Articles

Retinoic acid (RA) is the biologically active form of Vitamin A, playing an important role in regulating cell growth, differentiation, and tissue maintenance in the body.^[1]Peehl, D.M., Wong, S.T., Stamey, T.A. (1993). Vitamin A regulates proliferation and differentiation of human prostatic epithelial cells. Prostate. 23(1). 69-78. Available at: … Continue reading Its signaling pathway is essential not only for embryonic development but also for the maintenance of healthy skin and hair.^[2]VanBuren, C.A., Everts, H.B. (2022). Vitamin A in Skin and Hair: An Update. Nutrients. 14(14). 2952. Available at: https://doi.org/10.3390/nu14142952 

Interest in using retinoids (RA and its derivatives, such as tretinoin and retinol) as hair loss treatments stems from their potential to regulate the hair growth cycle and potentially prolong the anagen (growth) phase of hair follicles. In this article, we will explore what RA is and its derivatives, as well as how they can impact the hair follicle. We will also evaluate the available efficacy and safety data.

Key Takeaways

• Drug. Retinoic acid (RA), especially in the form of tretinoin, is a vitamin A derivative that regulates hair follicle stem cell activation through Wnt/β-catenin signaling. It is available in various topical formulations and is often used in combination with minoxidil to enhance hair regrowth in androgenetic alopecia (AGA).

• Clinical Data.  RA/tretinoin shows moderate standalone efficacy in promoting hair regrowth, particularly in early-stage AGA, but results improve significantly when used with minoxidil. Clinical trials from 1986 to 2024 have demonstrated enhanced hair density, thickness, and stem cell activity with combination therapy. RA also improves sulfotransferase enzyme activity, boosting minoxidil’s effectiveness, and has shown positive results in alopecia areata when combined with pimecrolimus.

• Safety. Generally well-tolerated at concentrations ≤0.025%, but may cause local irritation (redness, itching, dryness). Adverse effects are dose-dependent and typically self-limiting. Systemic side effects are rare with topical use but retinoids should be avoided during pregnancy and in individuals with photosensitivity or scalp inflammation.

• Evidence Quality.  Retinoic Acid scored 34/100 for evidence quality by our metrics.

• Best Practices. 
  • Use in combination with 5% minoxidil for optimal results, especially in early AGA.
  • Apply tretinoin in low concentrations (≤0.025%) once daily to minimize irritation.
  • Consider tretinoin if you’re a minoxidil non-responder or wish to reduce application frequency.
  • Avoid if pregnant, photosensitive, or prone to dermatitis.
  • Always consult a dermatologist before starting treatment.

What is Retinoic Acid?

RA is a biologically active metabolite of vitamin A (all-trans-retinol) and serves as a potent regulator of cell differentiation and proliferation. It plays essential roles in embryonic development, immune function, male fertility, and the regulation of bone growth and development.^[3]de Mendoca Oliveira, L., Teixera, F.M.E., Sato, M.N. (2018). Impact of Retinoic Acid on Immune Cells and Inflammatory Diseases. Mediators of Inflammation. 9(3067126). Available at: … Continue reading 

RA is produced in the body through a two-step oxidation process: retinol (vitamin A) is first reversibly oxidized to retinaldehyde, and then retinaldehyde is irreversibly oxidized to retinoic acid.^[5]Kedishvili, N.Y. (2017). Retinoic Acid Synthesis and Degradation. Subcellular Biochemistry. 81. 127-161. Available at: https://doi.org/10.1007/978-94-024-0945-1_5 This process is catalyzed by retinol dehydrogenases and retinaldehyde dehydrogenases (RALDH1, RALDH2, RALDH3). RA cannot be converted back to retinol, making its synthesis a tightly regulated process.

Structurally, RA is a polyunsaturated carboxylic acid with a long conjugated hydrocarbon chain and a terminal carboxyl group.^[6]Sani, B.P., Hill, D.L. (1990). [3] Structural characteristics of synthetic retinoids, Methods in Enzymology, Academic Press, 189. 43-50. Available at: https://doi.org/10.1016/0076-6879(90)89274-L The most prevalent naturally occurring form is all-trans-retinoic acid (ATRA), but other isomers such as 13-cis-retinoic acid (isotretinoin) and 9-cis-retinoic acid (alitretinoin) also exist in lower concentrations.^[7]Bayeva, N., Coll, E., Piskareva, O. (2021). Differentiating Neuroblastoma: A Systematic Review of the Retinoic Acid, Its Derivatives, and Synergistic Interactions. Journal of Personalized Medicine. … Continue reading 

RA is part of a broader class of compounds called retinoids, which includes both natural and synthetic derivatives of vitamin A.^[8]Bushue, N., Wan, Y-J, Y. (2010). Retinoid pathway and cancer therapeutics. Advanced Drug Delivery Reviews. 62(13). 1285-1298. Available at: https://doi.org/10.1016/’j.addr.2010.07.003 

Retinoids are categorized into generations based on their structure:^[9]Baldwin, H., Webster, G., Gold, L.S., Callender, V., Cook-Bolden, F.E., Guenin, E. (2021). 50 Years of Topical Retinoids for Acne: Evolution of Treatment. American Journal of Clinical Dermatology. … Continue reading 

• First Generation: Naturally occurring compounds and their isomers, including retinol, retinal, tretinoin (ATRA), isotretinoin, and alitretinoin.

• Second Generation: Synthetic analogs such as etretinate and acitretin, primarily used for severe psoriasis.

• Third Generation: Polyaromatic retinoids, such as adapalene, bexarotene, and tazarotene, are designed to achieve greater receptor sensitivity and reduced side effects.

• Fourth Generation: Newer compounds with enhanced selectivity, such as trifarotene.

Other commonly used derivatives include retinyl esters (e.g., retinyl palmitate), retinol, retinaldehyde, and synthetic esters like hydroxypinacolone retinate.

How Does Retinoic Acid Work?

RA acts primarily by binding to nuclear receptors in cells, specifically retinoic acid receptors (RARs) and retinoid X receptors (RXRs).^[10]Jin, Q., Huo, C., Yang, W., Jin, K., Cai, S., Zheng, Y., Huang, B., Wei, L., Zhang, M., Han, Y., Zhang, X., Liu, Y., Wang, X. (2022). Regulation of Tyrosinase Gene Expression by Retinoic Acid Pathway … Continue reading Once activated, these receptors function as transcription factors, directly regulating the expression of genes involved in cell proliferation, differentiation, and programmed cell death, also known as apoptosis. This ability to modulate gene expression is what gives RA its wide range of biological effects, from skin remodeling to influence over hair follicle dynamics.

What is the Impact of Retinoic Acid on Hair Follicle Biology?

Retinoic acid (RA) plays a powerful but finely tuned role in hair follicle biology. It affects how hair grows by turning certain genes on or off, acting through specialized receptors found in hair follicle cells, oil glands, and nearby skin tissue.

Too little or too much RA can disrupt the hair cycle. That’s why the body tightly regulates how much RA is made and broken down inside the follicle.

How Is Retinoic Acid Synthesized in the Hair Follicle?

RA is produced in two steps:

The enzyme SDR16C5 converts vitamin A (retinol) into an intermediate form called retinaldehyde.^[11]Wu, L., Belyaeva, O.V., Adams, M.K., Klyuyeva, A.V., Lee, S-A., Goggans, K.R., Kesterson, R.A., Popov, K.M., Kedishbili, N.Y. (2019). Mice lacking the epidermal retinol dehydrogenases SDR16C5 and … Continue reading This mostly occurs in the hair follicle bulge, a crucial area where stem cells reside, and in the dermal papilla, which plays a key role in controlling hair growth. SDR16C5 activity peaks during the growth phase (anagen) and helps stimulate both stem cell activity and hair matrix cell development.

In mice, the absence of SDR16C5 and its related enzyme, SDR16C6, results in an 80% decrease in RA levels.^[12]Foitzik, K., Spexard, T., Nakamura, M., Halsner, U., Paus, R. (2005). Towards Dissecting the Pathogenesis of Retinoid-Induced Hair Loss: All-Trans Retinoic Acid Induces Premature Hair Follicle … Continue reading 

This causes hair follicles to exit their resting phase (telogen) prematurely, leading to abnormal cycling and lower levels of key stem cell markers, such as Lgr5 and Sox9.^[13]Goggans, K.R., Belyaeva, O.V., Klyuyeva, A.V., Studdard, J., Slay, A., Newman, R.B., Christine, VanBuren, A., Everts, H.B., Kedishvili, N.Y. (2024). Epidermal retinol dehydrogenases cyclically … Continue reading  

Another enzyme, ALDH1A2, completes the process by converting retinaldehyde into the active form of retinoic acid. ALDH1A2 is most active in the outer root sheath of the follicle and especially in the bulge during the early growth and regression phases.^[14]Everts, H.B., King Jr, L.E., Sundberg, J.P., Ong, D.E. (2004). Hair cycle-specific immunolocalization of retinoic acid synthesizing enzymes ALDH1A2 and ALDH1A3 indicates complex regulation. Journal … Continue reading One of its key roles is to lower levels of BMP4, a protein that keeps stem cells in a resting state. By reducing BMP4, ALDH1A2 helps “awaken” stem cells and initiate new hair growth.^[15]Suo, L., VanBuren, C., Hovland, E.D., Kedishvili, N.Y., Sundberg, J.P., Everts, H.B. (2021). Dietary Vitamin A Impacts Refractory Telogen. Frontiers in Cell and Developmental Biology. 9. Available … Continue reading When this enzyme is missing, hair follicles take longer to enter the growth phase, and their circadian rhythm becomes disrupted.

How is Retinoic Acid Broken Down?

While synthesizing RA is important, too much can be harmful. That’s where CYP26B1 comes in. CYP26B1 is an enzyme that breaks down RA into inactive forms. During the growth phase, it is found in the dermal papilla and pre-cortex; during rest, it shifts to the bulge to prevent RA levels from building up excessively.^[16]Okano, J., Levy, C., Lichti, U., Sun, H-W., Yuspa, S.H., Sakai, Y., Morasso, M.I. (2012). Cutaneous retinoic acid levels determine hair follicle development and downgrowth. Journal of Biological … Continue reading 

This careful back-and-forth between making and breaking down RA shows how tightly the hair follicle controls its environment. Low, well-regulated levels of RA can support stem cell activity and help promote healthy hair growth. However, high or unbalanced levels can actually prompt follicles to regress or block growth altogether.

To put it plainly: Your hair follicles need just the right amount of retinoic acid. When the balance is right, it may help stimulate hair growth, but when it’s off, it can slow or even reverse it.

Importantly, these regulatory mechanisms are not just theoretical; they appear to be directly involved in common hair disorders, such as androgenic alopecia (AGA).

In vivo/In vivo Evidence

Recent research has demonstrated that retinoic acid signaling is suppressed in miniaturized hair follicles from AGA patients which coincides with impaired hair follicle stem cell (HFSC) activation.^[17]Wen, L., Fan, Z., Huang, W., Miao, Y., Zhang, J., Liu, B., Zhu, D., Dai, D., Zhang, J., Le, D., Zhang, Y., Qu, Q., Hu, Z., Chen, R. (2024). Retinoic acid drives hair follicle stem cell activation via … Continue reading  

Using transcriptomic, in vivo (mouse), ex vivo (human hair follicle organ culture), in vitro (HFSC culture), and clinical approaches, the authors showed that retinoic acid supplementation restored HFSC function by activating Wnt7a/7b and downstream ꞵ-catenin signaling. This promotes HFSC proliferation, differentiation into progenitor cells, and entry into the anagen phase, resulting in improved hair follicle growth (Figure 2), accelerated hair regrowth in mice (Figure 3), and improved hair density and diameter in AGA patients, particularly in early treatment (more on that below). 

Mechanistically, blocking either retinoic acid receptors or Wnt signaling reduced these effects, confirming that retinoic acid acts via Wnt/ꞵ-catenin to drive HFSC activation and hair regeneration. 

Is Retinoic Acid Clinically Effective at Treating Hair Loss?

Retinoic acid and its derivative, tretinoin, have been investigated in clinical trials for treating both androgenetic alopecia (AGA) and alopecia areata (AA). Studies have shown potential synergistic effects with minoxidil, including improved enzyme activity and increased hair regrowth rates, although efficacy typically varies by condition and formulation. 

Study One -1986 (AGA)

This study was an open-label trial of 56 participants with AGA treated with tretinoin alone or in combination with 0.5% minoxidil for 1 year.^[20]Bazzano, G.S., Terezakis, N., Galen, W. (1986). Topical tretinoin for hair growth promotion. Journal of the American Academy of Dermatology. 15.880-883. Available at: … Continue reading Twelve participants received 0.025% topical tretinoin, 36 participants received a combination of 0.025% tretinoin and 0.5% minoxidil, 3 participants received 0.5% minoxidil alone, and 5 participants received a topical placebo.

Hair growth was evaluated through photographs and hair counts in a defined 1-inch diameter target area on the scalp. The duration of participation averaged 8-10 months, with some subjects following the protocol up to 18 months. Participants were categorized as:

• Good responders (Group A): ≥46% increase in terminal hairs.
• Moderate responders (Group B): 21–45% increase.
• Non-responders (Group C): <20% increase.

Placebo and Minoxidil Alone:

Placebo goup: No participants showed hair growth

Minoxidil alone: No participants showed terminal hair regrowth; one participant showed vellus hair growth.

Tretinoin Alone:

12 participants: 58% (7 participants) responded positively, 16% (2 participants) shows a “good response”, 42% (5 participants) had a “moderate” response, and 42% had no response.

However, one woman appeared to be highly responsive to treatment with a 1100% increase in hair counts after 18 months of tretinoin-only treatment.

Combination of Tretinoin and Minoxidil:

36 participants: 66% (24 participants) responded positively, 44% (16 participants) had a “good” response, 22% (8 participants) had a “moderate” response, and 33% (12 participants) had no response.

Responses were observed within 4 to 18 months, with photographic documentation showing visible regrowth in both men and women.

Ultimately, this study showed that tretinoin alone moderately improved hair regrowth, but combining the treatment with minoxidil was more effective, with two-thirds of participants showing terminal hair regrowth.

Study Two – 2007 (AGA)

31 male participants aged 28-45 were recruited for this 18-week study, which compared the efficacy and safety of a combined solution of 5% minoxidil and 0.01% tretinoin applied once daily versus conventional 5% minoxidil applied twice daily for male AGA.^[21]Shin, H.S., Won, C.H., Lee, S.H., Kwon, O.S., Kim, K.H., Eun, H.C. (2007). Efficacy of 5% minoxidil versus combined 5% minoxidil and 0.01% tretinoin for male pattern hair loss. American Journal of … Continue reading 

Five parameters were evaluated: total hair count, non-vellus hair count, anagen hair ratio, linear hair growth rate, and mean hair diameter. Subjective global assessments were also conducted by patients and investigators at 9 and 18 weeks. 

Both groups showed significant increases in total hair count and non-vellus hair count after 18 weeks. Mean hair diameter increased significantly in the minoxidil-only group. However, there were no significant changes in anagen hair ratio or linear hair growth rate in either group. Furthermore, there were no statistically significant differences between groups in any hair growth parameter after 18 weeks.

No significant differences were observed between the two groups in patient-reported improvement or satisfaction scores at any time point. Furthermore, the investigator’s global assessment also showed no significant differences between groups.

Safety outcomes showed that mild adverse effects (itching, irritation) were observed in 5/15 patients in the combined group and 4/14 in the minoxidil-only group, but these were all self-limiting.

The conclusion? The once-daily application of combined 5% minoxidil and 0.01% tretinoin was as effective and safe as twice-daily 5% minoxidil for treating AGA in men. This means it could potentially be a more convenient alternative to twice-daily minoxidil.

Study Three – 2019 (AGA)

Another study found that combining tretinoin with minoxidil could increase follicular sulfotransferase activity and therefore responsiveness to minoxidil.^[23]Sharma, A., Goren, A., Dhurat, R., Agrawal, S., Sinclair, R., Trueb, R.M., Vano-Galvan S., Chen, G., Tan, Y., Kovacevic, M., Situm, M., McCoy, J. (2019). Tretinoin enhances minoxidil response in … Continue reading  

Sulfotransferase (SULT1A1) is the enzyme responsible for converting minoxidil, a prodrug, into its active metabolite minoxidil sulfate within hair follicles.^[24]Dhurat, R., Daruwalla, S., Paj, S., Kovacevic, M., McCoy, J., Shapiro, J., Sinclair, R., Vano-Galvan, S., Goren, A. (2022). SULT1A1 (Minoxidil Sulfotransferase) enzyme booster significantly improves … Continue reading This sulfation reaction is critical because minoxidil sulfate directly stimulates hair growth.

Twenty participants (10 male and 10 female) with AGA were recruited for this study, which determined the effect of topical tretinoin on follicular sulfotransferase. Non-responders to minoxidil often exhibit follicular SULT1A1 activity <0.4 OD 405 nm. In this trial, pretreatment SULT1A1 levels in participants who were minoxidil non-responders averaged 0.28 OD 405 nm. 

Treatment with topical tretinoin (0.1%) increased SULT1A1 activity by 1.8-fold in 75% of subjects after 5 days, raising levels to around 0.51 OD 405 nm. This shift moved 43% of non-responders above the 0.4 OD cutoff, enabling sufficient minoxidil activation.

Study Four – 2024 (AGA)

The most recent trial was conducted in 2024, with 60 total participants with AGA.^[25]Wen, L., Fan, Z., Huang, W., Miao, Y., Zhang, J., Liu, B., Zhu, D., Dai, D., Zhang, J., Le, D., Zhang, Y., Qu, Q., Hu, Z., Chen, R. (2024). Retinoic acid drives hair follicle stem cell activation via … Continue reading 30 participants received a 0.025% topical tretinoin cream, while 30 received 5% minoxidil solution alone. Each treatment was applied twice daily to the bald scalp. 

Hair growth was measured using photography and dermoscopy assessments at 1, 3, and 6-month follow-ups.

The participants treated with the topical tretinoin cream showed a significant improvement in mean hair count, density, and diameter after the first month compared to the Baseline. A significant increase was also observed in hair count, density, and terminal hair ratio in the tretinoin group compared to the minoxidil-treated group.

Study 5 – 2014 (AA)

A randomized controlled trial was conducted with 80 participants with alopecia areata aged 18-25 years, with one to four lesions on the scalp, and lesion diameter of 1.5 to 6 cm.^[27]Jalai, M.H.A., Mobasher, P., Rabbani, R., Jazi, G.A. (2014). Comparing the Efficiency of Elidel Cream and Elidel Accompanied with Tretinoin Cream in Treatment of Alopecia Areata. Journal of Skin Stem … Continue reading 

Participants were treated with either 1% Elidel (pimecrolimus cream) (40 participants) or Elidel + 0.05% tretinoin (40 participants) twice daily for three days. Treatment response was categorized as complete cure, relative cure, no change, or aggravation of lesions. 

Elidel Group:

• Complete cure: 8 patients (20%)
• Relative cure: 14 (35%)
• No change: 10 (25%)
• Aggravation: 8 (20%)

Eliden and Tretinoin Group:

• Complete cure: 18 patients (45%)
• Relative cure: 12 (30%)
• No change: 8 (20%)
• Aggravation: 2 (5%)

The combination therapy group had significantly higher rates of complete cure and lower rates of disease aggravation. However, adverse effects (mainly redness and burning) were more common in the combination group (45%), leading to dose reduction or discontinuation in some cases, but no serious complications were reported.

Unfortunately, the study included no images to show what the initial hair loss severity was and whether the improvements were actually noticeable/

Overall, the clinical evidence suggests that retinoic acid/tretinoin may be most effective as part of a combination therapy, and that patient selection, dosing, and timing play crucial roles in treatment success.

Another point that we can learn from these studies is that tretinoin appears to enhance the effectiveness of minoxidil (and potentially Eliden). This could be due to several mechanisms:

• Enhanced Penetration: Tretinoin may increase skin permeability, allowing better minoxidil absorption.
• Boosts Sulfotransferase Enzymes: Tretinoin upregulates SULT1A1, the enzyme responsible for converting minoxidil into its active form (minoxidil sulfate).
• Stimulates Stem Cell Activity: Both agents independently promote anagen phase entry and follicle regeneration via different pathways (minoxidil via potassium channels, RA via Wnt signaling).

Together, they work on complementary pathways, which helps explain why multiple trials (1986, 2007, 2019, 2024) found better hair growth outcomes with combined use.

How Safe is Retinoic Acid/Tretinoin?

While generally safe, retinoic acid and tretinoin can cause local irritation, especially when used topically on the scalp:

• Common Side Effects: Redness, itching, dryness, and burning sensations.^[28]Yoham AL, Casadesus D. Tretinoin. [Updated 2023 Mar 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: … Continue reading
• Dose-Dependent: Higher concentrations (e.g., 0.1%) are more likely to cause irritation.^[29]Griffiths, C.E., Kang, S., Ellis, C.N., Kim, K.J., Finkel, L.J., Ortiz-Ferrer, L.C., White, G.M., Hamilton, T.A., Voorhees, J.J. (1995). Two concentrations of topical tretinoin (retinoic acid) cause … Continue reading
• Mitigation: Reducing application frequency or using lower strengths can improve tolerability. Some studies reported treatment discontinuation due to discomfort.
• Systemic Risks: Rare with topical use, but oral retinoids like isotretinoin carry higher risks and should not be used for hair loss without medical supervision.

In clinical trials, adverse events were mild and reversible, making tretinoin a relatively low-risk addition to hair loss regimens, especially in concentrations ≤0.025%.

Is Retinoic Acid/Tretinoin for Me?

Retinoic acid or tretinoin may be right for you if:

• You’ve had limited success with minoxidil alone, especially if you’re a non-responder.
• You’re seeking enhanced regrowth or wish to reduce the frequency of minoxidil application (e.g., once-daily combo vs. twice-daily minoxidil).
• You’re in the early stages of hair loss, where interventions tend to be more effective.

Caution is warranted if:

• You are hypersensitive to the drug, drug class, or drug formulation. 
• If you are prone to sunburn.
• You have photosensitivity issues.
• You have eczema, seborrheic dermatitis, or other scalp inflammation problems.
• You are pregnant and in the first trimester (retinoids are dangerous for the fetus if they become systemic).

Always consult a dermatologist before starting any retinoid-based hair regimen.

Final Thoughts

Retinoic acid and tretinoin offer a scientifically grounded, mechanistically rich approach to hair loss treatment, particularly for androgenetic alopecia. Although not a magic bullet, they can:

• Enhance minoxidil efficacy
• Support hair follicle stem cell activation
• Offer a new avenue for patients who have plateaued on existing treatments.

That said, results are highly individual, and the treatment must be carefully tailored, balancing dose, frequency, and formulation to optimize results while minimizing irritation. Therefore, we don’t recommend using it by itself.

For now, tretinoin appears best used in combination, especially for those seeking to maximize outcomes from minoxidil therapy.

Cetirizine is a second-generation antihistamine that is approved by the FDA for the treatment of allergies. It works by blocking the H1 receptor and preventing the function of histamine, the biological compound that is responsible for causing allergic symptoms.^[1]Curran, M. P., Scott, L. J., & Perry, C. M. (2004). Cetirizine: a review of its use in allergic disorders. Drugs. 64. 523-561. Available at: https://doi.org/10.2165/00003495-200464050-00008

In this article, we will explore the way in which cetirizine has been proven to work and look at some additional functions that may influence hair health. We will also look to see if there are any clinical studies that show cetirizine can promote hair growth, as well as any safety data that indicates whether it is safe to use.

Key Takeaways

• What is it? Cetirizine is a second-generation antihistamine that is approved for use as an oral medication to treat allergies. It primarily works by binding the H1 receptor, preventing histamine from binding and causing allergic symptoms. Studies have also shown that cetirizine has anti-inflammatory effects, inhibiting the migration of inflammatory mediators. Moreover, it has been shown to reduce PGD2 production, a molecule with strong links to hair loss.
• Clinical Data. In clinical studies, the topical application of cetirizine has been shown to increase hair density, hair thickness, hair regrowth, and the proportion of hairs in the anagen (growing) phase. This indicates that topical cetirizine may promote hair growth, but there are also several limitations that are discussed in detail below.
• Safety. Oral cetirizine is FDA-approved and has been shown to cause limited side effects, none of which are considered serious. No conclusive safety data for topical cetirizine exists, but it is likely to be safe based on the safety profile of oral cetirizine. That said, people who are breastfeeding or have kidney failure may not be able to use cetirizine. 
• Evidence Quality.  Cetirizine scored 57/100 for evidence quality by our metrics.
• Best Practices. Cetirizine is approved for use at the following dosages: 10mg within a 24-hour period in adults, 5mg twice daily in children aged 6-11 years, 2.5mg twice daily in children aged 2-5 years. No recommended dosages exist for the use of topical cetirizine, but 1% cetirizine formulations applied at 1-2 mL daily have shown benefit in several clinical studies.

