectively and more rapidly, preventing further follicle miniaturization in AGA.
3. Stimulates the transition to the anagen phase faster, thereby halting shedding and promoting hair regrowth in a shorter amount of time.

But with increasing efficacy, drugs often come with an increased risk of side effects. This is why clinical researchers often test several dilutions and doses of any drug: they’re trying to uncover which dilution or dose maximizes clinical efficacy while minimizing the risk of side effects.

So, with 1% versus 2% ketoconazole, does the increased concentration lead to an increased risk of side effects?

Does a 2% ketoconazole have a higher risk of side effects compared to 1% ketoconazole?

Although oral ketoconazole comes with significant side effects, these same side effects haven’t been reported with topical ketoconazole or ketoconazole shampoos.

This is because topical and shampoo formulations of ketoconazole are metabolized rapidly within the skin tissues, so very little (if any) topical ketoconazole actually reaches the bloodstream.

On that note, research continues to demonstrate that for the overwhelming majority of people, both 1% and 2% topical ketoconazole concentrations do not come with a notable risk of side effects.

Some individuals may experience a hypersensitivity reaction to ketoconazole topicals, however, this is relatively rare.

That being said, there is a small risk associated with the formulation of a 2% ketoconazole topical cream containing sodium sulfite. But this is a risk with the sodium sulfite, not the ketoconazole itself. And to be clear: sodium sulfite is not a standard ingredient in ketoconazole shampoo formulations (which are the ones prescribed for hair loss); it’s typically only found in topical formulations used to treat conditions like acne.

The bottom line: ketoconazole is rapidly metabolized in the skin, and therefore has minimal risks of side effects. This is why its 1% shampoo formulations are sold over-the-counter.

Should you use a 2% ketoconazole shampoo or topical?

Much like comparative studies between 1% and 2% ketoconazole, no studies have been conducted to assess whether a shampoo or a leave-on topical is more effective for hair growth.

But for now, the 2% shampoo formulation is probably the best way to go, and for two reasons:

1. Topical ketoconazole hasn’t been studied for hair loss
2. Topical ketocoanzole is not easy to find

In other words, 2% ketoconazole shampoo has several clinical studies demonstrating its efficacy, whereas topical ketconazole has only been evaluated in very small clinical studies (i.e.,  6 participants), and typically for conditions like acne (not hair loss).

Moreover, 2% ketoconazole shampoo is readily available – all you need is a prescription from your doctor. Topical ketoconazole is typically only sold for research purposes. And while topical ketoconazole would remain on the skin for longer (and thereby potentially have a greater effect on the hair follicles), we don’t think the potential additional benefits of topical ketoconazole outweigh the risks associated with acquiring and using it.

And with 2% ketoconazole shampoo consistently demonstrating a significant benefit for AGA sufferers, it makes the most sense to opt for what we already know is safe and works.

2% ketoconazole shampoo: clinical efficacy for pattern hair loss

• This study demonstrated that a 2% ketoconazole shampoo improves hair counts in men with AGA. It also found that 2% ketoconazole is nearly twice as effective as minoxidil.
• This study compared a few singular and combination therapies: minoxidil alone, finasteride alone, minoxidil + finasteride, and 2% ketoconazole shampoo + finasteride. Although the minoxidil + finasteride combination outperformed the ketoconazole + finasteride combination, it demonstrates that 2% ketoconazole can enhance finasteride’s benefits.
• This study found that 2% ketoconazole shampoo works well in combination with finasteride in minoxidil. Participants experienced hair regrowth in as little as 30 days.

The verdict: opt for a 2% ketoconazole shampoo

The available evidence suggests that when it comes to treating pattern hair loss (AGA), a 2% ketoconazole shampoo produces better, more rapid results than a 1% ketoconazole shampoo.

Yes, you’ll need to get a prescription for 2% ketoconazole. Yes, this requires an appointment with a doctor. And yes, this is a hassle. But in all likelihood, the benefits of 2% ketoconazole outweigh the convenience of the 1% formulation.

Questions? Comments? Please reach out in the comments section.

Research continues to show that oral minoxidil is an effective off-label treatment for men with pattern hair loss. The general rule-of-thumb: the bigger the dose, the better hair regrowth. But there’s a catch…

Higher dosages of oral minoxidil come at a risk of higher risk of side effects: excessive body hair growth, limb swelling, low blood pressure, and even heart palpitations.

Knowing this, is there a “best dose” for oral minoxidil (in mg) for men with pattern hair loss? More specifically, which dose of oral minoxidil maximizes our chances for hair regrowth and minimizes our risks of adverse events?

This Quick Win uncovers the latest research. The short answer: studies show that 2.5mg daily seems to be a tolerable, effective dose for most men with pattern hair loss. But the right dose for you will depend on (1) your severity of hair loss, and (2) your tolerance with side effects (not all of them are bad).

Note: Quick Wins are short articles focused on answering one question about hair loss. Given their specificity, these articles are written in a more scientific tone. If you’re new to hair loss education, start with these articles.

Oral minoxidil: research at a glance

To date, there have been fewer than 10 studies published on oral minoxidil for androgenic alopecia (AGA). Doses studied range from 0.25mg to 5.0mg daily, and study durations (at least the ones we evaluated) range from 24-52 weeks.

Across studies, there is a clear trend: the higher the dose of oral minoxidil, the better the hair regrowth. But this relationship doesn’t tell the whole story ­– as these higher dosages seem to confer with higher reports of side effects.

So, here’s what you should know before starting any daily dose of oral minoxidil.

#1: Oral minoxidil dosages from 0.25mg to 5mg improve pattern hair loss

The three most recent (and most robust) studies on oral minoxidil all varied dosing by 0.25mg, 2.5mg, and 5.0mg daily. All of them showed benefit – with higher dosages demonstrating visual improvements. Just see these photos of a male who took 5mg of oral minoxidil daily for 3 months.^[1]Jimenez-Cauhe, Juan et al. Effectiveness and safety of low-dose oral minoxidil in male androgenetic alopecia. Journal of the American Academy of Dermatology, Volume 81, Issue 2, 648 – 649

Male with AGA: improvement with 5mg oral minoxidil over 3 months

So, let’s organize the findings of these three studies by dosage. Then, let’s evaluate their results in terms of:

1. Response rates (i.e., the percent of people who experienced an improvement), and…
2. Side effects (i.e., unintended effects of the drug)

Do we see any trends in data? Specifically, is there a “sweet spot” where most men can maximize their chances of hair regrowth from oral minoxidil while minimizing their risk of serious side effects?

Yes.

Oral minoxidil for AGA: study results by dosage

See each study’s summaries.

Daily Dose (Duration)	Response Rate	Side Effects
0.25 mg (6+ months)[2]Pirmez, Rodrigo et al. Very-low-dose oral minoxidil in male androgenetic alopecia: A study with quantitative trichoscopic documentation. Journal of the American Academy of Dermatology, Volume 82, … Continue reading	60%	90%: increased beard growth (52%), increased body hair (20%), hair shedding (16%), pedal edema (4%)
2.5 mg to 5 mg (6-12 months)[3]Jimenez-Cauhe, Juan et al. Effectiveness and safety of low-dose oral minoxidil in male androgenetic alopecia. Journal of the American Academy of Dermatology, Volume 81, Issue 2, 648 – 649	90%	29.3%: increased body hair (24.3%), lower limb edema (4.8%), hair shedding (2.4%)
5 mg (6 months)[4]Efficacy and safety of oral minoxidil 5 mg daily during 24-week treatment in male androgenetic alopecia. Journal of the American Academy of Dermatology, Volume 72, Issue 5, AB113	100%	100%: increased body hair growth (93%), pedal edema (10%), heart / EKG alterations (10%)

At first glance, the risk of side effects across even small dosages seems ridiculously high (90%+).

However, not all of these side effects are bad.

For instance, of the side effects reported in these studies, the overwhelming majority of them constituted increased body/facial hair growth. Most men aren’t going to care about this. In fact, man men might even prefer more body or facial hair.

Secondly, increased hair shedding was generally only reported at the beginning of each study. This is because, when starting minoxidil (topical or oral), the drug can “kickstart” a new anagen (growth) phase of hairs affected by androgenic alopecia (AGA). This can lead us to shed any hairs that were already primed to fall out soon anyway – specifically, catagen or telogen hairs – thereby giving the illusion of thinner hair in the first 1-2 months of treatment. However, as these hairs grow back, they’re usually much thicker, and thereby improve hair density. Long-story short: in most cases, hair shedding from minoxidil isn’t long-lived.

So, for this exercise, let’s discount increased body/facial hair growth and increased hair shedding as temporary and/or non-problematic side effects. Instead, let’s re-run our analysis and only consider serious side effects – edema, EKG alterations, etc.

Within this context, are all dosages of oral minoxidil as scary?

No. In fact, it seems like there’s a “sweet spot” for oral minoxidil where we can maximize hair regrowth while minimizing our risk of bad side effects: at 2.5mg daily.

Keep in mind the following chart is based on preliminary data on low-dose oral minoxidil, and that this article reflects the clinical studies available on oral minoxidil for androgenic alopecia as of 2020. As better-designed studies are published, these numbers will evolve:

Moreover, it’s really only at dosages of 5mg that we see an appreciable increase in concerning side effects – namely, edema (water retention / swelling) and cardiac alterations (i.e., lower heart rates).

So, 2.5 mg daily of oral minoxidil might be the “sweet spot” for most male pattern hair loss sufferers.

#2: Oral minoxidil’s efficacy may vary depending on hair loss severity

Most clinical trials on androgenic alopecia will select study participants who all have similar severities of hair loss. This is known as standardization. And for most trials, investigators usually prefer men who have medium-severity androgenic alopecia (i.e., Norwood 3-4). This is usually because men with Norwood 3-4 level hair loss (1) are representative of the population of hair loss sufferers who may later opt for this treatment, and (2) have enough hair follicle miniaturization and hair loss to effectively evaluate cosmetic improvements to hair thinning.

Having said that, most studies on oral minoxidil aren’t standardized to Norwood 3-4 participants. So, it’s a bit disingenuous to make comparisons across studies for response rates and side effects. In other words, please take our above analysis with a grain of salt.

With that said, with different age and/or hair loss severity across studies, we can get more granular data on who tends to respond well to oral minoxidil.

Based on the above studies (and others we looked into for our analysis), the trend aligned with intuition: if you don’t have severe hair loss, you can get away with lower dosages of oral minoxidil. If you do have severe hair loss, you’ll need a higher dose.

In other words:

• If you have mild male pattern baldness, 0.25mg daily might work fine as a starting point
• A more moderate case of hair loss might require a dose of 1-2.5mg daily
• If you have severe male pattern baldness, you’re probably going to need closer to 5mg daily
• If other treatments haven’t worked for you (resistant hair loss), you may also need a higher daily dose (2.5-5mg) or combination treatments with finasteride

Then again, higher doses come with more side effects. This is where dosing gets hyper-specific.

#3: If you’re going to try oral minoxidil, you’ll need to work with a doctor to figure out your unique risk profile and the right dose

Oral minoxidil is an antihypertensive drug (lowers blood pressure). It can also cause fluid retention. Therefore, if your health history indicates problems surrounding low blood pressure, fainting spells, or edema (swelling), you may be at a higher risk of complications from taking the drug.

Moreover, oral minoxidil can stimulate hair growth everywhere… not just on the scalp. For some men, this may be a bonus. For others, it might be a drawback. If this is a drawback for you, then it’s worth noting that reports of increased body / facial hair even occurred at lower dosages (0.25 mg) of oral minoxidil. So, if you’re concerned about this, maybe oral minoxidil isn’t right for you.

Long-tory short: for the safest and most effective use of oral minoxidil, discuss your medical history and preferences with your doctor. Then convince him or her to prescribe you oral minoxidil.

Note: a dermatologist specializing in hair loss is much more likely to write you a prescription. So, if you don’t want to waste any time, make a list of dermatologists in your area, call them to see if they’re open to prescribing oral minoxidil, and then only visit the ones who prescribe the drug.

#4: Like topical minoxidil, oral minoxidil likely works better alongside other treatments

When it comes to treating pattern hair loss, combination treatments tend to almost always outperform mono-treatments.

In some cases, combination therapies allow us to use the lowest dose of a drug possible without sacrificing results. Some studies suggest this is the case for women with pattern hair loss who take 0.25mg of oral minoxidil + 25mg of spironolactone: they minimize the risk of side effects of either drug while getting hair regrowth that often exceeds that of high dosages of either drug.

In other cases, combination therapies can actually enhance the efficacy of drugs. This tends to be true of men taking topical minoxidil, and who then add in once-weekly microneedling, thereby making topical minoxidil 400% more effective (according to some investigation groups). ^[5]English RS Jr, Ruiz S, DoAmaral P. Microneedling and Its Use in Hair Loss Disorders: A Systematic Review. Dermatol Ther (Heidelb). 2022 Jan;12(1):41-60. doi: 10.1007/s13555-021-00653-2. Epub 2021 Dec … Continue reading

While there aren’t many studies that exhaustively explore this relationship for oral minoxidil, the odds are that this medication also works better as a combination therapy. So, if you’re going to commit to oral minoxidil, consider stacking it with other therapies.

Again, research here is limited, but there are a host of things you can try in combination with oral minoxidil that might increase results.

• DHT reducers (finasteride, saw palmetto, etc.)
• Microneedling
• Massage
• Ketoconazole shampoo
• Low-level laser therapy (LLLT)
• Platelet-rich plasma therapy (PRP)

…and more.

The bottom line

When it comes to oral minoxidil, the best daily dosage for men with pattern hair loss may vary depending on(1) your tolerance for certain side effects, and (2) your severity of hair loss. Consider these recommendations a mere starting point until more research emerges:

• Men with mild AGA, men at a higher risk of complication, or men who don’t want extra hair growth on their body/face: 0.25-1mg.
• Men with moderate AGA: 1-2.5mg.
• Men with resistant AGA (you’ve tried other treatments and they haven’t worked) or severe AGA: 2.5-5mg.

Although these guidelines are a rough ballpark, chances are you fit into one of these categories and, with the help of a doctor, can find the best oral minoxidil dosage for you.

Questions? Comments? Please reach out in the comments section.

Caffeine & Hair Growth: A Scientific Deep-Dive

In recent years, there’s been an explosion of interest in caffeine shampoos / topicals and their potential to improve pattern hair loss (androgenic alopecia). The hope: that applying caffeine to our scalps might stimulate growth factors, improve blood flow, and maybe even reverse hair follicle miniaturization.

At first glance, caffeine use might look like a viable, natural intervention. But what does the research actually say?

In other words, does caffeine work? Is it a viable alternative to minoxidil? Is caffeine better if ingested, applied topically, or used as a shampoo? How much hair regrowth can we expect? And are there any longterm side effects?

This article dives in the science (and answers).

We’ll dispel a lot of common knowledge about caffeine’s efficacy for hair growth. We’ll also comb through the evidence, set realistic expectations, and reveal how to best use caffeine to maximize your chances of hair recovery.

Long-story short: caffeine isn’t a miracle cure. But it might not be completely useless, either.

Topical caffeine: highlights

• Effort. Low – daily topical application, shampoo use, or ingestion are all easy to implement
• Expectations. According to studies, hair improvements are typically observed by 6+ months
• Response rate: 75%
• Regrowth rate: 0-5%
• Cost. $10-25 per month
• Problems. Low-grade clinical evidence; studies measure outcomes like shedding rates and anagen:telogen ratios, not hair counts; lacking impressive before-after photosets; likely less effective than minoxidil; must be combined with other treatments or ingredients like azaleic acid for maximized benefit.

Key takeaways

Topical caffeine is clinically shown to reduce hair shedding rates and improve anagen:telogen ratios in men with androgenic alopecia. Unfortunately, it’s still unclear just how effective caffeine-based topicals and shampoos are for improving pattern hair loss.

Caffeine shampoos/topicals fall under an intervention umbrella of “low risk, low reward”. In other words, caffeine’s risk of significant side effects is minimal, as is the amount of hair growth it may initiate.

Having said that, not all caffeine is created equally. While topical caffeine products have been shown to improve shedding rates and anagen:telogen ratios, oral caffeine might actually increase hair loss in those who have insulin resistance or are hypothyroid.

Of all clinical studies on topical caffeine for pattern hair loss, the best results seem to occur when topical caffeine is combined with ingredients like azelaic acid or drugs like minoxidil.

