Articles

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.

The PTGES2 gene encodes the enzyme prostaglandin E synthase 2, which plays a crucial role in converting prostaglandin H2 to prostaglandin E2 (PGE2). This enzyme is significant in various physiological processes, including inflammation and hair growth. Notably, studies have identified higher levels of PGE2 in non-balding scalps compared to balding ones, highlighting the potential relevance of PTGES2 in hair loss. 

This article will delve into the role of PTGES2 in hair loss, its potential as a therapeutic target, and how genetic insights can guide more personalized and effective treatments.

What is PTGES2?

Prostaglandin E synthase 2 (PTGES2) gene encodes the enzyme prostaglandin E synthase 2. This enzyme catalyzes the conversion of prostaglandin H2 (PGH2) to prostaglandin E2 (PGE2). It is a key enzyme in the prostaglandin synthesis pathway and plays a crucial role in various physiological processes, including inflammation and hair growth.

The PTGES2 gene codes for the prostaglandin E synthase enzyme, which is a key element in the synthesis of PGE2. Studies on human scalp samples have found PGE2 to be more abundant in non-balding scalps compared to balding scalps.^[1]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

Can Targeting PTGES2 Help Hair Loss?

There is some evidence to suggest that PTGES2 might be worth targeting:

Elevated PGE2 levels in haired scalp

Multiple studies have consistently shown that PGE2 levels are diminished in balding scalp areas compared to haired areas. For instance, measurements in patients with AGA have shown that PGE2 and PGF2ɑ were significantly lower in bald areas, while PGD2 and prostacyclin were elevated.^[2]Chovarda, E., Sotiriou, E., Lazaridoi, E., Vakirlis, E., Ioannides, D. (2021). The Role of Prostaglandins in Androgenetic Alopecia. International Journal of Dermatology. 60. 730-735. Available at: … Continue reading

PTGES2 Expression in Androgenic Alopecia

A study on 16 Hispanic males with androgenic alopecia (AGA) found that PTGES2 expression was significantly increased in the balding scalp compared to 16 control participants. This overexpression of PTGES2 in early male pattern hair loss is hypothesized to be the body’s attempt to counteract hair loss.^[4]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

Furthermore, a recent study delved into the genetic factors associated with AGA. The researchers analyzed genetic data from 26,607 patients, focusing on 26 SNPS and their correlation with a diagnosis of AGA. Eight SNPs were found to show a statistically significant association with AGA, one of which was PTGES2 (rs13283456).^[6]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 However, it should be noted that no correlation was found between the SNP and AGA severity.

Moreover, the study does not mention the samples from which the genetic information was gained. Genetic analyses of human scalp hair follicles have found unique gene expression profiles not found in other tissues.^[7]Wu, S., Yu, Y., Liu, C., Zhang, X., Zhu, P., Peng, Y., Yan, X., Li, Y., Hua, P., Li, Q., Wang, S., Zhang, L. (2022). Single-cell transcriptomics reveals lineage trajectory of human scalp hair … Continue reading So, PTGES2 gene expression may not have the same association in tissue taken from the scalp.

Therefore, while general genetic studies do provide insights, they should be approached with caution when extrapolating these findings to hair growth processes.
Some believe that this SNP could affect responsiveness to minoxidil when targeting a gene for treatment efficacy. One study conducted on human dermal papilla cells found that minoxidil increased PGE2 production.^[8]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

So, if you have the gene variant leading to lower activity of PGE2 synthase, minoxidil may be more beneficial.

What Do Your Genetic Results Mean?

Your Result	PTGES2 (rs13283456)
	Variant 1 – CC genotype	Variant 2 – TT genotype	Variant 3 – CT genotype
What it means	Normal enzymatic activity of PGE2 synthase	Normal enzymatic activity of PGE2 synthase	Lower enzymatic activity of PGE2 synthase
The Implication	Will not affect the efficacy of minoxidil	Will not affect the efficacy of minoxidil	May be more beneficial to use minoxidil as a treatment for hair loss

What Relevance Does PTGES2 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. Studies have found that PGE2 levels are elevated in scalps of patients with a normal amount of hair compared to those with hair loss. (score = 1)

• Does the totality of evidence implicate PTGES2 as a causal agent for hair loss? (1 point)

Whilst this may be a causal agent for hair loss, there doesn’t appear to be literature to support this yet. Furthermore, there have been no studies to determine if a lack of PGE2 leads to the development of hair loss disorders.  (0 = score)

• Does the totality of evidence implicate PTGES2 as a predictive factor for hair loss treatment responsiveness? (2 points)

No, the studies show that the gene variant that leads to reduced PTGES2 activity does not have any predictive value in determining patient response to hair loss treatment. (0 = score)

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

Since PTGES2 fails question #3, it cannot be awarded points for question #4 (score = 0)

Total Score = 1

Final Thoughts

The PTGES2 gene has shown potential in hair loss treatment. However, current evidence is not sufficient to make definitive treatment recommendations based on PTGES2 genotypes. Research indicates that PGE2 levels are higher in non-balding scalps, and PTGES2 expression is increased in balding areas. Yet, there is still no conclusive proof that PTGES2 is a causal factor in hair loss. Moreover, the genetic variant rs13283456 associated with PTGES2 does not appear to predict treatment responsiveness effectively. Further research is necessary to better understand the role of PTGES2 in hair growth and to determine its potential as a target for hair loss treatments.

SRD5A1 and SRD5A2 are both part of the SRD5A gene family, encoding type I and type II 5α-reductase, respectively. With regard to hair loss, 5α-reductase is a type of enzyme that catalyzes the conversion of testosterone into dihydrotestosterone (DHT). DHT is a driving factor in androgenic alopecia (AGA) and, as a result, 5α-reductase inhibitors are a primary treatment for AGA. A collection of studies have investigated genetic variation in SRD5A1 and SRD5A2, with the results suggesting that some variants may cause differential responses to treatment with 5α-reductase inhibitors. This article will explore how relevant SRD5A1 and SRD5A2 are to hair treatment effectiveness and how to interpret your genetic results to make the correct treatment choice.

What Are the SR5DA Genes?

The Steroid 5α-Reductase (SRD5A) gene family is thought to be composed of up to five genes, the most prominent being SRD5A1, SRD5A2, and SRD5A3. Despite the name, only SRD5A1 and SRD5A2 exhibit strong 5α-reductase activity, meaning that they are highly efficient at converting testosterone to DHT.^[1]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 

Both SRD5A1 and SRD5A2 are expressed throughout the body, but it is their expression in the scalp that is important for hair growth outcomes. Type I 5α-reductase (produced by SRD5A1) is only strongly expressed in the sebaceous glands, the part of the hair follicle that produces sebum and keeps the skin moisturized. In contrast, type II 5α-reductase (produced by SRD5A2) is primarily expressed in the infundibulum (upper portion), inner root sheath, and outer root sheath of the hair follicle, indicating that type I and type II 5α-reductase have distinct localization within the skin and hair follicle.^[2]Bayne, Flanagan, Einstein, Ayala, Chang, Azzolina, Whiting, Mumford and Thiboutot. (1999). Immunohistochemical localization of types 1 and 2 5α‐reductase in human scalp. British Journal of … Continue reading

Although they do have other roles, the primary function of these enzymes is to convert testosterone into dihydrotestosterone (DHT). One of four androgens (steroid hormones), DHT is known to be a driving factor of androgenic alopecia (AGA) and is implicated in the miniaturization of hair follicles.^[3]Marchetti, P.M. and Barth, J.H. (2013). Clinical biochemistry of dihydrotestosterone. Annals of Clinical Biochemistry, 50(2), 95-107. Available at:  https://doi.org/10.1258/acb.2012.012159

Due to the aforementioned role of DHT, 5α-reductase is a key target when it comes to the treatment of AGA. Thus, one of the main classes of AGA and hair loss treatments is 5α-reductase inhibitors. These inhibitors work by targeting the 5α-reductase enzymes, reducing their levels in order to disrupt the conversion of testosterone to DHT. Finasteride is the only FDA-approved 5α-reductase inhibitor for the treatment of AGA, which inhibits type II 5α-reductase. Dutasteride, a dual-inhibitor of type I and type II 5α-reductase, is only FDA-approved for the treatment of an enlarged prostate but is also prescribed off-label for AGA.^[4]Gupta, A.K., Bamimore, M.A., Wang, T. and Talukder, M. (2024). The impact of monotherapies for male androgenetic alopecia: A network meta‐analysis study. Journal of Cosmetic Dermatology. Available … Continue reading 

Other 5α-reductase inhibitors exist, including naturally occurring substances such as saw palmetto and some green tea catechins, but they have varying levels of evidence quality.