What is Cetirizine?

Cetirizine is a second-generation antihistamine that is widely used for its anti-allergic properties, which makes it particularly effective for treating the symptoms of seasonal allergic rhinitis (otherwise known as hayfever) and chronic idiopathic urticaria (hives).^[2]Curran, M. P., Scott, L. J., & Perry, C. M. (2004). Cetirizine: a review of its use in allergic disorders. Drugs. 64. 523-561. Available at: https://doi.org/10.2165/00003495-200464050-00008 Such is the importance of cetirizine that it is included in the World Health Organizations List of Essential Medicines.^[3]World Health Organization. (2023). WHO Model List of Essential Medicines – 23rd list, 2023. WHO/MHP/HPS/EML/2023.02. Available at: … Continue reading

Origin and Structure

Cetirizine, a second-generation antihistamine, is derived from the metabolism of hydroxyzine, a first-generation antihistamine. A common feature of second-generation antihistamines, including cetirizine, is limited crossing of the blood-brain barrier and the rapid efflux of any molecules that do enter the brain.^[4]Pagliara, A., Testa, B., Carrupt, P.A., Jolliet, P., Morin, C., Morin, D., Urien, S., Tillement, J.P. and Rihoux, J.P. (1998). Molecular properties and pharmacokinetic behavior of cetirizine, a … Continue reading This reduced uptake limits the effects on the central nervous system, thus lowering the potential for side effects such as drowsiness which were common in the first-generation.^[5]Curran, M. P., Scott, L. J., & Perry, C. M. (2004). Cetirizine: a review of its use in allergic disorders. Drugs. 64. 523-561. Available at: https://doi.org/10.2165/00003495-200464050-00008

How Does Cetirizine Work?

When used for treating the symptoms of allergies, cetirizine is delivered orally as a liquid or tablet. Cetirizine has been used to treat allergies since the 1980s and its mechanism of action, as well as its therapeutic effects, are very well documented. We’ll start by summarizing these effects, before taking a closer look at more recent research that has explored the potential benefits of topical cetirizine in the treatment AGA.

H1-Receptor Antagonism

Cetirizine primarily functions as a potent and selective antagonist of the histamine H1 receptors. Hypersensitive reactions, which manifest as allergies, are initiated when allergens trigger the release of histamine from cells of the immune system. The released histamine binds to H1 receptors, which is the mechanism that is responsible for producing the classic symptoms of allergies.^[6]Ghosh, S., Debnath, I., Bhunia, S., Hazra, S., Nandi, S., & Mandal, S. K. (2025). A Review on Mechanism of Histamine Mediated Allergic Reactions: Therapeutic Role, Safety, and Clinical Efficacy … Continue reading Cetirizine blocks this mechanism by binding to the H1 receptors and blocking the histamine, preventing it from activating the allergic response.^[7]Curran, M. P., Scott, L. J., & Perry, C. M. (2004). Cetirizine: a review of its use in allergic disorders. Drugs. 64. 523-561. Available at: https://doi.org/10.2165/00003495-200464050-00008

Anti-inflammatory Properties

Beyond its role as an antihistamine, cetirizine exhibits significant anti-inflammatory effects that contribute to its therapeutic value. This is particularly beneficial because allergic reactions are characterized by inflammation and the infiltration of immune cells into the different tissues of the body.^[8]Curran, M. P., Scott, L. J., & Perry, C. M. (2004). Cetirizine: a review of its use in allergic disorders. Drugs. 64. 523-561. Available at: https://doi.org/10.2165/00003495-200464050-00008

In an animal study, rats were orally administered cetirizine (900µg/kg; equivalent to the standard human dose of 10mg/kg) or a control substance. Acute inflammation was then induced by injecting the pro-inflammatory substance carrageenin into the paw. After 3 hours, the volume of edema (swelling) in the paw was quantified and compared between the treated and untreated rats. This revealed that there was significantly less swelling (-41.93%) in the cetirizine-treated rats compared to the untreated rats.^[9]Vardhamane, S. H., Santoshkumar, J., & Vardhamane, S. H. (2013). Anti-inflammatory activity of H1 receptor antagonist Cetirizine in animal models. Journal of Evolution of Medical and Dental … Continue reading

The same authors also tested cetirizine in rats with chronic inflammation. Once again, rats were provided with orally administered cetirizine (900µg/kg; equivalent to the standard human dose of 10mg/kg) or a control substance. Inflammation was induced by inserting rexin pellets underneath skin and the rats monitored for 7 days, receiving a daily dose of cetirizine. After 7 days, the granuloma (area of tissue indicative of inflammation) was excised from the rats and weighed. They showed that treatment with cetirizine reduced the granuloma weight (-50.05%), indicating that cetirizine inhibited inflammation.^[10]Vardhamane, S. H., Santoshkumar, J., & Vardhamane, S. H. (2013). Anti-inflammatory activity of H1 receptor antagonist Cetirizine in animal models. Journal of Evolution of Medical and Dental … Continue reading

There are also several clinical trials that have shown its anti-inflammatory properties. In one such study, a total of 12 patients faced an allergen-specific conjunctival challenge, where a known allergen was dropped into the eye. These patients were randomly assigned into one of two groups – 10 mg cetirizine or placebo, both twice daily. Although the number of inflammatory cells increased following the allergen challenge, their levels were still significantly lower in the cetirizine group than the untreated controls.^[11]Ciprandi, G., Buscaglia, S., Pesce, G., Passalacqua, G., Rihoux, J. P., Bagnasco, M., & Canonica, G. W. (1995). Cetirizine reduces inflammatory cell recruitment and ICAM-1 (or CD54) expression on … Continue reading

A double-blinded, placebo-controlled study was also conducted in 14 patients with atopic dermatitis (eczema) and 16 healthy subjects. Participants either received cetirizine (10mg in the morning, 20mg in the evening) or the placebo, and they consumed their respective product every day for 3 days. They took blood samples after Day 2 and then tested the ability of monocytes, key cells of the immune system, to migrate towards a chemical stimulus. The migration of these cells forms a key part of their ability to induce inflammation, so a reduction in the ability to migrate would suggest a reduced inflammatory response. Their results showed that treatment with cetirizine reduced or even abolished ex vivo monocyte migration in both the healthy subjects and the patients with atopic dermatitis.^[12]Jinquan, T., Reimert, C. M., Deleuran, B., Zachariae, C., Simonsen, C., Thestrup-Pedersen, K., & May, R. (1995). Cetirizine inhibits the in vitro and ex vivo chemotactic response of T lymphocytes … Continue reading

Therefore, the literature strongly suggests that cetirizine exhibits anti-inflammatory properties.

Mast Cell Stabilization

Studies also suggest that some of the effects of cetirizine may be mediated by its regulation of mast cells. These white blood cells are found throughout the body and they form part of the immune response, particularly the allergic response. This is because they contain inflammatory mediators (including histamine). When mast cells are stimulated by an allergen, they degranulate and release their inflammatory compounds, driving inflammation and the classic signs of allergy.^[13]Amin, K. (2012). The role of mast cells in allergic inflammation. Respiratory medicine. 106(1). 9-14. Available at: https://doi.org/10.1016/j.rmed.2011.09.007

The effect of cetirizine on mast cells has been demonstrated in vitro. Mast cells were isolated from rats and then treated with increasing concentrations of cetirizine, before exocytosis (degranulation) was induced using a chemical compound. The authors observed a significant decrease in degranulation at a cetirizine concentration of 100µM, while the highest concentration of 1mM induced near-total suppression of degranulation (Figure 1). Furthermore, cetirizine was also shown to significantly outperform a first-generation antihistamine (diphenhydramine) when comparing the relative reduction of degranulation.^[14]Fujimura, R., Asada, A., Aizawa, M., & Kazama, I. (2022). Cetirizine more potently exerts mast cell-stabilizing property than diphenhydramine. Drug Discoveries & Therapeutics. 16(5). 245-250. … Continue reading Thus, this study provides evidence that cetirizine may exert its anti-allergic and anti-inflammatory effects via the mediation of mast cell activity.

Histamine and Hair Loss: Why It Matters

What is Histamine?

Histamine is a biologically active compound that is derived from the amino acid histidine. As previously noted, histamine is stored in the mast cells that are found throughout the body, but it can also be found in basophils (another type of white blood cell). Histamine may also be found in the neurons of the brain, but the white blood cells are its primary store.^[16]Carthy, E., & Ellender, T. (2021). Histamine, neuroinflammation and neurodevelopment: a review. Frontiers in neuroscience. 15. 680214. Available at: https://doi.org/10.3389/fnins.2021.680214

Histamine primarily functions by binding to the H1, H2, H3, and H4 receptors that are found in the brain, blood vessels, heart, neurons, and many other tissues throughout the body. Depending on the receptor it binds to, histamine can exert effects that include initiating inflammation, changing the blood flow, or making the blood vessels more permeable which facilitates the leakage of fluid into surrounding tissues (causing swelling).^[17]Branco, A. C. C. C., Yoshikawa, F. S. Y., Pietrobon, A. J., & Sato, M. N. (2018). Role of histamine in modulating the immune response and inflammation. Mediators of inflammation. 2018(1). … Continue reading

This wide range of functions means that histamine can exert influence over many bodily processes, so it is not surprising that histamine has been linked to hair loss.

Histamine’s Role in Hair Biology

Although the evidence is rather limited, there are a number of studies that have suggested histamine could be contributing to hair loss.

Scalp biopsies from patients with telogen effluvium (TE; 10 patients), alopecia areata (AA; 7 patients), androgenetic alopecia (AGA or ANDRO; 9 patients) were compared to those of healthy volunteers (8 patients). They stained each of these biopsies to count the number of mast cells and determine if there was a difference between conditions. Sure enough, they found that the TE biopsies contained a significantly greater number of mast cell granules (indicated by Giemsa staining) and a greater abundance of the enzyme tryptase (Figure 2).^[18]Grace, S. A., Sutton, A. M., Abraham, N., Armbrecht, E. S., & Vidal, C. I. (2017). Presence of mast cells and mast cell degranulation in scalp biopsies of telogen effluvium. International journal … Continue reading

These results are indicative of an increased number of mast cells and greater mast cell activation in the scalp of people with TE. It has been suggested by this and a number of other studies that mast cells play an important role in hair loss, involved in a system that is triggered by stress and characterized by a switch to a pro-inflammatory phenotype.^[19]Arck, P. C., Handjiski, B., Hagen, E., Joachim, R., Klapp, B. F., & Paus, R. (2001). Indications for a brain‐hair follicle axis: inhibition of keratinocyte proliferation and up‐regulation of … Continue reading

A separate study investigated scalp biopsies from 55 patients with AA and quantified the levels of immune cells and inflammatory mediators, comparing the results to healthy controls. They showed increased CD4+ T cells, CD8+ T cells, and mast cells in the deep perifollicular and deep perivascular areas of the scalp (Figure 3). They also observed increased expression of nerve growth factor, which is potentially indicative of inflammation within the scalp.^[21]Zhang, X., Zhao, Y., Ye, Y., Li, S., Qi, S., Yang, Y., Cao, H., Yang, J. and Zhang, X. (2015). Lesional infiltration of mast cells, Langerhans cells, T cells and local cytokine profiles in alopecia … Continue reading

This provides further evidence that suggests mast cells, and therefore histamine, may play a role in hair loss. Indeed, histamine release from mast cells can trigger the release of T cells, so it is possible that the increase in T cells was driven by increased histamine.^[22]Jutel, M., Watanabe, T., Klunker, S., Akdis, M., Thomet, O.A., Malolepszy, J., Zak-Nejmark, T., Koga, R., Kobayashi, T., Blaser, K. and Akdis, C.A. (2001). Histamine regulates T-cell and antibody … Continue reading

There is also evidence that mast cells may contribute to the extracellular matrix remodelling that is seen in patients with AGA. Biopsies were taken from the balding (vertex) and non-balding (occipital) areas of 10 males with AGA, as well as biopsies from the same regions of 5 healthy control subjects. Using tryptase quantification, they showed that active mast cell counts were almost 2-fold greater in the scalps of AGA patients relative to the healthy controls (Figure 4). Furthermore, they showed an increase in the number of collagen bundles and elastic fibres within the balding regions of the scalp, and a positive correlation between the number of active mast cells and the number of elastic fibres.^[24]Won, C.H., Kwon, O.S., Kim, Y.K., Kang, Y.J., Kim, B.J., Choi, C.W., Eun, H.C. and Cho, K.H. (2008). Dermal fibrosis in male pattern hair loss: a suggestive implication of mast cells. Archives of … Continue reading

It should be noted that the small study size is a limiting factor. However, the results suggest that mast cells may contribute to the remodelling that is observed in AGA. This is supported by studies that have linked tryptase to fibroblast proliferation, collagen production, and elastin production.

It is possible that this recruitment and activation of mast cells (and, potentially, histamine) is caused by changes to the skin microbiome. A study was conducted on hairless mice to compare mast cell activation against control mice with hair. They found that the number of activated mast cells was significantly greater in the hairless mice. Additionally, the patchy sections of hair had fewer mast cells than the hairless sections, but more than the control mice (with a full coat of hair). This difference was associated with a greater amount of gram-positive bacteria on the skin of the hairless mice. Interestingly, when the TLR2 receptor (that recognizes the bacteria) was deleted in hairless mice, the number of mast cells reduced.^[26]Wu, C. C., Kim, J. N., Wang, Z., Chang, Y. L., Zengler, K., & Di Nardo, A. (2019). Mast cell recruitment is modulated by the hairless skin microbiome. Journal of Allergy and Clinical Immunology. … Continue reading

Collectively, these studies suggest that mast cell activation may contribute to hair loss. As an effector of mast cell activity, this might suggest that histamine is also contributing to hair loss. Therefore, this raises the question of whether antihistamines could be used to prevent hair loss.

How Does Cetirizine Have an Impact on Hair Follicles?

To answer the following question, we checked the literature for studies that have investigated the use of antihistamines in hair loss treatment. Despite the limited research, cetirizine has been tested in a number of different studies and generated some interesting results. Let’s start by looking at the mechanistic effects of cetirizine that suggest it could influence hair health.

A double-blind, placebo-controlled crossover study was conducted in 10 people with ragweed allergies. The patients were given oral cetirizine (20mg) or placebo once a day, for two days, before their skin was exposed to the allergen. The exposed portion of the skin was then biopsied for testing. Surprisingly, although erythema (reddening) was reduced, cetirizine did not inhibit the release of histamine. However, the authors found that cetirizine treatment did significantly reduce the production of prostaglandin D2 (PGD2), and there was also a significant reduction in the migration of inflammatory cells white blood cells (eosinophils and neutrophils) to the exposed site.^[27]Charlesworth, E. N., Kagey-Sobotka, A., Norman, P. S., & Lichtenstein, L. M. (1989). Effect of cetirizine on mast cell-mediator release and cellular traffic during the cutaneous late-phase … Continue reading

These results are interesting when it comes to hair health. PGD2 has a previously documented role in promoting hair loss, particularly in those with AGA. PGD2 is thought to block key receptors within hair follicles and prevent hairs from entering the anagen (growth phase). This consequently prevents hair growth and contributes to hair follicle miniaturization. Furthermore, suppression of PGD2 has been shown to have beneficial effects, suggesting that it may be a therapeutic target.^[28]Shin, D. W. (2022). The physiological and pharmacological roles of prostaglandins in hair growth. The Korean Journal of Physiology & Pharmacology: Official Journal of the Korean Physiological … Continue reading

However, it should be noted that recent studies using PGD2 inhibitors are yet to show improvement in hair loss outcomes. You can read more about this in our GPR44 article.

Studies have also shown that inflammation plays a role in driving hair loss. Numerous studies have shown a significant inflammatory response in the scalp of people suffering with hair loss, driven by infiltration of inflammatory mediators (including mast cells) into the hair follicles. This then disrupts the hair cycle and impairs hair growth.^[29]Peyravian, N., Deo, S., Daunert, S., & Jimenez, J. J. (2020). The inflammatory aspect of male and female pattern hair loss. Journal of inflammation research. 879-881. Available at: … Continue reading

Therefore, it is plausible that cetirizine could be beneficial for hair loss.

Clinical Evidence

Thankfully, a number of clinical studies have been conducted to test the efficacy of cetirizine as a hair loss treatment.

One study was conducted on 60 males with AGA between the ages of 22 and 55. The study was double-blinded and the participants were randomized into the placebo or cetirizine group. Those in the cetirizine group were required to apply 1mL of a topical lotion (1% cetirizine) to their scalp every day, while the placebo group followed the same procedure with their respective product. At the beginning and end of the study, assessments of hair regrowth were performed by a dermatologist, photographs were assessed by dermatologists to provide a Hamilton-Norwood classification, and subjective assessments were provided by the participants in the form of questionnaires. The change in each parameter relative to the start of the study was then compared between groups.^[30]Zaky, M. S., Abo Khodeir, H., Ahmed, H. A., & Elsaie, M. L. (2021). Therapeutic implications of topical cetirizine 1% in treatment of male androgenetic alopecia: a case‐controlled study. … Continue reading

Dermatological assessment determined hair regrowth to be significantly greater in the cetirizine group, with 43.3% of participants exhibiting hair regrowth compared to 0% of the placebo group. Similarly, photographic assessment determined that 43.3% of the cetirizine group exhibited improvements in Hamilton-Norwood classification, compared to 0% of the placebo group, which was also a significant difference. Finally, self-assessment by questionnaire revealed significantly greater satisfaction in the cetirizine group, with 43.3% stating that their hair growth had shown an improvement compared to 0% of the placebo group.^[31]Zaky, M. S., Abo Khodeir, H., Ahmed, H. A., & Elsaie, M. L. (2021). Therapeutic implications of topical cetirizine 1% in treatment of male androgenetic alopecia: a case‐controlled study. … Continue reading

In another study, 40 males between the ages of 18 and 49 were recruited to compare topical cetirizine (1%) and minoxidil (5%), and FDA approved therapy for hair loss. Participants in this single-blind study were randomized into one of the two groups and then applied 1mL of solution per day to the balding area of their head. After 16 weeks, every participant was switched to a placebo product for a further 8 weeks.^[33]Mostafa, D. H., Samadi, A., Niknam, S., Nasrollahi, S. A., Guishard, A., & Firooz, A. (2021). Efficacy of cetirizine 1% versus minoxidil 5% topical solution in the treatment of male alopecia: a … Continue reading

Using Trichoscan to conduct objective assessments of the hair, they found that both cetirizine and minoxidil caused a significant increase in total hair density and vellus hair density after 16 weeks, with minoxidil outperforming cetirizine. The percentage of hair in anagen phase increased in both groups after 16 weeks, then subsequently diminished after placebo use. Assessments completed by physicians suggested that a comparable percentage of participants in each group showed improvement in hair density, although 17% of the cetirizine group were determined to have exhibited a reduction compared to 0% of the minoxidil group. Furthermore, the participants in the minoxidil group reported greater satisfaction with their treatment.^[34]Mostafa, D. H., Samadi, A., Niknam, S., Nasrollahi, S. A., Guishard, A., & Firooz, A. (2021). Efficacy of cetirizine 1% versus minoxidil 5% topical solution in the treatment of male alopecia: a … Continue reading

A third study recruited 85 males and females between the ages of 20 and 65 with AGA. 67 participants were placed in the treatment group and used 1mL of topical cetirizine (1%) daily for 6 months, with 18 participants using a placebo product for the same length of time. Using macrophotographs and Trichoscan, they found that total hair density and terminal hair density were both significantly increased in the cetirizine treatment group.^[36]Rossi, A., Campo, D., Fortuna, M.C., Garelli, V., Pranteda, G., De Vita, G., Sorriso-Valvo, L., Di Nunno, D. and Carlesimo, M., 2018. A preliminary study on topical cetirizine in the therapeutic … Continue reading

One last study recruited 60 female patients, with AGA, between the ages of 20 and 50. The study was double-blinded and randomized. Both groups applied 1mL topical minoxidil (5%) every morning for 6 months; one of these groups also applied 1mL topical cetirizine (1%) in the evening, while the other group applied a placebo. Phototrichscopy was used to show that both groups exhibited a significant increase in frontal and vertex terminal and vellus hair density. Interestingly, the minoxidil+cetirizine group also showed a significant increase in hair thickness and number of hairs per follicular unit, which was not present in the minoxidil only group. However, it should be noted that change relative to baseline in both groups was comparable across all parameters. Participants in the minoxidil+cetirizine group also scored better in the self-assessment of new hairs, hair growth, bald areas, and satisfaction with the treatment.^[38]Bassiouny, E. A., El-Samanoudy, S. I., Abbassi, M. M., Nada, H. R., & Farid, S. F. (2023). Comparison between topical cetirizine with minoxidil versus topical placebo with minoxidil in female … Continue reading

Collectively, these studies provide evidence that suggests topical cetirizine may be beneficial in the treatment of hair loss. However, there are limitations with the studies that have been described. For one, it would be good to assess the efficacy of cetirizine over a longer period of time (more than 6 months), to determine whether its beneficial effects improve further, plateau, or even reverse. Larger studies would be highly beneficial, particularly with the inclusion of more females. All of these studies were also limited to the inclusion of AGA patients which, while useful, means that the efficacy of cetirizine in treating other hair loss conditions remains unknown. Some of the studies also lack placebo controls, which means definitive conclusions on the effectiveness of cetirizine cannot be drawn from their results. That said, the results are promising, and seemingly suggest that cetirizine may provide some beneficial effects.

Safety and Side Effects

Oral cetirizine has received FDA approval for treating allergies and is considered safe at the recommended dose (10mg within a 24-hour period in adults, 5mg twice daily in children aged 6-11 years, 2.5mg twice daily in children aged 2-5 years).^[40]NICE. (No date). Cetirizine hydrochloride. National Institute for Health and Care Excellence. Available at: https://bnf.nice.org.uk/drugs/cetirizine-hydrochloride/ (Accessed: 29 April 2025)

Common side effects include feeling of sleepiness and tiredness, as well as headaches, dizziness, dry mouth, diarrhea, sore throat, and sneezing. However, it has been reported that small amounts of cetirizine can get into breast milk, so those who are breastfeeding should use cetirizine with caution. Additionally, people with kidney failure may be unable to use cetirizine.^[41]NHS. (2025). Side effects of cetirizine. National Health Service. Available at: https://www.nhs.uk/medicines/cetirizine/side-effects-of-cetirizine/ (Accessed: 29 April 2025)

In the three clinical studies that used topical cetirizine (1%) alone, no notable adverse events or side effects were reported. In the study that used minoxidil (5%) together with cetirizine (1%), itching, dry hair, initial hair loss, and dandruff were reported. However, these are known side effects of minoxidil, and there were no differences in the number of adverse events between the two groups. Although there is no conclusive safety data related to topical cetirizine, it is safe to use (up to the recommended dosage) as an oral therapeutic. Given that oral therapeutics are more likely to trigger systemic effects, this suggests that topical cetirizine may be safe for use, though some side effects may occur in relation to its application on the skin. However, please note that there is no recommended dosage for topical cetirizine.

 Is Cetirizine For Me?

You may want to experiment with topical cetirizine if:

• You are happy to use a product with limited evidence of efficacy.
• You are happy to use a product with no evidence of efficacy beyond 6 months of use.
• You have not seen beneficial effects from treatment with minoxidil and would like to try something else.
• You want to try a combined treatment with other products like minoxidil.

Final Thoughts

Cetirizine is a second-generation antihistamine that has been FDA approved (as an oral medication) for the treatment of allergies since the 1990s. It primarily works by binding the H1 receptor and preventing histamine from binding there, the molecule that is responsible for allergic symptoms. Alongside its well documented function, oral cetirizine has been shown to both reduce inflammation and inhibit the production of PGD2, the activity of which is strongly linked to hair loss. Several clinical studies have been conducted in AGA patients who used topical cetirizine as a treatment, with the results showing improvements in hair growth, hair density, and hair thickness. Furthermore, no side effects were associated with the topical use of cetirizine, and the oral version of the therapeutic is considered safe for use. Although there is a lack of large, long-term studies that have investigated topical cetirizine, the results suggest that it may provide help to improve hair loss.

Methylene blue, a compound originally developed as a medical dye, has recently been stirring up attention due to its potential therapeutic applications beyond its initial purpose, particularly in the realm of age-related concerns such as cognitive and skin health. However, some are now exploring its potential use in hair regrowth.