In any case, a 0.2% caffeine dilution for topical solutions and a 1% caffeine dilution for shampoo formulations seem to be the best studied (and most promising), so look for brands that meet these criteria.

If you’re going to use caffeine as a potential hair loss intervention, please understand that this stimulant is only clinically tested on androgenic alopecia, and that it’s likely not effective as a standalone treatment.

More information on the science behind caffeine – its mechanisms, as well as the optimal delivery methods, dilution, and more for hair recovery – can be found below.

What is caffeine?

Caffeine is a stimulant derived from plants – namely, coffee and tea. It’s the most popular stimulant on the planet.

Caffeine structure

As a stimulant, caffeine has a variety of effects on the human body – from better focus to improvements in endurance. But interestingly, the magnitude of these effect often vary per person, and as a result of differences in our genetic constitution, food consumption, and even past caffeine exposure.

What popularized caffeine as a potential hair loss treatment?

In general, caffeine has been studied for its effects on:

• The cardiovascular system – i.e., increased heart rate and possible vasodilation and/or vasoconstriction
• Longevity – i.e., muscular development, cellular metabolism
• Hormones – i.e., cortisol and thyroid hormones (these may play a role in caffeine’s “energizing” effects)

And interestingly, vasodilation, cellular metabolism, cortisol, and thyroid hormones have all been studied as potential treatments to different hair loss disorders.

For instance, hair loss drugs like minoxidil improve hair growth by increasing vasodilation; thyroid drugs like levothyroxine help to improve hypothyroid-related hair loss by restoring thyroid functionality.

This begs the question: what sort of impact might caffeine have on our hair follicles?

Can caffeine – ingested orally or applied topically – mimic the mechanisms of hair loss interventions? And if so, are the effects of caffeine strong enough to actually improve hair loss outcomes?

These connective points are what prompted scientists to start studying caffeine as a potential hair loss intervention. And taking a deeper look, there is some mechanistic overlap in how this stimulant might improve hair loss outcomes.

Caffeine is one of the most popular stimulants. It’s well-studied in terms of its effects on vasodilation, cellular metabolism, and hormonal health. And interestingly, these research avenues have left scientists wondering if caffeine can also be reoriented as a hair loss solution.

How might caffeine help with hair regrowth?

It’s hard to say. On the one hand, caffeine does have some hair-promoting effects. On the other hand, caffeine also has some issues that may actually contribute to hair loss. All in all, the way it will effect you will boil down to (1) the dose and (2) the ingestion type (oral or topical), and (3) your genetic constitution.

Here are a few effects that caffeine has – both positive and negative – in regard to hair health.

1. Topical caffeine may improve vasodilation (good)

Caffeine’s effects on blood flow vary depending on the mode of ingestion (i.e., topical versus oral) and the actual tissue being measured. Just see this chart demonstrating how oral caffeine impacts blood flow across body tissues.

Caffeine’s location-dependent effects on blood flow

(source)

Interestingly, both topical caffeine and oral caffeine seem to improve blood flow in microcapillary networks – the blood vessel networks that supply our peripheral tissues (i.e., skin) – and the same blood vessel networks that help support the growth of our hair follicles.

This is because in vascular smooth muscle cells, caffeine acts as a phosphodiesterase inhibitor. In other words, caffeine helps to block the enzyme phosphodiesterase.

This enzyme helps inactivate a molecule called cyclic adenosine monophosphate – a biological messenger molecule that regulates vasolidation (i.e., blood flow) in smooth muscle cells. In the absence of phosphodiesterase, more cyclic adenosine monophosphate accumulates, thus expanding vasodilation in smooth muscle tissues.

This is also why phosphodiesterase inhibitors are often prescribed for a variety of blood flow-related health conditions – i.e., erectile dysfunction, hypertension, and even vascular disease. They all help promote blood flow.

Caffeine happens to be one of these phosphodiesterase inhibitors. And while it’s a weak inhibitor, it still has an effect on these capillary networks.

But, there’s one caveat here. While it’s true that a defining characteristic of androgenic alopecia (AGA) is reduced blood flow, it’s still debated whether blood flow is a cause or consequence to hair follicle miniaturization. So, we don’t yet know if caffeine’s vasodilation effects will really have any impact to our hair.

2. Caffeine may increase cellular metabolism (good)

Caffeine doesn’t just inhibit phosphodiesterase. It also inhibits adenosine receptors – a type of neural receptor that helps to regulate cellular metabolism and our own sense of “wakefulness”.

In the absence of caffeine, a molecule called adenosine normally binds to an adenosine receptor in our brain. When adenosine binds to an adenosine receptor, our brain’s neural activity begins to quiet. The end-result: we feel a bit sleepier.

Caffeine is an adenosine receptor antagonist. That means that when it’s ingested, caffeine blocks adenosine receptors so that adenosine cannot bind to them. This prevents the “quieting” of neural activity – and thus promotes longer periods of wakefulness.

Interestingly, there’s also evidence that caffeine’s inhibition of both phosphodiesterase and adenosine receptors may promote cellular metabolism. To put it more bluntly, caffeine ingestion might help to improve (1) energy utilization in the body, and (2) the mobilization of free fatty acids for energy usage.

This may have pro-hair effects, as many genes that are upregulating in balding scalp tissues tend to have an association with impaired cellular metabolism. But again, we just don’t know for sure.

3. High-dose oral caffeine may increase insulin resistance (bad)

Unfortunately, not all effects from caffeine are pro-hair. While improving cellular metabolism may help support the growth stage of our hair follicles, there are also consequences to the way in which caffeine improves cellular metabolism that may negatively impact our hair.

For instance, one study found that oral caffeine consumption decreased insulin sensitivity by 15% in healthy adults. That’s not good – especially for young men and women who are balding, as insulin resistance is almost always a commonly confounding factor in early-onset AGA.

Moreover, there’s also evidence that at high dosages, oral caffeine’s “liberation” of free fatty acids also promotes hyperglycemia and insulin resistance in peripheral tissues (i.e., our skin) – possibly as a result of increased stress hormones like cortisol. Which brings us to our second concern…

4. Oral caffeine increases cortisol levels, and may impair thyroid function and skin quality.

Evidence strongly implicates oral caffeine consumption and an increase in cortisol levels. Unfortunately, the hormone cortisol, when chronically elevated, can negatively impact hair-related bodily functions and in two major ways:

• It can lead to skin degradation around the follicle and disrupt the hair cycle
• It can reduce thyroid functionality, which can increase hair loss for those susceptible to hypothyroidism.

Another noteworthy mention is that coffee can also impair the absorption of thyroxine. So, if you are taking this medication for a thyroid disorder, it’s likely in your best interest to avoid consuming coffee around the same time. But, it’s unclear whether this effect is a result of the caffeine content or other compounds found in coffee.

Again, we don’t yet have any data correlating oral caffeine consumption to pattern hair loss. But these concerns are worth noting for anyone who’s balding and has had a history of hyperglycemia, insulin resistance, hypothyroidism, or adrenal dysregulation.

What about topical caffeine?

In contrast to high dose oral caffeine, it doesn’t seem like topical caffeine elicits the exact same anti-hair effects. Rather, topical caffeine (as a lotion or shampoo) might have some therapeutic benefit to our scalp hair.

For reference, in vitro studies in humans and in vivo studies in mice suggest that caffeine’s effects on (1) phosphodiesterase inhibition and (2) adenosine receptor binding probably will improve hair growth, and through a variety of means.

Specifically, topical caffeine might…

• Prolong the growth phase of the hair cycle (i.e., the anagen phase)
• Stimulate matrix keratinocyte proliferation – or encourage the growth of new hair fibers
• Increase IGF-1 – a signaling protein that helps regulate hair growth
• Inhibit apoptosis – or the “death” of cells responsible for regulating hair growth
• Promote blood flow – which is historically much lower in balding versus non-balding scalps

So, overall, it seems like mechanistic evidence supports at least the use of topical caffeine as a potential hair loss intervention. And this conclusion is why so many researchers have bothered studying caffeine lotions and shampoos for the improvement of AGA.

Caffeine is a (1) phosphodiesterase inhibitor and (2) an adenosine receptor antagonist. While its effects vary on a tissue-by-tissue basis, oral and topical caffeine seem to improve microcapillary networks in periphery tissues (where our hair follicles reside). Moreover, caffeine can help improve cellular metabolism by liberating free fatty acids for energy use. Improvements to both (1) vasodilation and (2) cellular metabolism should theoretically benefit our hair.

At the same time, oral caffeine seems to also increase insulin resistance in peripheral tissues. This is problematic – as reduced insulin sensitivity may interfere with the growth cycles of our hair follicles. Moreover, oral caffeine consumption can increase cortisol levels and decrease thyroid functionality – which may also negatively impact hair growth cycles.

Despite concerns of oral caffeine use for hair, evidence does support the use of topical caffeine for hair growth – at least from a mechanistic standpoint. In vitro research suggests that, in human hair follicles, topical caffeine helps to prolong anagen duration, increase IGF-1, inhibit cell death, and improve blood flow. While this doesn’t mean that these effects will translate in vivo, it does give credence to the idea that topical caffeine is worth testing as a hair loss intervention.

This all brings us to our next question: what does the clinical data say about topical caffeine and its use as a hair growth stimulant?

Is topical caffeine effective for hair loss?

This is harder to answer than it may seem.

At face-value, the answer is yes. This is because there are a lot of studies showing that caffeine in a topical or shampoo (or caffeine in conjunction with minoxidil and/or azelaic acid) can improve hair loss outcomes.

For instance, this recent literature review on topical caffeine dives into over a dozen clinical studies, many of which report:

• “…Statistically significantly better results” when used in conjunction with minoxidil versus minoxidil alone
• Higher patient satisfaction when used with minoxidil compared to minoxidil alone
• Decrease in hair loss after washing when using caffeine + minoxidil + azelaic acid, with similar results to a minoxidil solution after 36 weeks
• Decrease in hairs lost in a hair pull test after 6 months of using a caffeine shampoo (no placebo) and 4 months of using a caffeine-containing lotion.

Reading these conclusions, it’s no wonder why caffeine topical sales have spiked in the last few years.

However, taking a closer look, these studies might not be as encouraging as their conclusions imply. Here’s why.

Quality analysis: how do caffeine-hair loss studies stack up?

When it comes to research, not all peer-reviewed papers are created equally.

Some studies are published in predatory journals that circumvent the peer review process; others are published in low-ranking journals; others simply have major methodological concerns that draw the findings of those studies into question.

When it comes to the studies on caffeine and hair regrowth, it’s that last issue that’s most prevalent. That’s not to say that we should dismiss caffeine’s effects entirely. But, there are several concerns worth highlighting.

1. Methodological concerns

In the above literature review, most of the feature studies don’t measure hair count increases. Rather, they measure endpoints like patient self-satisfaction surveys, changes to anagen:telogen ratios, and a reduction in hair fall during “wash tests” or “tug tests”.

These measurements are difficult to standardize and are notoriously unreliable, meaning it can be hard to determine the true effectiveness of caffeine from any study designed this way.

In fact, it’s my belief that a lot of industry-funded research purposefully chooses these measurement endpoints because of their unreliability. For reference, these types of endpoints are why so many low-level laser therapy studies will report almost unbelievable hair improvement – i.e., “200% hair diameter increases” or “80% hair density improvements” in their clinical trials – while paradoxically, having no visual improvements to show subjects’ photographic assessments.

The bottom line: these measurement endpoints aren’t very strong, and some investigators who choose these endpoints may be doing so to deliberately skew caffeine’s perception of efficacy. But no matter what, the weaker the hair measurement endpoints, the less reliable the results.

2. Topical caffeine is rarely measured as a standalone treatment

Most of these studies measure topical caffeine alongside enhancer ingredients – like azelaic acid, minoxidil, or both – and not caffeine as a standalone treatment. This makes it hard to evaluate whether caffeine by itself is very effective.

In fact, there’s just one study that we could find that measured topical caffeine as a standalone treatment. Unfortunately, it measures topical caffeine versus minoxidil, not a placebo. That study’s takeaway? That topical caffeine is similarly effective to 5% minoxidil… at least when we compare weak measurement endpoints (see #1).

3. Conflicts of interest

Of all the clinical research done on caffeine and hair growth, most of it is industry-funded.

At face-value, this isn’t necessarily a problem. After all, a significant portion of hair loss studies comes from industry-funded research teams. Where there’s financial incentive for a treatment, there will be attempts at peer-reviewed research to prove efficacy.

Having said that, this does become a problem when the studies are typically designed with poor measurement outcomes – such that the odds of achieving “favorable” results increases dramatically. Nearly all of the topical caffeine studies on AGA have this very problem. Compile that with the issue of almost never measuring caffeine alone, and you have even more problems (see #1 and #2).

4. Manufacturers publish research on topical caffeine, but sell you shampoo-based caffeine

One of the most frustrating aspects of hair loss products are that manufacturers will publish a study showing their product demonstrating benefit, but then sell you a product that’s different from the one studied.

This happens all the time with LLLT devices, and it seemingly also happens with caffeine products for hair loss.

Case in point: Alpecin’s study on a topical caffeine solution. The findings showed that this topical did improve hair loss outcomes. But ironically, Alpecin doesn’t sell this topical; it sells a caffeine shampoo. Topicals are leave-in for hours, whereas shampoos may only come into contact with the scalp for 60 seconds. It was this issue in addition to #1-#3 that got Alpecin banned in certain countries from saying their “shampoos” could reduce hair loss.

It was a combination of these issues that led researchers in the above literature review to conclude that while caffeine might help improve aspects of our hair, there isn’t yet enough evidence to support most claims being made by manufacturers.

Topical caffeine does have clinical research supporting its use for hair loss. However, in literature reviews of the dozen or so studies on topical caffeine, concerns of endpoint measurements, lacking study as a standalone treatment, conflicts of interest, and discrepancies in what’s studied versus sold to consumers raises red flags as to caffeine being a truly viable long-term solution.

Despite all of this, there is evidence that topical caffeine might help our hair

Circling back to that literature review, there is accumulating evidence that caffeine can help reduce hair shedding from androgenic alopecia and even improve anagen:telogen ratios. It’s just that if we’re going to use it, we shouldn’t set our expectations at regrowth; we should set our expectations at a slowing of hair loss.

This leaves us with an interesting dilemma: if we want to leverage caffeine as a hair growth promoter, we need to do so in topical or shampoo form. And that means we need to know:

1. What’s the best caffeine formulation: topical or shampoo?
2. Is there a difference in regrowth reported between 0.2% and 1% caffeine dilutions?
3. What’s the optimal frequency of application? Once a week, once a day, etc.?
4. Does the effectiveness of caffeine wane over time – like minoxidil and other hair loss drugs?

Sifting through the literature review, there are studies that answer these questions. But again, they’re all subject to significant bias.

Even still, we can use these studies to guide some caffeine best practices – at least for those who want to make the investment and try it out.

Using caffeine for hair growth: best practices

The best caffeine formulation is likely within a shampoo or topical

Oral caffeine likely doesn’t accumulate in the scalp at a high enough degree to elicit adverse or beneficial effects. However, it may have peripheral action through increased cortisol levels, and this may indirectly impede hair growth for those with insulin resistance and/or hypothyroidism.

Knowing this, the safest and most effective way to use caffeine for hair growth is through topical means, either through some sort of lotion or shampoo.

Considering one study found that caffeine solutions penetrate the hair follicle after 2 minutes and peak at 2 hours, a leave-on caffeine solution may be optimal over a shampoo formulation.

The best caffeine dilution is 0.2% for topicals and 1% for shampoos (as far as we can tell)

But to be clear: the answer likely depends on whatever other ingredients are also in the topical (i.e., azelaic acid, minoxidil, etc.). Here’s why.

