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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.

Seborrheic dermatitis is a common, chronic inflammatory skin condition that primarily affects areas with a high concentration of sebaceous (oil-producing) glands, such as the scalp, face, upper back, and chest. It is characterized by red, itchy patches of skin covered with greasy, yellowish scales or flakes.

In the scalp, seborrheic dermatitis is also called dandruff. It can vary widely in symptoms and severity, and a number of treatment options are marketed to treat and prevent dandruff. But what is actually happening to your scalp and hair follicles when seborrheic dermatitis hits, and what are the best treatment combinations? Let’s find out below.

Key Takeaways

• What is it? Seborrheic dermatitis is a chronic inflammatory skin condition that affects areas rich in oil glands, like the scalp, causing red, itchy patches with greasy, yellowish flakes.
• What are the symptoms? Symptoms include visible flakes (dandruff), itchiness, redness, and, in severe cases, crusting and hair shafts around hair follicles.
• What Is The Prevalence of Seborrheic Dermatitis in Patients with AGA? One study found that out of 250 patients with AGA, 56.9% also had seborrheic dermatitis.
• What are the most common treatments? Antifungal topicals are most often used (e.g., ketoconazole and selenium sulfide), topical corticosteroids, and newer options like roflumilast foam to reduce inflammation and yeast overgrowth.
• How else can I improve it? Lifestyle changes, like reducing stress, eating a balanced diet, and avoiding known triggers like harsh hair products or cold weather, can help manage symptoms.
• Final thoughts. Managing seborrheic dermatitis often involves trial and error with different therapies, but with the right combination, most people can achieve long-term symptom control.

What Are the General Features of Seborrheic Dermatitis?

• Appearance: The condition manifests as oily patches with yellow or white scales, which may appear darker or lighter in people of color and redder in those with white skin.
• Common locations: Scalp, face, sides of the nose, eyebrows, ears, eyelids, chest, armpits, and groin area.
• Symptoms: Itching, flaking skin, and sometimes a ring-shaped (annular) rash called petaloid seborrheic dermatitis.

Why Does Seborrheic Dermatitis of the Scalp Happen?

Seborrheic dermatitis of the scalp (also called dandruff) occurs due to a combination of factors, one of which is sebum production. The condition primarily affects areas with a high concentration of sebaceous glands, including the scalp.^[1]Ro, B.I., Dawson, T.L. (2005). The role of sebaceous gland activity and scalp microfloral metabolism in the etiology of seborrheic dermatitis and dandruff. The Journal of Investigative Dermatology. … Continue reading Excess sebum creates a favorable environment for the growth of Malassezia yeasts, which are naturally present on the skin. 

Another factor is the overgrowth of Malassezia yeasts. Malassezia species, particularly M.globosa and M.restricta, are commonly found on the scalps of individuals with seborrheic dermatitis. These yeasts are normally harmless but can trigger an inflammatory response when they overgrow.^[2]Wikramanayake, T.C., Borda, L.J., Miteva, M., Paus, R. (2019). Seborrheic dermatitis-looking beyond Malassezia. Experimental Dermatology. 28(9). 991-1001. Available at: … Continue reading 

Malessezia lipase breaks down human sebum, releasing free fatty acids (FFAs) and other metabolites. These FFAs can penetrate the stratum corneum (the outer layer of the skin), altering skin barrier permeability and leading to inflammation and abnormal keratinization, which are key features of seborrheic dermatitis.^[3]Dawson Jr. (2007). Malassezia globosa and restricta: breakthrough understanding of the etiology and treatment of dandruff and seborrheic dermatitis through whole-genome analysis. Journal of … Continue reading

Genetic predisposition is also a contributing factor in the pathogenesis of seborrheic dermatitis.^[4]Karakadze, M.A., Hirt, P.A., Wikramanayake, T.C. (2018). The genetic basis of seborrheic dermatitis: a review. Journal of the European Academy of Dermatology and Venereology. 32(4). 529-536. … Continue reading Several gene mutations and protein deficiencies have been associated with the condition or similar phenotypes. The affected genes are involved in the immune response (e.g., ACT1, C5, IKBG/NEMO) and epidermal maturation (differentiation) (e.g., ZNF750, MPZL3).