This research aligns with a broader trend in the pharmaceutical industry: repurposing old compounds for new indications. This offers several advantages, including reduced development time, lower costs, and decreased risk due to established safety trials. Approximately 30% of repurposed drugs typically gain approval compared to only 10% of new drug applications, making this strategy increasingly attractive for pharma companies.^[2]Hernandez, J.J., Pryszlak, M., Smith, L., Yanchus, C., Kurji, N., Shahani, V.M., Molinski, S.V. (2017). Giving Drugs a Second Chance: Overcoming Regulatory and Financial Hurdles in Repurposing … Continue reading

In this article, we will examine the evidence surrounding methylene blue and whether it could translate to better hair growth outcomes.

Key Takeaways

• What Is It? Methylene blue is a medical dye with antioxidant, mitochondrial-supporting, and anti-inflammatory properties. It has been studied for neurodegenerative diseases, skin health, and aging, but its role in hair regrowth is unproven.
• Clinical Data. There are no human clinical trials testing methylene blue for hair regrowth. Most research comes from in vitro and animal studies. One study in hair transplants found no benefit over saline.
• Evidence Quality. Methylene blue scored 6/100 for evidence quality by our metrics.
• Safety. While generally safe at therapeutic doses, methylene blue can cause nausea, headaches, and urine discoloration. More serious risks include serotonin syndrome (when combined with SSRIs/SNRIs) and hemolytic anemia in G6PD-deficient individuals. The long-term effects of cosmetic use remain unknown.
• Best Practices. Given the lack of evidence and potential risks, methylene blue should not be considered a proven hair loss treatment. For those seeking regrowth solutions, clinically tested treatments remain the safest bet.

Let’s start off by exploring why people are so excited about methylene blue.

Methylene blue is purportedly a potent mitochondrial-targeting antioxidant that effectively scavenges reactive oxygen species (ROS).^[3]Xue, H., Thaivalappil, A., Cao, K. (2021). The Potentials of Methylene Blue as an Anti-Aging Drug. Cells. 10(3379). 1-12. Available at: https://doi.org/10.3390/cells10123379 According to the free radical theory of aging, ROS are closely linked to cellular aging. ROS accumulation can cause a cellular state called oxidative stress, which damages DNA, protein, and lipids.^[4]Labunskyy, V.M., Galdyshev, N.M. (2013). Role of Reactive Oxygen Species-Mediated Signaling in Aging. Antioxidants & Redox Signaling. 19(12). 1362-1372. Available at: … Continue reading

What Beneficial Properties Might Methylene Blue Have?

Methylene blue has shown promise for improving several aging pathways. Let’s take a look at the pre-clinical evidence and see how it might translate into improvements in hair regrowth.

Anti-Aging

In cultured human skin, fibroblasts derived from healthy donors and patients with progeria (a genetic disorder leading to rapid aging in children) were used to evaluate the antioxidant activity of methylene blue.^[5]Xiong, Z-M., O’Donovan, M., Sun, L., Choi, J.Y., Ren, M., Cao, K. (2017). Anti-aging potentials of methylene blue for human skin longevity. Scientific Reports. 7(2475). 1-12. Available at: … Continue reading Compared to other widely used mitochondrial-targeting antioxidants, the researchers found that methylene blue reduced levels of ROS (MitoSOX) and improved skin fibroblast proliferation more effectively (Figure 1).

The researchers also found that methylene blue could reduce signs of aging in old skin cells. Before treatment, the old fibroblasts (harvested from two subjects over 80 years old) showed signs of cellular senescence, including increased ꞵ-galactosidase (a marker of senescence) and higher levels of mitochondrial ROS than younger cells (harvested from two subjects below 30 years old). Both the old and young cells were grown in a medium supplemented with methylene blue for four weeks. Compared to a control, methylene blue significantly reduced levels of mitochondrial ROS, reduced ꞵ-galactosidase marker signal and decreased the gene expression of senescence marker p16 in the old cells. It also improved cell growth in both old and young cells (Figure 2).

In addition to this, the researchers analyzed the effect of methylene blue on the expression of key antioxidant response genes. Methylene blue was found to upregulate the expression of Nrf2, which is an important transcription factor involved in the antioxidant response. In 3D reconstructed human skin, it was also found to promote wound healing, increase tissue viability, skin thickness and hydration, and upregulate elastin and collagen 2A1, which are important for maintaining skin elasticity and thickness.

UV Protection

Another in vitro (in cells) study was conducted in which primary human keratinocytes were irradiated with UV rays and treated with methylene blue to test if it had any protective effects against UV-induced DNA damage and cell death.^[8]Xiong, Z-M., Mao, X., Trappio, M., Arya, C., el Kordi, J., Cao, K. (2021). Ultraviolet radiation protection potentials of methylene blue for human skin and coral reef health. Scientific Reports. … Continue reading

The cells were treated with 100 nM of methylene blue for two weeks and then exposed to 0, 5, 10, and 20 seconds of UVB rays at 1 W/cm2 (Watt per cm2). A common marker for DNA damage, ℽH2AX, was measured, with methylene blue treated cells showing significantly reduced expression at each dosage compared to the control (PBS) (Figure 3).

The researchers also found that it prevented human keratinocytes from undergoing UVB irradiation-induced cell death and that it was more effective at blocking high-energy UVB/C rays than a common UV blocker used in most sunscreens, oxybenzone. 

They also found that methylene blue was a more robust scavenger of ROS (meaning that it can effectively neutralize and remove ROS) than oxybenzone, Vitamin A, and Vitamin C in keratinocytes. A separate experiment was also conducted on young and old fibroblasts derived from males and females treated with either PBS, DMSO (controls), methylene blue, Vitamin A, Vitamin C, or a combination of Vitamin C and methylene blue. The combination treatment showed increased cell growth in both young and old cells (male and female) compared to all other treatments. When it came to ROS levels, the methylene blue alone treatment and the combination treatment both showed the most effective reductions in ROS levels (Figure 4).

Anti-Inflammatory

One study has shown that methylene blue decreases inflammation by reducing serum levels of interleukin-6 (a pro-inflammatory cytokine that plays a significant role in both acute and chronic inflammatory responses) and inhibiting the activation of STAT3 in the skin.^[11]Li, Y., Ying, W. (2023). Methylene blue reduces the serum levels of interleukin-6 and inhibits STAT3 activation in the brain and the skin of lipopolysaccharide-administered mice. Frontiers in … Continue reading STAT3 is implicated in the pathogenesis of alopecia areata.^[12]Roche, F.C., Hedberg, M.L. Fischer, A.S., Ray, A., Dentchev, T., Rice, X., Taylor, S.C., Seykora, J.T. (2023). Activation of STAT3 in lymphocytes associated with central centrifugal cicatricial … Continue reading  

Mice were split into four groups: control (PBS injected intraperitoneally every day for 3 days), and 5 mg/kg, 10 mg/kg, and 20 mg/kg methylene blue groups (injected intraperitoneally every day for 3 days). Another three groups of mice were treated with lipopolysaccharide (1 mg/kg) to induce inflammation, with two groups also being treated with 10 mg/kg of methylene blue and 20 mg/kg of methylene blue.

Mice treated with both 10 and 20 mg/kg methylene blue alongside LPS showed a significant reduction in serum levels of LPS-induced IL-6 (Figure 5) and STAT3 (Figure 6). Other markers of inflammation that were reduced after methylene blue treatment were iNOS (inducible nitric oxide synthase, which can induce or enhance the inflammatory response) and COX2 (an enzyme implicated in inflammation by producing prostaglandins).

Based on the positive effects seen in these studies, methylene blue could assist in hair growth through several mechanisms:

1. Reduction of Oxidative Stress (ROS Regulation)

Hair follicle stem cells and dermal papilla cells are highly susceptible to oxidative stress, which can impair hair follicle cycling and contribute to hair loss. Methylene blue has demonstrated the ability to effectively scavenge reactive oxygen species (ROS), reducing oxidative damage and potentially improving hair follicle resilience and function.

2. Enhancement of Mitochondrial Function and ATP Production

Hair follicles require significant energy (ATP) for active growth during the anagen phase. Methylene blue has been shown to enhance mitochondrial function, increase ATP production, and improve cellular energy metabolism, which may support hair follicle growth and maintenance.

3. Stimulation of Fibroblast Proliferation and Extracellular Matrix Support

Dermal fibroblasts and dermal papilla cells play crucial roles in hair follicle anchoring and signaling. Methylene blue can enhance fibroblast proliferation and extracellular matrix production, which could promote a supportive environment for robust hair follicle development.

4. Anti-Senescence Effects

Cellular senescence in hair follicle stem cells is linked to age-related hair thinning and loss. Methylene blue has been found to reduce markers of cellular senescence, such as p16 and β-galactosidase expression, which may help maintain hair follicle stem cell viability and prolong the anagen phase in aging individuals.

5. Upregulation of Antioxidant Response (Nrf2 Activation)

Methylene blue activates Nrf2, a transcription factor involved in cellular defense against oxidative stress. Since Nrf2 is associated with protection against chemotherapy-induced alopecia and inflammatory hair loss conditions (e.g., lichen planopilaris), its activation by methylene blue could offer therapeutic benefits for hair regrowth.

6. Improvement in Wound Healing and Scalp Thickness

A healthy scalp environment is critical for hair follicle regeneration. Methylene blue has been shown to promote wound healing, increase skin thickness, and enhance tissue hydration, which may contribute to a more favorable microenvironment for hair growth.

7. Reduction of Inflammatory Markers

Chronic inflammation, mediated by IL-6 and STAT3 activation, is implicated in autoimmune and scarring alopecia (e.g., alopecia areata, central centrifugal cicatricial alopecia (CCCA)). Methylene blue can significantly reduce inflammatory markers such as IL-6 and STAT3, potentially mitigating inflammatory hair loss conditions.

What Clinical Evidence Shows Methylene Blue’s Positive Effects?

The only evidence that we could find in humans showing positive effects from methylene blue are those surrounding neurodegenerative diseases and cognitive enhancement.

Neurodegenerative diseases

A double-blind, dose-finding Phase II clinical trial involving 321 patients with mild-to-moderate Alzheimer’s disease tested three doses of methylene blue.^[15]Wischik, C.M., Staf, R.T., Wischik, D.J., Bentham, P., Murray, A.D., Storey, J., Kook, K.A., Harrington, C.R. (2015). Tau Aggregation Inhibitor Therapy: An Exploratory Phase 2 Study in Mild or … Continue reading 

The study met its predefined primary efficacy endpoint at 24 weeks of reduction in cognitive decline at the 138 mg/day dose. The beneficial effect was sustained for 50 weeks in both mild and moderate subjects at this dose, with a 90% reduction in the rate of cognitive decline overall. 

Cognitive enhancement

In a randomized controlled trial involving 26 healthy subjects aged 22-62, low-dose methylene blue (280 mg) improved memory performance and increased brain activity in regions associated with attention and short-term memory.^[16]Rodriguez, P., Zhou, W., Barrett, D.W., Altmeyer, W., Gutierrez, J.E., Li, J., Lancaster, J., Gonzalez-Lima, F., Duong, Q.T. (2016). Multimodal Randomized Functional MR Imaging of the Effects of … Continue reading 

Do These Results Show That Methylene Blue Can Regrow Hair?

While methylene blue has shown potential in preclinical studies for various therapeutic applications, its efficacy in promoting hair regrowth remains unproven. The enthusiasm surrounding the potential benefits of methylene blue is primarily based on in vitro and animal studies, which often do not translate directly to human outcomes.

As you can see above, preclinical studies have demonstrated that methylene blue possesses antioxidant properties, improves mitochondrial function, and exhibits anti-inflammatory effects. However, we could not find any preclinical or clinical studies looking at its potential effects on hair regrowth, so we can’t say for sure whether it will work or not.

In fact, the only study we could find that included methylene blue and hair follicles is a pilot study testing methylene blue as a storage solution during hair transplants. In this study, normal saline solution outperformed methylene blue in graft survival rates at 8, 12, and 18 months post-surgery.^[17]Tangjaturonrusamee, C., Thientaworn P., Arunrattanapong, N., Castillejos, D.K.O., Patjomvanich, D. (2016). Methylene blue: Its Efficacy and Safety as a Storage Solution in Hair Transplantation. … Continue reading

Potential Safety Risks

While methylene blue is considered to be safe at therapeutic doses, it can cause some side effects:^[18]Michael. (2025). Is Methylene Blue Safe for Long-Term Use? Covenant Health Products. Available at: https://covenanthealthproducts.com/our-blog/is-methylene-blue-good-for-you (Accessed: March 2025),^[19]Drugs.com. (2024). Methylene Blue Side Effects. Drugs.com. Available at: https://www.drugs.com/sfx/methylene-blue-side-effects.html (Accessed: March 2025)

• Common: Skin/urine discoloration, nausea, dizziness, and headaches.
• Severe: Serotonin syndrome (when combined with SSRIs/SNRIs), hemolytic anemia in G6PD-deficient individuals, and rate causes of organ toxicity.

There is also some evidence that prolonged use may strain liver and kidney function due to metabolism demands. Furthermore, there have been no rigorous studies confirming the safety of chronic, low-dose methylene blue use for cosmetic purposes.

Risk vs. Reward: Is It Worth It?

Considering the potential side effects, drug interactions and lack of evidence, we would say that it is currently not worth trying methylene blue to counteract your hair loss. Long-term safety data for methylene blue has not been collected at this point, so it is worth waiting until new research has been conducted.

Final Thoughts

While methylene blue shows promise in anti-aging and cellular health, there’s no clinical evidence supporting its use for hair regrowth. Most findings come from in vitro and animal studies, which don’t always translate to real-world results.

Beyond the lack of evidence, potential risks—including drug interactions and unknown long-term effects—make it a high-risk, low-reward option for hair loss. Until human trials confirm its efficacy and safety, methylene blue remains speculative. For now, clinically tested treatments are the safer bet.

Minoxidil is a widely used medication for treating androgenic alopecia (AGA) in both men and women. Originally developed as a treatment for high blood pressure, minoxidil was found to improve hair growth outcomes as a side effect, making its topical form one of only two (the other being finasteride) FDA-approved treatments for AGA. 

Minoxidil is primarily available in two forms: topical and oral. The topical form, which includes both solutions and foams, is more commonly used and can be purchased over the counter. Oral minoxidil, however, is prescription only and is typically given at doses of 2.5 mg or 5 mg for hair loss treatment.

While minoxidil is generally considered safe, it’s important to understand its potential side effects and who might be more at risk from them. In this article, we will examine the side effects of topical and oral minoxidil and discuss how you can adjust your treatment regimen to mitigate these.

How Does Minoxidil Work?

Minoxidil was originally developed as an antihypertensive medication. However, when treated participants started experiencing hypertrichosis (excessive hair growth), studies were conducted to find out if it could improve hair regrowth outcomes in humans (spoiler alert – it could!).^[1]Bryan, J. (2011). How minoxidil was transformed from an antihypertensive to hair-loss drug. The Pharmaceutical Journal. Available at: … Continue reading

Minoxidil’s mechanism of action is not fully understood, but it is thought to work through two main mechanisms:

• Vasodilatory effects: It activates vascular endothelial growth factor (VEGF), increasing blood flow, oxygen, and growth factor delivery to the hair follicle.^[2]Alhayaza, G., Hakami, A., AlMarzouk, L.H., Al Qurashi, A.A., Alghamdi, G., Alharithy, R. (2023). Topical minoxidil reported hair discoloration: a cross-sectional study. Dermatology Reports. 16(1). … Continue reading 
• Potassium channel activation: This prolongs the growth (anagen) phase and shortens the resting (telogen) phase. 

Research also shows that minoxidil can act on androgenic receptors, suppressing the expression of the androgen receptor and CYP17A1 and boosting the activity of CYP19A1. This decreases the formation and binding of dihydrotestosterone and enhances the production of estradiol, which may also benefit those with AGA.^[3]Shen, Y., Zhu, Y., Zhang, L., Sun, J., Xie, B., Zhang, H., Song, X. (2023). New Target for Minoxidil in the Treatment of Androgenetic Alopecia. Drug Design, Development and Therapy. 17. 2537-2547. … Continue reading 

How is Minoxidil Activated in the Body?

Minoxidil needs to be converted into its active form, minoxidil sulfate, by sulfotransferase enzymes before it can effectively stimulate hair growth.^[4]Dhurat, R., Daruwalla, S., Pai, S., Kovacevic, M., McCoy, J., Shapiro, J., Sinclair, R., Vano-Galvan, S., Goren, A. (2021). SULT1A1 (Minoxidil Sulfotransferase) enzyme booster significantly improves … Continue reading This conversion primarily occurs in the scalp for topical minoxidil and in the liver for oral minoxidil.

However, enzyme activity varies significantly among individuals, meaning that some people naturally produce higher levels of sulfotransferase, allowing for better activation and increased effectiveness of the drug, while others have lower enzyme activity, which can limit its impact. You can read our article on how your genetics can influence sulfotransferase activity here.

Topical Minoxidil Vs. Oral Minoxidil: Activation Pathways

Topical minoxidil and oral minoxidil differ in application and effectiveness. Topical minoxidil is applied directly to the scalp, while oral minoxidil is taken as a pill. 

The efficacy of these two treatment routes differs because of their distinct metabolic pathways. 

Topical Minoxidil

Topical minoxidil is applied directly to the scalp, presenting a challenge for drug activation. The drug requires conversion to its active form, minoxidil sulfate, by sulfotransferase enzymes in the scalp. However, research has shown that 40-60% of people may lack sufficient enzyme levels to effectively activate the medication. This enzymatic variability means that for many users, topical minoxidil may not be 100% effective.

Around 1.4% of topical minoxidil is systemically absorbed, further limiting minoxidil efficacy. To counteract this limitation, researchers have explored combining minoxidil with treatments like microneedling or retinoic acid. It was found that with these combinations, minoxidil efficacy can significantly increase.^[6]Lama, S.B.C., Pérez-González, L.A., Kosoglu, M.A., Dennis, R., Ortega-Quijano, D. (2024). Physical Treatments and Therapies for Androgenetic Alopecia. Journal of Clinical Medicine. 13(15). 4534. … Continue reading 

Oral Minoxidil

Oral minoxidil, however, is metabolized in the liver, where sulfotransferase enzymes are abundant. The activated minoxidil sulfate then enters the bloodstream, where it reaches the hair follicle. Studies consistently demonstrate higher response rates for oral minoxidil compared to topical.^[7]Gupta, A.K., Talukder, M., Venkataraman, M., Bamimore, M.A. (2022). Minoxidil: a comprehensive review. Journal of Dermatological Treatment. 33(4). 1896-1906. Available at: … Continue reading However, because oral minoxidil involves systemic absorption, it comes with a broader potential for side effects.

What Are the Side Effects of Topical Minoxidil?

Common Side Effects

While topical minoxidil typically has a great safety profile, there are some side effects that people can experience.

Common side effects include:

• Scalp Irritation and Contact Dermatitis: Redness, itching, flaking, and burning sensations. 

These are the most frequently reported side effects from minoxidil. One retrospective study found that 6.4% of men reported mainly irritant and allergic reactions to minoxidil.^[8]Shadi, Z. (2023). Compliance to Topical Minoxidil and Reasons for Discontinuation among Patients with Androgenetic Alopecia. Dermatology and Therapy (Heidelb). 13(5). 1157-1169. Available at: … Continue reading These effects are typically due to an allergic reaction to propylene glycol rather than the minoxidil itself.^[9]Lessmann, H., Schnuch, A., Geier, J., Uter, W. (2005). Skin-sensitizing and irritant properties of propylene glycol. Contact Dermatitis. 53(5). 247-259. Available at: … Continue reading 

To mitigate the negative skin effects of topical minoxidil, you can do several things. Starting with a lower concentration, such as 2% instead of 5%, can reduce the risk of irritation while still providing benefits. Additionally, reducing application frequency from twice to once daily can limit exposure. Switching to a foam-based minoxidil product can be particularly effective, as these formulations typically don’t contain propylene glycol, which is often responsible for uncomfortable side effects like irritation, redness, and scalp burning. Furthermore, incorporating a moisturizer into your scalp care routine can help keep the skin hydrated and comfortable, further alleviating potential irritation.

• Shedding Phase: Temporary increase in hair loss when starting treatment.

One study reported that 55% of topical minoxidil users experience minoxidil shedding.^[10]Ghonemy, S., Bessar, H., Alarawi, A. (2019). Efficacy and safety of a new 10% topical minoxidil versus 5% topical minoxidil and placebo in the treatment of male androgenetic alopecia: a trichoscopic … Continue reading This is considered a normal side effect and usually indicates that the treatment is working. The shedding phase typically begins 2 to 4 weeks after starting treatment and subsides within 6 to 8 weeks as the hair cycle normalizes. After a few months of continuous use, most users should start seeing visible new hair growth.^[11]Kaiser, M., Abdin, R., Gaumond, S.I., Issa, T. N., Jiminez, J.J. (2023). Treatment of androgenetic alopecia: current guidance and unmet needs. Clinical Cosmetic and Investigational Dermatology. 16. … Continue reading 

• Facial Hypertrichosis: Unwanted excess facial hair. 

Women, especially those over 50 or with pre-existing facial hair, seem to be at higher risk of developing hypertrichosis from topical minoxidil use, and as with other side effects, it is more common when using the 5% than the 2% concentration.^[12]Dawber, R.P.R, Rundegren, J. (2003). Hypertrichosis in females applying minoxidil topical solution and in normal controls. Journal of the European Academy of Dermatology and Venereology. 17(3). … Continue reading 

There are several theories for why hypertrichosis occurs in people using topical minoxidil. 

1. Product application: The product wasn’t applied carefully enough or was not completely dried before bed, leading to product transfer from the pillow to the face. However, this doesn’t account for hypertrichosis seen away from the site of application and is unlikely to cause the effects seen in case studies.
2. Percutaneous absorption: Although topical minoxidil is primarily intended for local effects, a small amount can be absorbed systemically through the skin. This can lead to circulating minoxidil reaching hair follicles in distant areas of the body. 
3. Follicular hypersensitivity: Some people may have hair follicles that are exceptionally responsive to minoxidil. In these cases, even minimal systemic exposure might be sufficient to stimulate hair growth in distant follicles. This hypersensitivity appears to occur randomly, depending on the person.
4. Dose-dependent response: Higher concentrations are more likely to cause hypertrichosis.

While hypertrichosis can occur, it is generally reversible once minoxidil treatment is stopped and typically resolves within 3-4 months.

There are a number of ways that hypertrichosis can be avoided or treated once it occurs. 

Starting with a lower concentration can reduce the risk, especially for women and those with a history of excess facial hair. Careful application to the scalp only, allowing proper drying time, and adhering to the recommended dosage can also minimize systemic absorption and unintended spread.

Switching to a foam version may help those experiencing side effects. If you are experiencing mild hypertrichosis and don’t want to stop using minoxidil, you could use hair removal methods while continuing treatment. 

For more severe cases, spironolactone (~25 mg daily) ando/or low-dose bicalutamide (~10 mg daily) have shown promise in managing minoxidil-induced hypertrichosis. However, these medications should be used under medical supervision.^[14]Darendeliler, F., Bas, F., Balaban, S., Bundak, R., Demirkol, D., Saka, N., Gunoz, H. (1996). Spironolactone therapy in hypertrichosis. European Journal of Endocrinology. 135(5).604-608. Available … Continue reading,^[15]Moussa, A., Kazmi, A., Bakhari, L., Sinclair, R.D. (2022). Bicalutamide improves minoxidil-induced hypertrichosis in female pattern hair loss: a retrospective review of 35 patients. Journal of the … Continue reading 

• Headaches

Some people also experience headaches after using topical minoxidil. One study found that in users applying 2% minoxidil solution, 0.6% reported headaches, compared to 3% of participants using 5% minoxidil solution.^[16]Suchonwanit, P., Thammarucha, S., Leerunyakul, K. (2019). Minoxidil and its use in hair disorders: a review. Drug Design, Development and Therapy. 13. 2777-2786. Available at: … Continue reading

Some people may simply experience headaches due to the smell of the product they are using, in which case, switching to an alcohol-free or unscented alternative may help. Others may be particularly sensitive to minoxidil and its vasodilatory effects, which might contribute to headaches. In this case, switching to a lower concentration or consulting with a healthcare provider might be preferable.

Some of our members have also switched to nanoxidil, an analogue of minoxidil that may offer a better safety profile (you can read more about the research quality of nanoxidil here), and found that their headaches resolved.

The above side effects are more often seen in the 5% than 2% solutions and are typically considered to be non-serious.^[17]Nestor, M.S., Ablon, G., Gade, A., Han, H., Fischer, D.L. (2021). Treatment options for androgenetic alopecia: Efficacy, side effects, compliance, financial considerations, and ethics. Journal of … Continue reading

Some of the rarer side effects include:

• Water Retention

While less common than with oral minoxidil, topical minoxidil application can lead to water retention. Some topical minoxidil users have reported under-eye bags, which may be due to increased water retention near the application areas. There are also anecdotal reports of “puffy face” from topical minoxidil application, suggesting localized fluid retention.^[18]Gungor, S., Kocaturk, E., Topal, I.O. (2015). Frontal Edema Due to Topical Application of %5 Minoxidil Solution Following Mesotherapy Injections. International Journal of Trichology. 7(2). 86-87. … Continue reading 

Anecdotally, there have also been reports of swollen feet and weight gain from using topical minoxidil; however, we couldn’t find these reports reflected in peer-reviewed literature. These effects may also stop with continued use of the drug, so some people keep an eye on the symptoms and wait to see if they go away.