• This study, the only study measuring the efficacy of caffeine alone, found that a 0.2% caffeine topical (Alpecin) was just as effective as 5% minoxidil at improving anagen hair percentages.
  • Problems: does not measure total hair count changes, thus improvements to anagen:telogen ratio can also be achieved by simply just shedding more telogen hairs for either treatment group; study only went for 6 months and results (i.e., improvements to anagen:telogen ratio for both caffeine topical and minoxidil) are within range for what we’d expect from seasonality
• Pazoki-Toroudi et al. (2013) assessed the combination of caffeine 1%, minoxidil 5%, and azelaic acid 1.5% versus minoxidil 5%. The combination therapy was more effective than minoxidil alone.
  • Problems: does not measure caffeine alone, so we can’t really say.
• Bussoletti et al. (2010, 2011) found that a 1% caffeine shampoo alone and caffeine lotion alone both resulted in less hair lost to a pull test after 6 and 4 months, respectively.
  • Problems: no concentration specified for the lotion; no control group used to assess true efficacy.
• Golpur et al. (2013) found that caffeine + 2.5% minoxidil was more effective than 2.5% minoxidil alone.
  • Problems: no percentage of caffeine was indicated.
• Sisto et al. (2013) analyzed the effects of a caffeine-containing shampoo vs a caffeine-free shampoo and found that the active treatment was superior to the placebo.
  • Problems: no concentration specified.

So, from what we can garner from the limited studies available, a 0.2% solution for topical application seems to be somewhat effective. However, keep in mind that this is only for a leave-on treatment, not a shampoo.

We don’t really have much information on optimal shampoo dilution. A 1% dilution was the only concentration reported for caffeine shampoo alone, but this treatment wasn’t compared against a placebo and, so, results aren’t super applicable. Even still, 1% seems to be comparably effective to minoxidil.

A 1% caffeine, minoxidil 5%, and 1.5% azelaic acid topical was considered more effective than minoxidil alone, but we can’t extrapolate this 1% dilution to a caffeine-only shampoo.

0.2% for topical solutions and 1% for shampoo formulations is all we can really extract from the current body of evidence, but it should be noted that these recommendations aren’t necessarily reliable given the minimal evidence.

What is the optimal frequency of use?

Like concentration, data on the frequency of use is also sparse. In the highest quality study, subjects used a 0.2% caffeine topical twice a day, every day. Another study instructed subjects to apply a caffeine lotion (unspecified concentration) once daily.

Other studies likely using shampoos most likely involved subjects using the treatment product however often they would normally shampoo their hair. So, it can be difficult to quantify just how often is optimal because use wasn’t standardized, as far as we can see.

With the knowledge we have, daily use of a topical seems to be optimal. Conversely, using a shampoo daily may be drying to the hair and the scalp, so it’s safe to say that using a caffeine-containing shampoo however often you would normally shampoo is probably best.

Does caffeine’s efficacy wane over time?

While no studies measure caffeine’s effectiveness for long enough to see if regrowth is sustained, we can assume – like nearly all topicals – that its hair-promoting effects will likely lessen over time.

The reasons why will be explained in a future article – one comparing the long-term outcomes of antiandrogenic versus non-antiandrogenic hair loss interventions. But the short answer is that we can liken any sort of topical formulation for hair loss – even minoxidil – as a bandaid that won’t necessarily fully address the underlying roots of the problem.

Summary

Topical caffeine may help to elongate the anagen phase of the hair cycle, improve anagen:telogen ratios, decrease hair shedding, and slow the progression of androgenic alopecia (AGA). But it’s by no means a miracle cure, and evidence so far suggests that this topical isn’t any better than 5% minoxidil.

The limited evidence we do have on topical caffeine is relatively biased, poorly designed, and has only been studied for androgenic alopecia. Until studies with better designs are published, it’s hard to say with certainty just how much of an effect topical caffeine will have on our hair.

Nevertheless, topical caffeine leave-on treatments have more quality evidence to support their use (as opposed to shampoos). 0.2% dilutions for topicals and 1% dilutions for shampoos seem to be the most promising. Moreover, the best way to utilize caffeine seems to be in conjunction with minoxidil and, possibly, azelaic acid.

Paradoxically, oral caffeine consumption may have an adverse effect on hair growth through increased cortisol release, increased hyperglycemia in periphery tissues, and potentially decreased thyroid functionality. For these reasons, anyone with a history of insulin resistance or hypothyroidism is probably better off avoiding oral caffeine altogether – particularly for hair health.

If you do decide to implement caffeine into your regrowth regimen, the first thing you’ll notice is how difficult it is to field the market. Almost all companies that have any merit in this space don’t quantify the caffeine dilution in their products. Considering most caffeine treatments are upwards of $35 USD, you may want to call around and see if their customer service representatives can give you more information.

Let us know if you have personal experience or testament in using (or excluding) caffeine. If you start using caffeine, report your progress here for others to see! Any questions or comments? Please reach out in the comments section.

This article explores the characteristics, causes, and unknowns of pattern hair loss – also known as androgenic alopecia (AGA).

If you’re new to hair loss research, this is a good starting point to learn the science behind AGA as well as the concepts that come up frequently in the literature.

• Hair follicle miniaturization
• Telogen:anagen ratios
• Dihydrotestosterone, 5-alpha reductase, androgen receptors, and androgen receptor co-activation
• Prostaglandin activity
• Wnt-ß catenin pathways
• Future research focuses: olfactory receptors, galea interaction, and more

After all, the better we understand a condition, the better equipped we are to treat it.

We’ll explore how the interplay between genetics and male hormones may lead to hair follicle miniaturization. Then, we’ll reveal what still puzzles researchers about AGA, despite 50+ years of study.

Finally, we’ll dive into more recent evidence on AGA that is paving a new direction of research – and reshaping the future of treatments.

What is androgenic alopecia?

Androgenic alopecia (AGA), also known as pattern hair loss, is one of the most common hair loss disorder in the world. It’s chronic, progressive, and affects up to 50% of women and 80% of men at some point in their lives. In the U.S. alone, 30 million women and 50 million men are dealing with AGA that is severe enough to become diagnosable (NIH).

What does AGA look like?

AGA can occur both in men and women, but it manifests differently between the two sexes.

In men, classic pattern balding appears as:

• Recession of the hairline at the temples
• Loss of hair at the vertex (crown)

Norwood-Hamilton Scale (Male Pattern Hair Loss)

However, female pattern hair loss can present in a few different ways (Herskovitz et al., 2013):

• Diffuse, even thinning of the crown with preservation of the front hairline
• Christmas tree-pattern hair loss, with a widening of the scalp beginning at the front and tapering towards the crown
• Thinning at the temples

Ludwig Scale (Female Pattern Hair Loss)

What are the hallmark characteristics of AGA?

AGA has specific features that distinguish it from other types of hair loss.

For starters, it primarily affects hair at the top part of the scalp – above the galea aponeurotica (the dense fibrous membrane that stretches across the top of the scalp).

Secondly, scalp regions affected by AGA show three defining characteristics of the condition:

1. Hair follicle miniaturization
2. Increased telogen:anagen hairs
3. Shortened anagen cycling

Each of these phases are covered below.

Hair follicle miniaturization

Follicle miniaturization is unique to AGA. It is a process by which AGA-affected hair follicles progressively get smaller until they produce fewer hairs. The hairs that are left may transition into fine, wispy hairs – known as vellus hairs.

Hair follicle miniaturization: a defining characteristic of AGA

While the causes and step-processes of hair follicle miniaturization are still debated, this process is often accompanied by histological (i.e. structural) changes – particularly to the tissues surrounding these hair follicles.

In fact, researchers believe these structural changes help to explain why pattern hair loss is a progressive condition – as they limit miniaturized hair follicles’ capabilities of returning back to full-size. They are:

1. Dermal sheath thickening
2. Perifollicular fibrosis

Both of these histological changes can be considered forms of scarring.

Dermal sheath thickening and perifollicular fibrosis

Dermal sheath is a term used to describe the skin tissues that surround our hair follicles. Dermal sheaths are comprised of collagen (i.e., skin), blood vessels, sweat glands, lymphatic networks, and more.

In men and women with AGA, dermal sheaths surrounding miniaturizing hair follicles have thickened. Specifically, their collagen bundles are up to 2.5 times larger – a characteristic of early scar tissue development (Jaworsky et al., 1992).

As dermal sheaths thicken, they widen into the space occupied by hair follicles – thereby impeding their growth space. And as AGA progresses, these dense collagen bundles turn into scar tissue – also known as perifollicular fibrosis.

Together, dermal sheath thickening and perifollicular fibrosis restrict the growth space of surrounding hair follicles, which creates a spacial barrier for miniaturizing hair follicles to recover back to their original size.

Fibrosis (scar tissue) surrounding an AGA-affected hair follicle

Dermal sheath thickening is consistently observed in AGA. However, its advancement to perifollicular fibrosis has been found, according to some studies, in over 71% of AGA sufferers – with moderate levels observed in at least 37% (Whiting et al., 1996).

By progressively restricting the growth space of miniaturizing hair follicles, these histological changes also explain the chronic, progressive nature of AGA – along with why most treatments are limited mainly to stopping the progression of pattern hair loss rather than fully reversing it (English, 2018).

Hair follicle miniaturization is a hallmark of AGA. This is when the size of each hair follicle shrinks and thus starts producing smaller, wispier hairs.

This process is accompanied by dermal sheath thickening around miniaturizing hair follicles. This skin thickening is an early step-process of scarring. In later stages of AGA, this turns to perifollicular fibrosis.

Dermal sheath thickening and perifollicular fibrosis prevent AGA-affected hair follicles from rebounding to their full size. They help to explain the chronic, progressive nature of AGA.

Increased telogen:anagen ratio

Beyond hair follicle miniaturization, the second defining characteristic of AGA is an increase in telogen versus anagen hairs.

Telogen and anagen are terms used to describe specific stages of the hair cycle.

The hair cycle is the natural, ever-repeating cycle of regeneration and degeneration of hair follicles. A hair grows, stops growing, and eventually falls out – at which point a new hair follicle reforms and a new hair starts growing again. In human scalps, these hair cycles last between two to seven years.

 

The Hair Cycle

In non-balding scalps, 80-85% of  scalp hairs are in their growth (anagen) phase, 1-2% have stopped growing and are in their resting (catagen) phase, and 10-15% have already fallen out and entered their shedding (telogen) phase.

In healthy scalps, this cycle repeats indefinitely. Thus, many hair loss disorders can sometimes be identified by measuring the number of shedding versus growing hairs – and then comparing that ratio to what is seen in normal scalps. If the ratio is high, this suggests abnormal hair loss. If it’s low, this suggests normal, healthy hair.

This is the telogen:anagen ratio.

In normal scalps, there is generally one telogen hair for every 12 anagen hairs, or a 1:12 ratio.

However, in men with AGA, the telogen:anagen ratio can exceed 1:4 (or 25%). In women, this ratio often exceeds 2:5 (or 40%).

Shortened anagen cycling

Moreover, in balding scalps, the anagen phase of a miniaturizing hair is shortened. This means that rather than growing for 2-7 years, these hairs may only grow for a few months (Ho et al., 2019).

This is why so many AGA-affected men and women notice short terminal hairs near their hairline or vertex – hairs that won’t grow more than a few inches. This is the result of a shortened anagen phase and an increased telogen:anagen ratio.

In AGA, balding regions have an elevated ratio of shedding to growing hairs. This is called the telogen:anagen ratio.

While healthy scalps have a telogen:anagen ratio of 10-15%, balding regions will have a ratio of 25-40%, and sometimes higher.

Moreover, growing (anagen) hairs in balding regions often do not grow for more than a few months. This is called a shortened anagen phase. This helps to explain why so many balding men and women see shorter hairs in balding regions that never reach more than an inch or two in length.

What causes AGA?

While the exact step-processes of AGA aren’t yet determined, there is general consensus on two contributing factors: genetics and androgens (i.e., male hormones).

Genetics

AGA has an undisputed genetic component, with one study measuring a 2.5-fold increased risk of developing pattern hair loss in men whose fathers had pattern hair loss, as compared to those whose fathers didn’t (Chumlea et al., 2004). Moreover, women affected by AGA often report having other family members affected by the same condition (Ramos et al., 2015).

However, the exact genes involved in androgenic alopecia have not yet been discovered.

In fact, research suggests that there is no one gene involved in AGA. Rather, pattern hair loss is likely a polygenic disorder, meaning there are many gene variances that are involved in the predisposition of its development.

Scientists are still trying to uncover which polymorphisms may prompt individual susceptibility to AGA. Particular focus is on genes that code for androgen receptors (more on this soon).

Androgen activity

Male hormones (i.e., testosterone) are closely tied to AGA. In the 1940’s, researchers observed that (Hamilton et al., 1942):

• Men castrated before puberty (i.e., before their sex hormones spike) never develop AGA later in life.
• Men with AGA who are castrated (and thereby lose 95% of androgen production) also see a stop in AGA progression.
• Castrated men who are injected with testosterone begin to develop temple recession and/or vertex thinning.

Thirty years later, scientists uncovered the specific male hormone involved in AGA: dihydrotestosterone (DHT).

DHT: the main hormone implicated in pattern baldness

Dihydrotestosterone (DHT)

DHT – a metabolite of testosterone – is causally linked to pattern hair loss (English, 2018).

• Men who cannot make scalp DHT never develop AGA.
• Balding scalp regions have higher amounts of DHT versus non-balding regions.
• Drugs that reduce scalp DHT improve AGA outcomes in 80-90% of men.

DHT drives part of hair follicle miniaturization

However, not all types of DHT are implicated in pattern hair loss. Rather, research is focused more so on one specific type of DHT: DHT made from an enzyme called type II 5-alpha reductase.

Type II 5-alpha reductase

In the body, nearly all DHT is created when unbound testosterone comes into contact with the enzyme 5-alpha reductase. This enzyme binds to free testosterone and then changes testosterone’s structure into DHT.

There are different types of 5-alpha reductase, and most types correspond to a specific tissue or region in which the enzyme expresses (i.e., the skin, brain, prostate, etc.).

When it comes to AGA, the type II 5-alpha reductase is most heavily implicated.

This is because (1) type II 5-alpha reductase is greatly expressed in scalp tissues, and (2) men with a gene mutation who cannot produce type II 5-alpha reductase never go bald (Adachi et al., 1970). Moreover, drugs that inhibit the type II 5-alpha reductase enzyme (i.e., finasteride) help to improve pattern hair loss in men.

Together, these findings implicate DHT and the type II 5-alpha reductase enzyme in AGA. But there’s at least one more androgenic factor involved in the onset and progression of pattern hair loss: that of androgen receptors.

Androgen receptors

When free testosterone comes into contact with type II 5-alpha reductase and converts into DHT, that DHT needs a place to bind to a cell. Once DHT is bound to a cell, this hormone can begin to influence that cell’s functionality.

Androgen receptors are where DHT binds to cells. They’re considered cellular “landing pads” – a place for male hormones to attach, so that they can begin to change cellular behavior.

That means that for (most) scalp DHT to form, we need (1) free testosterone, (2) type II 5-alpha reductase, and (3) an androgen receptor.

This is why androgen receptors are a major focus of AGA research: without androgen receptors, DHT cannot bind to scalp cells and influence their functionality.

“DHT sensitivity”

Type II 5-alpha-DHT has a 5x higher affinity for the androgen receptor than other hormones like testosterone (Trüeb, 2002). This means that in balding scalps, DHT will begin preferentially bind to androgen receptors and exert more effects on cell function, at least compared to other male hormones.

This is why some researchers speak of AGA sufferers developing a “genetic sensitivity” to DHT. In the scalp, the more type II 5-alpha-DHT bound to androgen receptors, the more likely a person is to suffer from pattern hair loss.

Is DHT also involved in female pattern hair loss?

DHT is still involved, but there’s debate over its degree of involvement.

Some studies have demonstrated that both men and women have elevated levels of 5α-reductase in the frontal hair follicles (Orme et al, 1999, Sawaya et al., 1997). This suggests that DHT may play a role in at least some female AGA cases.

At the same time, case studies have demonstrated female pattern hair loss can occur in women who are androgen-deprived, meaning they lack the ability to produce any male hormones at all (Orme et al., 1999).

While some have argued that these instances are just cases of mistaken identity (i.e., not AGA), others have used these findings as starting points to explore other aspects of AGA – and what the DHT-genetic sensitivity argument might not be telling us.

Other potential factors: prostaglandin D2, retinoid receptors, and PPAR pathways

A new wave of AGA research is focusing more so on non-androgenic factors that might influence hair follicle functionality.

In 2014, excitement was generated over prostaglandin D2 and its potential connection to pattern hair loss. Prostaglandin D2 is a fatty acid derivative that, theoretically, can express as a result of androgenic activity (i.e., DHT) (Nieves et al., 2014).