Other genetic mutations that can affect the complement system, which is part of the immune response, have been associated with an increased risk of seborrheic dermatitis. This dysfunction can lead to an inability to effectively restrict the growth of Malassezia.^[5]Adalsteinsson, J.A., Kaushik, S., Muzumdar, S., Guttman-Yassky, E., Ungar, J. (2020). An update on the microbiology, immunology, and genetics of seborrheic dermatitis. Experimental Dermatology. … Continue reading 

In addition to these, a number of other elements can influence the development of seborrheic dermatitis and its exacerbation. These include immune system abnormalities, such as reduced numbers of helper T cells.^[6]Bergbrant, I.M., Johansson, S., Robbins, D., Scheynius, A., Faergemann, J., Soderstrom, T. (1991). An immunological study in patients with seborrheic dermatitis. Clinical and Experimental … Continue reading Hormonal changes can also aggravate the condition.^[7]Kashiri, A., Maghsoudloo, N. (2024). Exploring the Impact of Vitamin D and Zinc Deficiencies on Sebhorreic Dermatitis: A Comparative Study. Health Science Reports. 7(12). E70283. Available at: … Continue reading Furthermore, cold weather can worsen symptoms, and stress can trigger or exacerbate flare-ups.

What Are the Symptoms of Seborrheic Dermatitis in the Scalp?

We can split the symptoms of seborrheic dermatitis into three levels: cosmetic, symptom, and microscopic levels.

Cosmetic Level

At the cosmetic level, the most noticeable sign of seborrheic dermatitis on the scalp is the presence of visible flakes on the scalp, which may fall onto clothing. These flakes can range from mild dandruff to more severe scaling.^[8]Schwartz, R.A., Janusz, C.A., Janniger, C.K. (2006). Seborrheic dermatitis: an overview. American Family Physician. 74(1). 125-130. Available at: PMID:16848386 The scales often appear greasy and may have a yellow-brown color. In more pronounced cases, you might see white or yellowish scales covering patches of skin on the scalp. These scales can sometimes form crusts, especially in areas where the scalp meets the hairline or behind the ears. The flakiness can be accompanied by noticeable redness (erythema) and bumps or pustules.^[9]Saunte, D.M., Gaitanis, G., Hay, R.J. (2020). Malassezia-Associated Skin Diseases, the Use of Diagnostics and Treatment. Frontiers in Cellular and Infection Microbiology. 10. 112. Available at: … Continue reading 

Symptom Level

On a symptom level, itchiness (pruritis) is often the most bothersome aspect of seborrheic dermatitis.^[11]Zhang, F., Li, Y., Ren, W., Li, S. (2023). Establishment of clinical evaluation criteria for scalp seborrheic dermatitis. Journal of Cosmetic Dermatology. 22(11). 3042-3046. Available at: … Continue reading The itching can range from mild to intense and may lead to scratching, which can further irritate the scalp and, in some cases, cause hair loss.^[12]National Eczema Associations. (no date). Seborrheic Dermatitis. Available at: https://nationaleczema.org/eczema/types-of-eczema/seborrheic-dermatitis/ (Accessed: February 2025)  Some people may experience soreness or tenderness in the affected areas, especially if the condition is severe and there has been excessive scratching. In the most severe cases, the rash may weep or ooze, leading to the formation of crusts.

Microscopic Level

At the microscopic level, several distinctive factors characterize seborrheic dermatitis. One of the most notable is the presence of dandruff casts, which are accumulations of dead skin cells and sebum around hair shafts.^[13]Franca, K., Villa, R.T., Silva, I.R., de Carvalho, C.A., Bedin, V. (2011). Hair Casts or Pseudonits. International Journal of Trichology. 3(2). 121-122. Available at: … Continue reading These casts are typically white, firm, and tubular in shape and can range from 2 to 7 mm in length.

Several characteristic vascular patterns can be observed in seborrheic dermatitis under dermoscopy, a noninvasive imaging tool.^[15]Kim, G.W., Jung, H.J., Ko, H-C., Kim, M.B., Lee, W-J., Lee, S-J., Kim, D-W., Kim, B-S. (2011). Dermoscopy can be useful in differentiating scalp psoriasis from seborrheic dermatitis. British Journal … Continue reading These include arborizing red lines (ARL), which appear as branching blood vessels, and twisted red loops (TRL), which are coiled blood vessels specific to seborrheic dermatitis. Comma vessels (CV) and short-curved blood vessels are also indicative of this condition. These vascular patterns help differentiate seborrheic dermatitis from other skin conditions.