What is The Evidence For Targeting SR5DA for Hair Loss?

So, SRD5A1 and SRD5A2 are closely linked to 5α-reductase activity, DHT production, and, therefore, AGA. Owing to this, it is feasible that genetic variation in either SRD5A1 or SRD5A2 could influence the efficacy of 5α-reductase inhibitors in the treatment of hair loss.

In one study, the genotypes of 42 males with AGA were investigated. They had been using dutasteride for 6 months in a clinical trial, which had produced variable results. For the purposes of this study, patients were put into the poor responder (control) group or the good responder (cases) group, based on their increase in hair count during the original study. In their investigation, they identified a number of genetic variants that were statistically significantly associated with the strength of the response to the treatment (Figure 1).^[5]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

Three of these were single nucleotide polymorphisms (SNPs) within the SRD5A1 gene – rs3822430, rs8192186, and rs3736316. Each of these SNPs was positively associated with the response to dutasteride; in other words, patients with these genetic variants responded better to dutasteride treatment.

Despite the positive associations, some of the patients who possessed these SNPs were still considered to be poor responders. This suggests that having a ‘positive’ SNP in SRD5A1 does not provide a definitive indication that you will respond well to dutasteride. Rather, the study’s results suggest that the combination of SNPs you possess and how they interact with each other is more important.

Interestingly, SRD5A2 was not associated with the response to dutasteride in the same study and no other studies have investigated the effects of SRD5A2 variants on the efficacy of dutasteride or finasteride treatment for hair loss, but that does not mean there are no effects.

Genetic variation in the SRD5A gene family appears to influence the efficacy of dutasteride treatment, so the question then turns to why this might happen.

In a study conducted on 57 males with type II diabetes, an association was found between the SRD5A1 HinfI SNP and the DHT/testosterone ratio, which is used as an indicator of 5α-reductase enzyme activity.^[7]Ellis, J.A., Panagiotopoulos, S., Akdeniz, A., Jerums, G. and Harrap, S.B. (2005). Androgenic correlates of genetic variation in the gene encoding 5α-reductase type 1. Journal of Human Genetics, … Continue reading

HinfI is an enzyme that binds to a specific series of bases (called a restriction site) and cuts the DNA. Any changes to that sequence of bases will prevent HinfI from cutting the DNA, so it can be used to identify SNPs within known restriction sites. Individuals who lacked the SRD5A1 HinfI restriction site had a higher ratio of DHT/testosterone ratio than those with other genotypes, indicating increased activity of 5α-reductase.

In patients with increased levels of DHT, due to genetic variation, treatment with 5α-reductase inhibitors may look different. Higher concentrations of 5α-reductase inhibitors may be necessary, and it might take longer to see results, but the treatment may also have a more noticeable effect on hair loss as DHT levels can be reduced more than normal.

A different study was conducted on 104 patients with metastatic prostate cancer, investigating SNPs in SRD5A1 and SRD5A2. The authors discovered that patients with the GG genotype in SRD5A2 rs523349 exhibited increased 5α-reductase enzyme activity than those with the GC or CC genotype. #

The patients did not have their DHT levels measured, however, it is possible that increased 5α-reductase enzyme activity would lead to increased levels of DHT, which might make patients with the GG genotype a better candidate for treatment with a 5α-reductase inhibitor.^[9]Shiota, M., Fujimoto, N., Yokomizo, A., Takeuchi, A., Itsumi, M., Inokuchi, J., Tatsugami, K., Uchiumi, T. and Naito, S. (2015). SRD5A gene polymorphism in Japanese men predicts prognosis of … Continue reading

These findings were supported by another study, which investigated several genetic variants of the SRD5A2 gene in healthy men. The authors found that, although the expression levels of the type II 5α-reductase enzyme were similar throughout, some of the variants produced type II 5α-reductase with very different properties to the normal (wild-type) enzyme.^[10]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

Importantly, the activity of the enzyme (the speed at which it catalyzes reactions) was lower than normal in some variants and higher in others suggesting that DHT production may be lower in people with some SRD5A2 variants and higher in people with others. In contrast to those with higher levels, patients with lower DHT levels than normal may require a reduced dose of 5α-reductase inhibitor, and it is possible that treatment will be less efficient as DHT levels are already low. Or, other treatments that don’t primarily target DHT might be more appropriate. 

To investigate this further, the authors produced lab-grown animal cells which contained each of the genetic variants. They then tested finasteride and dutasteride on all of the cells and measured 5α-reductase activity, to determine how efficiently the 5α-reductase inhibitors worked on each variant. They found that finasteride and dutasteride could be more, less, or equally effective as normal, depending on the variant(s).

Moreover, finasteride could be more effective than normal against a variant, while dutasteride was less effective than normal, and vice versa. This suggests that genetic variation could significantly affect the outcomes of treatment with finasteride or dutasteride.

Collectively, the results of these studies suggest that genetic variation in the SRD5A family of genes should be considered when designing treatment regimens for hair loss. However, the data is not without its limitations.

For the most part, studies conducted on SRD5A (including the ones here) have only included male participants. As males and females display differences in DHT expression, it would not be surprising if there were also differences in SRD5A gene expression and 5α-reductase inhibitor activity.

Furthermore, these studies were only conducted on a small number of participants. This reduces the power of a study, as you may not have an accurate representation of the wider population, and it can lead to results being misleading. Repeating the study on a much larger scale would produce more conclusive results. Also, some of the studies were not conducted on patients with AGA or hair loss-related conditions, so the findings are not directly relevant to hair loss treatment.

The final study, which investigated 5α-reductase inhibitor activity on each variant, was performed in vitro. In other words, it was performed on cells that had been genetically modified to express each variant. Furthermore, these cells were not even human cells found in the scalp or hair follicle, but rather animal cells.

Although models such as this can be very useful, the results they produce are not definitive, as the model (cells, in this case) is not a true representation of human anatomy. 

Despite these limitations, there is sufficient evidence to suggest that genetic variation in SRD5A1 or SRD5A2 may influence your response to treatment with a 5α-reductase inhibitor. Below are some of the variants which may be relevant to hair loss and treatment.

What Do Your Genetic Results Mean?

Your Result	SRD5A1 (rs248793)
	Variant 1 – GG genotype	Variant 2 – CC genotype	Variant 3 – GC genotype
What it means	At a lower risk of presenting with higher DHT/T ratio	At a slightly higher risk of presenting with an increased DHT/T ratio	At a higher risk of presenting with a significant increase in DHT/T ratio
The Implication	You might not be a good candidate for 5α-reductase inhibitors	May be a good candidate for normal/increased concentrations of 5α-reductase inhibitors	May be a good candidate for increased concentrations of 5α-reductase inhibitors
Your Result	SRD5A1 (rs3822430)
	Variant 1 – AA genotype	Variant 2 – AG genotype	Variant 3 – GG 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
Your Result	SRD5A1 (rs8192186)
	Variant 1 – AA genotype	Variant 2 – AG genotype	Variant 3 – GG genotype
What it means	May be a good responder to 5α-reductase inhibitors	May be a good responder to 5α-reductase inhibitors	May be a normal/poor responder to 5α-reductase inhibitors
The Implication	May be a good candidate for lower dosages of 5α-reductase inhibitors	May be a good candidate for lower dosages of 5α-reductase inhibitors	May be a good candidate for typical/higher dosages of 5α-reductase inhibitors
Your Result	SRD5A2 (rs523349)
	Variant 1 – GG genotype	Variant 2 – GC genotype	Variant 3 – CC genotype
What it means	Associated with increased 5α-reductase activity	Significantly lower 5α-reductase activity	Significantly lower 5α-reductase activity
The Implication	May be a good candidate for 5α-reductase inhibitors	May not be a good candidate for 5α-reductase inhibitors	May not be a good candidate for 5α-reductase inhibitors

What Relevance Dose SR5DA 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. Increased DHT is associated with hair follicle miniaturization and the onset of androgenic alopecia, and these genes encode enzymes that synthesize DHT (score=1)

• Does the totality of evidence implicate SRD5A1 or SRD5A2 as causal agents for hair loss? (1 point)

Yes, as mentioned above, an increase in DHT is associated with androgenic alopecia, and these genes create an enzyme that synthesizes DHT (score = 1)

• Does the totality of evidence implicate SRD5A1/SRD5A2 as predictive factors for hair loss treatment responsiveness? (2 points)

Yes, there is evidence to suggest that SRD5A1 may be a predictive factor for hair loss treatment responsiveness, however, some of the patients with the SNP’s for treatment responsiveness still performed poorly, indicating that there are a number of factors involved in responsiveness to treatments. (score = 1)

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

No. (score = 0)

Total Score = 3

Final Thoughts

While some small studies suggest that genetic variation in SRD5A1 and SRD5A2 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. Larger and more robust studies are needed to confirm the true predictive value of genetic testing for SRD5A1 and SRD5A2 for personalizing hair loss treatments.