Prostaglandin D2 was once found to be elevated in balding scalp regions and even impede hair lengthening. However, follow-up studies have shown conflicting findings – suggesting that prostaglandin D2 might be less involved in AGA than initially believed (Villarreal-Villarreal et al., 2019).

Interestingly, evidence is accumulating that in addition androgenic activity, retinoid receptors and the PPAR pathway are intimately tied to hair follicle miniaturization – and may even explain why some women develop AGA despite having normal scalp DHT levels (Siu-Yin Ho et al., 2019).

Evidence implicates genes and androgen activity in the onset of AGA.

The hormone DHT is causally linked to AGA. Men who can’t produce DHT never go bald, DHT levels are higher in the scalps of balding men, and drugs that reduce scalp DHT help to stop AGA’s progression.

Scalp DHT is formed when free testosterone comes into contact with the enzyme, type II 5-alpha reductase. This enzyme converts free testosterone into DHT, and then that DHT attaches to an androgen receptor in scalp tissues – thereby influencing cell function.

For these reasons, type II 5-alpha reductase and androgen receptors have been targets of both AGA research and AGA-related drugs. Finasteride is a type II 5-alpha reductase inhibitor; spironolactone and RU58841 are androgen receptor blockers. While these drugs don’t lead to complete AGA reversals, they do seem to improve AGA outcomes.

“DHT sensitivity” is a term used to describe how, in scalp tissues, DHT might begin to preferentially bind to androgen receptors – thereby having up to 5x greater influence over these cells’ behavior than other male hormones like testosterone.

While DHT is causally linked to AGA, it’s still unclear how this hormone causes hair follicle miniaturization. Research in female pattern hair loss brings to question DHT’s involvement in AGA – and suggests that in addition to androgens, other factors must be involved.

What don’t we know about AGA?

Despite AGA’s prevalence and decades of study, there are still a lot of unknowns about this hair loss disorder.

The specific genetics involved

As mentioned, AGA is a polygenic disorder. It has been unequivocally established that male pattern baldness is more likely to occur in men whose fathers suffer from AGA.

However, recent evidence suggests that genetic variances in the gene that encodes for androgen receptors are prevalent among men with male pattern baldness (Ellis et al., 2001). Because the androgen receptor gene is located on the X chromosome, which inherited by men from their mother, this raises questions about whether or not AGA is strictly related to paternal genetics.

Even more confounding is female AGA. Of the genetic components explore in male AGA, none seem to be present in women suffering from pattern hair loss (Ramos et al., 2015).

However, some research has demonstrated is that female pattern hair loss may be associated with polymorphisms in the aromatase gene (aromatase helps synthesize estrogen). Aromatase enzymes help convert testosterone into estrogen. However, it’s still unclear how (or why) these polymorphisms impact both female pattern hair loss – especially as this hair loss disorder has been characterized as “androgenic” since the 1970’s.

From the current body of evidence, it’s almost impossible to distinguish a specific gene or set of genes that is indisputably linked to all cases of AGA.

What causes DHT to increase in balding scalp regions?

If DHT is elevated in balding scalps of most men (and some women), what causes DHT to increase in these regions? This is one question researchers are still trying to answer.

One small-scale study indicates that whole-body DHT may not be the culprit – or that AGA patients don’t seem to have elevated serum DHT versus controls (Urysiak-Czubatka et al., 2014). This gives the impression that elevated DHT in balding scalp tissue is likely a local issue, and not a systemic problem.

So, then, what causes DHT to increase in scalp tissues, specifically? Elevated 5α-reductase activity has been implicated, which explains the ability of 5α-reductase inhibitors like finasteride to halt the progression of AGA (English, 2018). However, finasteride treatment doesn’t fully reverse AGA; it generally just stop its progression.

Findings that AGA is not associated with polymorphisms in the 5α-reductase genes suggest that this enzymatic upregulation is unrelated to genetic predisposition (Ellis et al., 1998). This indicates a possible environmental factor. This assumption is supported by studies showing that in genetically identical twins, one twin can bald faster than his counterpart – despite both twins having the same sets of genes (Nyholt et al., 2003).

Although research is sparse regarding environmental factors influencing 5α-reductase activity, there are some clues.

In women with PCOS, insulin resistance is related to increased 5α-reductase activity, possibly explaining why pattern hair loss is often a feature of the disorder (Wu et al., 2017). Male AGA is also associated with insulin resistance, however, whether this is a result of enhanced enzyme activity is unclear (González-González et al., 2009).

But again, no research team has discovered a definitive answer to this question.

How, exactly, does DHT miniaturize hair follicles?

No one is sure. The closest answers we have (so far) come from DHT and its link to a signaling protein called transforming growth factor beta 1 (TGF-β1).

Follicular miniaturization, as well as dermal sheath thickening and perifollicular fibrosis, are key features of AGA. In vitro studies strongly implicate the role of a growth factor, TGF-β1, in these processes (Yoo et al., 2006).

One of TGF-β1’s primary roles in the body is promoting both wound healing and the deposition of fibrous scar tissue (Pakyari et al., 2013). Thus, elevated TGF-β1 activity is likely involved in AGA follicle miniaturization and may even contribute to the process.

TGF-β1 expression can be triggered by the binding of androgens – like DHT – to androgen receptors, and in a potentially dose-dependent manner (Yoo et al., 2006). TGF-β1 may also enhance androgen activity through an androgen co-activator, Hic-5, that allows androgens like DHT to more effectively influence gene expression, like TGF-β1, within cells (Dabiri et al., 2008).

Essentially, increased androgen activity enhances TGF-β1 expression, and TGF-β1 exacerbates androgen activity. This feedback loop creates a vicious cycle that may underpin AGA progression.

Genetically-determined increased androgen receptor expression in AGA tissue contributes to this upregulated androgen activity, but this genetic component alone isn’t enough to dictate AGA progression (Nyholt et al., 2003).

This begs the question: in AGA, what causes androgen activity to increase?

If activity is dictated by androgen availability in the hair follicle, the rate of DHT conversion by 5α-reductase (which is controlled by the number of 5α-reductase enzymes and their activity), and the involvement of co-activators, then what, beyond genetics, could trigger any one of these factors?

Future research will hopefully begin to answer these questions.

Why is DHT also associated with body and facial hair growth?

DHT is linked to hair loss in AGA scalps. But ironically, this same hormone also enhances facial and body hair growth (Thornton et al.,1993). This occurs in spite of a 3-5 times higher 5α-reductase activity in beard follicles.

Given androgens and their negative impact on hair growth in the scalp, one would assume that elevated 5α-reductase activity would result in beard hair loss, not growth. But, this isn’t true for either case. Why might this be?

Why is there a pattern to androgenic alopecia?

No one is sure. Initially, researchers thought the pattern of AGA was due to different levels of androgen activity in balding regions. However, anecdotes of females with AGA and no androgen activity have raised questions about whether this actually makes sense.

In AGA scalps, there are differences in androgen receptor density and 5α-reductase activity in balding and non-balding regions (Cranwell et al., 2016). This may be explained by in vitro research that proposes individual follicles can “self-regulate”, modulating levels of androgen receptors and 5α-reductase enzymes.

Another question is then: what triggers these follicles to self-regulate? The current state of evidence leaves the answers to these questions purely speculative.

The activation of androgen co-activator, Hic-5, also increases follicle sensitivity to androgens, allowing androgens to more effectively influence hair loss-related gene expression (Tellez-Segura, 2015). Interestingly, stretching forces on follicle cells and oxidative stress have been shown to activate Hic-5 (Kim-Kaneyama et al., 2005, Shibanuma et al., 2003).

Elevated levels of reactive oxygen species (ROS, also known as free radicals) and increased stretching forces in these localized regions may explain increased androgen sensitivity, TGF-β activity, and, thus, the patterning of AGA.

What is not known is what events may trigger increased tension or free radical concentration in these areas. There’s still much to be explored.

The current model of AGA doesn’t fully explain (1) what causes DHT to increase in balding regions, (2) how DHT actually miniaturizes hair follicles, (3) why DHT is associated with scalp hair loss, but body and facial hair growth, and (4) why there is a unique pattern and progression to AGA.

Where is AGA research heading?

As scientists try to answer these questions, they’re beginning to stumble into new (and exciting) areas of AGA research.

Wnt/β-catenin signaling

The hair cycle is a degenerative and regenerative process that requires stem cells. Without the activity of these stem cells, the hair follicle can’t properly regenerate hair or maintain the integrity of the hair follicle itself.

Each compartment of the hair follicle possesses its own stem cell reservoir from which it draws. They are used to repair the epidermis around the hair follicle following injury, maintain the structure of the hair follicle, and help regulate hair follicle cycling (Yang et al., 2010).

Wnt/β-catenin signaling is essential for this process. These pathways help with the differentiation of stem cells in and around the hair follicle.

If this signaling pathway is blocked, hair follicle shaft regeneration is impaired. Blockade of this pathway may also impede the re-entry to the anagen phase from telogen.

In AGA, elevated levels of DHT effectively stimulate androgen-related gene transcription. One of the genes that androgens regulate is dickkopf 1 (DKK-1), a direct inhibitor of the Wnt/β-catenin pathway (Kwack et al., 2008).

When DHT binds to ARs in the dermal papilla cells, it enhances the expression and secretion of DKK-1. It acts in a paracrine fashion, meaning it affects hair components outside of the dermal papilla and may impair stem cell function throughout the hair follicle.

As a result, the hair follicle loses its integrity and may become inactive. However, evidence from animal studies indicates that, thankfully, even long-term DKK-1 inhibition of hair growth may be reversible (Choi et al., 2014).

	Current Model	Alternative Model
How do androgens cause hair loss?	Genetic predispositions	Increased androgen activity and genetic sensitivity work synergistically to inhibit Wnt/β-catenin signaling, preventing hair follicle regeneration and anagen re-entry.

Galea interaction

The galea aponeurotica is a fibrous connective tissue that extends over the top of the scalp. It is attached to and connects all the muscles surrounding it.

The galea is a key component of the scalp tension theory of AGA. Interestingly, the “pattern” observed in AGA directly correlates to the highest points of tension in the GA (English, 2018).

Hair follicles are fashioned within both the dermis and fatty tissue beneath the skin, which is directly fused with the GA. Tension in the galea may be transmitted to these tissues and the follicles that are housed within.

Stretch-induced mechanical tension can enhance free radical production and trigger chronic inflammation in various types of tissues, potentially including the GA and the tissues that surround it. Cellular mechanical tension, free radicals, and inflammation can all enhance androgen activity and the fibrosis-mediating TGF-β1 (English, 2018).

This may, in part, explain the origin of follicle miniaturization in AGA.

Other research groups have developed similar hypotheses, arguing that fibrosis may not only drive hair follicle miniaturization, but that this process is potentially mediated by interactions between the galea and cells that transition adipose (fat) tissue into scar tissue (Kruglikov et al., 2017).

	Current Model	Alternative Model
What causes increased androgen activity in AGA follicles?	Genetic predisposition to androgen sensitivity.	Mechanical stretch, free radical production, and chronic inflammation as a result of galea tension enhance androgen activity.
Why is there increased androgen activity in localized regions?	Genetics don’t yet offer any direct explanation.	The points of highest tension within the galea directly correlate to the pattern seen in AGA. The mechanical stretch, free radical production, and chronic inflammation may all upregulate androgen activity.
Why does DHT cause hair loss on the scalp but not in facial or body hair?	Genetics don’t yet offer any explanation.	Mechanical stretch, free radical production, and chronic inflammation as a result of GA tension trigger TGF-β1 expression that leads to follicle miniaturization.

Olfactory receptors

An interesting finding of one 2018 study was the identification of OR2AT4 receptors in human hair follicles. OR2AT4 is an olfactory or smell receptor that is activated by certain scents (Chéret, et al. 2018).

In this study, researchers demonstrated that activation of this receptor by a synthetic sandalwood scent prolonged the anagen phase of the hair cycle. In fact, their findings suggest that activation of OR2AT4 may actually be indispensable for maintaining anagen.

While OR2AT4 is primarily considered an olfactory receptor activated by scent, this study also suggests that it may be activated by other compounds such as scalp microflora (bacteria) metabolites and short-chain fatty acids.

Current Model	Alternative Model
Inhibition of androgen activity is the best way to treat AGA.	Many different cellular receptors in the hair follicle, like olfactory receptors, may help counteract the effects of androgens in the scalp.

In addition to PPAR pathways and retinoid receptors – Wnt-β catenin signaling, galea interactions, and olfactory receptors may help explain much of the unexplained phenomena in AGA pathology.

What are the treatment targets for AGA?

Most AGA treatments target to (1) decrease the telogen:anagen ratio, and (2) stop the progression of hair follicle miniaturization.

There are many ideas as to how to do this, but the most successful FDA-approved approach (so far) seems to be finasteride (Propecia®), a type II 5-alpha reductase inhibitor.

1mg daily of oral finasteride reduces scalp DHT levels by 50-70%. Subsequently, it stops AGA progression in 80-90% of men and leads to a 10% increase in hair count over two years, along with some additional hair thickening (English, 2018).

However, prolonged finasteride use is sometimes associated with sexual side effects. And, when considering all of the evidence that not just androgens are involved in AGA, it’s likely that finasteride is not a complete solution.

As such, here’s a list of current treatment targets in AGA research. Many of these targets overlap with one another.

• Type II 5-alpha reductase
• Androgen receptors
• Reactive oxygen species
• Wnt-β catenin pathways
• DKK-1
• TGF-β1
• Prostaglandin analogues
• Olfactory receptors
• PPAR pathways
• Retinoid receptors
• Potassium ion channels
• Mechanical tension
• Adipose-myofibroblast transitions
• Scalp microflora

In the years to come, this list will undoubtedly grow as researchers elucidate more of the molecular mechanisms behind AGA.

The bottom line

AGA can affect men and women, in both similar and completely different patterns.

AGA is characterized by (1) an increased telogen:anagen ratio, and (2) hair follicle miniaturization. Dermal sheath thickening and perifollicular fibrosis are also present in balding regions, and may partly explain the chronic, progressive nature of AGA.

Both genetics and androgens are established as causally linked to AGA. Androgen receptor density, type II 5α-reductase activity, and DHT are elevated in balding scalps.

The DHT “genetic sensitivity” argument for AGA is incomplete, and for several reasons. (1) Elevated whole-body DHT and polymorphisms in the 5α-reductase gene are not associated with AGA. (2) Female pattern hair loss has been observed in women who cannot produce androgens. (3) More recent research now implicates non-androgenic factors like retinoid receptors and PPAR pathways in the onset of hair follicle miniaturization from AGA.

The current model of AGA doesn’t fully explain (1) what causes DHT to increase in balding regions, (2) how DHT actually miniaturizes hair follicles, (3) why DHT is associated with scalp hair loss, but body and facial hair growth, and (4) why there is a unique pattern and progression to AGA.

Wnt-β catenin signaling, galea interactions, and olfactory receptors are a few new research areas in AGA that might help explain part of the unexplained phenomenon in AGA.

(1) Wnt/β-catenin signaling regulates the stem cell activity in hair follicles needed for follicle regeneration and anagen re-entry. Androgens stimulate DKK-1 secretion by dermal papilla cells which inhibits Wnt/β-catenin signaling and impairs stem cell activity.

(2) Mechanical tension in the galea, which directly corresponds to the patterning in AGA, may play some sort of regulatory role in the inflammation, free radical production, and TGF-β1 expression that seems to mediate scarring and hair follicle miniaturization. However, research here is limited.

(3) Activation of one olfactory receptor by short-chain fatty acids, scalp microflora metabolites, and specific scents may prolong the anagen phase, providing one possible avenue for counteracting AGA progression outside of the traditional anti-androgen treatment approach.

AGA researchers are now turning focus toward non-androgenic factors – PPAR pathways, retinoid receptors, and more – to explain the unexplainable in AGA pathology. If research keeps heading in this direction, newer treatment options will likely better target AGA’s step-processes, resulting in better hair recovery and with a greatly reduced potential for side effects.

Can “the pill” cause hair loss in women?

Hormonal birth control is incredibly effective at achieving its intended effect: to prevent pregnancy. However, many online anecdotes suggest that birth control might also harbor unintended consequences: namely, hair loss.

So, do these anecdotes align with reality? Can hormonal contraceptives actually cause hair loss? Are there factors that increase (and decrease) this risk? And if so, what can we do to minimize our likelihood of hair thinning?