In addition to these, other microscopic characteristics include spongiosis (buildup of fluid between skin cells in the epidermis) in acute seborrheic dermatitis lesions, psoriasiform hyperplasia (thickening of the epidermis), swelling, and infiltration of antibodies.^[17]Park, J-H., Park, Y.J., Kim, S.K., Kwon, J.E., Kang, Y.H., Lee, E-S., Choi, J.H., Kim, Y.C. (2016). Histopathological Differential Diagnosis of Psoriasis and Seborrheic Dermatitis of the Scalp. … Continue reading In some cases, the opening of a hair follicle can become blocked with excess skin cells (follicular plugging), and maturation (differentiation) of keratinocytes can become impaired, leading to cells in the stratum corneum retaining nuclei (shoulder parakeratosis). This contributes to the scaling characteristic of seborrheic dermatitis.

As epidermal cells differentiate through the skin layers, they usually lose their nuclei and become filled with keratin. By the time they reach the stratum corneum, they are typically flat, dead cells without nuclei, forming a protective barrier.^[18]Alberts, B., Johnson, A., Lewis J. Molecular Biology of the Cell. 4th edition. New York: Garland Science; 2002. Epidermis and Its Renewal by Stem Cells. Available from: … Continue reading

How Common is Seborrheic Dermatitis?

A comprehensive meta-analysis published in JAMA Dermatology in 2024 found that the global pooled prevalence (meaning all body locations, including the scalp) of seborrheic dermatitis is 4.38%, which is higher than previous large-scale global estimates.^[20]Polaskey, M.T., Chang, C.H., Daftary, K., Fakhraie, S., Miller, C.H., Chovatiya, R. (2024). The Global Prevalence of Seborrheic Dermatitis: A Systematic Review and Meta-Analysis. JAMA Dermatology. … Continue reading In the US, the prevalence is 5.86%, which appears to be middle-of-the-road compared to places like South Africa, which has a prevalence of 8.82%, and India, with a prevalence of 2.62%.

Is Seborrheic Dermatitis More Common in People with Pattern Hair Loss?

Recent studies have shown a significant association between seborrheic dermatitis and androgenic alopecia (AGA). 

• One five-year study from 2006 to 2010 found that seborrheic dermatitis was the most commonly associated disease in both men and women with AGA.^[22]Jang, W.S., Son, I.P., Yeo, K.I., Park, K.Y., Li, K., Kim, B.J., Seo, S.J., Kim, M.N., Hong, C.K. (2013). The Annual Changes of Clinical Manifestation of Androgenetic Alopecia Clinic in Korean Males … Continue reading 
• A retrospective study published in 2024 found that out of 250 patients with AGA, 56.9% also had seborrheic dermatitis.^[23]Faghihkhorasani, A., Sadeghzadeh, A., Goodarzi, A., Rohaninasab, M. (2024). The Relationship between Seborrheic Dermatitis and Androgenetic Alopecia in Patients Referred to a Skin Clinic in Tehran, … Continue reading 
  • A significant correlation was found between the pattern of AGA in men and the severity of seborrheic dermatitis.
  • A significant relationship was also observed between dandruff symptoms and AGA patterns. 
  • In men, the highest severity of seborrheic dermatitis (grade 3) was related to the Hamilton Norwood type 2 pattern of hair loss (triangular hair loss on both sides of the frontoparietal line).
  • In women, the highest severity of seborrheic dermatitis (grade 2) was observed in the Ludwig type 2 hair loss pattern (thinning of hair about 1-3 cm behind the hairline).

What Is the Biology Behind This Correlation?

Although there is no established explanation, there are several factors that could explain the correlation between seborrheic dermatitis and AGA.