SULT1A1 is a gene that encodes for sulfotransferase, an enzyme that catalyzes various reactions throughout the body. Regarding hair loss, sulfotransferase is crucial for activating minoxidil, which requires sulfonation to exert its effects.

Some studies suggest that measuring sulfotransferase levels may be possible to predict whether minoxidil will be effective. Others have claimed that the expression of a specific variant of the SULT1A1 gene can indicate whether the drug is likely to work.

This article will explore how relevant SULT1A1 is to hair treatment effectiveness and how to interpret your genetic results to make the correct treatment choice.

What is SULT1A1?

The SULT1A1 gene codes for an enzyme called sulfotransferase 1A1 (SULTS). The SULT family of enzymes catalyzes the transfer of a sulfonate (SO3-) group from the universal donor  3’-phosphoadenosine 5’-phosphosulfate (PAPS) to an acceptor molecule. This reaction is known as sulfation or sulfurylation.^[1]Negishi, M., Pederson, L.G., Petrochenko, E., Shevtsov, S., Gorokhov, A., Kakuta, Y., Pederson, L.C. (2001). Structure and function of sulfotransferases. Archives of biochemistry and biophysics. … Continue reading

These reactions play a crucial role in the metabolism and detoxification of various compounds, including hormones, neurotransmitters, and drugs (including minoxidil which we will get to), increasing their water solubility and facilitating their elimination.^[2]Gamage, N., Barnett, A., Hempel, N., Duggleby, R.G., Windmill, K.F., Martin, J.L., McManus, M.E. (2006). Human Sulfotransferases and Their Role in Chemical Metabolism. Toxicological Sciences. 90(1). … Continue reading 

The SULT1 family in humans consists of at least nine members, including SULT1A1, SULT1A2, SULT1A3, SULT1A4, SULT1B1, SULT1C2, SULT1C3, SULT1C4, and SULT1E1. Genetic variations in SULT1A1 can influence enzyme activity and have been associated with differences in drug response, toxicity, and disease susceptibility.^[3]National Library of Medicine. (2024). SULT1A1 sulfotransferase family 1A member 1 [Homo sapiens (human)]. NIH. Available at: … Continue reading 

Some studies have found different variants of the SULT1A1 gene, which are associated with different activity levels. The GG variant was associated with high activity, whereas GA and AA variants were associated with low activity.^[4]Ramos, P.M., Gohad, P., McCoy, J., Wambier, C., Goren, A. (2021). Minoxidil Sulfotransferase Enzyme (SULT1A1) Genetic Variants Predicts Response to Oral Minoxidil Treatment for Female Pattern Hair … Continue reading 

So, we know what SULT1A1 is and about the enzyme it codes for. But how relevant is it to hair loss outcomes?

What is the Evidence For Targeting SULT1A1 for Hair Loss?

One crucial piece of evidence for targeting SULT1A1 for hair loss is the link between sulfotransferase and minoxidil. SULT1A1 codes for the sulfotransferase enzyme that catalyzes the conversion of minoxidil (a prodrug that needs activation to exert its effect) to minoxidil sulfate (the activated form of the drug). As such, some studies have evaluated the correlation between minoxidil efficacy and sulfotransferase activity. 

One study was conducted with 34 patients who had been treated with minoxidil alone for a minimum of 6 months.^[5]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 These patients were evaluated as “responders” or “non-responders” based on global photographic assessment. Hairs in the growing (anagen phase) were plucked from the border between bald and non-bald scalp areas and evaluated for sulfotransferase activity. Each patient’s sulfotransferase activity was measured and compared to their “responder” or “non-responder” status. The researchers found that most “responders” had a higher sulfotransferase activity, whereas most “non-responders” had a lower sulfotransferase activity.

Another study of the same group also measured sulfotransferase activity in 21 women with female pattern hair loss who had been treated with 5% minoxidil for a minimum of 6 months.^[7]Roberts, J., Desai, N., McCoy, J., Goren, A. (2014). Sulfotransferase activity in plucked hair follicles predicts response to topical minoxidil in the treatment of female androgenetic alopecia. … Continue reading Fifteen “responders” and 6 “non-responders” were identified, with only two not correctly identified after the assay. 

Why Do Some People Have Lower SULT1A1 Activity Levels Than Others?

Well, the SULT1A1*2 variant of the SULT1A is associated with low enzyme activity and thermal stability of SULT1A1.^[8]Raftogianis, R.B., Wood, T.C., Otterness, D.M., Loon, J.A.V., Weinshilboum, R.M. (1997). Phenol Sulfotransferase Pharmacogenetics in Humans: Association of Common SULT1A1 Alleles with TS PST … Continue reading Therefore, it can be reasonably inferred that those with lower sulfotransferase activity might have this gene variant and, therefore, be less responsive to minoxidil.

SULT1A1 Gene Variants & Minoxidil: Clinical Studies

There are two studies that explore different gene variants of SULT1A1 and their effect on minoxidil efficacy. 

In the first study, 17 males and 18 females with androgenic alopecia were included.^[9]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 The participants had been using topical minoxidil for at least 3 months before being assessed for response and allocated into “responder” and “non-responder” groups. The participants were then genotyped to determine what allele variant was present in the SULT1A1 gene and compared.

84% of participants who carried the G allele of the SULT1A1 gene were in the “responder” group, compared to only 16% of those with the A allele. 

Furthermore, of those carrying the GG variant, 68.8% were “responders” compared to 15.8% who were “non-responders”. Conversely, 84.2% of “non-responders” had the GA genotype compared to 31.2% of “responders”. 

Interestingly, a higher proportion of “responders” were female (25.7%), indicating a potential for women to respond better to minoxidil (possibly due to more women having the GG allele variation) – however, this would need to be confirmed in further studies.

A further study was conducted in 2020 in which 10 participants with female pattern hair loss were treated with 1 mg oral minoxidil daily for six months.^[13]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 Hairs were counted within a 2.2 cm2 area, with a minimum 13% increase in hair count considered as a “responder”. Genotyping was conducted alongside this. Participants with the GG allele variant showed a 13.3% average increase in hair count, while participants with the GA allele variant showed a 6.9% average increase.

The researchers concluded that this gene variant can predict response to oral minoxidil treatment, but we see some issues. There are clearly some are some exceptions to the rule (which you can see below).

One person with the GA allele variant showed a 21.8% increase in hair which is a larger increase than nearly all of the GG allele variants! Furthermore, three of the GG variants did not reach the minimum 13% increase in hair count to actually be labeled a “responder”.

To confirm whether the variants actually affect response rates to minoxidil treatment, larger-scale studies are needed.

Can I Get Better Results with Oral Minoxidil?

On the internet, some individuals have mentioned that if you have a variant of SULT1A1, that means you’re less likely to respond to topical minoxidil, then you should take low-dose oral minoxidil. This is because the liver has abundant sulfotransferase activity which can also convert oral minoxidil to its active form. This active form could then circulate through the bloodstream to the scalp and exert its effects that way.

But is this true?

Well, it is true that the liver has high sulfotransferase activity. This suggests that individuals with low sulfotransferase activity in their hair follicles (due to SULT1A1 gene variants) might still benefit from oral minoxidil. However, as you can see above, studies have shown mixed results regarding the efficacy of oral minoxidil in “non-responders”.

Would Switching From Topical to Oral Help?

Switching to oral minoxidil may help some who don’t respond to topical minoxidil. One study by Ramos et al. found that in their study population of female patients, oral minoxidil slightly outperformed topical minoxidil in improving hair density and reducing shedding over 24 weeks.^[15]Ramos, P.M., Sinclair, R.D., Kasprzak, M., Miot, H.A. (2020). Minoxidil 1 mg oral versus minoxidil 5% topical solution for the treatment of female-pattern hair loss: a randomized clinical … Continue reading

Another study, however, found that although topical minoxidil had a better overall effect than 1 mg oral minoxidil, there was no significant difference between the two groups, indicating that switching might actually just lead to the same response.^[16]Asilian, A., Farmani, A., Saber, M. (2023). Clinical efficacy and safety of low-dose oral minoxidil versus topical solution in the improvement of androgenetic alopecia: a randomized controlled … Continue reading

Will Switching Make a Difference?