This in-depth article ­­uncovers the evidence (and answers).

Key Takeaways

Some (but not all) forms of birth control may contribute to hair loss.

• Some forms of birth control may exacerbate pattern hair loss (androgenic alopecia)
• Certain oral contraceptives may cause temporary hair shedding – similar to what’s observed at the beginning of pregnancy.
• Certain oral contraceptives, when stopped, may lead to temporary hair shedding – similar to “postpartum molting” observed after pregnancy.

These effects are likely due to birth control’s impacts on progesterone, testosterone, and estrogen levels.

Some hormonal birth control is also linked to nutrient depletion and increased inflammatory biomarkers – which may increase the risk of hair loss for certain groups of women. However, research here is still ongoing.

Women with a familial history of female pattern hair loss (androgenic alopecia) should avoid birth control pills with a higher androgen index. Instead, they may want to try options like the NuvaRing®, the Depo-Provera shot, low-androgen implants, or low-androgen combination oral contraceptives (i.e., “the pill”).

Women concerned with all forms of hormonal birth control may want to seek alternative contraceptive options – like condoms or natural family planning (both of which have their own shortcomings, but aren’t connected to hair loss).

The rest of this guide dives deeper into the science behind hormonal birth control, its connection to hair loss, and which options are (and aren’t) as concerning for hair.

Note: we strive to provide content that is error-free and medically accurate. At the same time, it’s unrealistic to get things 100% right, 100% of the time. This is because evidence, opinions, and recommendations are constantly evolving in light of new research. Consider this guide a starting point for your own research, and not medical advice. As always, consult your physician before acting on any information from any resource – including this site.

What is hormonal birth control?

Hormonal birth control is a pharmaceutical intervention designed to prevent pregnancy. It works by suppressing ovulation.

If we were to grossly oversimplify things, female hormonal birth control changes hormone levels to better match what’s observed during pregnancy. This “tricks” the body into thinking it’s already pregnant, so that ovulation stops.

Hair loss & birth control: is there a connection?

Yes and no. The answer varies based on (1) the type of hair loss, and (2) the type of birth control.

For reference, nearly all forms of hormonal birth control use synthetic progesterone and/or estrogens to regulate menstruation and ovulation. Here are some examples:

• Intrauterine device (IUD): A progesterone-only form of hormonal birth control. It is a T-shaped device made of polyethylene that slowly releases progesterone into the uterus to prevent pregnancy.
• Implant: Another progesterone-only form of hormonal birth control placed under the skin of the arm. It is an ethylene device that releases progesterone progressively into the bloodstream directly.
• Depo-Provera Shot: The hormonal birth control shot is another progesterone-only option, administered directly to the bloodstream. It involves quarterly appointments for continued protection.
• Combined oral contraceptive pill (COCs): The combined oral contraceptive pill is a combination of both ethinyl estradiol (estrogen) and various forms of progesterone. Pill administration is every day, with each pill-pack consisting of 28 daily doses. It is administered orally where it is absorbed into the bloodstream via the gut lining.
• Mini-pill: The mini-pill is a progesterone-only hormonal birth control pill. Like COCs, the mini-pill is also absorbed via the digestive system.
• NuvaRing®: A vaginal ring that contains both ethinyl estradiol and progesterone. It is inserted once a month and progressively secretes these hormones to prevent pregnancy.

When it comes to hair loss, newer forms of birth control – i.e., the NuvaRing®, Depo-Provera Shot, and IUD’s – aren’t as well-studied as oral contraceptives. This is because oral contraceptives (i.e., “the pill”) have been around since the 1960’s, whereas newer birth control formulations have really only been on-the-market for the past 10-20 years.

Having said that, nearly all hormonal birth control use progesterone and/or estrogens to block ovulation. Consequently, physicians often apply data on oral contraceptives and hair loss (from the 1970’s) to generalize what we can expect for all hormonal birth control – both new and old.

So, what does the data have to say? The answers might surprise you.

Oral contraceptives

This 1973 literature review catalogued all clinical trials on oral contraceptives and their observed effects of hair health.

Across dozens of studies, the authors found three instances where oral contraceptives can contribute to hair thinning. One instance relates to pattern hair loss; two instances relate to temporary hair shedding.

Pattern hair loss (after starting)

Many oral contraceptives contain synthetic progesterone to help stop ovulation. Interestingly, synthetic progesterone is made from the male hormone testosterone.

Progesterone

Unfortunately, some testosterone-derived synthetic progestins still maintain a certain degree of androgenic (male hormone) activity… which means that in addition to stopping ovulation, they may increase a woman’s testosterone levels.

The male hormone dihydrotestosterone (DHT) is made from testosterone, and it’s believed to be the primary hormone involved in pattern hair loss. So, for women who have pattern hair loss (or a familial history of it), progesterone-containing contraceptives with a “high androgen index” can exacerbate or accelerate this condition.

What can we do about this?

According to that 1973 review, women at-risk of female pattern hair loss should avoid oral contraceptives made from progestins that have a “high androgenic index”. This includes progestins like:

• Levonorgestrel
• Dl-norgestrel
• Norethindrone
• Norgestrel

So, if you’re at-risk of female AGA, you may want to avoid the following hormonal birth control:

• IUD/vaginal rigs: The IUD contains levonorgestrel as its progesterone and may have especially androgenic effects in the absence of estrogen.
• COCs containing the most androgenic progestins.
• The mini-pill: The mini-pill contains norethindrone, an androgenic progestin, as its active ingredient. There are no other variations of the mini-pill.

But even if you’re not at-risk of female pattern hair loss, you might still see fluctuations to you hair health when starting (and stopping) oral contraceptives. Here’s why.

Hair shedding (after starting)

In early pregnancy, fluctuations in progesterone and estrogen levels (alongside increases to stress) can lead to temporary hair shedding. Oral contraceptives help to emulate the hormonal profile of a pregnant woman.

As such, it’s no surprise that one study found that 50% of women using them also experienced temporary hair shedding in the first few months (that usually resolved within six months).

Hair shedding (after quitting)

By mid-pregnancy, many women actually see increased hair density. This is believed to be due to a steady rise in estrogen levels, which may confer protective effects on hair and elongate the growth phase of the hair cycle. Post-pregnancy, estrogen levels drop, these protective effects dissipate, and, consequently, many women experience more hair shedding.

The same is true after quitting birth control: estrogen levels drop, a female experiences oestrogen withdrawal, and Hair typically recovers within 3-6 months.

What can we do about this?

According to that 1973 review, we shouldn’t worry about temporary shedding from “the pill” – because this shedding doesn’t present significantly at the population-level.

“The incidence of diffuse alopecia in women between 1952 and 1971 has remained unchanged although [oral contraceptive] use has increased. This suggests the effect of [oral contraceptives] on alopecia is insignificant.”

In some cases, that review even argues that birth control can improve hair growth… with one study showing that 22% of females on oral contraceptives saw increases to hair density.

Again, this aligns with observations during mid-to-late pregnancy when the protective effects of estrogen kick in, the hair growth cycle elongates, and hair counts increase (temporarily).

As such, the authors concluded that:

“Such findings suggest that when the pill produces any clinically significant effect on hair cycles it is likely to be a favourable one.”

Summary (so far)

According to a widely cited resource on birth control and hair loss (from 1973)…

• Most women should not be concerned about hair loss from oral contraceptives.
• Oral contraceptives with a high androgen index may exacerbate pattern hair loss (androgenic alopecia). For these women, low androgen index birth control is recommended (if any birth control is necessary).
• Upon starting oral contraceptives, 50% of women experience slight increases to hair shedding, which normalizes within six months.
• Upon stopping oral contraceptives, some women experience hair shedding as estrogen levels normalize (similar to postpartum molting). This is temporary.
• In 22% of women, oral contraceptives actually increase hair density.

Have expert opinions evolved since the 1970’s?

To our knowledge, not really.

Nearly forty years after that literature review was published, these conclusions still stand. That means if you visit a doctor with questions about birth control, you’ll likely hear:

• “If you’re at risk of female pattern hair loss, avoid high androgen index contraceptives. Otherwise, don’t worry…” (more on this later)
• “You might shed a little when you start and stop birth control. Otherwise, don’t worry…”

And that’s even despite the explosion of new birth control forms… and even despite the surge in anecdotes of a connection between contraceptive use and hair loss.

So, is it possible that we’re missing something – and these reports online of birth control-related hair loss are more than just anecdotes?

Maybe.

In the last forty years, our understanding of biology has evolved – as has our data on birth control and its myriad effects on the female body.

Not all of its effects are positive.

In fact, a few downstream effects of birth control may contribute to problems indirectly linked to hair loss, namely:

• Inflammation
• Nutrient depletion

…none of which were catalogued in that 1973 review (as we didn’t yet have the data).

Inflammation

When we examine the research on hair loss, there is a clear emerging trend: inflammation, one of the body’s natural immune responses.

The presence of chronic, unresolved inflammation seems to be a significant contributor to almost every form of hair loss, whether that be telogen effluvium (TE), diffuse hair loss, androgenic alopecia (AGA), or even alopecia areata (AA).

In AGA, inflammation seems to lead to hair follicle miniaturization (and thereby hair loss). In AA and TE, inflammatory mediators seem to signal the early transition of the hair follicle into the catagen phase, where hair stops growing. Eventually, these hairs shed.

The bottom-line: if we’re trying to fight hair loss, it may be in our best interest to lower our levels of systemic inflammation ­– as to not amplify any inflammation already present in the scalp.

So, how does this connect to birth control? Well, it all depends on which hormones are inside your contraceptive: estrogens and/or progestins.

Estrogen-based contraceptives

Preliminary research suggests that estrogen-containing birth controls – like COCs and the NuvaRing® ­– may have an amplifying effect on inflammation.

In PCOS patients, estrogen-based contraceptives may increase inflammation

For women with polycystic ovarian syndrome (PCOS), birth control – which is usually prescribed as a treatment for PCOS – may ironically exacerbate inflammatory biomarkers that are already elevated in the condition (more on this later).

This has been most notably demonstrated in PCOS patients taking oral contraceptives and subsequently seeing a rise in levels of c-reactive protein (here, here, and here) – one of the foremost biomarkers of inflammation.

It’s unclear what (if any) impact this might have on hair health. Having said that, PCOS is a condition closely tied to (and potentially even causative of) female pattern hair loss.

Knowing this, we probably want to keep any additional inflammation at bay – whether it’s derived from bad food choices or the wrong contraceptive.

Estrogen-based contraceptives may also exacerbate autoimmunity

This literature review found that estrogen-based contraceptive use was associated with an increased risk of various autoimmune conditions, including:

• Multiple sclerosis
• Ulcerative colitis
• Crohn’s disease
• Systemic Lupus Erythematosus
• Interstitial cystitis

Why could this be the case?

Generally, estrogens are proliferative, meaning they stimulate the division of cells. Interestingly, some researchers have hypothesized that the estrogen-autoimmunity connection is due to its potential proliferative effect on immune cells.

The idea: that estrogen may increase immune cell count, causing the immune system to go into overdrive. Estrogen might also promote the survival of these cells, potentially prolonging our immune responses.

On top of this, preliminary in vitro studies suggest that estrogen disrupts the gut lining by inhibiting an important barrier-protective protein, zonulin. This may lead to increased permeability of the intestinal barrier, allowing bacteria, toxins, and inflammatory bacteria membranes into systemic circulation.

As a result, you may experience system-wide inflammation as your body responds to these pathogens that were never supposed to reach our circulation in the first place.

But do these effects actually translate to hair health?

We don’t yet know. But for anyone dealing with hair loss alongside inflammatory-based conditions – like PCOS and/or autoimmunity – you may want to speak with your doctor before jumping on any birth control containing estrogen.

Nutrient depletion

Many drugs reduce our absorption of nutrients. Many drugs also increase our need for nutrients. But birth control pills (specifically, COCs) are one of the worst offenders.

This isn’t just because they’re so widely prescribed, but also because so few women are actually notified of the risks of nutrient repletion while taking them.

Specifically, COCs have been known to deplete the following nutrients:

• Folate. Depletion of folate impairs the cell division and DNA synthesis that promotes hair growth at the most basic level. However, folate is also needed for homocysteine detox and plays a role in metallothionein production, the protein needed for heavy metal detoxification. So, depletion of folate may contribute to the overall free radical load on the body.
• Vitamin B2. Vitamin B2 is needed for adenosine triphosphate (ATP; energy for the body and essential for fueling hair growth) production and is a co-factor in metallothionein synthesis.
• Vitamin B6. Much like B2, B6 is a co-factor in ATP and metallothionein production, along with a plethora of other enzymatic reactions.
• Vitamin B12. B12 is necessary for energy production, metallothionein synthesis, and cell proliferation.
• Vitamin C. Vitamin C is required for the production of collagen, carnitine (an amino acid that promotes metabolic health), wound healing, and reducing the free radical load on the body.
• Vitamin E. Vitamin E is a fat-soluble antioxidant that is especially important for skin and possibly hair health. One small human trial demonstrated that 100mg of vitamin E supplementation for 8 months resulted in an average increase of 98.3 in hair count.
• Selenium. Selenium is a mineral that acts as a co-factor in glutathione activity (that of which seems to be lowered in hair loss patients), supports the thyroid, and prevents oxidative stress.
• Magnesium. Magnesium is involved in so many reactions in the body, it’s hard to pick just a few to list. But, some of the noteworthy effects of magnesium include supporting healthy insulin levels, decreasing inflammation, and promoting skin health.
• Zinc. Zinc is an antioxidant, immune-supportive mineral and deficiency likely contributes to hair loss. Researchers hypothesize that zinc may regulate gene transcription required for hair growth, prevent regression into the catagen phase, and acceleration of hair follicle recovery.

Although it’s unclear just how much of a factor nutrient deficiencies are in hair loss, we know that some specific ones are likely to be an issue, especially in TE.

So, if have taken birth control in the past or are currently taking birth control, it’s important that you be made aware of potential increases in nutrient requirements and potential deficiencies you may encounter.

Birth control for PCOS: will it help my hair loss or make it worse?

Hormonal birth control, especially COCs, is often the first line of treatment for relieving the symptoms of PCOS.

In theory, this makes sense. The estrogen may interfere with androgen activity, ameliorating some of the symptoms associated with excess androgens in PCOS.

However, COCs don’t address the insulin resistance, inflammation, and oxidative stress that are a factor in a lot of the PCOS issues, even for lean patients. In fact, sometimes it may get worse (many women report this).

Considering the depletion of antioxidant nutrients, the potential inflammatory response of the body, the androgenic effect of some synthetic progestins, and the role these may all play in PCOS pathology, the reports of women whose PCOS symptoms get worse on COCs are not unfounded.

The truth is that every women’s experience on birth control will be different. Individual physiology and biochemical milieu determine the response.

So, determining whether COCs will benefit or worsen PCOS symptoms is kind of like Russian roulette. No one can predict how you may react to it. Your best bet is to work with your physician to assess the risks and benefits of utilizing COCs.

So, what are your options?

Navigating pregnancy prevention while avoiding side effects is no easy feat.

Based on the evidence provided, here is what seems to be the safest for preventing contraceptive-associated hair loss:

• NuvaRing®. The NuvaRing® contains a less-androgenic progesterone in combination with estrogen. However, the estrogen content may be problematic, considering some of its effects on the body.
• COCs with less-androgenic progestins. Like the Nuva-Ring, these oral contraceptives with less androgenic progestins avoid possible adverse effects on hair related to male hormones. Though it should be noted that estrogen may not necessarily be favorable for hair growth.
• Depo-Provera shot. This shot is progesterone-only and contains a progesterone with less androgenic activity.
• Implant. The implant is solely formulated with a low androgen activity progesterone.

There are also non-hormonal methods available, like the copper IUD and the natural family planning method (NFP). However, the copper IUD may throw off zinc levels and NFP is time-intensive, requires a lot of mental awareness, and has a failure rate of about 25%.

Deciding which birth control is for you is a really individual choice and should be made based on the time you have and how much concentration you are willing to commit to avoid possible issues with hair loss.

Final thoughts

Based on the evidence currently available to us, hormonal birth control can very well influence hair loss in certain groups of women.

However, there are mixed results. Some women experience hair loss after starting and/or stopping hormonal contraceptives, while others find that “the pill” can improve their hair density or even hair loss from PCOS.