1. Androgen sensitivity: Both conditions are influenced by androgens, particularly dihydrotestosterone (DHT). The enzyme 5-alpha reductase (5-AR) converts testosterone to DHT, which affects both sebum production and hair follicle miniaturization.^[24]Kim, B.J., Kim, J.Y., Eun, H.C., Kwon, O.S., Kim, M.N. (2006). Androgenetic alopecia in adolescents: A report of 43 cases. The Journal of Dermatology. 33(10). 696-699. Available at: … Continue reading
2. Sebum production: Increased sebum production is characteristic of both conditions. In AGA, there are increased levels of 5-AR in the follicles of the temporal, frontal, and crown regions.^[25]Kure, K., Isago, T., Hirayama, T. (2015). Changes in the sebaceous gland in patients with male pattern hair loss (androgenic alopecia). Journal of Cosmetic Dermatology. 14(3). 178-184. Available at: … Continue reading This excess sebum creates an environment conducive to the overgrowth of Malassezia yeast.
3. Microbiome imbalance (dysbiosis): Patients with AGA exhibit scalp dysbiosis, with an increased abundance of Cutibacterium and a decreased abundance of Corynebacterium.^[26]Suzuki, K., Inoue, M., Cho, O., Mizutani, R., Shimizu, Y., Nagahama, T., Sugita, T. (2021). Scalp microbiome and sebum composition in Japanese male individuals with and without androgenetic alopecia. … Continue reading This altered microbiome may contribute to inflammation and exacerbate both conditions.
4. Malassezia yeast: Malassezia restricta is more abundant on the scalps of patients with AGA and is also implicated in seborrheic dermatitis, which may exacerbate the condition.

While there is no established causality for AGA and seborrheic dermatitis, these underlying factors mean that seborrheic dermatitis and AGA can exacerbate one another.

So, what can you do to treat seborrheic dermatitis on the scalp?

What Are the Typical Treatments for Seborrheic Dermatitis on the Scalp?

Seborrheic dermatitis of the scalp can be managed through various treatment options. It can be attacked in multiple ways, such as through the use of antifungals, anti-inflammatories, treatments that suppress sebum, corticosteroids, and topical keratolytic agents.

FDA-Approved Options

Among the FDA-approved treatments, Roflumilast foam 0.3% (Zoryve) is a recent addition, approved on December 2023, for treating seborrheic dermatitis in individuals aged 9 and older.^[28]Arcutis Biotherapeutics. (no date). FDA Approves Arcutis’ ZORYVE (roflumilast) Topical Foam, 0.3% for the Treatment of Seborrheic Dermatitis in Individuals Aged 9 Years and Older. Available at: … Continue reading This treatment is a topical non-steroidal phosphodiesterase 4 (PDE4) inhibitor. PDE4 plays a key role in the inflammatory response, so by inhibiting this, it reduces inflammation and associated symptoms like redness, scaling, and itching.^[29]Zirwas, M.J., Draelos, Z.D., DuBois, J., Kircik, L.H., Moore, A.Y., Gold, L.S., Alonso-Llamazares, J., Bukhalo, M., Bruce, S., Eads, K., Green, L.J., Guenthner, S., Ferris, L.K., Forman, S.B., … Continue reading 

Ketoconazole is FDA-approved for patients 12 years of age and older with healthy immune systems. It acts through multiple mechanisms to treat seborrheic dermatitis in the scalp. It inhibits the production of lanosterol, a precursor for ergosterol biosynthesis, which is essential for fungal membrane integrity.^[30]Tynes, B.E., Johnson, C.D., Vaish, M.H., Abbott, B., Vucenovic, J., Varrassi, G., Potharaju, P., Torres, Y.L., Lee, Z., Ahmadzadeh, S., Shekoohi, S., Kaye, A.D. (2024). Ketoconazole Shampoo for … Continue reading 

This halts the growth of Malassezia yeasts associated with seborrheic dermatitis. It also strongly binds to the cytochrome p450 mono-oxygenase complex, hindering the fungal biosynthesis of triglycerides and phospholipids and shifting sebum secretion in the stratum corneum, addressing the hypersecretion of sebum characteristic of the condition.^[31]Borgers, M., Degreed, H. (2007). The Role of Ketoconazole in Seborrheic Dermatitis. Therapeutics for the Clinician. 80. 359-363. Available at: … Continue reading

Ketoconazole also exhibits anti-inflammatory properties and antiproliferative effects and may favor biotin-producing bacteria, which could improve the skin microbiome.^[32]Goularte-Silva, V., Paulino, C.L. (2021). Ketoconazole beyond antifungal activity: Bioinformatics-based hypothesis on lipid metabolism in dandruff and seborrheic dermatitis. Experimental Dermatology. … Continue reading 

Ciclopirox shampoo is approved for people 16 years of age and older with seborrheic dermatitis on the scalp. It works differently from other common antifungals. It acts like a magnet for certain metals, especially iron and aluminum, which are important for fungal survival.^[34]LOPROX® (cicloporox) Shampoo 1%. (2006). MEDICIS Pharmaceutical Corp. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021159s009lbl.pdf (Accessed: February 2025) By grabbing these metals, ciclopirox prevents important fungal enzymes from working properly, leading to peroxide build-up and cellular damage.