Not necessarily. It looks like the effectiveness of oral minoxidil can still be influenced by the same genetic factors that affect topical minoxidil response. Additionally, oral minoxidil carried potential safety risks, as it is not FDA-approved for hair loss and may have systemic side effects that need to be carefully managed.

In recent years, genetic testing companies have sprung up that claim to analyze your genotype to help you choose a personalized hair loss treatment. However, concerns remain about the accuracy of their recommendations, privacy issues regarding genetic data, and the potential for overpromising results without comprehensive clinical validation.

These companies often include the SULT1A1 gene as a predictor of responsiveness to minoxidil. So, we collated all of the potential SULT1A1 gene variants that might be relevant to hair loss and recommendations, depending on your genotype.

SULT1A1 genetic variants play a significant role in predicting the effectiveness of minoxidil for hair loss treatment. While the enzyme’s activity in hair follicles can indicate responsiveness to topical minoxidil, switching to oral minoxidil may offer limited additional benefits due to similar genetic influences on enzyme activity. Enhancing sulfotransferase activity through methods like tretinoin application and microneedling has shown promise in improving treatment outcomes for non-responders.

What Do Your Genetic Results Mean?

There are a number of variants that your genetic testing results might tell you that you have. You can see the possible variants that might come up within your own gene testing and reference these tables once you get your results to find out what they mean. 

Your Result	SULT1A1-1 Variant 1	SULT1A1-1 Variant 2	SULT1A1-1 Variant 3
	rs9282861 GG genotype	rs9282861 GA genotype	rs9282861 AA genotype
What it Means	High sulfotransferase activity	Moderate sulfotransferase activity	Low sulfotransferase activity
The Implication	May respond well to topical minoxidil. Recommend treatment.	May respond normally to topical minoxidil.	May not respond well to topical minoxidil. You may want to try oral minoxidil or an alternative treatment.
Your Result	SULT1A1-2 Variant 1	SULT1A1-2 Variant 2	SULT1A1-2 Variant 3
	rs1042028 GG genotype	rs1042028 GA genotype	rs1042028 AA genotype
What it Means	High sulfotransferase activity	Moderate sulfotransferase activity	Low sulfotransferase activity and low thermal stability
The Implication	May respond well to topical minoxidil. Recommend treatment.	May respond normally to topical minoxidil.	May not respond well to topical minoxidil. You may want to try oral minoxidil or an alternative treatment.
Your Result	SULT1A1-3 Variant 1	SULT1A1-3 Variant 2	SULT1A1-3 Variant 3
	rs1042157 TT genotype	rs1042157 CT genotype	rs1042157 CC genotype
What it Means	Low sulfotransferase activity. You may want to try oral minoxidil or an alternative treatment.	Moderate sulfotransferase activity	High sulfotransferase activity
The Implication	May not respond well to topical minoxidil. You may want to try oral minoxidil or an alternative treatment.	May respond normally to topical minoxidil.	May respond well to topical minoxidil. Recommend treatment.
Your Result	SULT1A1-4 Variant 1	SULT1A1-3 Variant 2	SULT1A1-4 Variant 3
	rs6839 GG genotype	rs6839 AG genotype	rs6839 AA genotype
What it Means	Low sulfotransferase activity	Moderate sulfotransferase activity	High sulfotransferase activity
The Implication	May not respond well to topical minoxidil. You may want to try oral minoxidil or an alternative treatment.	May respond normally to topical minoxidil.	May respond well to topical minoxidil. Recommend treatment.

Table 1: Different potential allele variants of the SULT1A1 gene and the implication in terms of hair treatments.

What Relevance Does SULT1A1 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. 

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

Yes. Some studies have shown that people with variations in the SULT1A1 gene may respond differentially to minoxidil. (score = 1)

• Does the totality of evidence implicate SULT1A1 as a causal agent for hair loss? (1 point)

There is no evidence to suggest that SULT1A1 variations cause hair loss (score = 0)

• Does the totality of evidence implicate SULT1A1 as a predictive factor for hair loss treatment responsiveness? (2 points)

Yes. There are a number of studies implicating SULT1A1 as a predictive factor for minoxidil responsiveness. (score =2)

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

No. One paper was published in a journal with a low/no impact factor. The sample sizes were small, and the results where genotyping was actually conducted were variable. (score= 0)

Total Score = 3

How Can I Improve My Sulfotransferase Activity?

So, you have tried minoxidil, but the regrowth hasn’t been as impactful as you hoped, and you find out that this is because your sulfotransferase levels are low. How can you boost it? Well, studies show that combining retinoic acid or tretinoin with minoxidil can increase sulfotransferase activity.

The topical application of tretinoin increases the expression and activity of follicular sulfotransferase enzymes. One study was conducted on 20 participants (10 males and 10 females) with androgenic alopecia.^[17]Sharma, A., Goren, A., Dhurat, R., Agrawal, S., Sinclair, R., Trueb, R., Vano-Galvan, S., Chen, G., Tan, Y., Kovacevic, M., Situm, M., McCoy, J. (2019). Tretinoin enhances minoxidil response in … Continue reading

The participants’ hair follicles were analyzed using the Minoxidil Response Test and determined as “responders” or “non-responders” to minoxidil treatment. The participants then underwent 5 days of treatment with 0.1% topical tretinoin. The average sulfotransferase activity for the whole cohort did not significantly improve after the five days, however, when the cohort was separated into “responders” and “non-responders”, something interesting happened. Those predicted to be “non-responders” to topical minoxidil did show a significant increase in sulfotransferase activity, with a total of 43% of “non-responders” converted to “responders” after five days of application.

Another way to improve sulfotransferase levels and, therefore, minoxidil efficacy is by undergoing microneedling. One study by Sharma et al. investigated the effect of microneedling on follicular sulfotransferase enzymes in male subjects with androgenic alopecia.^[19]Sharma, A., Surve, R., Dhurat, R., Sinclair, R., Tan, Y., Zou, Y., Muller Ramos, R., Wambier, C., Verner, I., Kovacevic, M., Goren, A. (2020). Microneedling improves minoxidil response in … Continue reading Six male subjects underwent 3 weekly sessions of microneedling at 1.5 mm depth on a target area of the scalp. Sulfotransferase enzyme activity was analyzed in the hair follicle at the baseline and at the end of the three weeks. 66% of participants had an increase in sulfotransferase activity compared to the baseline, and 16% of subjects who were previously classified as “non-responders” to topical minoxidil were converted to “responder” status.

Final Thoughts

While some small studies suggest that testing for SULT1A1 variants might help to predict minoxidil efficacy, 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 SULT1A1 for personalizing hair loss treatments.

GPR44 is a gene that encodes the G-protein-coupled receptor 44, also known as the prostaglandin D2 receptor (DP2). This receptor plays a pivotal role in various physiological processes, including inflammation and immune responses.

GPR44 is considered significant in the context of hair loss because some believe it is involved in hair growth inhibition. 

Early studies evaluating prostaglandin activity in the hair follicle found that elevated levels of prostaglandin D2 (PGD2) have been found in the scalps of individuals with androgenic alopecia. PGD2 exerts its effects through the GPR44 receptor. 

This article will delve into the importance of the GPR44 gene in hair loss, its potential as a therapeutic target, and the significant role that understanding your genetic makeup can play in making informed treatment decisions.

What is GPR44?

The GPR44 gene (also called CRTh2) codes for the expression of a type of receptor for prostaglandins, specifically PGD2.^[1]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.) Prostaglandin D2 is a bioactive lipid compound that belongs to the family of prostaglandins, which are derived from arachidonic acid. Prostaglandins are involved in various physiological processes, including inflammation, allergic reactions, and regulation of sleep-wake cycles. PGD2 is produced by several types of cells, including mast cells, dendritic cells, and other types of immune cells.

Studies suggest that PGD2 has been found to inhibit hair growth in isolated human hair follicles and mice. Furthermore, PGD2 has been found to be elevated in the scalps of balding men diagnosed with androgenetic alopecia.^[2]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^[3]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

What is the Evidence for Targeting GPR44 for Hair Loss?

As mentioned above, PGD2 binds to its receptor, GPR44, to exert its effects. Studies on human scalp samples from the bald and haired areas of balding men found that the level of PGD2 was significantly higher in the scalps of the balding areas (Figure 1). Furthermore, PGE2, which has been linked to human hair growth, was found to be significantly lower in the bald scalp (Figure 1).^[4]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

The same study evaluated the effect of high levels of PGD2 in mouse skin, hypothesizing that it might lead to the initiation of features of androgenic alopecia. The researchers used K14-Ptgs2 transgenic mice that are genetically modified to overexpress the Ptgs2 gene (also known as COX-2) specifically in the skin. These mice are often used in prostaglandin signaling studies as these specific genetic modifications increase levels of PGD2, PGE2, and 15-dPGJ2.