In short, there’s no way to predict what could happen on the individual level. That means you’ll likely need to do some personal experimentation.

Your best bet is to talk over your concerns with your doctor who, with the knowledge of your individual physiology, can help you better understand your unique risk and what contraceptive option might be best for you.

It’s hard to predict who is (and isn’t) susceptible to contraceptive-related hair loss. Sometimes, it requires some personal experimentation. If you have a good doctor, it may help to speak with him or her about your unique risk profile.

The Ultimate Guide To Platelet-Rich Plasma Therapy (PRP)

In the last decade, thousands of dermatologists have started offering platelet-rich plasma (PRP) therapy as a treatment for hair loss. At first glance, PRP seems like an enticing therapy: a hands-free, drug-free approach to improve our hair thinning…

…but with a $1,000+ price tag, is the therapy worth it? Is PRP right for all hair loss sufferers? And if platelet-rich plasma therapy does work, how much hair can we expect to regrow?

This ultimate guide to platelet-rich plasma therapy uncovers the answers. Here we’ll reveal how platelet-rich plasma therapy works, how it compares to similar therapies, and what most dermatologists don’t tell you about their PRP “before-after” photos.

We’ll also reveal how hair regrowth from PRP depends largely on your form of hair loss, whether you combine PRP with other treatments, and the type of PRP your dermatologist provides (Acell, etc.).

If you’re considering PRP as a hair loss treatment, this guide will help you determine if the costs make sense for your situation and, if so, how to select the right provider.

PRP Therapy: Highlights

• Effort. Medium (requires a few dermatology appointments, but is otherwise a hands-free therapy)
• Expectations. According to studies, regrowth can occur in as little as 3 months.
• Response rate: 80%+
• Regrowth rate: this varies depending on if PRP is done alone or alongside other therapies.
  • PRP (alone): 25-30%
    • PRP + finasteride: +1%
    • PRP + microneedling: +5%
    • PRP + minoxidil: +5%
    • PRP + microneedling + minoxidil: +5-10%
    • PRP + ACell: no studies (yet), but anecdotes suggest better results than PRP alone
• Cost. $1,000-$4,000+
• Problems. Expensive; real-world results often don’t match those of studies; similar mechanisms targeted with massaging and microneedling; results vary wildly depending on the clinic; results contingent upon continued sessions

Key takeaways

PRP is effective for androgenic alopecia and alopecia areata, but it’s expensive and requires ongoing injections to maintain results. It works best as an adjunct treatment alongside other hair loss therapies, and while it has helped both men and women, evidence suggests that it’s less effective for females overall. If you’re going to try PRP, don’t just go to any clinic; rather, vet your cosmetic surgeon by asking them a list of questions we’ve suggested (below).

What is platelet-rich plasma therapy (PRP)?

Platelet-rich plasma therapy (PRP) is an injection-based therapy. It’s the injection of a modified version of our own blood into a tissue site – with the goal to accelerate healing, reduce scarring, and improve injury outcomes.

PRP has been used for dentistry, facial reconstruction surgery, orthopedics, sports injuries, acne scarring, and fat grafting. But in the last decade, it’s been given serious attention as a potential treatment for thinning hair.

How does PRP work?

PRP therapy is a multi-step process that involves drawing a sample of our blood, separating out its platelets, concentrating those platelets, and then re-injecting those platelets into a targeted location (like our scalp).

If you’re considering PRP, the procedure usually takes around an 30-90 minutes, and the process looks something like this:

1. Obtain blood from the patient
2. Centrifuge once – under a low speed – to separate out platelet-rich plasma from the blood
3. Remove anything that isn’t plasma
4. Centrifuge again
5. Repeat step 3
6. Mix the solution to make it uniform

Why focus on platelets?

Our blood volume contains roughly 55% plasma, 40-45% red blood cells, 6% platelets, and 1% white blood cells. Whenever our tissues incur a wound – for example, a paper cut – an inflammatory reaction begins, and our bodies will send blood to our injury site to initiate repair.

Interestingly, our platelets – which constitute just 6% of our blood volume – are responsible for a huge part of the entire repair process. Specifically, platelets do two things:

1. Platelets help clot a wound to prevent excessive bleeding
2. Platelets carry with them dozens of growth factors, all of which help to coordinate the entire healing process.

This begs the question: what if we could concentrate our platelets so that instead of sending only 6% of platelets to a wound tissue, we could send a much higher percentage? Would we see better injury outcomes? Would we see less scarring?

Well, this is exactly what platelet-rich plasma therapy does. In fact, recent advents in “centrifugation” – or the swirling, mixing, and separation of platelets from our blood – have enabled dermatologists to achieve blood platelet concentrations higher than 94%+. That’s a huge jump from the 6% typically carried within our normal blood volume.

And as of today, it seems like platelet concentrations do improve injury outcomes and scarring. Decades of studies show that, on average, if we concentrate high levels of plasma and send that plasma to an injury site, we can improve injuries, reduce scar tissue, and in doing so, maybe even regrow some hair.

How, exactly, does PRP improve hair loss?

There are several growth factors carried within plasma linked to hair growth, most notably:

• Platelet-derived growth factor
• Transforming growth factor
• Vascular endothelial growth factor
• Epidermal growth factor
• Fibroblast growth factor
• Connective tissue growth factor
• Insulin-like growth factor (IGF-1)

And when injected into balding scalp tissues, the arrival of these growth factors can do a few things:

1. They reactivate dormant hair follicles and encourage them to reenter the anagen phase, thus increasing hair counts.
2. They prevent hair follicles from entering the catagen phase or undergoing cell apoptosis (programmed cell death).
3. They help to resolve longstanding inflammation and reduce scar tissue surrounding miniaturizing hair follicles, thereby increasing the hair thickness of miniaturized hairs.
4. The promote blood vessel growth around the hair follicles to aid in hair regeneration.

Isn’t this similar to how massaging and microneedling work?

Yes. PRP’s mechanisms overlap with one of the ways by which massaging and microneedling improve hair loss: they both increase the number of growth factors in balding scalp regions. But, they do it in slightly different ways.

Massaging and microneedling first generate acute inflammation (i.e., micro-wounding), which then increases growth factors, which then helps to promote hair recovery. The order of operations is as follows:

Massaging / microneedling >> evokes micro-inflammation >> evokes platelets / growth factors >> decreases scarring proteins / increases angiogenesis >> reduces perifollicular fibrosis >> improves blood flow to miniaturizing hair follicles / increases follicle growth space >> increases hair growth

But there’s a key difference between PRP and these two therapies. With massaging and microneedling, you need to first evoke inflammation to increase growth factors to a wound site. With platelet-rich plasma, you essentially skip that first step, and instead, you simply inject platelets directly into the tissue of your choosing.

When it comes to balding scalp tissues, we can think of the mechanistic difference between these therapies as this:

Now, there is some wounding involved in PRP procedures. But that wounding / acute inflammation is a consequence to the injection of the platelets. In this way, PRP is sort of like a supercharged microneedling or massage session – only with many more platelets present.

Is platelet-rich plasma therapy effective?

This is a tricky question to answer.

If forced to give a one-word answer, then yes. Most studies on PRP show positive outcomes for hair loss. But if you’re going to invest thousands of dollars into the therapy, there are caveats of which you should be made aware.

The reality is that PRP’s effectiveness for regrowth depends on the study you reference and how you define the term, “effective”. Moreover, PRP efficacy varies greatly by:

• Hair loss type (i.e., androgenic alopecia, alopecia areata, etc.)
• Whether we combine PRP with other treatments (i.e., minoxidil, finasteride, microneedling)
• The type of PRP procedure (i.e., PRP alone, PRP + Acell, etc.).

We’ll cover all of this below.  First, we’ll start with PRP’s issues. Then, we’ll dive into PRP’s benefits (and its effects on our hair).

Cons

Problem #1: most PRP studies have a high risk of bias

Most PRP studies are conducted by dermatologists who offer PRP procedures at their clinics. That creates an incentive to achieve positive results – because those positive results might encourage patients to do the procedure at their specific clinic.

However, this problem isn’t necessarily game-ending. In fact, nearly all hair loss research contains some level of bias. For instance, despite our efforts to control for bias in our own study on the massages, technically you could argue that because this site conducted it, our results are at risk of bias, too.

In any case, there are plenty of well-controlled studies on platelet-rich plasma and hair loss. We’ve filtered for these. But if you go digging through the literature and find a PRP study with crazy results, just know that if it wasn’t included in our analysis, there’s probably a good reason why.

Problem #2: most platelet-rich plasma studies aren’t standardized

Nearly every PRP study has a different patient profile (i.e., ages and hair loss severities), methodology (i.e., injection methods, rounds, treatment regions), trial duration (i.e., three months versus two years), and hair assessment method.

For instance, here are just a few ways PRP studies have measured hair loss “improvements” (ranked from worst to best).

1. Hair tug tests (i.e., when an investigator yanks at a subject’s hair before and after treatment, then counts the number of hairs that fell out)
2. Reduction in hair fall (i.e., hair shedding collected in the shower, by patients, pre- and post- treatment)
3. Patient satisfaction scores (i.e., when a patient fills out a survey saying whether they’re happy with the treatment)
4. Independent visual assessments (i.e., when a dermatologist eyeballs photos to give their input on hair improvements)
5. Follical unit survival rates (for PRP + hair transplant studies) (i.e., how many transplanted hairs survived the transfer)
6. Hair thickness (i.e., the change in the diameter of hair shafts in a specific scalp region)
7. Terminal/vellus hair ratio (i.e., the number of thick and healthy versus thin and wispy hairs in a specific region)
8. Hair counts (i.e., when a region is marked – usually with a temporary tattoo – to count hairs before and after treatment)

To be fair, this isn’t just a problem with PRP; it’s a problem with all of hair loss research. It’s why literature reviews have a hard time drawing conclusions about most treatments – because there are rarely apples-to-apples comparisons.

But again, we’ve sorted through all the PRP studies we could find to standardize the research (as best we can) and give you ballpark assessments of regrowth rates (i.e., increases to hair count in balding regions).

Problem #3: platelet-rich plasma therapy likely requires ongoing treatments

When you look into the research on minoxidil or finasteride, studies show that within 3-12 months of quitting either drug, your hair loss will return to what it was prior to the intervention. So, how long will results hold for platelet-rich plasma after quitting?

Well, it’s unclear how long results will last after you stop doing PRP treatments, but evidence suggests that a percentage of people will start seeing their hair return to baseline after a year.

Out of all PRP studies, the one with the longest follow-up period (two years) included 20 patients. Interestingly, four of them experienced a relapse in hair loss one-year post-PRP. In fact, their androgenic alopecia progressed beyond their pre-trial hair counts by the 16-month mark. This suggests that for about 20% of people, PRP’s effects start to wane 12-18 months after the treatment.

This wouldn’t be such an issue if the procedure were cheap, but it isn’t: several therapeutic rounds of PRP cost $1,000-$4,000+. So, if you’re going to give this procedure a try, make sure you’re financially comfortable with the investment.

Problem #4: PRP might not work for every person with hair loss

Out of all the research on PRP, only two studies found that PRP was an ineffective treatment option. One study was on females with androgenic alopecia. The other study was on men with advanced androgenic alopecia (Norwood gradients 4+).

If you were to ask me why the first study failed to produce results, I would say that it was probably because (like most women with hair loss) the females in that study likely had other undiagnosed hair loss types (like telogen effluvium / hair loss related to a chronic condition).

And as far as the study on men with advanced androgenic alopecia (AGA) – we need to keep in mind that the investigation team only did two rounds of PRP injections. For what it’s worth, in all of the PRP studies which saw improvement, a minimum of three PRP injection rounds were performed. So, it’s likely that either this study didn’t do enough injections to see results, or that men with advanced AGA needed several more injections before PRP begins to repeat significant benefit.

Problem #5: most PRP studies don’t measure PRP by itself

In fact, the overwhelming majority of studies measure PRP alongside other hair loss treatments – like minoxidil, finasteride, or even a hair transplant. So, it’s important to delineate between the studies you reference when evaluating whether PRP is right for you (we’ve done this below).

This also brings up another problem: dermatologists showcasing their PRP results online often don’t tell you something important: that they’re showing you PRP results alongside drugs like minoxidil and finasteride.

This is incredibly disingenuous, and I suggest that if you’re shopping around for a PRP clinic, you call ahead and ask the doctor if the results they showcase on their website are from PRP alone. If they are, great. If they’re not, but they’re labeled to make it seem as such, then that means these dermatologists are intentionally misleading prospective patients, and they should lose your business (and their license to practice).

Pros

While we might’ve just painted a problematic picture for PRP, this isn’t the whole story. In fact, PRP is an incredibly effective treatment for hair loss under the right circumstances. This is all covered below.

Alopecia areata

PRP has shown great promise for the hair loss disorder alopecia areata. This is an autoimmune condition that leads to hair loss in patchy spots throughout the head. In some cases, it can advance to complete baldness (alopecia universalis).

In fact, studies show that PRP is very effective in treating at least 70% of alopecia areata cases. Here are some of the really promising photos (source):

Androgenic alopecia

PRP alone (no other treatments)

When looking at PRP as a standalone treatment, most studies measuring hair counts suggest that the average patient will regrow 15 hairs per square centimeter (i.e., half the size of a penny). That’s about a 25-30% regrowth rate at 3-6 month follow-ups.

Quantitatively, that’s pretty impressive. For a benchmark, most studies on finasteride show just a 10% increase in hair count over two years.

Across studies, some of the less quantitative outcomes for PRP alone (at least at the 3-6 month mark) are:

• Patients report about a 75% increase in hair quality and thickness, and a decrease in the rate of hair loss.
• Patients usually perform better on the hair pull test, meaning that when they pull on a clump of the patient’s hair, fewer hairs came out compared to control groups.
• Patients report somewhat high satisfaction with the procedure at month three of follow up

Finally, a common trend mentioned among researchers is that PRP treatment seems to be more effective for patients with less severe forms of AGA. So, if you’re in the early stages of hair loss, PRP might be a great option for you.

PRP + hair transplantation

In one study examining hair transplantation, two areas with 50 grafts each(not a lot to measure, especially for hair transplantation) were compared with or without PRP injections. The area with PRP had, on average, 46.75 units that survived compared to the non-PRP which had, on average, 41 units that survived.

While this isn’t that drastic of an increase – we have to keep in mind that transplant procedures are incredibly costly… and that means that every hair follicle unit counts.

So, if you’re considering a hair transplant, you’ve spent the finances to secure a skilled surgeon, and you still have some extra spending money you’d like to throw into improving your results – do it alongside PRP. Chances are your hair transplant survival rates will improve, as will your overall hair count.

PRP + microneedling

In this study, 30 male participants received 6 PRP injections following microneedling sessions. At the six month follow-up, the average patient had a hair density increase of about 30%. This study also noted that the most significant improvement was seen in patients with less severe AGA.

PRP + minoxidil or PRP + finasteride

In this study comparing the efficacy of PRP + minoxidil and PRP + finasteride, while both outcomes were deemed effective, the PRP + minoxidil treatment actually achieved significantly better results than the PRP + finasteride group. In fact, the PRP + minoxidil group showed five-fold better hair increases versus the PRP + finasteride group.

Now, you might read these results and think that makes no sense. Finasteride is clinically more effective than minoxidil. So, why would PRP + minoxidil outperform PRP + finasteride?

Well, the devil is in the details. For one, the sample size of each PRP subgroup was less than 15 people. So, it’s possible these differences might’ve been due to statistical noise which would’ve canceled itself out with subgroups of 150+ people.

And secondly, while a five-fold improvement might sound drastic, we’re actually dealing with the law of small numbers here. Yes, PRP + finasteride saw an additional hair count lift of 1% versus 5% for the PRP + minoxidil group. And yes, that is technically a five-fold improvement. But in all reality, that’s just a few percentage points better.

PRP + minoxidil + microneedling

In this study comparing PRP + minoxidil + microneedling versus minoxidil alone, the earlier treatment proved to be much more effective than the latter, although exact numbers were not given in this study to show this. However, we can assume that PRP + minoxidil + microneedling is probably better than PRP + minoxidil, and that PRP + minoxidil is probably better than PRP alone.

PRP + Acell

PRP + Acell is a relatively new procedure that a lot of PRP practitioners are offering now. Acell is a protein matrix derived from pig bladder (you read that right) that creates a “scaffold” for new hairs. Acell essentially offers a platform by which all of our growth factors (and hair) can cling to. It also helps to stimulate stem cell activity.