Other Treatments

Some over-the-counter treatments are used to treat seborrheic dermatitis. These are often antifungal shampoos containing ingredients such as:

• Selenium sulfide: A treatment with antifungal, cytostatic, keratolytic, anti-inflammatory, and sebum regulatory properties. In clinical studies, 2.5% selenium sulfide shampoo improved dandruff scores by 78.3% after 4 weeks.^[35]Godse, G., Godse, K. (2024). Safety, Efficacy and Attributes of 2.5% Selenium Sulfide Shampoo in the Treatment of Dandruff: A Single-Center Study. Cureus. 16(3). E57148. Available at: … Continue reading 
• Coal tar: This helps to reduce inflammation and redness associated with seborrheic dermatitis and has antifungal and keratolytic properties. It also slows the rate of skin cell production, helping to minimize the buildup of scales and dry patches. However, it has been found to be less effective than ciclopirox and ketoconazole.^[36]Davies, D.B., Boorman, G.C., Shuttleworth, D. (1999). Comparative efficacy of shampoos containing coal tar (4.0% w/w; Tarmed), coal tar (4.0% w/w) plus ciclopirox olamine (1.0% w/w Tarmed AF), and … Continue reading 
• Salicylic acid: Salicylic acid helps to slough off dead skin cells and remove flakes from the scalp, which can be beneficial for those with seborrheic dermatitis. It also has keratolytic, oil-controlling, anti-inflammatory, and anti-fungal effects.^[37]Ge, L., Liu, Z., Xu, S., Li, C., Jin, M., Luo, Y., Kong, Y., Meng, J., Zheng, G., Gao, J., Wang, P., Bai, W., Na, H., Zhou, X., Jin, Z., Pi, L. (2025). A Cohort Clinical Study on the Efficacy of … Continue reading 
• Zinc pyrithione: Zinc pyrithione increases cellular copper levels, which damages iron-sulfur clusters of proteins essential for fungal metabolism. This, alongside its antifungal, antibacterial, anti-inflammatory, and sebum-regulatory properties, contributes to its effectiveness in treating seborrheic dermatitis. One study found that a shampoo containing 1% zinc pyrithione was effective in controlling dandruff when used on half of the scalp.^[38]Marks, R., Pearse, A.D., Walker, A.P. (1985). The effects of a shampoo containing zinc pyrithione on the control of dandruff. British Journal of Dermatology. 112(4). 415-422. Available at: … Continue reading 
• Piroctone olamine: A number of clinical studies have used piroctone olamine alongside other treatments to improve seborrheic dermatitis, with one study showing a clinical improvement of 80%.^[39]Ge, L., Liu, Z., Xu, S., Li, C., Jin, M., Luo, Y., Kong, Y., Meng, J., Zheng, G., Gao, J., Wang, P., Bai, W., Na, H., Zhou, X., Jin, Z., Pi, L. (2025). A Cohort Clinical Study on the Efficacy of … Continue reading 

Prescription medications such as topical corticosteroids and calcineurin inhibitors may also be used off-label.^[40]Paula Ludmann. (2024). Seborrheic Dermatitis: Diagnosis and Treatment. American Academy of Dermatology Association. Available at: … Continue reading UVB light therapy can be used for widespread rash and scales. Other treatments include fluconazole 2%, naftifine hydrochloride 1% gel, and climbazole.^[41]Dall’Oglio, F., Nasca, M.R., Gerbino, C., Micali, G. (2022). An Overview of the Diagnosis and Management of Seborrheic Dermatitis. Clinical, Cosmetic and Investigational Dermatology. 6(15). … Continue reading 

Lifestyle and Dietary Modifications

In addition to these medical treatments, dietary and lifestyle changes can help manage seborrheic dermatitis. 

One case-control study involving 257 participants found associations between white bread, carbonated drinks, and daily fast food, with a higher percentage of seborrheic dermatitis compared to those without the condition.^[42]Alshaebi, M., Zahed, L., Osalyan, M., Sulaimani, S., Albahlool, A., Abduljabbar, M.H., Hariri, J. (2023). Association Between Diet and Seborrheic Dermatitis: A Case-Control Study. Cureus. 15(11). … Continue reading The same study reported that increased fruit consumption was associated with a lower risk of seborrheic dermatitis. Furthermore, adherence to a Western diet has been associated with a higher risk of seborrheic dermatitis in female patients.^[43]Woolhiser, E., Keime, N., Patel, A., Weber, I., Adelman, M., Dellavalle, R.P. (2024). Nutrition, Obesity, and Seborrheic Dermatitis: Systematic Review. JMIR Dermatology. E50143. Available at: … Continue reading 

It is recommended to increase the intake of high-fiber carbohydrates and lean protein foods, as well as foods rich in monounsaturated and omega-3 fatty acids.