However, you can try reducing the concentration or frequency of usage if the symptoms continue longer than you are comfortable with. Furthermore, excessive salt intake can exacerbate symptoms of edema. Limiting salt intake may help you resolve the edema without having to stop using minoxidil.^[19]Patel, P., Nessel, T.A., Kumar, D. (2023). In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482378/ (Accessed: … Continue reading

• Cardiovascular Issues

Some people also experience cardiovascular side effects. One case study found that applying large amounts of 2% topical minoxidil led to hypotension (low blood pressure) and feelings of faintness.^[20]Ponomareva, M.A., Romanova, M.A., Shapshnikova, A.A., Piavchenko, G.A. (2024). Topical Minoxidil Overdose in a Young Man with Androgenetic Alopecia: A Case Report. Cureus. 16(6). E62382. Available … Continue reading Another case also documented low blood pressure and fainting after applying 12.5% topical minoxidil daily.^[21]Dubrey, S.W., vanGriethuysen, J., Edwards, C.M.B. A hairy fall: syncope resulting from topical application of minoxidil. BMJ Case Reports. 1-2. Available at: https://doi.org/10.1136/bcr-2015-210945 

Other people may experience heart palpitations, feelings of the heart beating rapidly or “skipping a beat”. While this is rare, one study found that 3.5% of women developed heart palpitations or a rapid heart rate after usage of 2% topical minoxidil solution compared to 1.8% who were using a 5% foam.^[22]Blume-Peytavi, U., Hillmann, K., Dietz, E., Canfield, D., Bartels, N.G. (2011). A randomized, single-blind trial of 5% minoxidil foam once daily versus 2% minoxidil solution twice daily in the … Continue reading

Therefore, we would recommend seeking medical advice and potentially finding a new treatment for hair loss if you experience these side effects.

So we’ve covered the side effects of topical minoxidil, but what about oral?

What Are the Side Effects of Oral Minoxidil?

Oral minoxidil side effects are similar to those of topical minoxidil, and both forms exhibit dose-dependent effects. However, oral administration leads to significantly greater systemic exposure to the drug than topical application. As a result, oral minoxidil typically produces more pronounced hair regrowth and more pronounced systemic side effects. It should be noted that use of oral minoxidil to improve hair regrowth is an off-label use of the drug and it is not FDA-approved for this indication.

Common Side Effects

• Hair Shedding

Like with topical minoxidil, you may experience increased hair shedding when you start taking minoxidil. This is considered to be a normal part of the hair cycle remodeling process, typically beginning two to four weeks after starting treatment and subsiding within six to eight weeks as the hair cycle normalizes. 

• Hypertrichosis

While rare with topical minoxidil use, one of the most frequently reported side effects of oral minoxidil is hypertrichosis, which involves excessive hair growth on various parts of the body. This effect is dose-dependent, with some studies showing that increasing the dosage of oral minoxidil by just 1 mg daily is associated with a 17.6% increased risk of hypertrichosis.^[23]Gupta, A.K., Hall, D.C., Talukder, M., Bamimore, M.A. (2022). There is a Positive Dose-Dependent Association between Low-Dose Oral Minoxidil and Its Efficacy for Androgenetic Alopecia: Findings from … Continue reading 

Hypertrichosis frequently occurs on the face (sideburns, temples, upper lip, and chin), with rarer cases of generalized hypertrichosis occurring over the whole body.^[24]Desai, D.D., Nohria, A., Brinks, A., Needle, C., Shapiro, J., Lo Sicco, K.I. (2024). Minoxidil-induced hypertrichosis: Pathophysiology, clinical implications, and therapeutic strategies. JAAD … Continue reading 

• Fluid Retention

Fluid retention is another common side effect of oral minoxidil, occurring in about 1.3% of patients.^[25]Trueb, R.M., Caballero-Uribe, N., Luu, N.N.C., Dmitriev, A. (2022). Serious complication of low-dose oral minoxidil for hair loss. JAAD Case Reports. 30. 97-98. Available at: … Continue reading This can manifest as mild swelling in the face, hands, or feet. In some cases, it may lead to rapid weight gain. 

This weight gain can be significant and sudden, with some patients experiencing up to 20 pounds of weight gain (as water weight) in as little as one month.^[26]Patel.K., Omar, J. (2023). Low dose oral minoxidil causing peripheral edema and rapid weight gain. Journal of General Internal Medicine. 38(Suppl 3). S592. Available at: … Continue reading

Fluid retention can manifest in several ways:

1. Peripheral edema: Swelling in the extremities, particularly in the legs, ankles, and feet.
2. Facial swelling: Puffiness or swelling in the face.
3. Overall weight gain: A sudden increase in body weight, often 5 pounds or more.

This rapid retention can be concerning for patients and may lead to additional health risks if left unmanaged. Excess fluid in the body can potentially lead to congestive heart failure if not properly addressed.

To mitigate these side effects, there are a number of options:

• Use of diuretics: Doctors can prescribe a diuretic (water pill) alongside minoxidil to help counteract fluid retention. This is typically a low-dose loop diuretic.
• Sodium restriction: Limiting sodium intake can help reduce fluid retention. Patients are often not advised about this when starting minoxidil, which can exacerbate the problem.
• Dose adjustment: If fluid retention becomes severe, temporarily discontinuing minoxidil or significantly reducing the dose may be necessary. This allows the edema to resolve naturally before restarting at a lower dose.
• Regular monitoring: Daily weight monitoring can help identify fluid retention early, making it easier to manage.
• Gradual titration: Slowly increasing the dose of minoxidil over time, rather than starting with 5 mg, can help minimize side effects.

If these symptoms don’t resolve when trying these strategies, then it’s recommended to visit your doctor and potentially stop taking minoxidil.

• Lightheadedness, Tachycardia (high heart rate), Headache and Insomnia

Oral minoxidil can cause several cardiovascular and neurological side effects, including lightheadedness, tachycardia, headache, and insomnia.^[27]Trueb, R.M., Caballero-Uribe, N., Luu, N.N.C., Dmitriev, A. Serious complication of low-dose oral minoxidil for hair loss. JAAD Case Reports. 30. 97-98. Available at: … Continue reading These effects are generally dose-dependent and more common at higher doses.

Lightheadedness has been reported to occur in 1.7% of patients, tachycardia in 0.9%, headache in 0.4%, and insomnia in 0.2% of patients. These can all be symptoms of decreased blood pressure due to minoxidil’s vasodilatory properties. 

Headaches and insomnia are reported in around 0.4% and 0.2% of patients, respectively, using low-dose oral minoxidil. While the exact mechanism of these side effects is not clear, it is thought that it could be related to the vasodilatory effects of the drug.

What Are The Cardiovascular Concerns of Oral Minoxidil Usage?

The severity and frequency of cardiovascular side effects are closely tied to the dosage of oral minoxidil. A meta-regression analysis found a positive dose-dependent correlation between low-dose oral minoxidil and the risk of cardiovascular adverse events.

Low Dose (0.25-1.25 mg/day)

At lower doses, oral minoxidil is generally well-tolerated. Women typically start with doses ≤ 1 mg, which minimizes the risk of significant side effects. Lower doses are considered to be a safer starting point for most patients, and even very low doses (0.25 mg/day) have shown efficacy in some studies.^[28]Ramírez-Marín, H.A., Tosti, A. (2022). Role of oral minoxidil in patterned hair loss. Indian Dermatology Online Journal. 13(6). 729-733. Available at: https://doi.org/10.4103/idoj.idoj_246_22 If you are experiencing side effects at higher doses, you can reduce your dose at home using a pill cutter.

Moderate Dose (2.5-5 mg/day)

Men may be prescribed up to 5 mg of minoxidil daily, which can increase the likelihood of side effects such as dizziness and fluid retention. A recent study examined the effects of 7.5 mg/day oral minoxidil in patients with normal blood pressure and AGA.^[29]Sanabria, B.D., Perdomo, Y.C., Miot, H.A., Ramos, P.M. (2024). Oral minoxidil 7.5 mg for hair loss increases heart rate with no change in blood pressure in 24 h ambulatory blood pressure monitoring. … Continue reading The results showed a mild increase in heart rate but no significant changes in blood pressure, suggesting that doses slightly higher than the typical 5 mg can be tolerated. However, this should only be considered under medical supervision.

High Dose (10 mg/day and above)

Doses above 10 mg daily are associated with a higher risk of serious cardiac events and are typically not recommended for hair loss treatment. The hypotensive effect of oral minoxidil becomes more significant at these higher doses and is often prescribed alongside beta blockers and diuretics to manage the side effects.

How Can I Mitigate Oral Minoxidil Side Effects?

We have covered a number of ways to mitigate oral minoxidil side effects, but there are some further ways that you can adjust the use of minoxidil to reduce your risk.

Split-Dosing

Splitting the daily dosage of oral minoxidil into two administrations, one in the morning and one in the evening, can potentially optimize its efficacy while minimizing side effects. This approach is based on the pharmacokinetics of oral minoxidil, which has a relatively short half-life of approximately 3-4 hours.^[31]Vano-Galvan, S., Pirmez, R., Hermosa-Gelbard, A., Moreno-Arrones, O.M., Saceda-Corralo, D., Rodrigues-Barata, R., Jiminez-Cauhe, J., Koh, W.L., Poa, J.E., Jerjen, R., de Carvalho, L.T., John, J.M., … Continue reading 

By dividing the total daily dose, you can maintain more consistent blood levels of minoxidil throughout the day, potentially leading to more stable hair growth stimulation. For example, if 5 mg is prescribed daily, taking 2.5 mg in the morning and 2.5 mg in the evening may be more beneficial than a single 5 mg dose.

Sublingual Minoxidil

Some recommend using sublingual minoxidil as an alternative to traditional oral minoxidil. Sublingual administration involves a tablet that dissolves under the tongue. One 2021 randomized, double-blind, placebo-controlled phase 1b clinical trial investigated this delivery method.^[32]Bokhari, L., Jones, L.N., Sinclair, R.D. (2021). Sublingual minoxidil for the treatment of male and female pattern hair loss: a randomized, double-blind, placebo-controlled, phase 1B clinical trial. … Continue reading The study tested daily doses of 0.45 mg to 4.05 mg of sublingual minoxidil. 

This method offers several advantages:

1. Bypasses first-pass metabolism in the liver.
2. It allows for direct entry into the bloodstream, which can travel inactivated to the scalp and be activated by sulfotransferase at the site.
3. Reduces systemic side effects.
4. Improves bioavailability.

Key findings from the study included a dose-dependent improvement in hair parameters, with reduced side effects compared to oral minoxidil and no significant effect on blood pressure. In the blood, peak serum concentrations of minoxidil were only 10% of those seen with typical oral minoxidil.

At the 24-week follow-up, approximately 45% of patients in the 0.45 mg sublingual minoxidil group experienced improvements in frontal hair density, and 55% showed vertex improvement. Higher doses (4.05 mg) led to further results, with nearly 67% of patients experiencing improvements in both frontal and vertex hair density. 

Sublingual minoxidil appears to be particularly beneficial for people concerned about the side effects of oral minoxidil. The medication was undetectable in plasma after 24 hours, and the mean peak minoxidil plasma concentration was significantly below the threshold associated with changes in blood pressure.

While the results are promising, it should be noted that this is the only study using sublingual minoxidil for AGA, and further studies with larger patient numbers are needed.

Switch To Topical Minoxidil

There is a chance that none of these options will work out for you, so you can try to switch to topical minoxidil. The side effects are more manageable for topical treatments, meaning that you can increase the dose and try to pair them with other treatments like microneedling or retinoic acid to further improve hair growth outcomes.

Can I Use Minoxidil If I Am Planning a Family?

Medical professionals generally advise against using both topical and oral minoxidil for both men and women when planning a family and for women during pregnancy and while breastfeeding.

While there is limited data on human pregnancies, animal studies have shown potential risks, including evidence of increased fetal resorption at high doses, one case report of fetal malformation associated with topical minoxidil use, and neonatal hypertrichosis reported following exposure during pregnancy.^[34]Drugs. (2023). Minoxidil pregnancy and breastfeeding warnings. Drugs.com. Available at: https://www.drugs.com/pregnancy/minoxidil.html (Accessed: February 2025),^[35]Smorlesi, C., Caldarella, A., Caramelli, L., Di Lollo, S., Moroni, F. (2003). Topically applied minoxidil may cause fetal malformation: a case report. Birth defects research. Part A, Clinical and … Continue reading 

There is a significant lack of well-controlled studies on minoxidil use during pregnancy and lactation. However, given the animal studies, medical professionals typically recommend avoiding minoxidil use when planning pregnancy, during pregnancy, and while breastfeeding, using adequate contraception if taking minoxidil, and discontinuing minoxidil use before attempting to conceive.^[36]National Institute of Health and Care Excellence. (2021). Topical minoxidil. NICE. Available at: … Continue reading

Does Minoxidil Affect Male Fertility?

Current research suggests that minoxidil has minimal to no direct impact on male fertility. However, some research has linked minoxidil with oxidative stress and morphological changes to the testicles, which could indicate a potential negative impact.^[37]Santana, F.F.V., Lozi, A.A., Goncalves, R.V., Silva, J.D., Matta, S.L.P.D. (2023). Comparative effects of finasteride and minoxidil on the male reproductive organs: A systematic review of in vitro … Continue reading 

If you’re thinking about trying minoxidil and you are trying to conceive or have a pregnant partner, then it is advisable to talk to a medical professional before starting any treatment.

What if I’m Still Experiencing Side Effects?

Fortunately, minoxidil is just one of several treatment options available. If you’ve tried all of them and still experience side effects, you might consider exploring alternative therapies.

We have a wealth of information available so you can weigh your options and find out exactly how each treatment works and what your regrowth roadmap might look like. If you have any questions, reach out in the dedicated discussion thread below.

Final Thoughts

While minoxidil remains one of the most widely used treatments for AGA, both topical and oral formulations present unique challenges. The choice of which to use should be weighed carefully against the side effects, varying from mild scalp irritation to more significant cardiovascular effects. Ultimately, while the research supports minoxidil’s efficacy, it is not the only option out there, and if it isn’t working for you, then it is important to find the right one.

While the medical literature clearly advises women to avoid finasteride before conception during pregnancy, and while breastfeeding, the guidance for men is less definitive. The question of whether men can safely continue using finasteride during the conception period remains a topic of debate among healthcare professionals. 

However, a recent large dataset statistical analysis has sent ripples through the hair loss space and regulatory world, as it appears to show further evidence that the use of finasteride in men leads to a congenital anomaly called “cryptorchidism” (undescended testicles). But what does the data actually say? And can we link statistical association to causality? In this article, we will take a deep dive into what the paper shows (or doesn’t show) and whether we think it is a cause of major concern for men.

Let’s first take a look at what the study is all about.

The Study

We’ll begin by summarizing the data from the study and then go into detail about what it all means, how the statistics are analyzed, and whether this is a result to be concerned about.

The researchers analyzed data from the FDA Adverse Event Reporting System (FAERS) from 2010 to 2022 to assess potential safety concerns related to paternal drug exposure on fertility, pregnancy outcomes, and offspring health.^[1]Zeng, Y., Lin, W., Zhuang, W. (2024). Safety concerns of paternal drug exposure on fertility, pregnancy, and offspring: an analysis based on the FDA adverse event reporting system. Andrology. 1-12. … Continue reading The FAERS is a computerized database that supports the FDA’s post-marketing safety surveillance program for approved drugs and therapeutic biologic products.^[2]US Food and Drug Administration. (no date). FDA Adverse Events Reporting System (FAERS) Public Dashboard. US FDA. Available at: … Continue reading  It collects and stores information on adverse events, medication errors, and product quality complaints that may be associated with FDA-approved products. 

Reporting to FAERS can be done in two ways:

1. Mandatory reporting: Manufacturers are required by law to report adverse events to FAERS within 14 days of becoming aware of them.
2. Voluntary reporting: Healthcare professionals (such as physicians, pharmacists, and nurses) and consumers (including patients, family members, and lawyers) can voluntarily submit reports.

Importantly, anyone can submit to FAERS directly; it does not need to be done by a doctor. The FDA provides multiple options for voluntary reporting: 

1. Online submission through the FDA’s Electronic Submission Gateway (ESG) or Safety Reporting Portal (SRP).
2. Using FDA Form 3500, which can be submitted electronically or by mail.^[3]US Food and Drug Administration (2024). Reporting Serious Problems to FDA. MedWatch. Available at: … Continue reading

What Were The Study Results?

The researchers conducted a disproportionality analysis, specifically the Reporting Odds Ratio (ROR), to identify drugs disproportionately associated with reproductive-related adverse events. 

The study analyzed 16,180,533 total reports; 3,210 cases related to paternal drug exposure were identified, with 7,808 associated adverse events (e.g., spontaneous abortions and small babies). The study found that drugs used to treat rheumatoid arthritis, cancer, infections, and psychotropic conditions were the most frequently implicated. 

However, one of the strongest links between treatment and adverse health events was between finasteride and cryptorchidism, with an ROR of 891.7 based on 11 reports. This suggests that cryptorchidism was reported for finasteride-exposed fathers at a much higher rate than for most other drugs in the database. 

Understanding the Data

Before we go into what the data means, let’s explain some key concepts that are important to the study.

What is a Disproportionality Analysis?

A disproportionality analysis is a tool used in drug safety monitoring. It analyzes large databases of reported side effects from various medications and looks for unusual patterns – like if a particular side effect is reported much more often with one drug than others.^[5]Fusaroli, M., Salvo, F., Begaud, B., AlShammari, T.M, Bate, A., Battini, V., Brueckner, A., Candore, G., Carnovale, C., Crisafulli, S., Cutroneo, P.M., Dolladille, C., Drici, M.D., Faillie, J.L., … Continue reading 

Imagine a concert where five people in the front row get food poisoning after eating hotdogs from a nearby stall, while only one person in the entire back section reports feeling ill. You might suspect that the front-row hot dogs are bad—but this doesn’t prove the food stand actually caused the sickness. Maybe those five people already had food poisoning before coming. Disproportionality analysis works in a similar way: it flags patterns, i.e., five people sick in the front row, but it doesn’t prove causation.

What is the Reporting Odds Ratio (ROR)?

The ROR is a key statistical measure used in disproportionality analyses. It compares how often a specific side effect is reported for a particular drug versus all other drugs.^[6]Rothman, K.J., Lanes, S., Sacks, S.T. (2004). The reporting odds ratio and its advantages over the proportional reporting ratio. Pharmacoepidemiology and Drug Safety. 13(8). 519-523. Available at: … Continue reading If the ROR is high, it means the side effects are being reported more often for that drug than you’d normally expect. 

Think about flipping a coin 10 times, and imagine it lands on “heads” 7 times. You might think the coin is biased. But if you had flipped it 1,000 times, the results might have evened out to 50/50. The Reporting Odds Ratio (ROR) works similarly: when there are only a few cases, even small variations make the number seem exaggerated. A few extra reports in a small dataset can make an effect look much larger than it actually is.

Unlike incidence, which measures new cases over time, or prevalence, which measures total cases at a given time, ROR does not provide information about the actual risk of an adverse event occurring. Instead, it indicates whether there’s a disproportionate association between a drug and an adverse event in the reporting database.

The important point to remember is that ROR is primarily a hypothesis-generating tool, helping prioritize which drug-event combinations may need further investigation. 

What Do The Study Results Mean?

The ROR calculation was based on reports from the FAERS, which, as we mentioned above, is a system for self-reporting adverse events that anyone can report to. This means that more severe or unusual side effects are more likely to be reported, and as such, FAERS is at risk of reporting bias. This was acknowledged as a limitation in the study. 

Furthermore, unlike controlled clinical studies, FAERS does not track how many people take a drug; it only tracks how many people report an issue.

To calculate the true risk of cryptorchidism from finasteride, you need two numbers:

1. The number of reported cases (numerator) – FAERS provides this (11 cases).
2. The total number of fathers who took finasteride (denominator) – FAERS does not provide this. 

Since FAERS does not track drug exposure rates, it is impossible to calculate the incidence or prevalence of an event. This means we can’t determine what percentage of fathers taking finasteride had children with cryptorchidism or whether this percentage is actually higher than background rates in the general population.

Think about it this way: a phone company gets 100 customer complaints in a month. Without knowing how many total customers they have, you can’t tell if that’s a serious problem. If they have 200 customers, that’s bad (50% complaint rate). However, if they have 2 million customers, it’s insignificant (0.005% complaint rate). FAERS has the same issue—it counts events but doesn’t count the total number of people taking the drug.

Furthermore, the disproportionality analysis does not compare finasteride to a control group. Instead, it compares the number of cryptorchidism reports for finasteride (11) to the number of cryptorchidism reports for all other drugs (likely much lower because most drugs do not affect male hormone pathways).

This is problematic for several reasons:

1. This is Not a Matched Control Population

1. 1. Fathers who took finasteride should be compared to fathers who did not take finasteride while keeping other factors (like age, lifestyle, genetics) constant. 
   2. FAERS instead compares finasteride to all other drugs – but as we just mentioned, most drugs don’t affect male reproductive hormones, making the comparison flawed.

2. Selective Reporting Bias in FAERS

1. 1. Finasteride users are already aware of post-finasteride syndrome (PFS) and reproductive side effect concerns. 
   2. If a father taking finasteride has a child with any birth defect, they may be more likely to report it than a father taking, say, an antibiotic or a painkiller.
   3. This could artificially inflate the number of finasteride-related reports, making cryptorchidism appear more common than it is.

3. The Numerator is Small, But the ROR is Huge:

1. 1. FAERS recorded only 11 cryptorchidism cases for finasteride from 2010 – 2022.
   2. Cryptorchidism naturally occurs in 2-3% of all full-term male births.^[7]Leslie, S.W., Sajjad, H., Villanueva, C.A. (2024). In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470270/ … Continue reading

This creates a statistical illusion. If very few cryptorchidism cases are reported for other drugs, the ROR for finasteride skyrockets, even if the actual risk is low.

People fear shark attacks because they’re widely reported in the news, but statistical analyses have shown that the odds of dying from a falling vending machine are higher than being killed by a shark.^[8]United States Consumer Product Safety Commission. (1995). CPSC, Soda Vending Machine Industry Labeling Campaign Warns of Deaths and Injuries. US CPSC. Available at: … Continue reading The reason we think sharks are deadlier is that their attacks make headlines while vending machine accidents don’t. Similarly, if only one case of cryptorchidism is reported for another drug, but 11 cases are reported for finasteride, the ROR can look massive—even if the actual risk is tiny.

In 2022, about 2,626,865 men in the United States were estimated to have taken finasteride.^[9]ClinCalc. (no date). Finasteride Drug Usage Statistics, United States, 2013-2022. ClinCalc. Available at: https://clincalc.com/drugstats/Drugs/Finasteride (Accessed: January 2025) Even if all 11 reports of cryptorchidism were from distinct individuals and occurred solely in 2022 (instead of over 12 years), this would equate to an incidence rate of 0.00042% (or 4.2 per million users). This is notably below the background risk of cryptorchidism in the general population (2-3%), suggesting that the observed reports in FAERS are likely to be an artifact of a small sample size rather than evidence of a causal relationship.

So, to summarize, this study, while showing a statistical association between men taking finasteride and their children having cryptorchidism, does not show any causal relationship – meaning that it doesn’t actually show that finasteride causes this congenital anomaly.

Why Is This Study Even A Discussion?

Finasteride’s potential impact on reproductive health has been debated for years, largely due to animal studies and regulatory warnings for women. While the FAERS data discussed above suggest a statistical association between finasteride use in men and cryptorchidism in offspring, the underlying question is whether this link is biologically plausible or supported by stronger evidence.