The mice overexpressing this gene were found to have hair follicles that entered premature catagen with subsequent development of alopecia.^[6]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

In a series of experiments, researchers investigated the effects of prostaglandin D2 (PGD2) on hair growth using C57Bl/6 mice, a common laboratory strain. They topically applied PGD2 to the shaved backs of these mice and measured hair length 20 days after depilation.

The results showed a significant inhibition of hair growth in the treated areas. To further explore the mechanism, the team used a separate mouse model with the GPR44 gene (which encodes a PGD2 receptor) knocked out. Interestingly, these GPR44-deficient mice demonstrated resistance to hair loss when PGD2 was applied topically, indicating that PGD2’s effect on hair loss was through the GPR44 receptor.^[7]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

Clinical studies have found an association between the rs533116 and rs545659 polymorphisms of the GPR44 gene that enhances the expression of GPR44 in the lungs, resulting in an increase in asthma severity.^[9]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^[10]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 

This increase in the expression of receptors like GPR44 may increase responsiveness to PGD2, so it’s possible that these findings may also apply to people with androgenic alopecia.

What is the Evidence Against Targeting GPR44 for Hair Loss?

In 2012, a study from the University of Pennsylvania and Johns Hopkins University generated a lot of excitement about a potential new treatment avenue for hair loss. The researchers found that PGD2 was elevated in the balding scalp but not in non-balding areas of the scalp of men with hair loss. Furthermore, they found that PGD2 inhibits hair growth.^[11]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. This sparked an interest in prostaglandins as hair growth inhibitors.

Unfortunately, follow-up studies showed conflicting results – thanks to poorly controlled variables – and it is still unclear whether there is a causal relationship between prostaglandins and androgenetic alopecia.^[12]English, R., Ruiz, S. (2021). Conflicting Reports Regarding the Histopathological Features of Androgenic Alopecia: Are Biopsy Location, Hair Diameter Diversity, and Relative Hair Follicle … Continue reading

A randomized, double-blind, placebo-controlled Phase 2a trial on setipiprant, a drug designed to bind to GPR44 and block PGD2 from exerting its effect, was conducted on males aged 18-49 with androgenic alopecia. The study found that setipiprant at 1000 mg twice daily for 24 weeks did not demonstrate efficacy compared to a placebo in improving hair growth, as measured by target area hair count and participant self-assessment. While setipiprant was safe and well-tolerated, it failed to show significant improvements indicating that targeting PGD2 alone is not sufficient to treat male pattern hair loss.^[13]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

What Do Your Genetic Results Mean?

Your Result	GPR44-1 Variant 1	GPR44-2 Variant 2
	Rs545659 TT	Rs545659 AA
What it means	May be at a lower risk of having elevated levels of PGD2 in the lungs/scalp.	May be at an increased risk of having higher levels of GPR44 in the lungs/scalp.
The Implication	You might not be a good candidate for PGD2 inhibitors as a treatment for hair loss	You might be a better candidate for PGD2 inhibitors as a treatment for hair loss
Your Result	GPR44-1 Variant 1	GPR44-2 Variant 2	GPR44-2 Variant 3
	Rs533116 AA	Rs533116 GG	Rs533116 GA
What it means	May be at a lower risk of having elevated levels of PGD2 In the lungs/scalp.	May be at moderate risk of having higher levels of GPR44 in the lungs/scalp.	May be at an increased risk of having higher levels of GPR44 in the lungs/scalp.
The Implication	You might not be a good candidate for PGD2 inhibitors as a treatment for hair loss	You might be an average candidate for PGD2 inhibitors as a treatment for hair loss	You might be a better candidate for PGD2 inhibitors as a treatment for hair loss

What Relevance Does GPR44 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.

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

Yes, initial studies have shown that PGD2 levels are increased in the scalps of balding men. Experiments in mice suggest that PGD2 may inhibit hair growth. (score = 1)

• Does the totality of evidence implicate GPR44 as a causal agent for hair loss? (1 point)

There is not enough consistency of evidence to support the relationship between prostaglandin activity and androgenetic alopecia, due to further results conflicting with initial results. (score = 0)

• Does the totality of evidence implicate GPR44 as a predictive factor for hair loss treatment responsiveness? (2 points)

Although earlier studies showed that PGD2 is elevated in balding scalps, targeting this has not shown to be effective at treating hair loss. (score = 0)

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

No score on number (3). (score = 0)

Total Score = 1

Final Thoughts

While early research has highlighted the potential involvement of the GPR44 gene in hair loss through its interaction with prostaglandin D2 (PGD2), the current evidence is not robust enough to make definitive treatment recommendations based solely on the GPR44 genotype. Therefore, more comprehensive and consistent research is needed to validate the role of GPR44 in hair loss and its potential as a predictive factor for treatment responsiveness.

HMI-115 is a potential new treatment for hair loss that is licensed by Hope Medicine Inc. HMI-115 has been used in a phase 1 clinical trial for hair loss and has been approved by the FDA for phase 2 trials. This treatment is also in phase 2 clinical trials for use in endometriosis. HMI-115 is gathering media attention as a treatment that may come to the market within the next few years.

HMI-115 belongs to a class of drugs known as prolactin (PRL) receptor antagonists – it works by blocking the effects of prolactin within the hair follicle by binding to and blocking the prolactin receptor. In this article, we will take a look at what HMI-115 and prolactin are and then consider how prolactin might be involved in hair follicle biology and hair loss disorders. Furthermore, we will investigate the potential impact of HMI-115 in treating androgenetic alopecia and determine whether it is likely that phase 2 clinical trials for HMI-115 will return positive results. 

Key Takeaways

• Drug. HMI-115 is a drug that comes under a class of therapeutics called prolactin receptor antagonists. This drug is licensed by Bayer, which is investigating its use as a drug treatment for endometriosis. HMI-115 is also licensed by Hope Medicine Inc., which used the drug in a phase 1 clinical trial for patients with androgenetic alopecia. The FDA has also approved HMI-115 for phase 2 trials for treating hair loss, although these trials have not yet started. 
• Clinical Data. In a press release, Hope Medicine Inc. reported results from its phase 1 trial, which included a significant increase in the mean non-vellus total area hair count across the 12 males in the trial—an increase of 14 hairs/cm2 after 24 weeks. The study has not been peer-reviewed, nor have the full results been published. Furthermore, no data was provided for the 4 women included in the study.
• Safety. There was a phase 1 safety trial completed by Bayer (who licensed HMI-115 to Hope Medicine Inc.) in which up to 90 mg of the drug, delivered via subcutaneous injections every 2 weeks, was found to be well tolerated. This study, however, aimed toward using HMI-115 to treat endometriosis. The phase 1 clinical trial on hair loss, sponsored by Hope Medicine Inc., delivered 240mg of HMI-115 via subcutaneous injection every two weeks; they reported it to be safe and tolerable, though no supporting data was provided.
• Evidence Quality. HMI-115 serum scored 21/100 for evidence quality, by our metrics (this is subject to change depending on the results of clinical trials currently being undertaken).

What is HMI-115?

HMI-115 (also known as BAY1158061) is a new pharmaceutical drug developed by a biopharmaceutical company called Bioinvent and licensed by Bayer – a German multinational pharmaceutical and biotechnology company. HMI-115 has been subsequently licensed from Bayer by Hope Medicine Inc. for use as a hair loss treatment. So far, research around HMI-115 is geared toward treating endometriosis and male and female pattern hair loss. In terms of administration, HMI-115 is delivered via subcutaneous injection.

HMI-115 is a prolactin receptor antagonistic antibody.^[1]Hope Medicine, (no date). Clinical Development. Research and Development. Available at: https://www.hopemedinc.com/research-platform?tp2 (Accessed: 21 April 2023) This is a type of therapeutic antibody that binds to the prolactin receptor, thereby inhibiting its activity by stopping prolactin from binding to its receptor.^[2]Ferraris, J., Bernichten, S., Pisera, D., Goffin, V. (2013). Use of prolactin receptor antagonists to better understand prolactin regulation of pituitary homeostasis. Neuroendocrinology. 98. 171-179. … Continue reading Prolactin is a type of hormone produced by the pituitary gland. As indicated by its name, prolactin is a hormone that promotes lactation (milk production). In reality, prolactin is a pleiotropic hormone with many different functions in both men and women. We will go into more detail below about prolactin, its potential role in hair loss, and how HMI-115 might work to restore hair growth by inhibiting prolactin.

What is Hope Medicine Incorporated?