Should You Avoid Certain Hair Loss Treatments if You Have Seborrheic Dermatitis?

In our experience, those with seborrheic dermatitis may have problems if they use:

• Topicals containing retinoic acid
• Microneedling
• Scalp massaging
• PRP
• Mesotherapy

These may actually lead to more inflammation, so we would recommend avoiding these until you get your seborrheic dermatitis under control.

Which Treatments Are Best Used for Which Disease Severity?

Management of seborrheic dermatitis of the scalp often involves rotating or combining a number of therapies to target multiple aspects of the disease.

Mild to Moderate Severity

For patients with mild to moderate seborrheic dermatitis, first-line treatments typically include over-the-counter antifungals combined with topical anti-inflammatory agents. 

This can include:

• Anti-dandruff shampoos containing 2.5% selenium sulfide or 1-2% zinc pyrithione, used daily or every other day.^[44]Paula Ludmann. (2024). Seborrheic Dermatitis: Diagnosis and Treatment. American Academy of Dermatology Association. Available at: … Continue reading 
• Ketoconazole shampoo (1-2%) applied for 5-10 minutes before rinsing, used daily initially, then twice weekly for maintenance. 
• Topical corticosteroids, like hydrocortisone 1% cream, applied once or twice daily until inflammation clears, then as needed.
• One clinical trial found that the usage of traditional Chinese medicine can also show significant efficacy in treating mild to moderate seborrheic dermatitis without relapse, especially for those with moderate severity.^[45]Zhang, F., Li, Y-H., Ren, W., Li, S-R., Chen, Y-C. (2023). Clinical efficacy of a combination treatment of traditional Chinese medicine for scalp seborrheic dermatitis. Journal of Cosmetic … Continue reading 

Moderate to Severe

For more severe or persistent cases, treatment may include:

• Oral antifungal medications like itraconazole (200 mg/day for one week, followed by a maintenance dose).^[46]Goldenberg, G. (2013). Optimizing Treatment Approaches in Seborrheic Dermatitis. Journal of Clinical and Aesthetic Dermatology. 6(2). 44-49. Available at: PMID: 23441240 
• UVB light therapy, with 3 treatment sessions per week for up to 8 weeks. However, some studies have shown relapse within 1 month.^[47]Jaalouk, D., Pulumati, A., Algarin, Y.A., Kircik, L., Issa, N.T. (2024). Dermatologic Procedures for the Treatment of Seborrheic Dermatitis. Journal of Drugs in Dermatology. 23(10). 819-824. … Continue reading 
• Combination therapy of clobetasol propionate shampoo (0.05%) and ketoconazole (2%) twice weekly has been shown to provide greater efficacy than ketoconazole alone, with a more sustained effect in the treatment of moderate to severe seborrheic dermatitis.^[48]Ortonne, J-P., Nikkels, A.F., Reich, K., Oliver, R.M.P., Lee., J.H., Kerrouche, N., Sidou, F., Faergemann, J. (2011). Efficacious and safe management of moderate to severe scalp seborrheic dermatitis … Continue reading 
• A recent study conducted on 20 patients with moderate to severe seborrheic dermatitis combined salicylic acid, piroctone olamine, zinc PCA gel, and a cleansing lotion, finding that the combination significantly reduced dandruff, itchiness, redness, and greasiness scores over 4 weeks. Patients with moderate and those with severe seborrheic dermatitis improved to mild with an overall clinical improvement of 80%.^[49]Ge, L., Liu, Z., Xu, S., Li, C., Jin, M., Luo, Y., Kong, Y., Meng, J., Zheng, G., Gao, J., Wang, P., Bai, W., Na, H., Zhou, X., Jin, Z., Pi, L. (2025). A Cohort Clinical Study on the Efficacy of … Continue reading 

Shampoo Rotations

For people dealing with treatment-resistant seborrheic dermatitis, rotating shampoos may be beneficial. Some of our members have consulted with Dr. Donovan, a leading hair specialist and have experienced success with his approach.