Finasteride is classified as an FDA Pregnancy Category X drug, meaning that it is strictly contraindicated in pregnant women due to teratogenic effects observed in animal studies.^[10]Merck & Co. Inc. (no date). Propecia Prescribing Information. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020788s020s021s023lbl.pdf (Accessed: January 2025) These concerns stem from its mechanism of action: blocking the conversion of testosterone into dihydrotestosterone (DHT) by inhibiting the 5ɑ-reductase enzyme. Since DHT is crucial for normal male fetal development, any disruption during pregnancy can result in genital abnormalities.^[11]Bormann, C.L., Smith, G.D., Padmanabhan, V., Lee, T.M. (2011). Prenatal testosterone and dihydrotestosterone exposure disrupts ovine testicular development. Reproduction 142(1). Available at: … Continue reading

Studies in rodent and primate models have shown that exposure to high doses of finasteride during pregnancy can lead to: 

• Hypospadias – a condition where the urethral opening is misplaced on the underside of the penis instead of at the tip.^[12]An, N., Peng, J., He, G., Fan, X., Li, F., Chen, H. (2018). Involvement of activation of mitogen-activated protein kinase (MAPK)/extracellular signal-related kinase (ERK) signaling pathway in … Continue reading
• Cryptorchidism – as mentioned above, is an anomaly in which one or both testicles fail to descend into the scrotum during fetal development, a condition later associated with fertility issues and an increased risk of testicular cancer.
• Reduced anogenital distance (AGD) – a key marker of disrupted androgen signaling during development and is often used as a biomarker for endocrine disruption.^[13]Clark, R.L., Anderson, C.A., Prahalada, S., Robertson, R.T., Lochry, E.A., Leonard, Y.M., Stevens, J.L., Hoberman, A.M. (1993). Critical developmental periods for effects on male rat genitalia … Continue reading

One study in rhesus monkeys found that continuous finasteride exposure throughout gestation resulted in severe genital malformations in male offspring.^[14]Prahalada, S., Tarantal, A.F., Harris, G.H., Ellsworth, K.P., Clarke, A.P., Skiles, G.L., MacKenzie, K.I., Kruk, L.F., Ablin, D.S., Cukierski, M.A., Peter, C.P., vanZwieten, M.J., Hendrickx, A.G. … Continue reading This was particularly concerning because monkeys have hormonal systems that more closely resemble humans compared to rodents. Due to these findings, the FDA issued strong warnings that pregnant women should never ingest or even handle crushed finasteride tablets, as skin absorption could theoretically lead to fatal exposure.

For more information, see our article diving into the science behind finasteride & conception, and our article about how to use finasteride and minimize its exposure to your partner.

Can These Findings in Animals Be Directly Applied to Humans?

Although these studies raise legitimate concerns, there are important reasons why their findings may not directly apply to human males taking finasteride. For example, the doses used in animal studies are often much higher than those used in human treatment. The studies also involve direct maternal exposure during pregnancy, whereas paternal exposure (via sperm) results in much lower fetal exposure (we’ll discuss this further below). Furthermore, while rodents and monkeys have similar endocrine systems, their sensitivity to 5ɑ-reductase inhibition differs from that of humans.

Therefore, while animal models provide a biological basis for concern, they do not conclusively prove that paternal finasteride exposure affects offspring in humans.

Is It Biologically Plausible That Finasteride Could Cause Issues in Men?

To determine whether paternal finasteride use could biologically contribute to congenital anomalies in humans, we need to look at:

1. How much finasteride reaches semen and whether these lead to enough exposure in females to impact fetal development.
2. Whether finasteride alters sperm in a way that could lead to birth defects.

How Much Finasteride Reaches Semen?

One way finasteride could hypothetically impact fetal development is through semen exposure during conception or early pregnancy. However, semen levels of finasteride are extremely low.

Clinical data from GlaxoSmithKline (internal studies) measured finasteride concentrations in the semen of men taking a 50 mg dose (which is 10 x higher than the standard dose for hair loss). The result? Only 0.26 ng/mL of finasteride was detected in semen.^[15]US Food and Drug Administration. (no date). Propecia (finasteride). US FDA. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020788s017lbl.pdf (Accessed: January 2025) At the standard 1 mg dose used for hair loss, semen concentrations would likely be even lower.

How does this compare to doses known to cause fetal harm?

In the rhesus monkey studies, oral doses of finasteride given directly to pregnant females (at levels over 5,000 x higher than those found in human semen) caused genital abnormalities in male offspring. Therefore, the amount of finasteride that pregnant human women might absorb from semen exposure is likely so low that it falls below the threshold needed to affect fetal development.

Conclusion: There is no compelling evidence to suggest that the trace amounts of finasteride in semen are enough to cause congenital defects in humans.

Can Finasteride Affect Sperm Quality or DNA?

Another possible concern is whether finasteride negatively affects sperm itself, leading to:

1. Reduced fertility.
2. DNA damage that could increase congenital anomaly risk.

Some studies suggest finasteride can reduce sperm concentration and motility at higher doses (5 mg for prostate treatment), but these effects are reversible after stopping the medication, and studies in men taking the 1 mg dose for hair loss do not show significant sperm abnormalities. 

For example, a 2013 study by Samplaski et al. found that men taking an average of 1.04 mg/day of finasteride experienced an 11.6-fold increase in sperm count after stopping the drug, with no participants experiencing a decrease in sperm count post-discontinuation.^[16]Samplaski, M.K., Lo, K., Grober, E., Jarvi, K. (2013). Finasteride use in the male infertility population: effects on semen and hormone parameters. Fertility and Sterility. 100(6). 1542-1546. … Continue reading 

Similarly, a 1999 study found that 1 mg/day of finasteride did not significantly affect spermatogenesis or semen production in healthy men.^[17]Overstreet, J.W., Fuh, V.L., Gould, J., Howards, S.S., Lieber, M.M., Hellstrom, W., Shapiro, S., Carroll, P., Corfman, R.S., Petrous, S., Lewis, R., Toth, P., Shown, T., Roy, J., Jarow, J.P., … Continue reading  

A 2007 study observed that taking 5 mg/day of finasteride exhibited mild reductions in semen volume, sperm concentration, and motility, though these parameters returned just below normal after stopping.^[18]J.K., Amory., Wang, C., Swerdloff, R.S., Anawalt, B.D., Matsumoto, A.M., Bremner, W.J., Walker, S.E., Haberer, L.J., Clark, R.V. (2007). The effect of 5alpha-reductase inhibition with dutasteride and … Continue reading 

Could Finasteride Cause Epigenetic Changes to Sperm?

Some scientists have speculated that finasteride could cause epigenetic modifications to sperm, meaning it might alter gene expression without changing the DNA sequence. However, no studies have directly confirmed this in humans. Animal studies suggest some potential for altered gene expression, but these findings haven’t been replicated in human sperm research.^[20]Kolasa, A., Roginska, D., Rzeszotek, S., Machalinski, B., Wiszniewska, B. (2021). Paternal finasteride treatment can influence the testicular transcriptome profile of male offspring – … Continue reading 

In 2011 and 2012, two separate case reports documented men struggling with fertility issues after long-term finasteride use. While their sperm morphology appeared normal, both had elevated sperm DNA fragmentation-a marker of DNA damage. After stopping finasteride, one saw fragmentation drop from 30% to 16.5% within six months, while the other improved and successfully conceived.^[21]Salvarci, A., Istanbulluoglu, O. (2012). Secondary infertility due to use of low-dose finasteride. International urology and nephrology. 45(1). 83-85. Available at: … Continue reading,^[22]Tu, H.Y.V., Zini, A. (2011). Finasteride-induced secondary infertility associated with sperm DNA damage. Fertility and sterility. 95(6). e13-4. Available at: … Continue reading 

These reports suggest finasteride may contribute to sperm DNA damage, but since they lack controls, other lifestyle changes such as diet, exercise, or better sleep could also explain the improvements. You can read more about our thoughts on these case studies here.

The bottom line is that:

• Finasteride can mildly impact sperm quality, but this effect is reversible and not linked to congenital anomalies.
• No strong evidence exists that finasteride causes long-term DNA changes that could harm offspring.

So, is it biologically plausible that finasteride causes birth defects when taken by men? We think the current evidence for paternal risk is weak. 

Is There Any Other Evidence That Finasteride Causes Congenital Anomalies?

To date, no large-scale, well-controlled studies have confirmed an increased risk of congenital anomalies from paternal finasteride use. 

Danish Nationwide Study (2017)

Study Type: A large-scale epidemiological study using data from national birth registries.^[23]Anderson, J.T., Jenson, T.B., Horwitz, H., Clausen, S.S. (2019). Paternal exposure to finasteride – Before and during pregnancy. Pharmacoepidemiology and Drug Safety. 28(16). Conference … Continue reading 

Findings: No increased risk of congenital anomalies in children of men who had taken finasteride before conception. The risk of miscarriage was also not elevated.

Conclusion: No strong evidence linking paternal finasteride use to birth defects.

Case Reports and Small Studies

Some isolated case reports have suggested a potential association between paternal finasteride use and reproductive issues in offspring.^[24]Ahn, K.H., Shin, J., Hong, S.C., Han, JY., Lee, E.H., Lee, J.S., Oh, M.J., Kim, H.J. (2015). Pregnancy Outcomes with Paternal Exposure to Finasteride, a Synthetic 5-Alpha-Reductase Inhibitor: A Case … Continue reading However, these reports often lack proper controls and fail to rule out other factors such as genetics, environmental exposures, or maternal health conditions.

Final Thoughts

While the study we have discussed in this article highlights a statistical association between paternal finasteride exposure and cryptorchidism, it does not establish causation. The limitations of FAERS data, including reporting bias and the absence of a control population, make it difficult to draw firm conclusions. Additionally, biological plausibility remains weak, given the extremely low levels of finasteride in semen and the lack of strong evidence linking paternal exposure to congenital anomalies. Ultimately, while more research is warranted, current data does not suggest a major cause for concern. Men using finasteride should, however, discuss any reproductive concerns with their healthcare provider before making any decisions.

Imagine if your genes could predict how much hair you’ll regrow from minoxidil… or whether you could get side effects from finasteride. This would be a breakthrough in hair loss treatments. And yet, according to some genetic testing companies, this breakthrough is already here and available (for a price).

Certain telehealth companies now offer to sequence your DNA to help you create a more tailored, personalized treatment plan for your hair loss.^[1]TrichoTest. (no date). Personalizing alopecia treatment. Fagron Genomics. Available at: https://gxsciences.com/trichotest/. (Accessed: October 2024) Depending on your genetics, they might recommend substituting finasteride for dutasteride, oral over topical minoxidil, or adding corticosteroids – all based on the latest scientific data.

Who wouldn’t want to do this? It would enable you to create the highest-value and lowest-risk treatment plan for yourself. 

However, the quality of the evidence surrounding this approach isn’t so cut and dry. That’s why we conducted a four-month research project in which we identified 12 genes that some companies say are associated with treatment efficacy. We looked at the available literature to determine what the science says, the quality behind it, and whether it is even relevant to hair loss.

Single Nucleotide Polymorphisms (SNPs)

SNPs are changes at a single position in a DNA sequence. They can occur within genes or in the regions between genes. SNPs are the most common type of genetic variation in humans, occurring once in every 100-300 nucleotides in the human genome.^[2]Nelson, M.R., Marnellos, G., Kammerer, S., Hoyal, C.R., Shi, M.M., Cantor, C.R., Braun, A. (2004). Large-scale validation of single nucleotide polymorphisms in gene regions. Genome Research. … Continue reading  

In coding regions of genes, SNPs can be:

• Synonymous, i.e., they do not affect the protein sequence
• Nonsynonymous, i.e., they change the protein’s amino acid sequence ^[3]Sun, Y., Zhang, Y., Zhang, X. (2019). Synonymous SNPs of viral genes facilitate virus to escape host antiviral RNAi immunity. RNA Biology. 16(12). 1697-1710. Available at: … Continue reading 

SNPs in non-coding regions of genes can affect gene expression, gene splicing, or other regulatory processes.^[4]Degtyareva, A.O., Antontseva, E.V., Merkulova, T.I. (2021). Regulatory SNPs: Altered Transcription Factor Binding Sites Implicated in Complex Traits and Diseases. International Journal of Molecular … Continue reading Like genes, SNPs are inherited from parents to their children and contribute to genetic differences between people. 

SNPs in certain genes may increase susceptibility to specific diseases. For example, a large-scale genome-wide association study identified 71 significantly associated loci for male pattern baldness, indicating a genetic aspect to the pathogenesis of androgenic alopecia.^[5]Pirastu, N., Joshi, P.K., deVries, P.S., Cornerlis, M.C., McKeigue, P.M., Keum, N., Franceschini, N., Colombo, M., Giovannucci, E.L., Spiliopoulou, A., Franke, L., North, K.E., Kraft, Morrison, A.C., … Continue reading 

So, now that we’ve discussed genes and SNPs, let’s examine what we found. 

We’ve created a table of every gene we analyzed to give you an overview of the articles. Below, we will summarize each gene and its potential for advising treatment efficacy.

Gene	SNP	What the Genetic Testing Companies Say	What the Evidence Says	Treatment Relevance (1-5)
ACE	rs4341	People with a deletion variant of this polymorphism (CG or GG) may want to try treatments that improve blood flow to the scalp.	The deletion allele (G) is associated with increased ACE activity, which leads to vasoconstriction and reduced blood flow. No studies show an association between this polymorphism and the response to hair treatments that may improve blood flow.	1
	rs4343	People with a deletion variant of this polymorphism (AG or GG) may want to try treatments that improve blood flow to the scalp.	The deletion allele (G) is associated with increased ACE activity, which leads to vasoconstriction and reduced blood flow. No studies show an association between this polymorphism and the response to hair treatments that may improve blood flow.
BTD	rs13078881	People with the CC or CG variants may be good candidates for biotin supplementation.	The CC and CG genotypes were associated with biotinidase deficiency in a study of 19 children. Adults with this polymorphism exhibited biotinidase deficiency but presented no symptoms.  No studies show an association between this polymorphism and hair loss or the response to biotin supplementation.	1
COL1A1	rs1800012	People with the GT variant may benefit from supplementation that supports collagen formation.	People with the GT variant were found to have an increased ratio of α1 to α2 chains, which could lead to instability of the collagen molecules. No studies show an association between this polymorphism and the response to supplements that support collagen formation.	1
CRABP2	rs12724719	People with the AA variant may not benefit from standard retinoic acid supplementation and may require an increased dose or alternative treatment.	Newborn babies with the AA variant were found to have increased retinoic acid levels in their umbilical cord blood. It is not known if the same effect is seen in adults. No studies show an association between this polymorphism and the response to retinoic acid supplementation.	1
CYP19A1	rs2470152	People with the TC variant may benefit from treatment with replacement hormones (e.g., estradiol) or anti-androgens.	People with the TC variant were found to exhibit increased testosterone levels and a reduced ratio of estradiol to testosterone. No studies show an association between this polymorphism and hair loss or the response to replacement hormones and anti-androgens.	1
	rs700519	People with the CC variant may be a good candidate for the typical or higher dosages of 5α-reductase inhibitors. People with the CT or TT variants may be good candidates for lower dosages of 5α-reductase inhibitors.	People with the CT or TT variant were shown to respond better to treatment with dutasteride. However, some people with CT or TT were still classified as being poor responders to dutasteride treatment.
GPR44	rs533116	People with the AA variant may be good candidates for treatment with PGD2 inhibitors.	People with the AA variant exhibited increased GPR44 expression in their white blood cells, which may increase sensitivity to PGD2. No studies show an association between this polymorphism and the response to treatment with PGD2 inhibitors.	1
	rs545659	People with the GG variant may be good candidates for treatment with PGD2 inhibitors.	People with the GG variants exhibited greater GPR44 mRNA stability, which may increase PGD2 activity.  No studies show an association between this polymorphism and the response to treatment with PGD2 inhibitors.
GRα/GRꞵ (NR3C1)	rs6198	People with the GG variant may not respond as well to glucocorticoid treatment.	People with the GG variant exhibited a form of the glucocorticoid receptor that does not bind as well to glucocorticoids. No studies show an association between this polymorphism and the response to glucocorticoid treatment for hair loss.	1
IGF1R	rs2229765	People carrying at least one A allele may be good candidates for IGF-1 supplementation.	People with the AG or AA genotype were found to exhibit lower levels of IGF-1 in their plasma. No studies show an association between this polymorphism and the response to supplementation with IGF-1.	1
PGTFR	rs10782665	People carrying at least one T allele have an increased probability of a positive response to treatment with Latanoprost.	The presence of a G allele was found to increase the probability of a positive response to Latanoprost treatment for intraocular pressure in mice. No studies show an association between this polymorphism and hair loss response to treatment with Latanoprost.	2
	rs1328441	People carrying at least one G allele have an increased probability of a positive response to treatment with Latanoprost.	The presence of a G allele was found to increase the probability of a positive response to Latanoprost treatment for intraocular pressure in mice. No studies show an association between this polymorphism and hair loss response to treatment with Latanoprost.
	rs6686438	People carrying at least one G allele have an increased probability of a positive response to treatment with Latanoprost.	The presence of a G allele was found to increase the probability of a positive response to Latanoprost treatment for intraocular pressure in mice. No studies show an association between this polymorphism and hair loss response to treatment with Latanoprost.
PTGES2	rs13283456	People with the CT variant have reduced PTGES2 enzymatic activity, which reduces PGE2 levels. This makes them better candidates for treatment with minoxidil, which increases PGE2 levels.	The CT variant is associated with reduced BMI in males. However, no direct evidence exists that it is associated with PTGES2 activity or PGE2 levels. There are no studies that show an association between this polymorphism and the response to treatment with minoxidil.	1
SRD5A1 & SRD5A2	rs248793	People carrying at least one C allele have increased levels of DHT, which may make them good candidates for treatment with 5α-reductase inhibitors.	The presence of a C allele in adults was found to be associated with an increased DHT/T ratio. No studies show an association between this polymorphism and the response to treatment with 5α-reductase inhibitors.	2
	rs523349	People with the GG variant have increased 5α-reductase activity, which may make them good candidates for treatment with 5α-reductase inhibitors.	The GG variant is associated with increased 5α-reductase activity, which may increase DHT levels. No studies show an association between this polymorphism and the response to treatment with 5α-reductase inhibitors.
SULT1A1	rs9282861	People carrying at least one A allele have reduced sulfotransferase activity, which may alter their response to minoxidil.	Sulfotransferase activity was reduced in people with the GA variant and further in those with the AA variant. Sulfotransferase catalyzes the conversion of minoxidil to its active form, minoxidil sulfate. Small-scale human studies have shown that people with the GG variant may respond better to minoxidil treatment for hair loss.	3

Angiotensin-converting enzyme (ACE)

ACE is a key enzyme in blood pressure regulation. It converts angiotensin I to angiotensin II, causing vasoconstriction. The ACE gene has an insertion/deletion (I/D) polymorphism that affects enzyme activity, with the deletion (D) allele associated with higher ACE levels and increased vasoconstrictions.^[6]Wong, M. K. S. (2016). Angiotensin Converting Enzymes. In Handbook of Hormones. pp. 263-e29D-4. Elsevier. Available at: https://doi.org/10.1016/B978-0-12-801028-0.00254-3

Some research suggests a link between ACE gene polymorphisms and androgenic alopecia (AGA). Certain genetic testing companies propose that individuals with specific ACE polymorphisms may benefit from treatments that improve scalp blood flow. The theory is that higher ACE activity leads to increased vasoconstriction, potentially reducing blood flow to hair follicles. Therefore, treatments like minoxidil or caffeine, which may work partly through vasodilation, could be more effective for individuals with these genetic variants. 

However, while this hypothesis is intriguing, no direct evidence demonstrates that people with particular ACE polymorphisms respond differently to hair loss treatments that improve blood flow. 

Read our ACE gene article here.

Biotinidase (BTD)

The BTD gene encodes biotinidase, an enzyme crucial for recycling and utilizing biotin (Vitamin B7) in the body. Biotin is vital in various biological functions, including hair health, through its involvement in protein synthesis and keratin production.^[8]Leon‐Del‐Rio, A. (2019). Biotin in metabolism, gene expression, and human disease. Journal of Inherited Metabolic Disease, 42(4), 647-654. Available at: https://doi.org/10.1002/jimd.12073 

Mutations in BTD can lead to biotinidase deficiency, which can cause biotin deficiency or dependency. This condition can result in various symptoms, including hair abnormalities and alopecia. 

According to some, certain BTD polymorphisms might predict the efficacy of biotin treatment for hair loss. However, the evidence supporting this claim is limited and inconclusive.^[9]Bhattarai, D., Banday, A. Z., Sadanand, R., Arora, K., Kaur, G., Sharma, S., & Rawat, A. (2021). Hair microscopy: an easy adjunct to diagnosis of systemic diseases in children. Applied … Continue reading Studies have shown conflicting results regarding the impact of this polymorphism on biotinidase activity in adults and children, and none specifically address hair loss.

Read our BTD gene article here.

Collagen Type 1 Alpha 1 Chain (COL1A1)

COL1A1 encodes one of the chains of type I collagen, the most abundant collagen in the body. Type I collagen is crucial in supporting tissue structure throughout the body.^[10]Ricard-Blum, S. (2011). The collagen family. Cold Spring Harbor perspectives in biology, 3(1), a004978. Available at: https://doi.org/10.1101/cshperspect.a004978 

COL1A1 gene expression is upregulated in people with AGA.^[11]Michel, L., Reygagne, P., Benech, P., Jean‐Louis, F., Scalvino, S., Ly Ka So, S., Hamidou, Z., Bianovici, S., Pouch, J., Ducos, B. and Bonnet, M., 2017. Study of gene expression alteration in male … Continue reading Furthermore, studies have shown the SNPs in the COL1A1 gene can affect collagen stability.^[12]Mann, V., Hobson, E.E., Li, B., Stewart, T.L., Grant, S.F., Robins, S.P., Aspden, R.M. and Ralston, S.H. (2001). A COL1A1 Sp1 binding site polymorphism predisposes to osteoporotic fracture by … Continue reading 

While these findings suggest a potential role for COL1A1 in hair growth and loss, the exact mechanisms are not fully understood. More research is needed to clarify how variations in COL1A1 might influence hair loss and treatment responses. Currently, limited evidence supports targeting COL1A1 specifically for hair loss treatments.

Read our COL1A1 gene article here.

CRAPB2

CRABP2 is one of two genes in the cellular retinoic acid-binding protein family and is crucial for regulating retinoic acid by transporting it within cells and aiding its metabolism. Retinoic acid is important for hair health, but its deficiency and excess can lead to hair loss, indicating a dose-dependent relationship.^[14]Wei, L. N. (2016). Cellular retinoic acid binding proteins: Genomic and non-genomic functions and their regulation. The Biochemistry of Retinoid Signaling II: The Physiology of Vitamin A-Uptake, … Continue reading

This gene is highly expressed in dermal papilla cells, which are vital for hair follicle growth and development.^[15]He, M., Lv, X., Cao, X., Yuan, Z., Quan, K., Getachew, T., Mwacharo, J.M., Haile, A., Li, Y., Wang, S. and Sun, W. (2023). CRABP2 Promotes the Proliferation of Dermal Papilla Cells via the … Continue reading Overexpression of CRABP2 promotes cell growth, suggesting a positive role in hair maintenance. However, increased CRABP2 expression and elevated retinoic acid levels have also been associated with hair loss conditions like alopecia areata and AGA.^[16]Duncan, F.J., Silva, K.A., Johnson, C.J., King, B.L., Szatkiewicz, J.P., Kamdar, S.P., Ong, D.E., Napoli, J.L., Wang, J., King Jr, L.E. and Whiting, D.A. (2013). Endogenous retinoids in the … Continue reading

Despite this paradox, treatments using tretinoin have shown promise, stimulating hair regrowth in over half of patients, with further improvements observed after combination with minoxidil.^[17]Bazzano, G. S., Terezakis, N., & Galen, W. (1986). Topical tretinoin for hair growth promotion. Journal of the American Academy of Dermatology, 15(4), 880-893. Available at: … Continue reading 

One large study involving over 25,000 AGA patients found an association between this polymorphism and AGA, suggesting that genetic differences in CRABP2 could impact hair health and treatment efficacy.^[19]Francès, M. P., Vila-Vecilla, L., Russo, V., Caetano Polonini, H., & de Souza, G. T. (2024). Utilising SNP Association Analysis as a Prospective Approach for Personalising Androgenetic Alopecia … Continue reading Ultimately, further research is needed to show exactly how it might affect treatment efficacy.

Read our CRABP2 gene article here.

CYP19A1

CYP19A1 encodes the enzyme aromatase, which converts androgens like testosterone into estrogens like estradiol. Reduced expression of CYP19A1 and lower enzyme activity have been associated with female pattern hair loss (FPHL) and AGA. Aromatase levels are higher in non-balding scalp regions and significantly higher in women than men, possibly explaining gender differences in hair loss patterns.^[20]Nebert, D. W., Wikvall, K., & Miller, W. L. (2013). Human cytochromes P450 in health and disease. Philosophical Transactions of the Royal Society B: Biological Sciences, 368(1612), 20120431. … Continue reading

Aromatase helps decrease levels of DHT, and aromatase inhibitors have been linked to hair thinning, indicating a role for the enzyme in hair health. Treatments like minoxidil may increase aromatase activity, which can improve hair growth by increasing estradiol and reducing DHT levels.^[21]Gallicchio, L., Calhoun, C., & Helzlsouer, K. J. (2013). Aromatase inhibitor therapy and hair loss among breast cancer survivors. Breast cancer research and treatment, 142, 435-443. Available at: … Continue reading 

While certain genetic variations have been associated with better response to treatments like dutasteride, the study also showed that some people with this SNP can be poor responders, indicating that it is probably a combination of SNPs that affects treatment response.