Hope Medicine Inc. is a Chinese biopharmaceutical company founded by Professor Rui Ping Xiao of Peking University. According to their website, Hope Medicine Inc. was founded on the basis of a thorough understanding of disease biology and the practical application of medical research.^[3]Hope Medicine, (no date), About Hope Medicine. Available at: https://www.hopemedinc.com/ (Accessed: 21 April 2023) Hope Medicine Inc. focuses on developing small molecule drugs that target specific proteins or pathways involved in disease.

In 2019, Hope Medicine Inc. announced a license agreement with Bayer AG in which Hope Medicine will develop and commercialize HMI-115 as a treatment for male and female pattern hair loss, endometriosis, and other conditions.^[4]Cision, (no date), Hope Medicine announces global license agreement with Bayer AG to advance the development and commercialization of the monoclonal antibody directed against prolactin (PRL) … Continue reading

In 2022, Hope Medicine announced that the US Food and Drug Administration (FDA) had approved an application for HMI-115 to be used as an investigational new drug for the treatment of androgenetic alopecia or pattern hair loss, meaning that phase 2 clinical trials can begin in the US. Hope Medicine stated that the company’s plans for its phase 2 trial for androgenetic alopecia would be an international multi-center, randomized, double-blind, placebo-controlled study. Participating countries include the US, Australia, and others. ^[5]Cision, (no date), Hope Medicine announces a global license agreement with Bayer AG to advance the development and commercialization of the monoclonal antibody directed against prolactin (PRL) … Continue reading

Are these trials likely to work? Let’s get into the science of how this prolactin receptor antagonist, HMI-115, might function. First, we’ll take a deep dive into what prolactin is and how it might affect hair follicle biology.

What is Prolactin?

Prolactin is a hormone produced and secreted by the anterior pituitary gland. Prolactin is named for its stimulatory effect on lactation (milk production), but in actuality, prolactin has many different functions in both men and women.^[6]Freeman, M.A., Kanyicska, B., Lerant, A., Nagy, Gyorgy. (2000). Prolactin: structure, function, and regulation of secretion. Physiological Reviews. 80(4), 1523-1631. Available at: … Continue reading The normal range of prolactin in non-pregnant women is below 25 ng/ml and in men, below 20 ng/ml.^[7]Majumdar, A., Mangal, N.S. (2013). Hyperprolactinemia. Journal of Human Reproductive Sciences. 6(3). 168-175. Available at: https://doi.org/10.4103/0974-1208.121400 

High levels of prolactin can lead to a medical condition called hyperprolactinemia. Symptoms of hyperprolactinemia can include irregular menstrual periods/loss of menstrual periods in women, decreased sex drive and erectile dysfunction in men, infertility, overproduction of breast milk in non-pregnant or non-breastfeeding women, and also osteoporosis.^[8]Capozzi, A., Scambia, G., Pontecorvi, A., Lello, S. (2015). Hyperprolactinemia: pathophysiology and therapeutic approach. Gynecological Endocrinology. 31(7). 506-510. Available at: … Continue reading 

It is also thought that high prolactin levels may also be involved in hair loss (more on that below).^[9]Schmidt, J.B. (1994). Hormonal basis of male and female androgenic alopecia: clinical relevance. Skin Pharmacology. 7. 61-66. Available at: https://doi.org/10.1159/000211275

How is Prolactin Involved in Hair Cycling and Loss?

Prolactin upregulates several molecular signaling pathways that are associated with hair loss. For example, the Janus kinase-signal transducer and activator of transcription (JAK/STAT) pathway is activated by prolactin.^[10]Ma, F.Y., Anderson, G.M., Gunn, T.D., Goffin, V., Grattan, D.R., Bunn, S.J. (2005). Prolactin specifically activates signal transducer and activator of transcription 5b in neuroendocrine dopaminergic … Continue reading The JAK/STAT pathway is known to be involved in hair loss in patients with alopecia areata; therefore, elevated prolactin levels may subsequently enhance the JAK/STAT pathway, leading to worse severity of the disease.

Prolactin and prolactin receptors are expressed at both the mRNA and protein levels in the hair follicle. Furthermore, both of these appear to be up-regulated in the late growing stage (anagen) into the transitional stage (catagen) of the hair follicle cycle.^[11]Foitzik, K., Krause, K., Conrad, F., Nakamura, M., Funk, W., Paus, R. (2006). Human scalp hair follicles are both a target and a source of prolactin, which serves as an autocrine and/or paracrine … Continue reading The researchers also found that treatment of isolated human hair follicles with high doses of prolactin (around 400 ng/ml) resulted in significant inhibition of hair growth and premature transition into catagen compared to control hair follicles. Additionally, markers for cell growth and cell death were reduced and increased, respectively, following prolactin treatment. Hair follicles were also staged for the hair cycle following prolactin treatment, and there was a significant increase in the number of treated follicles in the catagen stage. These findings indicate that prolactin can impact hair follicle biology and that prolactin may function as an inducer of catagen.

 

In another study, in mice, it was found that prolactin is closely involved in regulating the hair follicle cycle. Prolactin levels increased in mice at 3 weeks, just before the onset of anagen (Figure 2), with a subsequent increase in the prolactin receptor at the start of the anagen stage. This increase in prolactin levels was associated with a concomitant increase in levels of prolactin receptors in the hair follicle.  Suppression of prolactin secretion (through oral treatment of a known inhibitor of prolactin called bromocriptine) from the pituitary gland induced hair growth 3-5 days earlier, which was returned to normal by treating the mice with prolactin for 3 days. Increasing the duration of treatment had an inhibitory effect on hair growth.^[13]Craven, A.J., Nixon, A.J., Ashby, M.G., Ormandy, C.J., Blazek, K., Wilkins, R.J., Pearson, A.J. (2006). Prolactin delays hair regrowth in mice. Journal of Endocrinology. 191. 415-425. Available at: … Continue reading 

There is some evidence demonstrating that prolactin is involved in regulating hair follicle cycling. However, is prolactin relevant to hair loss disorders in humans?

In women, hyperprolactinemia was found to be associated with androgenetic alopecia-pattern hair loss, as well as hirsutism (excess facial hair).^[15]Schmidt, J.B. (1994). Hormonal basis of male and female androgenic alopecia: clinical relevance. Skin Pharmacology. 7. 61-66. Available at: https://doi.org/10.1159/000211275 A study involving 65 males (mean age of 24) and 46 females (mean age of 34) with androgenetic alopecia was conducted, and levels of different hormones were measured in comparison to 58 male and 45 female healthy controls. Prolactin, however, was only measured in the females in the study. Using a TRH test – which stimulates prolactin release from the pituitary – the researchers measured the levels of TRH-induced prolactin in both hair loss patients and controls (Figure 3). The researchers wanted to see whether the total stores of prolactin were increased in those with hair loss or whether the prolactin system was hypersensitive in some way. The female Patients were administered 0.2 mg of TRH and then had blood taken after 0 minutes, 20 minutes, and 40 minutes of treatment. Prolactin levels were then measured. This was taken during the luteal phase of the menstrual cycle (around day 14 to 28) when prolactin levels were higher than normal. It is important to note, however, that prolactin levels can be highly dynamic.

The researchers found an increase in prolactin levels at minute 0 and minute 20 following TRH administration in patients with androgenetic alopecia compared to the control patients, but these results were not statistically significant. However, there was a significant increase in prolactin levels after 40 minutes of TRH administration (p=<0.05). In conclusion, the findings of this study suggest that prolactin levels may be elevated in patients with androgenetic alopecia. 

Another study looked at 40 women (aged between 30 and 65) with moderately increased prolactin levels, alongside androgenetic alopecia or diffuse hair loss, to determine the effects that prolactin might have on hair loss.^[17]Lutz, G. (2011). Hair loss and hyperprolactinemia in women. Dermato-Endocrinology. 4(1). 70-76. Available at: https://doi.org/10.4161/der.19472 Prolactin levels varied widely in these patients, with the lowest level being 25.1 ng/ml and the highest being 1390 ng/ml. Interestingly, there did not appear to be any correlation between the number of non-growing hairs and prolactin levels, leading the researchers to conclude that it was not likely that elevated prolactin levels were the cause of diffuse or androgenetic alopecia (Figures 4 & 5).