The key to this method is using different active ingredients rather than specific brands. If certain additives in a product don’t suit you, you can opt for alternative with the same active ingredients and concentrations.

• 2% Ketoconazole
• Selenium sulfide
• Coal tar
• Zinc pyrithione

Finding the most effective treatment often requires a trial-and-error approach.^[50]University of Utah Health. (no date). Seborrheic Dermatitis. Available at: https://healthcare.utah.edu/dermatology/conditions/seborrheic-dermatitis (Accessed: February 2025) You might be advised by your doctor to start with a basic regimen and assess response after 2-4 weeks. If no improvement has been observed, then your doctor might increase the strength, change the treatment, or add complementary therapies. Once control has been achieved, you can gradually reduce treatment frequency to find the minimal effective maintenance regimen.

When Should You See a Healthcare Professional?

While mild seborrheic dermatitis can be effectively treated with over-the-counter or off-the-shelf treatments, you should see a healthcare professional if any of the following occur:

1. Symptoms persist or worsen: If your symptoms don’t improve after using over-the-counter dandruff shampoos for at least two weeks or if they suddenly get worse.^[51]Cleveland Clinic. (2020). Seborrheic Dermatitis. Cleveland Clinic. Available at: https://my.clevelandclinic.org/health/diseases/14403-seborrheic-dermatitis (Accessed: February 2025)
2. Severity interferes with daily life: When the condition causes anxiety, embarrassment, or disrupts your daily routine.
3. Signs of severe disease appear: If you develop yellow-red scaling papules along the hairline, behind the ears, on the eyebrows, or in the others of the face and body.^[52]National Eczema Association. (2025). Seborrheic Dermatitis. National Eczema Association. Available at: … Continue reading
4. Suspected complications: If you notice signs of skin infection.
5. Difficulty in diagnosis: If you are unsure if it is seborrheic dermatitis or another skin condition.
6. Presence of other skin conditions: If you suspect you might have seborrheic dermatitis along with other skin conditions, this can complicate diagnosis and treatment.

Final Thoughts

Seborrheic dermatitis of the scalp is a complex condition influenced by factors such as sebum production, Malassezia overgrowth, genetics, and immune responses. While a range of treatments, from over-the-counter antifungal shampoos to prescription medications like roflumilast and ketoconazole, are available, their effectiveness varies depending on the individual and the severity of the condition. Finding the right approach often involves trial and error, with combination therapies frequently offering the best results. Ultimately, consistent management, lifestyle adjustments, and working closely with healthcare providers are key to keeping symptoms under control. If one treatment isn’t working, don’t get discouraged; there are plenty of options to explore.

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. 

The PGFTR gene encodes the prostaglandin F2 alpha (PGF2α) receptor, a critical component in various physiological processes. PGFTR is particularly significant in the context of hair loss due to its involvement in hair follicle and melanocyte growth. Studies have shown that PGF2α and its analogs, such as latanoprost, can stimulate hair growth and treat eyelash and eyebrow growth issues like hypotrichosis.

This article will explore the importance of the PGFTR gene in hair loss, its potential as a therapeutic target, and how understanding your genetic makeup could inform more effective treatment decisions.

What is PGTFR?

The PGTFR gene encodes the prostaglandin F2 alpha (PGF2α) receptor, which plays an important role in various physiological processes, including reproductive physiology, inflammation, and cancer progression.^[1]Ricciotti, E., FitzGerald, G.A. (2011). Prostaglandins and Inflammation. Arteriosclerosis, Thrombosis, and Vascular Biology. 31(5). 986-1000. Available at: https://doi.org/10.1161/ATVBAHA.110.207449.

Studies have suggested that PGF2α and its analogs, like latanoprost, stimulate the hair follicle and melanocyte growth in mice.^[2]Sasaki, S., Hozumi, Y., Kondo, S. (2005). Influence of Prostaglandin F2 alpha and its Analogues on Hair Regrowth and Follicular Melanogenesis in a Murine Model. Experimental Dermatology. 14(5). … Continue reading

Can Targeting PGTFR Help Hair Loss?

Latanoprost is an analog of PGF2α and is commonly used as a treatment for an eye condition called glaucoma. Some clinical studies looking at the responsiveness of patients to latanoprost have uncovered multiple gene variants that can either increase or decrease responsiveness to the drug.