[Note: since ACell is made from pig, people allergic to pig products should notify their physicians about their allergy prior to the treatment.]

There doesn’t seem to be any studies measuring the results of PRP + Acell compared to PRP alone, so it’s hard to objectively say whether it increases the effectiveness of PRP.

Are there any risks to PRP?

At least so far, there haven’t been any severe risks reported. However, some milder symptoms have been noted during and shortly after the procedure:

• Headaches
• Pain
• Itching
• Drowsiness
• Infection (rarer)
• Scarring or calcification of the injection site (for those with a propensity toward keloid scarring) (rarer)
• Blood vessel or nerve injury (rarer)

Who’s a good candidate for PRP? Who’s a bad candidate?

Androgenic alopecia treatments vary depending on your (1) finances, (2) willingness to invest time into a therapy, and (3) comfortability with FDA-approved drugs. Compared to some of the other AGA specific treatments, like standardized scalp massages and microneedling, PRP is a pricey option. At the same time, PRP is a lot less time consuming than microneedling or massaging because you may only go into a clinic for a handful of injection rounds before you start seeing results.

You are a great candidate for PRP if you…

• Are comfortable with the financial investment and ongoing treatments
• Want to stack PRP alongside other treatments in your hair loss regimen – like microneedling, massaging, minoxidil, or finasteride
• Are going to get a hair transplant and want to optimize your outcome of the procedure
• Have early-stage to mild AGA (and relatively small areas of hair loss)
• Have alopecia areata
• Are a poor candidate / do not want to try traditional hair loss medications
• Are physically healthy in general

You are not a great candidate for PRP if you…

• Do not want to spend thousands of dollars on the procedure
• Have advanced AGA and aren’t willing to commit to several rounds (and months-to-years) of injections
• Are a female with androgenic alopecia alongside conditions like hypothyroidism (treat that first!)
• Do not want to keep reinvesting money into a procedure that might not prove effective after a year.
• Have a bleeding disorder with clotting factor deficiencies or low platelet counts
• Use blood thinners
• Have a liver disorder
• Have a recent cancer history or sepsis (blood infection)
• Are a heavy smoker, alcoholic, or illicit drug user
• Have low blood pressure or chronic user of steroids

Do PRP study results hold true in the real world?

When evaluating any hair loss therapy, it’s important to note that, sometimes, study results don’t match up to real-world results. On hair loss blogs and forums, there’s sometimes an inkling that this might be the case with PRP.

For starters, while there are positive patient stories with PRP, there are also many anecdotes of patients who tried PRP without success. This video is a perfect example. And if you dig deeper, you’ll probably find more negative than positive anecdotes.

This can be confusing – as most of the literature tends to describe PRP as seemingly beneficial. And even more troublesome, it’s also worth noting that I’ve spoken with dozens of readers who’ve tried PRP… and most of them have also reported negligible improvements.

This begs the question: is PRP that effective? And regardless of the answer, why might there be a discrepancy between studies’ results and patient reports?

What could explain the discrepancies between PRP studies and real-world results?

For starters, it’s actually unclear if there are clinical versus real-world discrepancies for PRP. For instance, it’s possible that PRP treatments might just suffer from the “Yelp effect”. This is when someone with a negative experience is far more likely to leave a public review versus someone with a positive experience.

So, PRP might just be one of those treatments that have collected negative reviews over a period of years – much like finasteride and its reports of sexual side effects.

Secondly (and this is the more important point to make), clinical research does not always depict reality. For instance, while a 25-40% increase in hair count from PRP looks great on paper, it doesn’t always translate to cosmetic results.

This tends to be a problem with even the “best” FDA-approved treatments. Just take a look at these five men who did combination treatments of minoxidil, finasteride, laser combs, and even hair transplants – and their results after one year.

I’ll save you the suspense: their final “after” photos are darkened to obscure just how minimal their hair changes are. And, for the hundreds (to thousands) of dollars each of the men spent, their hair seems more-or-less cosmetically unchanged.

(Note: that video is just one of the reasons why, for most AGA sufferers, I recommend approaches like massaging / microneedling as a baseline for any regimen. Not only do these therapies enhance other hair loss treatments, but also without their inclusion, you’re statistically likely to see no cosmetic improvements from your other treatments).

Thirdly, we just learned that without follow-up sessions, PRP results will fade for 20% of patients starting 12-18 months after their last round of injections. So, if you’re reading a review of someone who got PRP once four years ago and never saw results (or is experiencing continued hair loss) – you’ll know that it’s probably because they didn’t do enough injection rounds and they didn’t keep up with the therapy.

In any case, it’s worth noting that of the readers with whom I’ve communicated, the ones who tried PRP + Acell all reported positive results. While there aren’t yet studies validating this combination therapy, it seems to be the most promising from an anecdotal standpoint (if that means anything to you).

How to choose the right PRP practitioner

If you’re going to invest $1,000+ into platelet-rich plasma, don’t give your money to the first PRP clinic you find.

Instead, find a few clinics near you that offer the procedure and make sure they have a proven track record. That means they should have a website with PRP before-after photos.

Make a list of these clinics. Then, call each clinic and ask if their online photos are of PRP alone or of PRP + finasteride / minoxidil.

If the photos are of PRP alone, great! If they’re of PRP + multi-therapies but advertised to represent only PRP… then hang up, cross them off your list, and consider reporting them the clinic to the Better Business Bureau.

Doing this should eliminate 60-70% of providers.

Next, call the remaining providers and ask about their PRP techniques. You’ll want to find a clinic that offers 1-4+ months between injection rounds. If someone offers you a package of 10 PRP sessions spaced out as one injection round per week, that goes against the literature’s recommendations (and our understanding of wound-healing timelines) – and you should probably find another provider.

Moreover, the actual PRP product that a clinic uses will vary by volume, number of injection rounds, color, platelet count, leukocyte count, and protein content. The best PRP providers will offer double-spin centrifugation preparation with an activator like thrombin or calcium chloride. While some evidence suggests that “platelet activators” are not necessary, they also don’t seem to hurt the procedure. In any case, it’ll be good to speak with your provider about all of this – so you can get a feel of whether they can actually answer these questions. If they can’t, then cross them off your list.

Lastly, ask your remaining clinics if they offer PRP + Acell. If they do (and the costs aren’t prohibitive), then this might be a better option versus PRP alone. If they don’t, it’s not the end of the world – and chances are you’ll still see benefit from the procedure.

Following this process should leave you a few great PRP clinic options. And, as long as you’re willing to commit to injections every 4-6 months, you should see a considerable lift in hair count… especially if you’re combining platelet-rich plasma with other therapies.

Summary

Platelet-rich plasma therapy is effective for both androgenic alopecia and alopecia areata, but the procedure is cost-prohibitive and requires repeated clinic visits to see sustained results. These factors are big turnoffs for most hair loss sufferers considering PRP as a treatment option.

PRP works best as an adjunct treatment alongside other hair loss therapies. So, don’t just try PRP as the only thing to help your hair. We recommend combining it with massaging and/or microneedling, and (if you’re comfortable), FDA-approved drugs (especially minoxidil) to maximize results. And, if you can, try to find a clinic that provides PRP + Acell.

While PRP can help both male and female hair loss sufferers, preliminary evidence suggests that it’s just not as effective for females. However, this might be because of the added complexities of female AGA – and the fact that women are so frequently misdiagnosed with AGA but instead actually have hair shedding disorders related to underlying chronic conditions.

Be careful about clinic selection for PRP. For instance, the photos you’ll see on most dermatology websites offering PRP are from patients doing PRP + finasteride / minoxidil (rather than PRP alone). The equivalent would be if I advertised a before-after photo of someone doing massaging + finasteride, but decided to position the photo as if the results were only from massaging. It’s just bad business. So, be aware of this. Call all clinics to confirm the regimens of their highlighted patients.

If you’re seeing improvements from PRP, chances are you’ve already navigated through this mess to find a good provider. So, steer the course and keep us posted with your progress!

Can Scalp Tension Cause Hair Loss? It’s Possible.

Is there a connection between scalp tension and pattern hair loss (androgenic alopecia)? Sixty years ago, researchers thought no. Today, many are changing their tune.

The scalp tightness theory recently regained popularity in hair loss forums, but it isn’t new. Over 100 years ago, Bernarr Macfadden noted an association between scalp tightness and androgenic alopecia (AGA) in his book Hair Culture. And in 1950, the scalp tension theory of hair loss even advanced into the academia. For the next decade, androgenic alopecia researchers supported its plausibility.

Then in 1959, everything changed. Most of the scalp tightness theory’s advocates turned from supportive to dismissive… and almost overnight.

What happened? Why did researchers change their minds?

Well, a series of hair transplantation studies were published that contradicted the scalp tightness theory of androgenic alopecia. This led researchers to assess the evidence, reevaluate their opinions, and abandon the scalp tightness theory altogether. For the next forty years, the idea that scalp tension could cause hair loss remained “unrealistic.”

That is, until recently.

In the last five years, new studies have emerged that are forcing researchers to reevaluate the scalp tension-androgenic alopecia hypothesis yet again. These studies not only help build a biological rationale for the scalp tightness hypothesis, but they also present evidence opposing the counterarguments of theory.

So what are these studies? And what’s making researchers waver yet again? This article series explains it all.

This is a three-part series on the scalp tightness theory of hair loss. In this article, we’ll uncover the science behind scalp tension and its potential relationship to pattern hair loss.

In the next article, we’ll dive into the debate over this theory. After all, a few studies from the 50’s and 70’s seemingly contradicted the theory entirely. But now – over forty years later, new evidence is challenging these counterarguments… and bringing the debate back to life again.

In the last article, we’ll try to settle this debate and uncover where scalp tension might come from. Does scalp tightness cause androgenic alopecia? Is scalp tension merely associative with hair loss? And if does cause pattern hair loss… what can we do about it? As always, when it comes to hair loss research, the answers aren’t so cut-and-dry.

Scalp Tension Theory: The Basics

We’ll soon get into the details of the scalp tension-androgenic alopecia hypothesis. For now, here are the basic principles.

Skin tension tends to restrict blood flow to tissues – much like a bent finger tightens our knuckle and turns it white. Interestingly, research suggests that balding men and women tend to have chronically tighter scalps than those without hair loss.

Across the body, excessive tissue tension can evoke an inflammatory response which, if left unresolved, leads to scar tissue formation. We’ve seen this in stressed periodontal ligaments, the eyelids of patients with Graves’ disease, enlarged prostates, and in the hand tissues of people with Dupuytren’s contracture. The bottom line: more tissue tension, more inflammation, more scar tissue.

As scar tissue settles in, it simultaneously restricts blood, oxygen, and nutrients to tissues. Fascinatingly, the same phenomena and observations – tissue tension, inflammation, reduced blood flow, lower oxygen, and increased scar tissue – are also seen in balding scalps. In fact, we see the onset of these observations in the same pattern and progression as hair loss.

Interestingly, studies on scarring-related diseases – like scleroderma – reveal that once enough scarring settles, hair cannot grow. Putting it all together, this suggests that scalp tension might be involved in the inflammatory cascade which leads to pattern hair loss.

Tension evokes inflammation, inflammation evokes scar tissue, scar tissue restricts oxygen and nutrients to the hair follicles, and this slowly miniaturizes the hair follicles until eventually… we’re left with pattern baldness. Thus, in its most basic form, the scalp tightness-androgenic alopecia theory looks something like this:

Scalp tissue tension >> inflammation >> scar tissue >> pattern hair loss

Does the scalp tension theory differ from our current understanding of androgenic alopecia?

Yes and no. The scalp tightness-hair loss theory fits well in the literature, and of what we already know about androgenic alopecia (or AGA). In fact, it might even enhance our understanding of AGA.

To get a full picture of why, we need to understand…

1. The current model of AGA pathology (what researchers currently believe is the cause of AGA).
2. Questions this AGA model cannot answer
3. How the scalp tension theory answers these questions while still making sense of previous findings in AGA research.

Let’s take these one-by-one.

What Causes AGA? Our Current Understandings

AGA is the world’s most common hair loss disorder – affecting 50% of women and 80% of men throughout a lifetime. And it’s unique because it only affects a certain region: the top part of our scalps.

In men, the hair loss often begins at the temples and vertex. In women, it begins as more globalized (diffuse) thinning. In both genders, the condition is chronic and progressive – meaning that with time and without treatment, it will continue to worsen.

If you’ve ever looked into the causes of AGA, you’ve probably come across the term dihydrotestosterone, or DHT. DHT is a hormone that’s made from testosterone. In fact, most dermatologists will tell you that an interaction of our genetics and DHT is what causes pattern hair loss. Hence the medical name, androgenic alopecia. Andro = androgens; genic = genes; alopecia = hair loss.

So is there any truth to this claim? Yes. There’s an overwhelming amount of evidence that DHT is causally linked to pattern hair loss.

Firstly, studies show that DHT is higher in the scalps of men with thinning hair. Secondly, if a man is castrated, his testosterone (and DHT) levels plummet permanently. Men castrated before puberty (i.e., before their DHT levels spike) don’t go bald later in life. And thirdly, men with a genetic deficiency in an enzyme that converts testosterone into DHT in scalp tissues never develop pattern hair loss.

These are pretty indicting findings. Just look at the endpoints: men who never produce DHT never develop pattern hair loss. Men with higher amounts of DHT in their scalps have AGA. Based on these findings, DHT must play some causal role in AGA.

But beyond that, things start to get complicated…

DHT is causally linked to AGA. But eliminating DHT doesn’t lead to a complete hair recovery

Finasteride is an FDA-approved drug that men use to help fight AGA. It works by reducing DHT levels. In fact, when taken as prescribed, finasteride can reduce scalp DHT levels by over 60%.

But just how effective is it at treating AGA?

Well, clinical studies suggest finasteride improves hair loss outcomes for 80-90% of users. That means it helps slow, stop, or partially reverse hair loss for 80-90% of the people taking it. But just how much hair can we expect to recover?

Over a two-year period, those same studies suggest that finasteride, on average, leads to just a 10% increase in hair count – with hair count plateauing thereafter.

This suggests that finasteride is mostly limited to stopping hair loss progression, rather than reversing the condition entirely. Similar observations were made in castrates. Castration (and thereby near-full DHT reduction) only seems to stop pattern baldness. It doesn’t fully reverse it.

And therein lies the first big “question” of the DHT-hair loss hypothesis.

Question: If DHT causes pattern hair loss, how come eliminating DHT only stops AGA? How come it doesn’t lead to a full hair recovery?

This actually isn’t impossible to answer.

Many researchers have hypothesized that this may be due to DHT’s relationship with scar tissue. In scalp tissues, the arrival of DHT seems to also remodel our scalps – causing increased disorganized collagen crosshatchings. In other words, scalp DHT causes fibrosis (or scarring).

In fact, balding scalp regions have four times the amount of excess collagen deposition (scar tissue) than non-balding regions. And as we’ve learned in scleroderma studies, where there’s scar tissue, hair cannot grow.

DHT >> scar tissue >> hair loss

So maybe the reason why eliminating DHT doesn’t fully reverse hair loss… is simply because stopping DHT only stops the progression of scar tissue. It doesn’t necessarily reverse the scar tissue already present.

This makes sense. In fact, this is the explanation many AGA researchers use to describe why our recovery from AGA is “limited”. But interestingly, this explanation brings up another question that the DHT-hair loss theory has a much harder time answering.

Question: If DHT causes scarring and hair loss in the scalp… why does DHT encourage hair growth in other parts of the body?

Why does DHT encourage hair loss in the scalp… but hair growth in the chest and face?

You may have noticed that a lot of bald men also have incredibly hairy bodies. Well, this is because DHT can have two totally opposite effects on hair. It all depends on its location in the body.

For instance, studies show that while DHT in our scalps appears to encourage hair loss, DHT in body tissues (i.e., facial and chest skin) appears to encourage hair growth.

How can that be? How can DHT encourage hair growth in secondary body and facial hair… while simultaneously encouraging hair loss in our scalps?

Unfortunately, this is something the current DHT-androgenic alopecia pathology model cannot explain. So its supporters chalk it up to genetics – explaining it must be due to gene variants that are associated with more androgen receptors and their co-activators.