 

A case-control study of 30 patients (16 men and 14 women) aged between 18-46 with alopecia areata (AA) and 20 controls (9 males and 11 females) aged between 18-45 was undertaken.^[20]Tahlawi, S.M.E., Eishi, N.H.E., Kahhal, R.K., Hegazy, R.A., Hanafy, G.M.E., Hay, R.M.A., Shaker, O.G. (2018). Do prolactin and its receptor play a role in alopecia areata? Indian Journal of … Continue reading When comparing the serum prolactin level between AA patients and controls using an ELISA assay, no significant differences were found. PCRs were then completed with RNA harvested from biopsies taken from the lesional skin of AA patients and the occipital scalp skin of controls.  An increase in the level of prolactin receptors was observed in the AA patients compared to the control patients (Figure 6). This indicates a potential hypersensitivity to prolactin in patients with AA rather than excess prolactin.

Furthermore, the levels of prolactin receptors correlate with the SALT score (Severity of Alopecia Tool) – a common score used in studies to assess the extent of scalp hair loss.

Overall, some evidence implicates prolactin in the pathogenesis of androgenetic alopecia. However, there are some contradicting findings about whether prolactin is involved in the pathogenesis of hair loss. Moreover, one might expect there to be more of a concrete link between pregnancy and hair loss, given the large changes in prolactin that occur during late pregnancy and throughout breastfeeding. However, there is little evidence of changes in hair loss and ratios of anagen/telogen hairs between different stages of pregnancy or breastfeeding status.^[22]Mirallas, O., Grimalt, R. (2016). The postpartum telogen effluvium fallacy. 1(4), 198-201. Available at: https://doi.org/10.1159/000445385

However, given the caveats above, let us assume for a moment that prolactin is a definitive cause of hair loss, so why not just use already-known treatments for hyperprolactinemia, such as the drug cabergoline?

A major mechanism regulating prolactin levels is dopamine secretion by neurons in the hypothalamus. Dopamine then inhibits the secretion of prolactin from the pituitary. Cabergoline is a dopamine agonist and so promotes the action of dopamine. Some case studies have indicated that dopamine agonists like cabergoline may cause hair loss in some people. One such study included a 71-year-old woman with Parkinson’s disease who experienced progressive hair loss after taking 3 mg of cabergoline for one month. After 4 months of decreasing the dose, however, (from 3 mg to 1 mg), the patient’s hair was completely re-grown.^[23]Miwa, H., Kondo, T. (2003). Hair loss induced by dopamine agonist: case report and review of the literature. Parkinsonism & Related Disorders. 10. 51-52. Available at: … Continue reading An earlier study also reports two women suffering from diffuse alopecia as a result of taking levodopa (dopamine replacement) as a treatment for Parkinson’s.^[24]Marshall, A., Williams M.J. (1971). Alopecia and levodopa. British Medical Journal. 2(5752), 47. Available at: https://doi.org/10.1136/bmj.2.5752.47 Whether dopaminergic drugs could benefit hair loss in otherwise healthy people is unclear. In any case, given the widespread importance of dopamine in regulating mood and behavior, targeting this system as a therapy for hair loss may not be a wise strategy. Therefore, other pharmaceutical approaches, like the blockade of prolactin receptors, may be a better method. That is if prolactin is indeed related to hair loss. 

So, let’s have a look at whether there is any evidence currently to suggest that the prolactin receptor antagonist HMI-115 might benefit those with hair loss.

Could HMI-115 work for Patients with Androgenetic Alopecia?

Recent data showing the potential effects of HMI-115 in humans has been released, but let’s first look at the published animal data.

Animals

Bayer AG did complete a study using a primate model of androgenetic alopecia, which Bayer AG goes into detail about in their patent application.^[25]Ekkehard, M., Joachim, S., Jorn, K., Christiane, O. (2017). Prolactin receptor antibody for male and female pattern hair loss. World Intellectual Property Organization. Available at: … Continue reading Unfortunately, this study does not appear to be published anywhere other than in the patent application that we found on Google  (such as in a peer-reviewed scientific journal). 

This study attempted to leverage an apparent phenomenon of spontaneous post-adolescence scalp hair loss in stump-tailed macaques as a model system to test the effects of HIM-115. Over a period of 6 months, the macaques were treated with HMI-115. The researchers claim that terminal hairs nearly doubled throughout the treatment. Unfortunately, the data is only given in terms of change from baseline, and there does not seem to be an untreated control group, which makes it difficult to conclude whether HMI-115 is doing anything (Figure 7).

Humans

There are two clinical trials currently recruiting for HMI-115: one phase 2 trial for endometriosis-associated pain and another phase 2 trial for treating male androgenetic alopecia over 24 weeks.^[27]Clinical Trials, (no date). HMI-115. Available at: https://clinicaltrials.gov/ct2/results?cond=&term=HMI-115&cntry=&state=&city=&dist= (Accessed: 02 May 2024) The latter of the two follows on from a now complete phase 1 trial, whereby HMI-115 was tested as a treatment for male and female androgenetic alopecia.^[28]Hope Medicine. (2023). An Open Label Study, to Evaluate Safety, Tolerability, and Efficacy in Male and Female With Androgenetic Alopecia Treated With HMI-115 Over a 24-Week Treatment Period (Clinical … Continue reading Importantly, this means that we have some information regarding the efficacy and safety of HMI-115 in humans – here’s what they found.

The study investigated the potential of HMI-115 as a treatment for both male and female androgenetic alopecia. 12 male and 4 female participants were given 240mg of HMI-115 every two weeks by subcutaneous injection for 24 weeks. The primary measurement was a change in target area hair count (TAHC) of non-vellus hair from baseline (week 0) to week 24.

In a press release, Hope Medicine Inc. (the sponsor of the trial) stated that “HMI-115 demonstrated positive efficacy results. It is also safe and well-tolerated”.^[29]Hope Medicine. (No date). Positive Outcome from a Phase Ib Study in Australia Treating Patients with Androgenic Alopecia. Hope Medicine Available at: https://www.hopemedinc.com/company-release-37 … Continue reading. The press release also showed that the mean non-vellus TAHC increased by 14 hairs/cm2 in the male group, which was reported as a statistically significant increase. Hope Medicine Inc. acknowledges that this is the first indication that a prolactin blockade receptor may promote hair growth in patients with androgenetic alopecia, potentially opening the door for its use as a novel therapeutic.

While this does sound promising, there are several drawbacks. First and foremost, these results have (at the time of writing) only been shared as a press release. This means that the study and the results have not been peer-reviewed. In other words, no external reviewers have evaluated the study and ensured its integrity.^[30]Kelly, J., Sadeghieh, T., Khosrow, A. (2014). Peer Review in Scientific Publications: Benefits, Critiques, & A Survival Guide. eJIFCC. 25(3). 227-243. PMID: 27683470 The lack of peer review means that we can’t be sure that unwanted results have not been omitted. Of the single measurement that has been reported, change in non-vellus TAHC, it is difficult to contextualize an increase of 14 hairs/cm2 – is that a large, moderate, or small change?

Furthermore, the study was conducted on a small number of participants. Generally speaking, the greater the sample size, the more reliable the results. In testing just 12 males and 4 females, the statistical power is low, and there is a risk of obtaining false-positive and false-negative results.^[31]Andrade, C., (2020). Sample Size and its Importance in Research. Indian Journal of Psychological Medicine. 42(1). 102-103. Available at: https://doi.org/10.4103/IJPSYM.IJPSYM_504_19 

On the one hand, it can be difficult to determine outliers, subjects who differ greatly from the average. For example, a few hyper-responders could see huge increases in their TAHC and cause the mean change of the group to be significant, while the majority of the subjects see no change. On the other hand, small sample sizes can obscure meaningful changes and smaller positive effects that do not reach significance. In either case, small sample sizes do not offer a good estimation of how the treatment may perform in the wider population. Furthermore, Hope Medicine didn’t include any results for the 4 women included, but it is unlikely that there would have been any statistically significant differences anyway.

With that said, HMI-115 does seem to have produced some positive effects, and the phase 2 trial should address some of the issues that hold back its phase 1 counterpart.

What are the Chances of HMI-115 Making it Through Phase 2 Clinical Trials?

So, as mentioned, Hope Medicine Inc. has been approved by the FDA to conduct Phase 2 clinical trials, and they are currently attempting to recruit 180 males with androgenetic alopecia for another 24-week study.

This may sound promising, but, in actual fact, phase 2 trials are generally considered to be the biggest milestone in drug development. The biggest reasons that phase 2 testing might fail are:

• Previously unknown serious side effects occur
• The trial shows insufficient efficacy – i.e., it doesn’t work as well as the researchers initially thought
• Poor commercial viability

It should also be noted that more than 30% of drugs entering phase 2 studies fail to progress, and more than 58% of drugs that do progress then go on to fail in phase 3 trials.^[32]Norman, G.A.V. (2019). Phase II trials in drug development and adaptive trial design. JACC Basic to Translational Science. 4(3). 428-437. Available at: https://doi.org/10.1016/j.jacbts.2019.02.005

While the odds are stacked against anyone trying to get their drug through phase 2 clinical trials, the phase 1 trial did provide some hope for HMI-115. Although the study has a number of drawbacks, if the positive effect seen in the males is true (and that’s a big ‘if’), then it provides the best (and only) indication thus far that prolactin receptor blockades may be compatible as a treatment for androgenetic alopecia.