One study involved 100 volunteers who applied latanoprost eye drops to one eye once daily for seven days. Intraocular pressure was measured at the beginning and end of the study.^[3]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

Two key single nucleotide polymorphisms (SNPs) in the PGTFR gene were found to be associated with response to latanoprost treatment. SNPs are single-base pair gene changes. These single changes can have varied effects, from dramatic impacts on gene function or protein structure to no noticeable effect at all.

The results showed that within the rs3753380 SNP, the CC genotype was associated with a greater response to latanoprost, and the CT and TT genotypes were significantly associated with a lesser response. The rs3766355 SNP also found specific genotypes associated with lower latanoprost response. The study also found that the C allele of rs3766355 and the T allele of rs3753380 were associated with lower transcriptional activity of PGTFR, which suggests that these alleles may lead to reduced expression of PGTFR, resulting in a decreased response to latanoprost.

This has been repeated in several studies that have evaluated various SNPs associated with the PGTFR gene for latanoprost’s effectiveness in treating glaucoma.
No studies have demonstrated whether SNPs in the PGTFR gene affect treatment responsiveness in relation to hair loss; however, PGF2ɑ analogs have been shown to improve hair growth outcomes.

One randomized, double-blind, placebo-controlled study involving 16 men with androgenic alopecia was conducted over 24 weeks. It found that daily application of latanoprost 0.1% significantly increased hair density compared to baseline and placebo-treated areas of the scalp, suggesting that latanoprost can stimulate hair growth.^[5]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

Furthermore, a recent paper explored the genetic factors associated with androgenic alopecia.^[7]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 The study analyzed data from 26,607 patients, examining 26 SNPs and their correlation with AGA diagnosis. Eight SNPs were found to show a statistically significant association with AGA, one of which was PTGFR (rs10782665). However, there was no correlation found between these SNPs and the severity of AGA.

While the studies above suggest an effect of PGTFR gene variants on latanoprost effectiveness, no studies have determined this in the context of hair growth.

What Do Your Genetic Results Mean?

Your Result	PGTFR (rs10782665)
	Variant 1 – TT genotype	Variant 2 – GT genotype	Variant 3 – GG genotype
What it means	Associated with a higher percentage of responders to latanoprost treatment	Associated with a moderately higher percentage of responders to latanoprost treatment	Associated with a higher percentage of non-responders to latanoprost treatment
The Implication	May benefit from latanoprost treatment	May benefit from latanoprost treatment	May benefit from treatments other than latanoprost
Your Result	PGTFR (rs6686438)
	Variant 1 – TT genotype	Variant 2 – GT genotype	Variant 3 – GG genotype
What it means	Associated with a higher percentage of responders to latanoprost treatment	Associated with a higher percentage of responders to latanoprost treatments	Associated with a higher percentage of non-responders to latanoprost treatment
The Implication	May benefit from latanoprost treatment	May benefit from latanoprost treatment	May benefit from treatments other than latanoprost
Your Result	PGTFR (rs1328441)
	Variant 1 – AA genotype	Variant 2 – AG genotype	Variant 3 – GG genotype
What it means	Associated with a higher percentage of responders to latanoprost treatment	Not associated with either responsiveness or non-responsiveness to latanoprost	Associated with a higher percentage of non-responders to latanoprost treatment
The Implication	May benefit from latanoprost treatment	May benefit from latanoprost treatment	May benefit from treatments other than latanoprost

Treatment Relevance

We have 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. Initial studies have indicated that latanoprost could work as a treatment for hair loss. (score = 1)

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

• There is no literature to suggest that PGTFR is a causal agent for hair loss. (score = 0)

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

• Although some studies have shown that PGTFR gene variations can affect latanoprost treatment responsiveness for patients with glaucoma, this has not also been shown to be true in the hair follicle. (score = 0)

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

• It may be worth trying or avoiding latanoprost treatments if you have certain gene variations. (score = 1)

Total Score = 2

Final Thoughts

While some small studies suggest that genetic variation in the PGTFR gene may influence responsiveness to treatments like latanoprost, the evidence is not yet strong enough to make definitive treatment recommendations based solely on genotype. Larger and more robust studies are needed to confirm the true predictive value of genetic testing for PGTFR in personalizing hair loss treatments. Understanding the genetic underpinnings of hair loss and treatment responsiveness could eventually lead to more effective and tailored therapeutic approaches, but current data is insufficient to guide clinical decisions at this time.