There’s some truth to this, but the reality is that nearly every single cell in our body carries the exact same genes. What differentiates a cornea cell from a skin cell is the combined influence of gene programming + a cell’s environment.

This means that “genetics” is sort of a blanket explanation for things we don’t understand. Not only is it the go-to answer for questions that exceed our knowledge base… it also completely undermines the influence of environment – which is often half (or more) of the equation.

In fact, there are several more questions that the DHT-AGA pathology model answers with the idea of “genetics” – but in reality, isn’t as supported by the literature as most tend to believe. Here they are:

Question #1: what causes DHT to increase in balding scalp tissues in the first place?

Question #2: why does DHT encourage hair loss in the scalp… but secondary hair growth in the body and face?

Question #3: why is there a pattern to AGA? Why does it begin at the temples and vertex for most men and generalized thinning for most women?

Question #4: why does AGA only affect the top part of our scalps – in areas that overlie the dense fibrous membrane known as the galea aponeurotica?

So, is it possible to answer these unanswered questions of AGA pathology, and in doing so, create a better model to explain the causes of pattern hair loss… all while not undermining any research demonstrating that DHT is causally linked to AGA?

Potentially. This is where the scalp tension theory of hair loss comes into play.

Scalp Tightness-Pattern Hair Loss Theory: A Deep-Dive

In 2017, I reintroduced the scalp tightness theory in a scholarly paper – particularly in light of new studies that reinforce its role in AGA. The rest of this article will explain the basics of that paper.

The best place to start is to attempt to provide answer those unanswered questions – and beyond “genetics”. Our first question: why does DHT increase in balding scalps?

Question #1: Why does DHT increase in balding scalps?

To get an idea of what might cause DHT to increase in balding scalp tissues, we need to have a bigger picture of what’s going on balding scalp tissues. That means it’s worth cataloguing most of the observations researchers have seen in balding scalps.

We’ve already discussed a few of these – like DHT and scar tissue. But there are many other things happening, too. And if we know what they are, maybe we can begin to parcel out a cause-and-effect relationship between balding scalps and increased DHT.

Here are the big ones from the paper.

Biological. Balding scalps have higher levels of androgen activity – specifically, DHT. And interestingly, balding scalps also express higher amounts of inflammation. We see this in the form of specific signaling proteins and reactive oxygen species (more on this later). These are things that commonly arrive in sites of “stress” – i.e., where the body senses an injury or an infection.

Physiological. Balding scalps have four-fold more disorganized collagen fibers (i.e., scar tissue) than non-balding scalps. And interestingly, the patterning and progression of this scar tissue appears to match the patterning and progression of AGA. In other words, where we see an increase in disorganized collagen cross-hatchings, we also see hair loss. Moreover, we also see that balding scalps have lower blood flow and lower oxygen levels than non-balding tissues – and that in all likelihood, the reduced blood flow occurs outside of our natural hair cycling.

Structural. Several dermatologists and AGA researchers have noted, anecdotally, that balding scalps appear to just “feel” tighter than non-balding scalps. This was also discussed by Dr. Brian Freund – a former university lecturer and hair loss researcher. He mentioned that his male and female patients with AGA almost always had incredibly tight scalps. There’s some evidence that this tension may come from involuntary contractions from our scalp’s perimeter muscles – which would pull the top of the scalp tightly – much like bending a finger pulls the knuckles tight.

Now that we have a better understanding of what’s going on in a balding scalp, we can revisit that initial question:

What causes DHT to increase in balding scalp tissues?

After all, maybe the answer is in one of these observations…

Clue #1: DHT is anti-inflammatory

Beyond its role in sexual maturation, studies also show that DHT can over-express in tissues as a response to inflammation – and that specifically, DHT is anti-inflammatory.

This is incredibly telling, especially in regard to androgenic alopecia research. After all, balding scalps show both increased inflammation and increased DHT. Maybe the inflammation observed in balding scalp tissues is what causes DHT to increase.

However, this opens a new question. If inflammation is what causes DHT to increase in balding scalps… what causes inflammation in the first place?

Reflecting back on our catalogue, there’s at least one possible culprit: chronic tissue tension.

Clue #2: tissue tension can “activate” inflammation and DHT

The relationship between tension, inflammation, and androgen activity isn’t very shocking. In fact, it’s been observed in several other regions. For instance…

1. Inflamed periodontal tissues can signal to increase androgen activity.
2. Men with a tendon-contracting condition known as Dupuytren’s contracture also express more inflammation and male hormones in the affected tissues.
3. Graves’ disease sufferers often have chronic eyelid retraction due to the involuntary contraction of the Mueller muscle). In biopsies, this muscle shows higher markers of inflammation and often androgen activity.
4. Prostate tissues, when exposed to cyclical stretching, induce inflammation and DHT-induced transforming growth factor beta-1 (more on that later).

All of this suggests that in balding scalps, chronic tension may induce the arrival of inflammation and DHT. To put it simply:

Chronic tension >> inflammation >> DHT

Now that we’ve have a potential reason for the “arrival” of DHT, we can ask a harder question:

Why is DHT linked to hair loss in the scalp… but hair growth in other body regions?

Fascinatingly, tension might also help explain this DHT paradox. Here’s how.

Chronic tension and androgens can induce scar tissue

Research shows that DHT behaves differently depending on its location. Specifically, DHT can increase hair loss in the scalp but also increase hair growth in the best and face. This suggests, at a minimum, that a tissue’s location has some sort of influence on the effects of DHT.

So, can tissue tension help us answer this DHT paradox?

Yes.

When DHT in chest and facial tissues, it induces more hair growth. But when DHT is expressed in the scalp – i.e., in tissues under chronic tension – DHT induces the arrival of a signaling protein called transforming growth factor beta 1 (or TGFβ-1).

This is interesting, because DHT doesn’t always appear to induce this signaling protein in tissues that aren’t under added contraction.

However, we do see DHT-induced TGFβ-1 in periodontal tissues, Dupreyene’s contracture, and in benign prostate hyperplasia. And fascinatingly, we also see DHT induce TGFB-1 in balding scalp dermal papilla cells (i.e., the cell clusters that influence the size of our hair follicle).

This signaling protein – TGFβ-1 – is universally condemned across biology as a biomarker for aging, and more specifically, as a prerequisite for the onset of fibrosis (scar tissue).

Studies have shown that wherever TGFβ-1 over-expresses, fibrosis soon follows. And as a reminder, balding scalps have four-fold more disorganized collagen crosshatchings (i.e., fibrosis) than non-balding scalps.

In fact, this scar tissue seems to develop alongside the pattern and progression of AGA. For men, it begins at the temples and vertex… and spreads to the rest of the scalp in accordance with hair follicle miniaturization.

The DHT-hair loss hypothesis suggests that fibrosis might be what limits our ability to regrow hair. But if fibrosis actually causes hair follicle miniaturization, then this would explain why DHT grows hair in the chest and face… but leads to hair loss in the scalp.

So, is there evidence that fibrosis or excess collagen deposition leads to baldness?

Yes.

Excess collagen (or scar tissue) can prevent hair growth

In the medical literature, one defining characteristic of scar tissue (i.e., fibrosis) is the absence of hair. In fibrosis-related disorders (like scleroderma), researchers have consistently observed that as fibrosis sets in, hair loss soon follows – even in the scalp.

And in this article, I lay out a few step-processes behind how fibrosis might contribute to hair follicle miniaturization. The gist is that excess collagen appears to onset outside of normal hair cycling and it seems to progress throughout hair follicle miniaturization – implying that its presence may possibly explain the production of smaller hairs in AGA.

This suggests that in AGA, fibrosis may cause hair loss, and through a few mechanisms: firstly, through the constriction of space for a hair follicle to grow. And secondly, through tissue degradation. Specifically, the restriction of blood, oxygen, and nutrients to the hair follicles.

DHT >> TGFβ-1 >> fibrosis >> reduced blood and oxygen >> hair loss

Taking a step back, DHT’s opposing “behavior” in the scalp versus the body might be explainable through the evidence that…

1. In the presence of chronic tension, DHT induces signaling proteins which lead to scar tissue (and thereby hair follicle miniaturization)
2. In the absence of chronic tension, DHT doesn’t induce these signaling proteins… so it simply encourages hair growth.

This is a subtle difference, but with potentially huge implications in the world of AGA. And we can now add these findings to our revised AGA model.

Chronic tension >> inflammatory response >> DHT >> TGFβ-1 >> fibrosis >> restricted blood flow >> hair follicle miniaturization >> pattern hair loss

However, there’s still one outstanding question… can tension also explain the pattern and progression of AGA? And if so, can it explain the differences in thinning patterns for both men and women?

The evidence points to yes.

Scalp tension may also explain the pattern and progression of AGA

In men with AGA, hair loss often starts at the temples and vertex. And fascinatingly, we also see this same patterning with scalp tension.

There are certain modeling softwares that allow us to estimate the tensile force of any surface – so long as we know the surface area and the direction and magnitude of forces applied to that surface.

In 2015, researchers decided to use a modeling software to map the tensile projections of the tops of male scalps. The forces applied to that surface? The contractions of the scalp perimeter muscles – the same chronic contractions noted by Dr. Brian Freund and other AGA researchers.

The findings? A near-perfect correlation between scalp tension peaks, the patterning of AGA, and the progression of male pattern hair loss. For a graphic reference…

(source)

Since scar tissue also onsets in the pattern and progression of male AGA – this perfectly aligns with the idea that scalp tension might be the beginning of the hair loss cascade.

But what about women?

Unlike most men, most women don’t start thinning at the temples or vertex. Rather, they tend to lose hair in a diffuse pattern.

And what about hair loss that occurs in advanced stages of AGA – like hair loss we see at the nape of the neck, or behind the ears? Could tension also explain this?

Preliminary research points to yes.

In fact, other investigators have used the same modeling software to “play” with these tension projections. What they’ve found is that by making small tweaks head shape, size, and contraction force, it’s possible to create tensile patterns that match the pattern of hair loss we see in women.

In fact, it’s also possible to do the same for more advanced stages of AGA – like hair loss above the ears and at the nape of the neck. One researcher even shared his findings for free – which you can access here.

Where might this scalp tension come from?

This is going to be saved for another article. The short answer is that there are likely three major sources of scalp tension, and each creates a feedback loop with the others:

1. The chronic involuntary contraction of muscles surrounding the perimeter of our scalps. Specifically, the muscles connected to the galea aponeurotica.
2. Skull bone growth and skull suture settlement during and after puberty.
3. Fascia remodeling surrounding the galea and its connected tissue networks.

Tying it all together – genetics, scalp tension, and AGA

This is a lot of information, and as such, it might help to see a visualization of everything above. As such, here’s the flowchart that I presented in my paper:

I know we didn’t cover every aspect on this flowchart. Doing so would’ve made this post twice as long. But I hope you can see the logic progression, and how everything ties together:

Scalp tension >> inflammation >> DHT >> TGFβ-1 >> fibrosis >> restricted blood flow >> hair follicle miniaturization >> pattern hair loss

So if scalp tension is a contributor to AGA… does relieving scalp tension improve AGA outcomes?

Yes.

Dr. Brian Freund demonstrated that in AGA sufferers, botox injections to relieve tension in chronically contracted scalp muscles increased hair counts by 18%. And this year, a new study confirmed Dr. Freund’s original findings. Finally, tension offloading devices also appear to improve hair growth in AGA subjects over 3-12 months periods. So at a minimum, it seems like targeting scalp tension improves hair growth in men and women with AGA.

Does the scalp tightness-hair loss hypothesis fit into all of the literature on AGA?

At face-value, the AGA theory of scalp tension satisfies the questions left unanswered in the current DHT-hair loss pathology model.

1. Why does DHT increase in balding scalp tissues? It increased as part of an inflammatory response, and this inflammation is mediated by skin tension.
2. Why is DHT associated with scalp hair loss and body hair growth? If expressed while under tension, DHT induces the expression of transforming growth factor beta 1, which leads to scarring and thereby hair loss. This tension is present in the scalp, but not in body tissues.
3. Why is there a specific pattern and progression to AGA? This patterning matches the tensile patterning and progression of scalp tissues – with the highest tension points as the first to suffer from hair loss.

But does the scalp tightness-AGA theory make sense of all aspects of AGA research?

Not necessarily.

The reality is that I just presented the entire scalp tension argument to you in a bubble. I didn’t yet  introduce a layer of complexity that, at first glance, could dismantle the theory entirely.

There is a complication to the scalp tightness hypothesis: a compelling counterargument. And it’s a big one. It’s the early findings from hair transplantation studies.

The scalp tension counterargument: hair transplantations

Remember in 1950 – when the scalp tension hypothesis made its way into academia? And in 1959 – how the scalp tightness theory was swiftly abandoned?

This is because that year (and the years following), researchers published several studies on hair transplants which completely changed the trajectory of hair loss research.

These studies sought to confirm if going bald had anything to do with the environment of our scalp tissues. Specifically, things like scalp tension.

To test this question, researchers decided to transplant skin grafts containing healthy hair into balding regions… and take skin grafts containing balding hair and transplant them into other parts of the body.

The findings? If we transplant hair follicles to or from a balding region…

1. Non-thinning hairs moved to balding scalps keep growing normally.
2. Thinning hairs moved to non-thinning regions keep thinning… at the same rate as thinning scalp hairs.

What did this suggest? That our scalp environment has nothing to do with balding.

Otherwise, why would thinning hairs transplanted out of a tense scalp environment keep thinning – even when placed in non-thinning regions? And why would healthy hairs transplanted into a tense environment keep growing – even as the hairs around them continue to thin?

This led researchers to abandon the scalp tension hypothesis, and instead conclude that baldness must be due to genetic programming within the hair follicle itself.

This idea of genetic determinism has been the prevailing theory for the last sixty years… until recently. Now new studies are making us question whether we drew the right conclusions about hair follicle miniaturization all those years ago.

And what are those studies? That’s for the next article.

Scalp Tension Summary

Research shows that balding men and women tend to have tighter scalp tissues than their non-balding counterparts. And interestingly, this scalp tension tends to align with the pattern and progression of AGA.

In men, tension is the highest where hair loss first begins (i.e., the vertex and temples), with skin tension dissipating alongside the “spread” of pattern hair loss. In women, equal tension can be modeled throughout the scalp skin – similar to a diffuse thinning pattern.

When our bodies sense a stressor (i.e., a cut, an impact, or an infection), they evoke an inflammatory response. Interestingly, this is also true for tissues under chronic tension. DHT has been shown to be anti-inflammatory, and when a tissue is under chronic tension, DHT tends to over-express. We’ve seen this in several disease states related to involuntary contractions. Resultantly, chronic scalp tension might not only explain the inflammatory biomarkers we see in balding scalps, but also the arrival of DHT (something the DHT-gene theory of AGA does not satisfactorily answer).

In cases where DHT is activated through tension, we also see DHT induce a signaling protein that causes scarring; specifically, TGFβ-1. This creates excess collagen deposition and scarring (or fibrosis), which then restricts blood, nutrient, and oxygen supplies to the affected tissues.

Interestingly, we see all of the above in balding tissues: increased DHT, increased TGFβ-1, increased fibrosis, lower blood flow, and lower oxygen levels… and in the exact same patterning as AGA.

Studies on scarring-related diseases demonstrate that where scar tissue accumulates, hair does not grow. And evidence suggests that fibrosis in our scalps may precede hair thinning. As fibrosis accumulates, this would cause hair follicle miniaturization through space restrictions alongside tissue degradation (i.e., reduced blood supply). The end-result: hair thinning in the pattern of AGA.

The scalp tension-AGA hypothesis, in my opinion, is the only hypothesis that satisfactorily makes sense of these unanswered questions in AGA research: 1) why does DHT increase in balding scalps, 2) why does DHT encourage hair loss and hair growth depending on its tissue location, and 3) why is there a “pattern” to pattern hair loss?

Unfortunately, hair transplantation studies from fifty years ago led researchers to conclude that our scalp environment – and specifically, scalp tension – have nothing to do with the onset of pattern hair loss. This led to the abandonment of the theory…

Until recently. In the next article, we’ll uncover why.

Note: Regardless of the evidence for or against scalp tension, there are potentially dozens of other factors kickstarting the inflammatory cascade that leads to hair loss. Therefore, scalp tension – if it truly does cause hair thinning – is just a contributor (and not a root cause). Future articles will explain why.