So, while there is evidence that CYP19A1 SNPs can affect treatment efficacy, studies have not been done to determine the relationship between these and hair growth.

Read our CYP19A1 gene article here.

GPR44

The GPR44 gene encodes G-protein-coupled receptor 44 (the prostaglandin D2 receptor or DP2). GPR44 is significant because it mediates the effects of prostaglandin D2, a lipid compound involved in inflammation and the immune response.^[23]National Library of Medicine. (2024). PTGDR2 Prostaglandin D2 Receptor 2 [Homo sapiens (human)]. NIH. Available at: https://www.ncbi.nlm.nih.gov/gene/11251 (Accessed: 12 July 2024.)

PGD2 levels are elevated in balding scalps compared to haired scalps. Additionally, PGD2 inhibits hair growth in isolated human hair follicles and mouse models. Overexpression of PGD2 has been shown to lead to premature hair follicle regression and alopecia in mice. Furthermore, mice lacking the GPR44 receptor did not exhibit hair loss when exposed to PGD2, indicating that GPR44 is important for PGD2’s hair growth inhibition.^[24]Nieves, A., Garza, L.A. (2014). Does Prostaglandin D2 Hold the Cure to Male Pattern Baldness? Experimental Dermatology. 23(4). 224-227. Available at: https://doi.org/10.1111/exd.12348,^[25]Garza, L.A., Liu, Y., Alagesan, B., Lawson, J.A., Norberg, S.M., Loy, D.R., Zhao, T., Blatt, H.B., Stanton, D.C., Carrasco, L., Ahluwalia, G., Fischer, S.M., Fitzgerald, G.A., Cotsarelis, G. (2012). … Continue reading

However, one clinical trial using setipiprant, a GPR44 antagonist, showed no significant improvement in hair growth compared to a placebo in men with AGA, indicating that PGD2 signaling through GPR44 alone might not be sufficient for treating hair loss.^[27]DuBois, J., Bruce, S., Stewart, D., Kempers, S., Harutunian, C., Boodhoo, T., Weitzenfeld, A, Chang-Lin, J.E. (2021). Setipiprant for Androgenetic Alopecia in Males: Results from a Randomized, … Continue reading

SNPs in GPR44 have been associated with increased receptor expression and asthma severity, hinting that similar mechanisms might affect hair loss.^[28]Campos Alberto, E., Maclean, E., Davidson, C., Palikhe, N.S., Storie, J., Tse, C., Brenner, D., Mayers, I., Vliagoftis, H., El-Sohemy, A., Cameron, L. (2012). The Single Nucleotide Polymorphism CRTh2 … Continue reading,^[29]Huang, J.L., Gao, P.S., Mathias, R.A., Yao, T.C., Chen, L.C., Kuo, M.L., Hsu, S.C., Plunkett, B., Togias, A., Barnes, K.C., Stellato, C., Beaty, T.H., Huang, S.K. Sequence Variants of the Gene … Continue reading

Nonetheless, conflicting study results and poorly controlled variables make it unclear whether targeting GPR44 is effective for treating hair loss.

Read our GPR44 gene article here.

IGF1R

IGF1R encodes the insulin-like growth factor-1 receptor, which mediates the effects of IGF-1, a protein crucial for hair follicle development and the hair growth cycle. IGF-1 promotes cell growth, division, and survival in hair follicles and regulates the transition between the growth (anagen) and red (catagen) phases.^[30]Ahn, S. Y., Pi, L. Q., Hwang, S. T., & Lee, W. S. (2012). Effect of IGF-I on hair growth is related to the anti-apoptotic effect of IGF-I and up-regulation of PDGF-A and PDGF-B. Annals of … Continue reading

Studies have linked low levels of IGF-1 to AGA and hair loss. For instance, individuals with Laron syndromes, characterized by deficient IGF-1 production, often experience thinner hair and alopecia in adulthood.^[31]Lurie, R., Ben-Amitai, D., & Laron, Z. (2004). Laron syndrome (primary growth hormone insensitivity): a unique model to explore the effect of insulin-like growth factor 1 deficiency on human … Continue reading IGF-1 is also significantly reduced in balding compared to non-balding scalps.^[32]Panchaprateep, R., & Asawanonda, P. (2014). Insulin‐like growth factor‐1: roles in androgenetic alopecia. Experimental dermatology, 23(3), 216-218. Available at: … Continue reading Additionally, middle-aged women with lower circulating IGF-1 levels have a higher risk of developing hair loss.^[33]Noordam, R., Gunn, D. A., Drielen, K. V., Westgate, G., Slagboom, P. E., Craen, A. D., & Heemst, D. V. (2016). Both low circulating insulin‐like growth factor‐1 and high‐density lipoprotein … Continue reading

Genetic variation in IGF1R influences plasma IGF-1 levels, with some maintaining normal levels and some exhibiting reduced levels. This suggests a potential role of IGF-1 supplementation in those with lower IGF-1 levels.^[34]Bonafè, M., Barbieri, M., Marchegiani, F., Olivieri, F., Ragno, E., Giampieri, C., Mugianesi, E., Centurelli, M., Franceschi, C. and Paolisso, G. (2003). Polymorphic variants of insulin-like growth … Continue reading

However, no direct link has been established between the rs2229765 SNP and specific hair loss disorders. 

Read the full IGF1R gene article here.

NR3C1

NR3C1 encodes the glucocorticoid receptor (GR), which mediates the action of glucocorticoids, impacting metabolism, immune response, and stress response. There are two main isoforms: GRɑ, which binds glucocorticoids, and GRβ, which can inhibit GRɑs activity.^[36]Oakley, R.H., Cidlowski, J.A. (2013). The Biology of the Glucocorticoid Receptor: New Signaling Mechanisms in Health and Disease. Journal of Allergy and Clinical Immunology. 132(5). 1033-1044. … Continue reading 

GRs regulate the transitions between different phases of the hair cycle. They can influence the transition from anagen (active growth) to catagen (regression) phases. Furthermore, GRs are expressed in various components of the hair follicle, including dermal papilla cells, outer root sheath keratinocytes, and hair matrix cells.^[37]Kwack, M.H., Hamida, O.B., Moon, K.K., Kim, J.C., Sung, Y.K. (2022). Dexamethasone, a Synthetic Glucocorticoid, Induces the Activity of Androgen Receptor in Human Dermal Papilla Cells. Skin … Continue reading 

Certain genetic variants in NR3C1 have been linked to glucocorticoid resistance due to altered mRNA stability, affecting GR function. While these variations do impact glucocorticoid activity, there is no evidence to connect these effects to responsiveness to corticosteroids in hair loss, as the study was conducted in children with acute lymphoblastic leukemia.^[38]Gasic, V., Zukic, B., Stankovic, B., Janic, D., Dokmanovic, L., Lazic, J., Krstovski, N., Dolzan, V., Jazbec, J., Pavlovic, S., Kotur, N. (2018). Pharmacogenomic Markers of Glucocorticoid Response in … Continue reading 

Read more about the NR3C1 gene here.

PGTFR

The PGTFR gene encodes the prostaglandin F2 alpha receptor and plays a key role in hair follicle health and pigmentation. This receptor also involves broader physiological processes, including reproduction, inflammation, and cancer. Still, its influence on hair growth has made it a target in hair loss research.^[40]Ricciotti, E., FitzGerald, G.A. (2011). Prostaglandins and Inflammation.  Arteriosclerosis, Thrombosis, and Vascular Biology. 31(5). 986-1000. Available at: … Continue reading Studies in animal models have shown that PGF2ɑ and its analogs, such as latanoprost, stimulate the hair follicle and melanocyte growth, hinting at potential therapeutic benefits for hair loss treatments.

Genetic variants within PGTFR have been linked to varied responses to latanoprost in glaucoma treatment. Those with one genotype have been associated with greater response to latanoprost, while others were associated with reduced effectiveness.^[41]Sakurai, M., Higashide, T., Takahashi, M., Sugiyama, K. (2007). Association between Genetic Polymorphisms of the Prostaglandin F2ɑ Receptor Gene and Response to Latanoprost. Ophthalmology. 114(6). … Continue reading Similarly, other SNPs have corresponded with lower receptor activity, indicating decreased response to PGF2ɑ analogs. 

In the context of hair loss, we know that some evidence exists to show that latanoprost might benefit hair regrowth.^[43]Blume-Peytavi, U., Lonngors, S., Hillmann, K., Bartels, N.G. (2012). A Randomized, Double-Blind, Placebo-Controlled Pilot Study to Assess the Efficacy of a 24-Week Topical Treatment by Latanoprost … Continue reading However, no studies have linked any SNPs to treatment efficacy in the hair follicle.

Read the PGTFR gene article here.

PTGES2

The PTGES2 gene encodes prostaglandin E synthase 2, an enzyme that converts prostaglandin H2 (PGH2) to prostaglandin E2 (PGE2). This enzyme is critical in the prostaglandin synthesis pathway and plays a role in inflammation and hair growth. PGE2 levels are higher in non-balding scalp regions than in balding ones, suggesting that PTGES2 and its product PGE2 might contribute to hair preservation and growth.^[44]Garza, L.A., Liu, Y., Alagesan, B., Lawson, J.A., Norberg, S.M., Loy, D.R., Zhao, T., Blatt, H.B., Stanton, D.C., Carrasco, L., Ahluwalia, G., Fischer, S.M., Fitzgerald, G.A., Cotsarelis, G. (2012). … Continue reading 

Studies on AGA patients have found that PTGES2 expression increases in balding areas, likely as a compensatory response.^[45]Villareal-Villareal, C.D., Sinclair, R.D., Martinez-Jacobo, L., Garza-Rodriguez, V., Rodriguez-Leon, S.A., Lamadrid-Zertuche, A.C., Rodriguez-Gutierrez, R., Ortiz-Lopez, R., Rojas-Martinez, A., … Continue reading Genetic association studies have also linked a PTGES2 SNP to AGA. However, this does not appear to correlate with the severity of hair loss.^[46]Frances, M.P., Vila-Vecilla, L., Russo, V., Polonini, H.C., de Souza, G.T. (2024). Utilizing SNP Association Analysis as a Prospective Approach for Personalising Androgenetic Alopecia Treatment. … Continue reading 

Interestingly, some research suggests PTGES2 could influence responses to minoxidil as it has been shown to increase PGE2 production in hair follicle cells.^[48]Michelet, J.F., Commo, S., Billoni, N., Mahe, Y.F., Bernard, B.A. (1997). Activation of cytoprotective prostaglandin synthase-1 by minoxidil as a possible explanation for its hair growth-stimulating … Continue reading This indicates that individuals with PTGES2 variants possibly associated with lower enzyme activity might benefit more from minoxidil, as the treatment could help elevate PGE2 levels. However, general genetic findings should be interpreted carefully, as gene expression patterns in hair follicles may differ significantly from those in other tissues.

Read the PTGES2 gene article here.

SRD5A1 & SRD5A2

The SRD5A1 and SRD5A2 genes encode type I and type II 5ɑ-reductase enzymes, which are crucial for converting testosterone into dihydrotestosterone (DHT).^[49]Scaglione, A., Montemiglio, L.C., Parisi, G., Asteriti, I.A., Bruni, R., Cerutti, G., Testi, C., Savino, C., Mancia, F., Lavia, P. and Vallone, B. (2017). Subcellular localization of the five members … Continue reading Inhibitors targeting these enzymes, particularly finasteride, and dutasteride, are central to AGA treatment. Genetic variations in SRD5A1 and SRD5A2 have shown potential in influencing the effectiveness of these treatments.

In a study of AGA patients treated with dutasteride, certain SNPs in SRD5A1 were positively associated with treatment response, meaning individuals with these variants responded better. However, even patients with these SNPs displayed varied responses, suggesting that the overall genetic profile, rather than individual SNPs alone, likely plays a role in treatment efficacy.^[50]Rhie, A., Son, H.Y., Kwak, S.J., Lee, S., Kim, D.Y., Lew, B.L., Sim, W.Y., Seo, J.S., Kwon, O., Kim, J.I. and Jo, S.J. (2019). Genetic variations associated with response to dutasteride in the … Continue reading Interestingly, no SRD5A2 SNPs were found to significantly impact dutasteride response in this study, although variations in SRD5A2 may still affect DHT production and, consequently, treatment outcomes.

Additional research hints that SRD5A gene variants influence enzyme activity. In particular, individuals with higher DHT levels due to SRD5A1 or SRD5A2  variants might require higher doses or longer treatment durations for 5ɑ-reductase inhibitors to show efficacy. Lab studies have further suggested that specific variants of SRD5A2 might respond differently to finasteride versus dutasteride, emphasizing that personalized treatment approaches could optimize hair loss management.^[51]Makridakis, N.M., di Salle, E., and Reichardt, J.K. (2000). Biochemical and pharmacogenetic dissection of human steroid 5α-reductase type II. Pharmacogenetics and Genomics, 10(5), 407-413. Available … Continue reading 

While further clinical studies are needed to confirm these findings, early data suggest that SRD5A1 and SRD5A2 genotyping could improve the efficacy of 5ɑ-reductase inhibitor treatments.

Read the full SRD5A1 and SRD5A2 gene article here.

SULT1A1

The SULT1A1 gene encodes the enzyme sulfotransferase 1A1, part of the sulfotransferase family. This enzyme plays a critical role in the metabolism and detoxification of various compounds. In hair loss treatment, SULT1A1 is especially important because it activates minoxidil through sulfonation, converting it into minoxidil sulfate, the active form needed to stimulate hair growth.^[52]Goren, A., Castano, J.A., McCoy, J., Bermudez, F., Lotti, T. (2014). Novel enzymatic assay predicts minoxidil response in the treatment of androgenetic alopecia. Dermatologic Therapy. 27. 171-173. … Continue reading 

Evidence suggests that specific SULT1A1 gene variants correlate with varying levels of enzyme activity and minoxidil responsiveness. Some genetic variations have been shown to lead to higher sulfotransferase activity and greater hair growth response after minoxidil treatment, whereas those with other genotypes exhibited lower enzyme activity and may have a weaker response to the drug.^[53]Raghad, N.A., Al-Gazally, M.E., Ewahd, W.A. (2017). Assessment the effect of different genotypes of sulfotransferase 1A1 gene on the response to minoxidil in patients with androgenic alopecia. … Continue reading

Recent studies have begun using SULT1A1 genotyping as a tool to optimize minoxidil treatment, especially in female-pattern hair loss. However, some people with the “favorable” gene variations still fail to respond, while others with “less favorable” gene variations show substantial hair regrowth. This highlights the need for larger validation studies..^[55]Ramos, P.M., Gohad, P., McCoy, J., Wambier, C., Goren, A. (2021). Minoxidil Sulfotransferase Enzyme (SULT1A1) genetic variants predict response to oral minoxidil treatment for female pattern hair … Continue reading

Read more about these studies in the SULT1A1 gene article here.

Should We Be Targeting Genes for Hair Loss Treatment Efficacy?

Based on the evidence in the articles, SULT1A1 currently has the most evidential support. This is especially true as it is one of (if not the only) gene that we have examined that actually examined these SNPs in the hair follicles of people with hair loss.

Aside from this, we don’t see the utility in using our genes to predict hair loss treatment efficacy. That is not to say that we won’t eventually see a use for this, however. As the research evolves, new information might come to light, which we will keep you updated on. 

Progesterone is a steroid hormone with a wide range of physiological and medical effects. It is linked to female fertility and pregnancy, and it plays roles in neuro- and immunoprotection and various gynecological treatments. Studies have linked changes in progesterone levels to androgenic alopecia and postpartum telogen effluvium. Still, mixed evidence, limited research, and potential side effects have led to this treatment not being widely adopted.

In this article, we will explore the association between progesterone and hair loss, particularly female pattern hair loss (FPHL), and determine whether supplementation with progesterone can improve hair loss outcomes.

Key Takeaways

• What Is It? Progesterone is a steroid hormone that is essential for a wide range of physiological processes. Deficiencies are associated with menstrual irregularities, fertility and pregnancy issues, mood and sleep disturbance, and physical symptoms. Other signs can include dry skin and thinning hair.
• Evidence Quality: The evidence quality is 31/100 based on our metrics.
• Clinical Data: There is very limited evidence supporting using progesterone to improve hair loss outcomes.
  • Study 1: 10 male patients with AGA were treated with a lotion containing 11a-hydroxyprogesterone. Improvements were observed in the “cranial” region of the scalp but not the left temporal region.
  • Study 2: 6 male patients with AGA were treated with 100 mg of progesterone for 6 months. Improvements were observed in new hair growth and the transition from vellus to terminal hairs.
• Dosing & Formulation Considerations: Know your progestins! Many synthetic progesterone formulations are actually androgenic in nature rather than anti-androgenic. While some have more recently been developed to behave more closely to natural progesterone, there is data lacking in their efficacy to improve hair regrowth. We recommend sticking with natural progesterone until further research is available. If you are using natural progesterone, micronized allows for better systemic absorption especially when taken orally. It is typically prescribed at 200 mg daily for 12 days per 28-day cycle. However, it has not been tested for hair loss. If you decide to use non-micronized progesterone, a topical formulation may be more beneficial as oral is heavily metabolized and, therefore, may not reach the strength needed to affect hair growth outcomes. If you decide to take synthetic progestins, you might find results with cyproterone acetate or drospirenone (Slynd); however, once again, data is limited.

What Is Progesterone?

Progesterone is an important steroid hormone that plays several key roles in the female reproductive system. It is primarily produced by the corpus luteum in the ovaries after ovulation in women. For men, progesterone is produced in smaller amounts by the adrenal glands and is associated with sperm development.^[1]Nio-Kobayashi, J., Miyazaki, K., Hashiba, K., Okuda, K., Iwanaga, T. (2016). Histological analysis of arteriovenous anastomosis-like vessels established in the corpus luteum of cows during … Continue reading,^[2]Mirihagelle, S., Hughes, J.R., Miller, D.J. (2022). Progesterone-induced sperm release from the oviduct sperm reservoir. Cells. 11(10). 1622. Available at: https://doi.org/10.3390/cells11101622

The association between progesterone and hair health is multifaceted, involving direct hormonal effects and indirect influences.

Studies have shown that progesterone, due to its 5-alpha-reductase (5-AR) inhibiting properties, can help balance the potentially negative effects of androgens like testosterone. When progesterone levels decline, increased conversion of testosterone to dihydrotestosterone by 5-AR can occur, leading to hair follicle miniaturization and hair thinning.^[3]Grymowicz, M., Rudnicka, E., Podfigurna, A., Napierała, P., Smolarczyk, R., Smolarczyk, K., Męczekalski, B. (2020). Hormonal effects on hair follicles. International Journal of Molecular Sciences. … Continue reading

Significant hormonal changes occur in menopausal women, including a decrease in estrogen and progesterone levels. Estrogen prolongs the growing (anagen) phase of the hair follicle cycle, and progesterone indirectly supports this through its androgen-inhibiting activity. Therefore, a reduction in both estrogen and progesterone can leave menopausal women vulnerable to increased androgen levels and subsequent hair loss.

Changes in progesterone levels can also affect postpartum women. During pregnancy, progesterone levels are significantly elevated but drop sharply after childbirth. This sudden decrease in progesterone and estrogen is believed to contribute to postpartum telogen effluvium (PPTE). However, unlike the other examples mentioned above, PPTE is generally self-limiting. It occurs 2-4 months after delivery and resolves typically within 6-24 weeks (although in rare cases, it can persist up to 15 months).^[4]Cleveland Clinic. (no date). Postpartum Hair Loss. Cleveland Clinic. Available at: https://my.clevelandclinic.org/health/diseases/23297-postpartum-hair-loss (Accessed: September 2024)

So, we know how progesterone deficits might lead to hair loss, but does progesterone supplementation improve hair loss outcomes?

Can Progesterone Improve Hair Loss Outcomes?

As previously mentioned, progesterone has some 5-AR inhibitory properties. However, there is limited evidence to show that it can improve hair loss outcomes.

One 1987 study treated ten male patients with AGA with a lotion containing 1% 11a-hydroxyprogesterone (a progesterone derivative) for one year, and 8 patients were treated with a control.^[5]Van der Willigen, A.H., Peereboom-Wynia, J.D.R., van Joost, TH., Stolz, E. (1987). A preliminary study of the effect of 11a hydroxyprogesterone on hair growth in men suffering from androgenetic … Continue reading Those treated with the progesterone derivative showed an increase in the number of anagen hairs (45 to 51) and mean hair shaft diameter (69.6 μm to 71.6 μm) in the “cranial” region of the scalp. Further improvements were seen with reduced regressing/non-growing (catagen/telogen) hairs (46-40). Unfortunately, without images, we can’t see if these improvements led to a clinically significant outcome.

Furthermore, the study also analyzed hair counts on the left temporal side of the scalp. Here, the number of anagen hairs reduced from 67 to 62, and the number of catagen/telogen hairs increased from 21 to 30, indicating a varied response to the treatment.

Another small study was conducted with 6 males with AGA, acne, and benign prostatic hyperplasia (BPH).^[7]Kalinchenko, S., Nikiforov, I., Samburskaya, O. (2022). BPH, Androgenic Alopecia, and Acne – Markers of Progesterone Deficiency. Journal of the Endocrine Society. 6. 431-432. Available at: … Continue reading The participants were treated with Vitamin D and 100 mg progesterone daily for 6 months. After this period, the authors reported that the patients had reduced hair loss, new hair growth, and increased vellus transition to terminal hairs. Unfortunately, the authors didn’t report the specific values or show any photos. Furthermore, it is not possible to know if the positive effects were due to supplementing with Vitamin D.

While there is a logical reasoning behind the use of progesterone for women undergoing menopause suffering from female pattern hair loss, there is no clinical evidence demonstrating its efficacy.

Progesterone Formulations

There are a number of formulations of progesterone, but how effective might they be at improving hair loss outcomes?

Oral

Oral progesterone is typically prescribed for hormone replacement therapy (HRT). However, due to its metabolism, oral progesterone may only have limited benefits for hair loss. It undergoes extensive first-pass metabolism in the liver, leading to significant degradation of the hormone before it reaches the systemic circulation, meaning that limited amounts of the hormone may reach the scalp.^[8]Coombes, Z., Plant, K., Freire, C., Basit, A.W., Butler, P., Conlan, R.S., Gonzalez, D. (2021). Progesterone metabolism by human and rat hepatic and intestinal tissue. Pharmaceutics. 13(10). 1707. … Continue reading

Topical

Topical progesterone has a few potential benefits, including:

• Localized application
• Fewer systemic side effects
• Bypass first pass metabolism, so more is reaching the target area

According to one source, the most common strength of progesterone applied topically is around 2%. However, this appears to be based on clinical experience rather than published studies.^[9]Roseway Labs. (2020). Topicals for Hair Loss. Roseway Labs. Available at: https://rosewaylabs.com/topicals-for-hair-loss/ (Accessed: September 2024)

Injection

While some clinics use injected progesterone combined with other treatments, like platelet-rich plasma (you can find videos of these if you search on YouTube) to treat hair thinning, there is no peer-reviewed, published clinical evidence to suggest that it improves hair loss outcomes.

Micronized

Recently, there has been interest in using micronized progesterone and its potential as a hair growth treatment. This formulation may offer improved absorption and efficacy in balancing hormone levels, potentially aiding hair growth.

Micronized progesterone is a formulation of progesterone that has been processed to create very small particles smaller than 10 μm in size. This process increases the surface area of progesterone particles, allowing for better systemic absorption, especially when taken orally.^[10]Hargrove, J.T., Maxson, W.S., Wentz, A.C. (1989). Absorption of oral progesterone is influenced by vehicle and particle size. American Journal of Obstetrics and Gynecology. 161(4). 948-951. Available … Continue reading

Micronized progesterone is chemically identical to the progesterone that is naturally produced in the human body, meaning it should work similarly.^[11]de Lignieres, B. (1999). Oral micronized progesterone. Clinical Therapeutics. 21(1). 41-60. Available at: https://doi.org/10.1016/S0149-2917(00)88267-3 It is currently used as an HRT for menopausal symptoms, to support pregnancy and fertility, and to treat gynecological disorders.^[12]Memi, E., Pavli, P., Papagianni, M., Vrachnis, N., Mastorakos, G. (2024). Diagnostic and therapeutic use of oral micronized progesterone in endocrinology. Reviews in endocrine and metabolic … Continue reading

While we have recently been getting a lot of emails from members about micronized progesterone, there is a significant gap in the literature about its potential efficacy in treating hair loss in menopausal women or people with AGA.

Synthetic Progesterone

We have discussed natural progesterone in-depth, so let’s also examine synthetic progesterone (progestins) and how it differs from natural progesterone.

Progestins differ from natural progesterone in their chemical structure, which results in different physiological effects. Some common synthetic progestins include norethindrone, medroxyprogesterone acetate (MPA), norethisterone (NET-A), and levonorgestrel. Unlike natural progesterone, many synthetic progestins can increase androgen activity. This is critical to keep in mind when choosing whether to take progestins if you suffer from hair loss. Furthermore, progestins can cause other unwanted side effects like acne, excessive hair growth in unwanted areas, and changes in skin texture, alongside more serious increased risks such as cardiovascular events (heart attacks and strokes) and cancers.

One study published in 2017 examined the androgenic and estrogenic properties of various progestins, including MPA and NET-A. The findings indicated that these progestins bind to the androgen receptor (AR) with affinities comparable to dihydrotestosterone (DHT), suggesting that they can exert androgenic effects in vivo (in cells).^[13]Louw-du Toit, R., Perkins, M.S., Hapgood, J.P., Africander, D. (2017). Comparing the androgenic and estrogenic properties of progestins used in contraception and hormone therapy. Biochemical and … Continue reading

Research on hormonal contraceptives highlighted that synthetic progestins can lead to hair loss. One review conducted on data on alopecia associated with the levonorgestrel IUD found a number of women who had the IUD implanted between 2000-2001 experienced hair loss. Furthermore, in some of these cases, when the IUD was removed, women recovered their hair loss, indicating a direct effect of levonorgestrel on hair loss for some people. Unfortunately, this study is limited in many ways, including being a retrospective study and only having 73 total reports of alopecia (in New Zealand and using World Health Organization data).^[14]Paterson, H., Clifton, J., Miller, D., Ashton, J., Harrison-Woolrych, M. (2007(. Hair loss with use of the levonorgestrel intrauterine device. Contraception 76. 306-309. Available at: … Continue reading

A case study from 2002, this time conducted on a woman taking a combination low-dose oral contraceptive (norethindrone and ethinyl estradiol), found shortly after starting, she experienced hair loss, which abated when stopped.^[15]Yokoyama, Y., Sato, S., Saito, Y. (2002). Alopecia related to low-dose oral contraceptives. Archives of Gynecology and Obstetrics. 47. 266-246. Available at: https://doi.org/10.1007/pl00007489

So, it seems like if you have AGA, you might want to avoid synthetic progestins. But are there exceptions to the rule? There might be.

Cyproterone Acetate

While cyproterone acetate is a progestin, it has shown potential in improving hair regrowth in women with androgenic alopecia. In a study involving 80 women with FPHL treated with either 200 mg spironolactone, 50 mg of cyproterone acetate, or 100 mg daily for 10 days per month if menopausal, 44% of those treated with cyproterone acetate experienced hair regrowth. However, another 44% saw no change, and 12% continued to lose hair. There was also no significant difference between the cyproterone acetate and spironolactone groups.^[16]Sinclair, R., Wewerinke, M., Jolley, D. (2005). Treatment of female pattern hair loss with oral antiandrogens. British Journal of Dermatology. 152(3). 466-473. Available at: … Continue reading

Another study reported that 77.1% of 35 women with androgenic alopecia observed hair regrowth after three months of treatment with the combined cyproterone acetate and ethinyl estradiol pill (2mg). 42.8% of participants had slight regrowth, 34.3% had moderate regrowth after trichoscopic assessment, and 22.8% showed no regrowth at all.^[17]Coneac, A., Muresan, A., Orasan, M.S. (2014). Antiandrogenic therapy with ciproterone acetate in female patients who suffer from both androgenic alopecia and acne vulgaris. Clujul Medical. 87(4). … Continue reading

A 12-month randomized trial found that cyproterone acetate was more effective than minoxidil at treating hair loss in women with signs of hyperandrogenism, which may be worth considering when considering hair loss treatments.^[19]Vexiau, P., Chaspoux, C., Boudou, P., Fiet, J., Jouanique, C., Hardy, N., Reygagne, P. (2002). Effects of minoxidil 2% vs. cyproterone acetate treatment on female androgenetic alopecia: a controlled, … Continue reading

Drospirenone

Drospirenone (also known under the brand name Slynd) is a newer synthetic progesterone that has a unique profile. It is derived from spironolactone, a drug you may be familiar with, as it also has anti-androgenic properties. Like cyproterone acetate, Slynd does not increase androgenic activity. Instead, it has androgenic properties similar to natural progesterone, which makes it an attractive potential treatment.^[20]Regidor, P.A., Mueller, A., Mayr, M. (2023). Pharmacological and metabolic effects of drospirenone as a progestin-only pill compared to combined formulations with estrogen. Womens Health (Lond). 19. … Continue reading

However, the data on hair loss is limited. One study evaluated the efficacy of oral finasteride therapy combined with an oral contraceptive containing drosperinone and ethinyl estradiol in premenopausal women with FPHL. The study found that 62% of patients showed some improvement in hair loss, but it was unclear whether the improvement was due to the higher dosage of finasteride or the combination with the oral contraceptive.^[21]Iorizzo, M., Vincenzi, C., Voudouris, S., Piraccini, B.M., Tosti, A. (2006). Finasteride treatment of female pattern hair loss. Archives of Dermatology. 142(3). 298-302. Available at: … Continue reading

Furthermore, if you are sensitive or respond poorly to spironolactone, you might also experience side effects with Slynd. Another factor is that as a synthetic progestin, it might also carry elevated cardiovascular and cancer risks.

Other “new” progestins have also been developed and designed to be closer in mechanism of action to progesterone than other synthetics. These are dienogest, nestorone, nomegestrol acetate, and trimegestone, which have anti-androgenic activity, that may benefit those with hair loss, but again, they haven’t been tested.^[22]Sitruk-Ware, R. (2006). New progestagens for contraceptive use. Human Reproduction Update. 12(2). 169-178. Available at: https://doi.org/10.1093/humupd/dmi046

Dosing Considerations

Oral micronized progesterone is typically prescribed at 200 mg daily for 12 days per 28-day cycle for postmenopausal women or 400 mg daily for 10 days for women who have not had a period for at least three consecutive months.^[23]Memi, E., Pavli, P., Papagianni, M., Vrachnis, N., Mastorakos, G. (2024). Diagnostic and therapeutic use of oral micronized progesterone in endocrinology. Reviews in endocrine and metabolic … Continue reading It may be beneficial for women with female pattern hair loss.

Topical progesterone creams are often used in doses ranging from 20 to 40 mg, applied once or twice daily. For example, one study conducted with post-menopausal women used 40 mg daily or 20 mg twice daily for 42 days.^[24]Carey, B.J., Carey, A.H., Patel, S., Carter, G., Studd, J.W. (2000). A study to evaluate serum and urinary hormone levels following short and long term administration of two regimens of progesterone … Continue reading

Injectable progesterone is injected primarily at around 150 mg every 12 weeks.^[25]Nelson, A., (2002). Merits of DMPA relative to other reversible contraceptive methods. Journal of Reproductive Medicine. 47(9). 781-784. PMID: 12380406

Based on the research above, the dose for cyproterone acetate is around 50 – 100 mg, but this was given with ethinyl estradiol. For Slynd, the standard contraceptive dose of 4 mg orally once daily for 24 days followed by 4 inactive days may have potential benefits.

Dosing should be individualized based on the patient’s age, health status, and specific hormonal imbalances. Patients should report any concerning side effects to their doctor straight away. Close monitoring and adjustment of dosage by a healthcare provider are important, as effects can vary between individuals.

Best Practices

• Premenopausal Women: Progesterone supplementation may be used to address hormonal imbalances contributing to hair thinning.
• Postmenopausal Women: HRT with progesterone is more common, particularly in combination with estrogen, to combat hair loss linked to reduced hormone levels during menopause.
• Individuals with Androgenic Hair Loss: Progesterone as an adjunct to other anti-androgen therapies (e.g., spironolactone) for hair loss management (if you are pre-menopausal).^[26]Brough, K.R., Torgerson, R.R. (2017). Hormonal therapy in female pattern hair loss. International Journal of Women’s Dermatology.  3. 53-57. Available at: … Continue reading
• Key Considerations: Before starting progesterone therapy, it is important to undergo individualized hormone testing and consult with a healthcare provider. Monitor for side effects such as mood changes, weight gain, or changes in menstrual patterns

Ultimately, due to the lack of evidence, we believe that steering clear of synthetic progestins, for the most part, would be best until newer data comes out supporting their use in hair growth. As it stands there may be some promising candidates, but its clear from our research that there is a gap in the evidence.

Final Thoughts

While progesterone, particularly in topical and micronized formulations, may benefit women suffering from FPHL or other hormonally influenced hair loss, more high-quality research is needed. If you are thinking about using progesterone, consult with your doctor or healthcare professional to ensure that it is tailored to your needs.

CRABP2 is one of two genes found within the CRABP family alongside CRABP1. CRABP2 is a key regulator of retinoic acid, a vitamin A derivative, transporting it around the cell and helping its metabolism. Both CRABP2 and retinoic acid have been suggested in the literature to have roles in the maintenance of hair health. This is particularly evident for retinoic acid, which has been suggested to regulate hair health in a dose-dependent manner. A few studies have also investigated genetic variation in CRABP2, suggesting that some variants may be linked to hair loss. This article will explore how relevant CRABP2 is to hair loss treatment effectiveness and how to interpret your genetic results to make the correct treatment choice.

What is CRABP2?

The cellular retinoic acid binding protein (CRABP) gene family is very small, consisting of just two members – cellular retinoic acid binding protein 1 (CRABP1) and cellular retinoic acid binding protein 2 (CRABP2). CRABP1 is expressed throughout the body, whereas CRABP2 expression is restricted to certain tissues, such as the skin. Both CRABP genes are high-affinity binding proteins of retinoic acid, which is a derivative of vitamin A. Although research has yet to fully elucidate their exact functions, it is understood that CRABP1 and CRABP2 both play a role in the transport and metabolism of retinoic acid.^[1]Wei, L. N. (2016). Cellular retinoic acid binding proteins: Genomic and non-genomic functions and their regulation. The Biochemistry of Retinoid Signaling II: The Physiology of Vitamin A-Uptake, … Continue reading

In sheep, it has been shown that CRABP2 is highly expressed in dermal papilla cells (DPCs), which play a key role in the growth and development of hair follicles. Moreover, they showed that CRABP2 regulates the proliferation of DPCs and that the overexpression of CRABP2 promoted increased DPC proliferation. Although this research was conducted in cells taken from sheep, it does suggest that CRABP2 may play a role in the maintenance of hair.^[2]He, M., Lv, X., Cao, X., Yuan, Z., Quan, K., Getachew, T., Mwacharo, J.M., Haile, A., Li, Y., Wang, S. and Sun, W. (2023). CRABP2 Promotes the Proliferation of Dermal Papilla Cells via the … Continue reading

These results suggest that increased expression of CRABP2 could be beneficial for hair loss. However, the association between CRABP2 and hair maintenance is slightly more complex than it first appears. In tissue taken from a mouse model of alopecia areata (AA), the expression of CRABP2 (both the gene and protein) was increased compared to control mice. Similarly, CRABP2 protein expression was higher in tissue taken from humans with AA. Ultimately, the findings of the paper suggest that increased retinoic acid synthesis may contribute to the pathogenesis of AA.^[3]Duncan, F.J., Silva, K.A., Johnson, C.J., King, B.L., Szatkiewicz, J.P., Kamdar, S.P., Ong, D.E., Napoli, J.L., Wang, J., King Jr, L.E. and Whiting, D.A. (2013). Endogenous retinoids in the … Continue reading

Conversely, it has also been shown that a reduction in retinoic acid signaling may be associated with hair loss. Mice lacking a key retinoic acid receptor exhibited impaired anagen initiation within their hair follicles (the growing phase), which was likely a contributory factor in the progressive alopecia that these mice developed.^[4]Li, M., Chiba, H., Warot, X., Messaddeq, N., Gérard, C., Chambon, P., & Metzger, D. (2001). RXRα ablation in skin keratinocytes results in alopecia and epidermal alterations. Development, … Continue reading

Further evidence has been added to support these findings, suggesting that retinoic acid signaling may contribute to AGA similarly to androgens. It is widely accepted that androgens drive the pathogenesis of AGA and lead to the miniaturization of hair follicles. However, a study conducted in 30 male patients with AGA revealed that genes involved in retinoic acid signaling are upregulated, suggesting that retinoic acid signaling may promote follicle miniaturization.^[5]Ho, B.S.Y., Vaz, C., Ramasamy, S., Chew, E.G.Y., Mohamed, J.S., Jaffar, H., Hillmer, A., Tanavde, V., Bigliardi-Qi, M. and Bigliardi, P.L. (2019). Progressive expression of PPARGC1α is associated … Continue reading

Despite appearing contradictory, it is possible that all of these studies are accurate and that both a deficiency and excess of retinoic acid can contribute to hair loss. Indeed, the literature suggests that retinoic acid may regulate hair health in a dose-dependent manner, whereby the optimal and ‘healthy’ level of retinoic acid sits somewhere between low and high.^[6]VanBuren, C. A., & Everts, H. B. (2022). Vitamin A in skin and hair: an update. Nutrients, 14(14), 2952. Available at: https://doi.org/10.3390/nu14142952

This leads to a somewhat paradoxical situation, as retinoic acid is necessary for hair growth, but it can also cause hair loss when present in high concentrations. Thus, the therapeutic use of retinoic acid in treating hair loss is a challenging prospect.^[7]Sadgrove, N. J., & Simmonds, M. S. (2021). Topical and nutricosmetic products for healthy hair and dermal antiaging using “dual‐acting”(2 for 1) plant‐based peptides, hormones, and … Continue reading

That said, several studies have shown that the application of tretinoin, a type of retinoic acid, has beneficial effects in treating hair loss. One study was conducted on 56 patients with AGA, who were treated with either a placebo, 0.5% minoxidil, 0.025% tretinoin, or a combination of minoxidil and tretinoin.^[8]Bazzano, G. S., Terezakis, N., & Galen, W. (1986). Topical tretinoin for hair growth promotion. Journal of the American Academy of Dermatology, 15(4), 880-893. Available at: … Continue reading Tretinoin treatment alone was shown to stimulate some hair regrowth in more than half of the patients who received the treatment. Further positive results were observed with combination treatment.

This was also shown in a study conducted on 31 male patients with AGA. The study showed that once-daily application of tretinoin and minoxidil, in combination, was as effective at treating hair loss as twice-daily minoxidil on its own (Figure 1).^[10]Shin, H. S., Won, C. H., Lee, S. H., Kwon, O. S., Kim, K. H., & Eun, H. C. (2007). Efficacy of 5% minoxidil versus combined 5% minoxidil and 0.01% tretinoin for male pattern hair loss: a … Continue reading

What is the Evidence for Targeting CRABP2 for Hair Loss?

Collectively, the evidence does suggest that CRABP2 and retinoic acid are key factors in hair loss. Owing to this, it is feasible that genetic variation in CRABP2 could influence the efficacy of hair loss treatments.

In a study conducted on newborn babies, it was found that the rs12724719 polymorphism was linked to retinoic acid levels. Specifically, those with the AA genotype had a greater concentration of retinoic acid in the blood of their umbilical cord than those with the GA or GG genotypes. It is believed that such an increase in retinoic acid may have been caused by reduced CRABP2 expression, impairing its ability to transport retinoic acid into the nucleus of the cell.^[12]Manolescu, D. C., El-Kares, R., Lakhal-Chaieb, L., Montpetit, A., Bhat, P. V., & Goodyer, P. (2010). Newborn serum retinoic acid level is associated with variants of genes in the retinol … Continue reading

Although this study was conducted in newborn umbilical cord blood, and so is probably not representative of how the genetic variant affects adults or hair, the results are still interesting. If adults with the AA genotype also exhibit increased levels of retinoic acid, then therapeutic supplementation with retinoic acid to treat hair loss may be less effective in those individuals. Moreover, given that retinoic acid levels are already high, increasing levels further may increase the risk of those individuals experiencing retinoic acid-induced hair loss, as discussed earlier.

A separate study was conducted on over 25,000 patients with AGA, a mix of both males and females. Interestingly, their analysis revealed an association between the rs12724719 polymorphism and AGA. Unfortunately, the authors did not specifically state which of the genotypes were linked to AGA and which were not. However, this is yet another indication that genetic variation in CRABP2 and the rs12724719 polymorphism may influence hair health and treatments.^[13]Francès, M. P., Vila-Vecilla, L., Russo, V., Caetano Polonini, H., & de Souza, G. T. (2024). Utilising SNP Association Analysis as a Prospective Approach for Personalising Androgenetic Alopecia … Continue reading

What Do Your Genetic Results Mean?

Your Result	CRABP2 (rs12724719)
	Variant 1 – GG genotype	Variant 2 – GA genotype	Variant 3 – AA genotype
What it Means	Associated with normal levels of retinoic acid in the blood	Associated with normal levels of retinoic acid in the blood	Associated with elevated levels of retinoic acid in the blood
The Implication	May benefit from retinoic acid supplementation	May benefit from retinoic acid supplementation	May not benefit from retinoic acid treatment (i.e, vitamin A supplementation or retinoid topicals)

What Relevance Does CRABP2 Have for Hair Loss Treatment?

We have also created a rubric that helps to determine the relevance of a specific gene to hair loss based on the quality of the evidence in the above studies.

On a scale of 1-5, how important are these genetic results? (1 is the lowest, 5 is the highest)

This score is a rating based on evidence quality.

• Does this gene have any potential relevance for hair loss? (1 point)

Yes. CRABP2 has been found to be upregulated in patients with alopecia areata (score = 1)

• Does the totality of evidence implicate CRABP2 as a causal agent for hair loss? (1 point)

No. There is very little published literature that indicates CRABP2 causes hair loss. (score = 0)

• Does the totality of evidence implicate CRABP2 as a predictive factor for hair loss treatment responsiveness? (2 points)

No. There is no published literature that shows that CRABP2 polymorphisms affect hair loss treatments (score = 0)

• Is this quality of evidence on (3) strong enough to influence treatment recommendations? (1 point)

Since CRABP2 fails question #3, it cannot be awarded points for question #4 (score = 0)

Total Score = 1

Final Thoughts

While there is evidence that genetic variation in CRABP2 is associated with AGA and may affect retinoic acid levels, the evidence is not yet sufficient to make definitive treatment recommendations based solely on genotype. Importantly, no studies have yet explored how genetic variation in CRABP2 affects treatment with retinoic acid or any other therapeutic. Additional studies that seek to answer this question must be conducted to confirm the true predictive value of testing CRABP2 variants to personalize hair treatments.

CYP19A1 is a gene within the cytochrome P450 superfamily, a large network of genes that regulate various critical processes throughout the body. CYP19A1 encodes the protein aromatase, which is involved in the conversion of androgens, such as testosterone, into estrogens. Aromatase is believed to play a key role in regulating hair growth, and several studies have also linked aromatase activity to hair loss. A handful of studies have also investigated genetic variation in CYP19A1, suggesting that some variants may cause differential responses to hair loss treatments. This article will explore how relevant CYP19A1 is to hair treatment effectiveness and how to interpret your genetic results to make the correct treatment choice.

What Is CYP19A1?

Cytochrome P450 Family 19 Subfamily A Member 1, known as CYP19A1, is part of the cytochrome P450 superfamily. The human genome contains at least 57 genes that belong to various CYP sub-families, collectively regulating several critical roles throughout the body. CYP19A1 encodes the protein aromatase, an enzyme involved in converting androgens to estrogens, such as androgen, into estradiol. For this reason, aromatase is also known as estrogen synthase.^[1]Nebert, D. W., Wikvall, K., & Miller, W. L. (2013). Human cytochromes P450 in health and disease. Philosophical Transactions of the Royal Society B: Biological Sciences, 368(1612), 20120431. … Continue reading

Many studies have linked aromatase as a key regulatory factor in hair growth for several years. One such study was conducted on growing (anagen) phase hairs taken from female participants with and without female pattern hair loss (FPHL). Analysis of the hairs revealed that CYP19A1 expression was significantly lower in the participants with FPHL.^[2]Sánchez, P., Serrano-Falcón, C., Torres, J. M., Serrano, S., & Ortega, E. (2018). 5α-Reductase isozymes and aromatase mRNA levels in plucked hair from young women with female pattern hair … Continue reading

Similarly, another study measured the aromatase levels in the hair follicles of men and women with androgenic alopecia (AGA). The follicles were taken from different regions of the head, revealing that aromatase levels were higher in the occipital (non-balding) region than in the frontal (balding) region. This difference was identified in both males and females. Still, interestingly, it was also found that aromatase levels were six times higher in the frontal hair follicles of women than in men. This could explain the differences in male and female hair loss patterns.^[3]Sawaya, M. E., & Price, V. H. (1997). Different levels of 5α-reductase type I and II, aromatase, and androgen receptor in hair follicles of women and men with androgenetic alopecia. Journal of … Continue reading

Associations between aromatase and hair loss have been underlined by the discovery that aromatase inhibitors can lead to the thinning and loss of hair. An analysis of 851 female breast cancer survivors revealed that those who underwent aromatase inhibitor therapy were significantly more likely to report hair loss and hair thinning than those who did not. Moreover, this association was independent of factors such as chemotherapy and radiotherapy, highlighting the importance of aromatase.^[5]Gallicchio, L., Calhoun, C., & Helzlsouer, K. J. (2013). Aromatase inhibitor therapy and hair loss among breast cancer survivors. Breast cancer research and treatment, 142, 435-443. Available at: … Continue reading

Although not yet fully understood, the role of aromatase in hair loss is thought to be based on its influence on estrogen, testosterone, and dihydrotestosterone (DHT). In converting testosterone to estradiol, aromatase reduces testosterone levels and, importantly, reduces the amount of testosterone converted to DHT. High levels of DHT have been implicated in the pathogenesis of AGA. These interactions could explain the association between reduced aromatase activity and hair loss.^[6]Rossi, A., Caro, G., Magri, F., Fortuna, M. C., & Carlesimo, M. (2021). Clinical aspect, pathogenesis and therapy options of alopecia induced by hormonal therapy for breast cancer. Exploration of … Continue reading

Indeed, it has been shown that aromatase inhibition in mice led to decreased levels of estradiol (a form of estrogen) and increased levels of DHT.^[7]Iqbal, R., Jain, G. K., Siraj, F., & Vohora, D. (2018). Aromatase inhibition by letrozole attenuates kainic acid-induced seizures but not neurotoxicity in mice. Epilepsy Research, 143, 60-69. … Continue reading Similar results were reported in men, with aromatase inhibition leading to increased levels of testosterone and DHT. However, it should be noted that this study was conducted on older men who generally have lower levels of testosterone, so the results may not be representative of testosterone modulation in the wider population.^[8]Leder, B. Z., Rohrer, J. L., Rubin, S. D., Gallo, J., & Longcope, C. (2004). Effects of aromatase inhibition in elderly men with low or borderline-low serum testosterone levels. The Journal of … Continue reading

A recent study has even suggested that Minoxidil, the first FDA-approved treatment for AGA, may exert its effects via interaction with aromatase. They found that Minoxidil increases the activity of aromatase, suggesting that Minoxidil may help to treat AGA by increasing the production of estradiol and decreasing the production of DHT.^[10]Shen, Y., Zhu, Y., Zhang, L., Sun, J., Xie, B., Zhang, H., & Song, X. (2023). New target for minoxidil in the treatment of androgenetic alopecia. Drug Design, Development and Therapy, 2537-2547. … Continue reading

What Is The Evidence for Targeting CYP19A1 For Hair Loss?

Collectively, a significant amount of evidence suggests that aromatase is a key factor in hair loss. Owing to this, it is feasible that genetic variation in CYP19A1 could influence the efficacy of hair loss treatments.

In a study conducted on patients with polycystic ovary syndrome (PCOS), the rs2470152 single nucleotide polymorphism (SNP) in CYP19A1 was suggested to be associated with decreased aromatase activity. Namely, participants with PCOS and the TC genotype were found to exhibit increased levels of testosterone and a reduced ratio of estradiol to testosterone. In participants without PCOS, those with the TC genotype also exhibited a lower ratio of estradiol to testosterone.^[12]Zhang, X.L., Zhang, C.W., Xu, P., Liang, F.J., Che, Y.N., Xia, Y.J., Cao, Y.X., Wu, X.K., Wang, W.J., Yi, L. and Gao, Q. (2012). SNP rs2470152 in CYP19 is correlated to aromatase activity in Chinese … Continue reading

People with the TC genotype may benefit from treatment with estradiol or anti-androgen drugs, given the associations between low estrogen levels, high androgen levels, and hair loss. However, it should be noted that this study was conducted on participants with PCOS; the rs2470152 SNP has not been linked to AGA or other types of hair loss, meaning it may not affect their treatment.

Furthermore, as stated earlier, the relationship between estrogen androgen levels and hair loss is still not understood. Although associations between low estrogen levels and hair loss have been identified, so too have associations between high estrogen levels and hair loss. A study involving 955 females discovered that participants with the rs4646 SNP CC genotype had an increased risk of developing FPHL.^[14]Yip, L., Zaloumis, S., Irwin, D., Severi, G., Hopper, J., Giles, G., Harrap, S., Sinclair, R. and Ellis, J. (2009). Gene‐wide association study between the aromatase gene (CYP19A1) and female … Continue reading

Interestingly, the rs4646 SNP CC genotype had previously been shown to be associated with higher estrogen levels in postmenopausal females.^[15]Haiman, C.A., Dossus, L., Setiawan, V.W., Stram, D.O., Dunning, A.M., Thomas, G., Thun, M.J., Albanes, D., Altshuler, D., Ardanaz, E. and Boeing, H. (2007). Genetic variation at the CYP19A1 locus … Continue reading The suggestion that higher estrogen levels may increase the risk of developing FPHL contradicts previous literature on the subject, indicating that genetics alone are not sufficient to make treatment recommendations.

Another study investigated the effects of genetic variation on dutasteride treatment, a drug used off-label in treating hair loss. They identified a positive association between the rs700519 SNP in CYP19A1 and the efficacy of dutasteride; in other words, people with this genetic variant responded better to treatment.^[16]Rhie, A., Son, H.Y., Kwak, S.J., Lee, S., Kim, D.Y., Lew, B.L., Sim, W.Y., Seo, J.S., Kwon, O., Kim, J.I. and Jo, S.J. (2019). Genetic variations associated with response to dutasteride in the … Continue reading

Despite this positive association, some patients classified as ‘poor responders’ also had the rs700519 SNP. This indicates that having a ‘positive’ SNP in CYP19A1 does not guarantee that you will respond well to dutasteride. Rather, the study presents the likelihood that the combination of SNPs that one possesses is more important.

What Do Your Genetic Results Mean?

Your Result	CYP19A1 (rs2470152)
	Variant 1 – TT genotype	Variant 2 – CC genotype	Variant 3 – TC genotype
What it means	Not associated with a change in testosterone or estrogen levels	Not associated with a change in testosterone or estrogen levels	Associated with reduced expression of CYP19A1 and, therefore, an increase in testosterone levels/decrease in estrogen levels
The Implication	May not benefit from estradiol or anti-androgens	May not benefit from estradiol or anti-androgens	May benefit from treatment with estradiol as a replacement hormone or anti-androgen drugs
Your Result	CYP19A1 (rs700519)
	Variant 1 – CC genotype	Variant 2 – CT genotype	Variant 3 – TT genotype
What it means	May be a normal/poor responder to 5α-reductase inhibitors	May be a good responder to 5α-reductase inhibitors	May be a good responder to 5α-reductase inhibitors
The Implication	May be a good candidate for typical/higher dosages of 5α-reductase inhibitors	May be a good candidate for lower dosages of 5α-reductase inhibitors	May be a good candidate for lower dosages of 5α-reductase inhibitors

What Relevance Does CYp19A1 Have For Hair Loss Treatment?

We have also created a rubric that helps to determine the relevance of a specific gene to hair loss based on the quality of the evidence in the above studies. 

On a scale of 1-5, how important are these genetic results? (1 is the lowest, 5 is the highest)

This score is a rating based on evidence quality.

• Does this gene have any potential relevance for hair loss? (1 point)

Yes. A decrease in aromatase may lead to an increase in testosterone and, subsequently, DHT, which are linked with androgenetic alopecia. (score=1)

• Does the totality of evidence implicate CYP19A1 as a causal agent for hair loss? (1 point)

While there are some hypotheses about how SNPs in CYP19A1 may lead to hair loss, there is no published evidence showing this possible association. (score = 0)

• Does the totality of evidence implicate CYP19A1 as a predictive factor for hair loss treatment responsiveness? (2 points)

No, the data does not suggest that CYP19A1 can be used as a predictor for hair loss treatment responsiveness. (score = 0)

• Is this quality of evidence on (3) strong enough to influence treatment recommendations? (1 point)

Since CYP19A1 fails question #3, it cannot be awarded points for question #4 (score = 0)

Total Score = 1

Final Thoughts

While one small study suggests that genetic variation in CYP19A1 may influence your response to treatment with a 5α-reductase inhibitor, the evidence is not yet strong enough to make definitive treatment recommendations based solely on genotype. Furthermore, some evidence regarding CYP19A1 and its associations with hair loss conditions is contradictory. Larger and more robust studies are needed to confirm the true predictive value of genetic testing for CYP19A1 variants to personalize hair loss treatments.

COL1A1 is a gene within the collagen superfamily, a large network that comprises at least 44 genes and 28 proteins. The collagen proteins have a variety of roles, with perhaps their most crucial being to support the structure of tissues throughout the body. COL1A1 and COL1A2 produce the protein chains that combine to form type 1 collagen, the most abundant type of collagen in the body, which has also been linked to regulating hair growth. Moreover, some studies have suggested that genetic variation in COL1A1 may cause differential responses to hair loss treatment.

This article will explore how relevant COL1A1 is to hair treatment effectiveness and how to interpret your genetic results to make the correct treatment choice.

What Is COL1A1?

Collagen Type I Alpha 1 Chain, or COL1A1, is part of the collagen superfamily. There are 44 genes encoding the proteins that make up the 28 different types of collagen, with some collagen types consisting of more than one protein (α chain).^[1]Ricard-Blum, S. (2011). The collagen family. Cold Spring Harbor perspectives in biology, 3(1), a004978. Available at: https://doi.org/10.1101/cshperspect.a004978 Collagens have a variety of key roles throughout the body, foremost of which is the promotion of cell growth and supporting the structure and organization of tissues.^[2]Sun, H., Wang, Y., Wang, S., Xie, Y., Sun, K., Li, S., Cui, W. and Wang, K. (2023). The involvement of collagen family genes in tumor enlargement of gastric cancer. Scientific Reports, 13(1), 100. … Continue reading

Type 1 collagen (COL1) is the most abundant of all collagen types within the body, representing over a quarter of the total protein content in mammals. It consists of two α1 chains, produced by COL1A1, and one α2 chain, produced by Collagen Type I Alpha 2 Chain (COL1A2). The three α chains assemble into a single procollagen and undergo multiple rounds of modification, with several molecules eventually assembling into a longer collagen fibril and, finally, a type 1 collagen fiber (Figure 1).^[3]Kruger, T. E., Miller, A. H., & Wang, J. (2013). Collagen scaffolds in bone sialoprotein‐mediated bone regeneration. The Scientific World Journal, 2013(1), 812718. Available at: … Continue reading

Given its abundance within the body, it is hardly surprising that COL1 has been detected in the scalp. Specifically, the connective tissue sheath surrounding the hair follicle was found to be a major source of type 1 procollagen, expressing greater amounts than other parts of the follicle. Moreover, they showed that the expression of type 1 collagen changes throughout the hair cycle, collectively indicating that type 1 collagen may play a key role in the growth and structure of hair follicles.^[5]Oh, J.K., Kwon, O.S., Kim, M.H., Jo, S.J., Han, J.H., Kim, K.H., Eun, H.C. and Chung, J.H. (2012). Connective tissue sheath of hair follicle is a major source of dermal type I procollagen in human … Continue reading

These results support an earlier study that found that Col1 levels in mice also changed based on the stage of the hair cycle. They found that levels of Col1 were approximately two-fold higher in the dermis of the skin in the anagen (growing) phase than skin in the telogen (resting) phase. Furthermore, they found that Col1 molecules underwent more modifications during the anagen phase. This indicates that the remodeling of collagen is more active in anagen skin, which may support the growth and migration of hair follicles.^[6]Yamamoto, & Yamauchi. (1999). Characterization of dermal type I collagen of C3H mouse at different stages of the hair cycle. British Journal of Dermatology, 141(4), 667-675. Available at: … Continue reading

What is the Evidence for Targeting COL1A1 For Hair Loss?

Although only a few studies have investigated COL1 in relation to hair health, the evidence they have provided is robust and certainly suggests that COL1 may well be an important factor in regulating hair growth. Owing to this, it is feasible that genetic variation in COL1A1 could influence hair loss treatments.

Research into the rs1800012 polymorphism of Col1 revealed that people with the GT genotype had a higher ratio of COL1A1:COL1A2 gene expression and α1:α2 chains than the GG genotype. Generally existing in a 2:1 ratio, due to the structure of COL1, any increase in this ratio would lead to an imbalance between the two types of α chain.^[7]Mann, V., Hobson, E.E., Li, B., Stewart, T.L., Grant, S.F., Robins, S.P., Aspden, R.M. and Ralston, S.H. (2001). A COL1A1 Sp1 binding site polymorphism predisposes to osteoporotic fracture by … Continue reading

This could lead to instability of the collagen molecules, indicating that it may be useful for people who exhibit this genotype to take supplements that might support collagen synthesis, such as silicon, cysteine, or collagen.

Furthermore, in an analysis of over 26,000 people, it was found that the rs1800012 polymorphism is associated with AGA. Unfortunately, the study does not state which specific genotypes are associated with AGA, but this does suggest that the rs1800012 polymorphism and COL1A1 play a role in hair loss. ^[9]Francès, M. P., Vila-Vecilla, L., Russo, V., Caetano Polonini, H., & de Souza, G. T. (2024). Utilising SNP Association Analysis as a Prospective Approach for Personalising Androgenetic Alopecia … Continue reading

It has also been found that COL1A1 expression is upregulated in people with AGA. However, the upregulation of COL1A1 was not linked to the rs1800012 polymorphism. Moreover, the same study also showed that the expression of COL1A2 is upregulated in people with AGA, which may cause the α1:α2 chain ratio to remain unchanged.^[10]Michel, L., Reygagne, P., Benech, P., Jean‐Louis, F., Scalvino, S., Ly Ka So, S., Hamidou, Z., Bianovici, S., Pouch, J., Ducos, B. and Bonnet, M., 2017. Study of gene expression alteration in male … Continue reading

Together, although these studies do suggest that COL1A1 and the rs1800012 polymorphism may be involved in hair loss, they also indicate that the underlying mechanism is not understood. Further studies are required to understand how the expression of COL1A1 and COL1A2, the rs1800012 polymorphism, and the α1:α2 chain ratio link to hair loss and AGA.

What Do Your Genetic Results Mean?

Your Result	COL1A1 (rs1800012)
	Variant 1 – GG genotype	Variant 2 – GT genotype
What it means	Normal α1 chain synthesis	Increased α1 chain synthesis
The Implication	May not benefit from supplementation that supports collagen formation	May benefit from supplementation that supports collagen formation, such as adenosine or cysteine

What Relevance Does COL1A1 Have for Hair Loss Treatment?

We have also created a rubric that helps to determine the relevance of a specific gene to hair loss based on the quality of the evidence in the above studies.

On a scale of 1-5, how important are these genetic results? (1 is the lowest, 5 is the highest)

This score is a rating based on evidence quality.

• Does this gene have any potential relevance for hair loss? (1 point)

Yes, COL1A1 and COL1A2 have been found to be overexpressed in patients with androgenetic alopecia (score=1)

• Does the totality of evidence implicate COL1A1 as a causal agent for hair loss? (1 point)

No, there is no published evidence to suggest that COL1A1 polymorphisms can cause hair loss (score = 0)

• Does the totality of evidence implicate COL1A1 as a predictive factor for hair loss treatment responsiveness? (2 points)

No, there is no data to suggest that COL1A1 polymorphisms can be used as a predictor for hair loss treatment responsiveness (score = 0)

• Is this quality of evidence on (3) strong enough to influence treatment recommendations? (1 point)

Since COL1A1 fails question #3, it cannot be awarded points for question #4 (score = 0)

Total Score = 1

Final Thoughts

While there is some evidence to suggest that genetic variation in COL1A1 may influence your response to treatment with collagen supplements, there is not yet strong enough evidence to make definitive treatment recommendations based solely on genotype. Furthermore, it is evident that the association(s) between COL1A1, rs1800012, and hair loss are not yet understood. Larger and more robust studies are needed to confirm the true predictive value of genetic testing for COL1A1 variants to personalize hair loss treatments.

Angiotensin-converting enzyme facilitates the conversion of angiotensin I to angiotensin II. This, alongside the degradation of bradykinin, leads to vasoconstriction (the tightening of blood vessels). As hair follicles require an adequate supply of blood for growth and health, it is thought that increased ACE activity can contribute to hair loss. In this article, we will explore the evidence (or lack thereof) linking ACE to hair loss and whether targeting changes in medication to single nucleotide polymorphisms (SNPs) in the ACE gene can improve hair growth outcomes.

What is ACE?

Angiotensin-converting enzyme (ACE) is an enzyme that catalyzes the conversion of angiotensin I to angiotensin II (as well as degrading bradykinin), which are important factors in the regulation of blood pressure.^[1]Wong, M. K. S. (2016). Angiotensin Converting Enzymes. In Handbook of Hormones. pp. 263-e29D-4. Elsevier. Available at: https://doi.org/10.1016/B978-0-12-801028-0.00254-3 Angiotensin II is known as a vasoconstrictor – i.e., it constricts blood vessels, reducing blood flow. Some research has implicated ACE activity and its gene polymorphisms have been associated with increased susceptibility to androgenic alopecia (AGA), and to the pathogenesis of alopecia areata.^[2]Ibrahim, M.A., Ezzat, I.S., Mostafa, G.Y., Fathy, A.H.N., Eman, F., Samir, E.S.O. (2021). Association between angiotensin-converting enzyme gene insertion-deletion polymorphism and androgenetic … Continue reading,^[3]Fahim, S., Montazer, F., Tohidinik, H.R., Naraghi, Z.S., Abedini, R., Nasimi, M., Ghandi, N. (2019). Serum and tissue angiotensin-converting enzyme in patients with alopecia areata. Indian Journal … Continue reading

Can Targeting ACE Help Hair Loss?

Insertion or deletion changes in the ACE gene can affect its activity, with the insertion typically leading to reduced ACE activity and the deletion leading to increased ACE activity (and, therefore, increased vasoconstriction).
Characterizing single nucleotide polymorphisms (SNPs) in the ACE gene may help predict responses to treatments that can affect blood flow, such as minoxidil or caffeine.

Evidence Supporting Targeting ACE  Polymorphisms For Hair Loss

ACE plays a key role in regulating blood pressure, converting angiotensin I to angiotensin II, and constricting blood vessels. Research in androgenic alopecia (AGA) indicates that the insertion/deletion gene mutation in the ACE gene is associated with increased susceptibility to AGA. The researchers found that the deletion/deletion and insertion/deletion genotypes were more frequently found in AGA patients, suggesting a genetic predisposition linked to ACE activity.^[4]Mustafa, A.I., Ibrahim, S.E., Gohary, Y.M., Al-Husseini, N.F., Fawzy, E., El-Shimi, O.S. (2022). Association between angiotensin-converting enzyme gene insertion-deletion polymorphism and … Continue reading

Another study also found a link between ACE activity and the pathogenesis of alopecia areata (AA). In a study conducted on 49 people (25 with alopecia areata and 24 controls), researchers found no significant difference in serum ace activity but a significantly lower ace activity in the tissue. Furthermore, among patients with alopecia areata, higher ACE activity was associated with more severe disease and non-patchy alopecia areata.^[6]Fahim, S., Montazer, F., Tohidinik, H.R., Naraghi, Z.S., Abedini, R., Nasimi, M., Ghandi, N. (2019). Serum and tissue angiotensin-converting enzyme in patients with alopecia areata. Indian Journal … Continue reading

While there appears to be a link between ACE and AGA, and AA, there are no studies linking ACE activity or gene polymorphisms to treatment efficacy in hair loss. Some genetic testing companies, however, believe that if you have the deletion polymorphisms of rs4343 or rs4341, you may want to try treatments that improve blood flow to the scalp.

The single nucleotide polymorphisms (SNP) rs4343 and rs4341 are variations in the ACE gene, part of the renin-angiotensin system (RAS). The RAS plays an important role in blood pressure regulation and fluid balance.
The G allele of rs4343 corresponds to the deletion allele of the ACE gene, which has been associated with higher ACE activity.^[7]Tsantes, A.E., Kopterides, P., Bonovas, S., Bagos, P., Antonakos, G., Nikolopoulos, G.K., Gialeraki, A., Kapsimali, V., Kyriakou, E., Kokori, S., Dima, K., Armagandis, A., Tsangaris, I. (2013).Effect … Continue reading

Higher ACE levels lead to increased production of angiotensin II, which leads to vasoconstriction. Some think that hair loss treatments (such as caffeine or minoxidil), which are thought to work at least in part through vasodilation, might improve hair loss outcomes.

Evidence Against Targeting ACE Polymorphisms For Hair Loss

While it is thought that minoxidil works by increasing blood flow to the hair follicle, no literature suggests that people with particular ACE polymorphisms will respond differently to hair treatments that may improve blood flow, such as caffeine or minoxidil.

Your Genetic Results

Your Result	ACE (rs4343)
	Variant 1 – AA genotype (insertion/insertion)	Variant 2 – AG genotype (insertion/deletion)	Variant 3 – GG genotype (deletion/deletion)
What it means	May have no abnormal vasoconstriction due to normal ACE activity	May have moderately elevated vasoconstriction in the scalp due to a slight increase in ACE activity	May have elevated vasoconstriction in the scalp due to increased ACE activity
The Implication	May not benefit from treatments that target blood flow, such as minoxidil or caffeine	May want to try managing hair loss with treatments targeting blood flow, such as minoxidil or caffeine	May want to try managing hair loss with treatments targeting blood flow, such as minoxidil or caffeine
Your Result	ACE (rs4341)
	Variant 1 – CC genotype	Variant 2 – CG genotype	Variant 3 – GG genotype
What it means	May have no abnormal vasoconstriction due to normal ACE activity	May have moderately elevated vasoconstriction in the scalp due to a slight increase in ACE activity	May have elevated vasoconstriction in the scalp due to increased ACE activity
The Implication	May not benefit from treatments that target blood flow, such as minoxidil or caffeine	May want to try managing hair loss with treatments targeting blood flow, such as minoxidil or caffeine	May want to try managing hair loss with treatments targeting blood flow, such as minoxidil or caffeine

Treatment Relevance

We have also created a rubric that helps to determine the relevance of a specific gene to hair loss based on the quality of the evidence in the above studies.

On a scale of 1-5, how important are these genetic results? (1 is the lowest, 5 is the highest)

This score is a rating based on evidence quality.

• Does this gene have any potential relevance for hair loss? (1 point)

There is no evidence to support its significance in hair loss treatments (score=0)

• Does the totality of evidence implicate ACE as a causal agent for hair loss? (1 point)

No, there is no published evidence to suggest that ACE polymorphisms can cause hair loss (score = 0)

• Does the totality of evidence implicate ACE as a predictive factor for hair loss treatment responsiveness? (2 points)

No, there is no data to suggest that ACE polymorphisms can be used as a predictor for hair loss treatment responsiveness (score = 0)

• Is this quality of evidence on (3) strong enough to influence treatment recommendations? (1 point)

Since ACE fails question #3, it cannot be awarded points for question #4 (score = 0)

Total Score = 0

Final Thoughts

ACE is essential in maintaining circulation throughout the body and may play some role in the pathogenesis of AGA. However, no evidence supports targeting it as a predictor of treatment efficacy.

The NR3C1 gene encodes the glucocorticoid receptor, which is essential for mediating the effects of glucocorticoids in various physiological processes, including metabolism, immune response, and stress regulation. This receptor plays a critical role in the body’s ability to respond to glucocorticoid medications, making it a key factor in conditions treated with these drugs.

This article will delve into the role of NR3C1 in glucocorticoid responsiveness and the evidence (or lack thereof) supporting it as a target for hair loss.

What is NR3C1?

The NR3C1 gene codes for the glucocorticoid receptor (GR). This receptor is involved in various physiological processes, including metabolism regulation, immune response, and stress response.^[1]GeneCards. (no date). NR3C1 Gene – Nuclear Receptor Subfamily 3 Group C Member 1. GeneCards. Available at: … Continue reading. Glucocorticoids are a type of steroid used to treat inflammatory and autoimmune diseases as well as cancer.^[2]Strehl, C., Ehlers, L., Gaber, T., Butthereit, F. (2019). Glucocorticoids – All Rounders Tackling the Versatile Players of the Immune System. Frontiers in Immunology. 10 GR is necessary for … Continue reading 

What is the Evidence for Targeting NR3C1 for Hair Loss?

GR is essential for glucocorticoids to exert their effects. There are two isoforms of GR encoded by the NR3C1 gene: GRα and GRβ. GRα is the classic GR protein, mediating the action of glucocorticoids. 

GRβ contains a unique extra sequence that gives it several distinct properties: GRβ does not bind to activators of glucocorticoids, resides in the nucleus of the cells, and is by itself inactive. However, when expressed alongside GRα, GRβ inhibits the activity of GRα.^[3]Oakley, R.H., Cidlowski, J.A. (2013). The Biology of the Glucocorticoid Receptor: New Signaling Mechanisms in Health and Disease. Journal of Allergy and Clinical Immunology. 132(5). 1033-1044. … Continue reading 

Simply put, if GRꞵ binds to GRɑ, it stops it from working correctly. This can lead to reduced sensitivity or even resistance to glucocorticoids in tissues expressing GRβ at higher levels.

In one retrospective study involving 122 children with acute lymphoblastic leukemia, researchers found that a specific genetic variant, called rs6198, can affect how the body responds to glucocorticoid medications.^[4]Gasic, V., Zukic, B., Stankovic, B., Janic, D., Dokmanovic, L., Lazic, J., Krstovski, N., Dolzan, V., Jazbec, J., Pavlovic, S., Kotur, N. (2018). Pharmacogenomic Markers of Glucocorticoid Response in … Continue reading 

When a patient had the GG allele variant, it was found that it stabilized the messenger RNA (mRNA), which is the molecule that carries instructions from DNA to make proteins. This stabilization leads to more of a particular form of the glucocorticoid receptor, which doesn’t bind to the medication as well as the normal form. 

Because this receptor doesn’t bind well, the treatment may not work as effectively, which could explain why some patients developed resistance to glucocorticoid therapy. This means their bodies don’t respond as well to the treatment, making it less effective in controlling their condition.

What is the Evidence Against Targeting NR3C1 for Hair Loss?

Some companies that test your genotype to suggest treatments use this gene as a marker for glucocorticoid sensitivity. While the evidence suggests that variations of NR3C1 can negatively affect glucocorticoid receptor activity, there is no published evidence showing that there are subsequent effects on corticosteroid treatment responsiveness in hair.

What Do Your Genetic Results Mean?

Your Result	NR3C1 (rs6198)
	Variant 1 GG genotype	Variant 2 GA genotype	Variant 3 AA genotype
What it means	Increased expression of the GRβ isoform	Moderate expression of the GRβ isoform	Normal expression of GR and less expression of the GRβ isoform
The Implication	You may want to avoid glucocorticoid treatment	You may respond less well to glucocorticoid treatment	You may respond normally to glucocorticoid treatment

What Relevance Does NR3C1 Have For Hair Loss Treatment?

We have also created a rubric that helps to determine the relevance of a specific gene to hair loss based on the quality of the evidence in the above studies.

On a scale of 1-5, how important are these genetic results? (1 is the lowest, 5 is the highest)

This score is a rating based on evidence quality.

• Does this gene have any potential relevance for hair loss? (1 point)

Yes. Due to the inhibitory effect of GRβ on GR activity, this variation may affect response to glucocorticoid treatment in cases of hair loss. (score = 1)

• Does the totality of evidence implicate GRα as a causal agent for hair loss? (1 point)

No, there doesn’t appear to be any evidence implicating GRα in hair loss.

• Does the totality of evidence implicate GRα as a predictive factor for hair loss treatment responsiveness? (2 points)

While there is evidence to suggest that the activity of GRα may be affected by this variation, there is no published evidence to indicate that it can predict responsiveness to glucocorticoid treatment. (score = 0)

• Is this quality of evidence on (3) strong enough to influence treatment recommendations? (1 point)

No, the quality of evidence is not strong enough to influence treatment recommendations due to the lack of published evidence. (score = 0)

Total Score = 1

Final Thoughts

The NR3C1 gene, which encodes the glucocorticoid receptor, plays a crucial role in various physiological processes, including stress response and inflammation. While variations in the gene, particularly the rs6198 variant, have been linked to altered glucocorticoid sensitivity, the evidence for its role in hair loss remains inconclusive. Therefore, more research is needed to determine its relevance and utility in predicting or treating hair loss.