Is HMI-115 Safe?

A safety study was conducted by Bayer AG in a randomized controlled trial with 29 healthy postmenopausal women.^[33]Nave, R., Jodi, S., Hoffman, A., Gashaw, I., Zollmann, F., Berse, M., Hochel, J., Kratzschmar, J., Rohde, B. (2019). Monoclonal antibody against prolactin receptor: a randomized placebo-controlled … Continue reading

Participants were split into four groups and administered either HMI-115 or a placebo via subcutaneous injection.  Treatments were administered either once every two weeks or once every 3 weeks. The treatment doses were 30 mg (14-day interval), 60 mg (28-day interval), or 90 mg (14-day interval) of HMI-115 or a placebo control on three occasions. 

The most frequently occurring adverse events in more than 10% of all study participants (including placebo) were headache, nasopharyngitis (common cold), nausea, lower abdominal pain, injection site bruises, general weakness, back pain, hot flush, oral herpes, temperature increase, and pain in extremities. The adverse events in more than 10% of participants that were associated with HMI-115 were headache, lower abdominal pain, hot flush, and nausea. Compared to the placebo, the frequency of adverse events was not increased with HMI-115, and no dose-dependent increase in adverse event frequency was observed.

Furthermore, the treatment was slowly absorbed, reaching peak concentrations approximately 5 – 11 days after dosing. After the final 90 mg dose, HMI-115 was eliminated from the blood plasma around 16 days later. The researchers determined that the three different dosages of HMI-115 were well-tolerated in healthy postmenopausal women, with no allergic reactions seen.

It remains to be seen if HMI-115 is safe in the long term, or across a larger, more representative group of patients. Furthermore, this study was completed in the context of treating endometriosis; therefore, the number of treatments, the concentration of the drug, and the duration of treatment time may differ from those who may be administered this drug for hair loss disorders.

For comparison, the completed phase 1 clinical trial, which Hope Medicine Inc. sponsored, treated patients with androgenetic alopecia 240 mg of HMI-115 every 2 weeks via subcutaneous injection, which is much higher than the concentrations used in the safety study completed by Bayer.^[34]Clinical Trials, (no date). HMI-115. Available at: https://clinicaltrials.gov/ct2/results?cond=&term=HMI-115&cntry=&state=&city=&dist= (Accessed: 21 April 2023) Hope Medicine Inc. reported that this delivery of HMI-115 proved safe and tolerable, though they did not provide any data to support this statement.

Is HMI-115 for Me?

Well, HMI-115 is not yet available, and it looks like it won’t be available for another few years, at least as we look to the beginning of the phase 2 trials. While it’s still too early to tell if this product will make it to the market, we look forward to seeing the full results from the phase 1 trial and those from further trials to come.

Pyrilutamide, also known as KX826, is an anti-androgenic drug with a mechanism of action similar to that of flutamide, albeit with potentially fewer side effects. Developed as a treatment for both androgenic alopecia and acne vulgaris, pyrilutamide is currently in phase III clinical trials in China and phase II clinical trials in the US. KX-826 is also included as the core ingredient of an anti-hair loss “cosmetic”, which is now being sold globally. In this ultimate guide, we’ll examine the available data on pyrilutamide: what it is, how it works, what the clinical studies show, and whom it might benefit.

Key Takeaways

• Drug. Pyrilutamide is an androgen receptor antagonist developed for treating androgenic alopecia and acne vulgaris. Topical pyrilutamide has completed phase III trials in China and phase II trials in the US and has recently gained approval for a trial using pyrilutamide in combination with minoxidil in China. 
• Clinical Data. There have been five as yet unpublished trials that were conducted in either China or the US. We only have information about these trials from press releases or conference poster presentations. The key information we do have is bulleted below:
  • A 24-week trial with 160 women with female pattern hair loss was conducted in China. The participants were randomized to six treatment groups (0.25% pyrilutamide applied once daily, 0.25% applied twice daily, 0.5% applied once daily, 0.5% applied twice daily, or two placebo groups – once daily and twice daily treatments). The 0.5% once-daily treatment appeared to perform the best, with an increase of 11.39 hairs per cm2 from the baseline compared to the placebo groups.
  • A 24-week trial with 120 men with male-pattern hair loss was conducted in China. During the trial, the participants were randomized to four treatment groups (0.25% pyrilutamide applied twice daily, 0.5% applied once daily, 0.5% applied twice daily, or a placebo). This time, the 0.5% twice-daily treatment appeared to perform the best by the end of the 24 weeks, with an increase of 15.34 hairs per cm2 from the baseline compared to the placebo groups.
  • A 24-week phase 1 trial investigating the safety, tolerability, and pharmacokinetics of pyrilutamide was conducted in the US. 40 men aged 18-60 with male-pattern hair loss were treated with ascending dose treatments of pyrilutamide (0.3%, 1.2%, 4.8%, and 9.6%). The study showed that the only reported adverse effects were mild contact dermatitis. Furthermore, pyrilutamide treatment was found to have a low risk of systemic effects, with low concentrations found in the blood after treatment.
  • A 24-week phase 2 trial investigating the efficacy and safety of pyrilutamide was conducted in the US. 123 male patients with male-pattern hair loss were treated with either 0.25% once daily, 0.5% once daily, or 0.5% twice daily. The study showed that pyrilutamide improved hair counts by 10 hairs per cm2; however, no significant improvement was observed compared to the placebo.
  • A 24-week phase 3 trial investigating the efficacy and safety of pyrilutamide was conducted in China. The participants were treated with either 0.5% pyrilutamide or a placebo. Similar to the phase 2 trial above, the study showed that pyrilutamide significantly improved hair counts compared to the baseline, however, no significant improvement was observed compared to the placebo.
• Evidence Quality. Pyrilutamide scored 37/100 for evidence quality by our metrics.
• Safety. Based on the information available, topical pyrilutamide treatment appears to be well-tolerated. However, none of the studies have been published, and there is the possibility that important information might have been omitted from the data that is available.

Best Practices. From the limited data available, a concentration of 0.5% pyrilutamide (once daily for women and twice daily for men) appears to be the most effective pyrilutamide treatment regimen. It appears to be a well-tolerated treatment for androgenic alopecia.

What is Pyrilutamide?

Pyrilutamide (also known as KX-826) is a topical nonsteroidal antiandrogen (NSAA) drug developed by Kintor Pharmaceuticals. It was developed as a treatment for androgenic alopecia and acne vulgaris, and the drug is currently undergoing phase III trials in China and phase II trials in the US.

What is the Link Between Pyrilutamide and Pattern Hair Loss?

Testosterone and dihydrotestosterone (or DHT) are androgens that have been implicated in pattern hair loss. To exert their effects, androgens must bind to the androgen receptor, and although the exact mechanisms are unknown, activating the androgen receptor in certain types of hair follicles appears to cause them to undergo miniaturization and eventually cause total hair loss.^[2]Trueb, R.M., (2021). Understanding pattern hair loss-hair biology impacted by genes, androgens, prostaglandins, and epigenetic factors. Indian Journal of Plastic Surgery, 54(4). 385-392. Available … Continue reading Because pyrilutamide binds to and blocks the androgen receptor, in theory, it should help to prevent the negative effects of androgens on hair follicles.

How Does Pyrilutamide Work?

Pyrilutamide works in a different way than other anti-androgenic drugs, such as finasteride or dutasteride. Instead of inhibiting the enzyme 5α-reductase that catalyzes the conversion of testosterone to dihydrotestosterone, it competitively binds to the androgen receptor. This stops dihydrotestosterone and testosterone from binding to the receptor and exerting their effects.^[3]Kintor, (2021), Kintor Pharmaceuticals Announced Successful Dosing of the First Batch of Patients for Acne Vulgaris Phase I/II Clinical Trial of Pyrilutamide. News Center. Available at: … Continue reading

Does Pyrilutamide Work to Regrow Hair?

There are currently no published data demonstrating the effects of pyrilutamide on hair loss; however, Kintor Pharmaceuticals has made some press announcements where they mention results from their clinical trials. 

Study 1

The first study, looking at female androgenic alopecia,  was a 24-week, multi-center, randomized, double-blind, placebo-controlled phase II trial conducted in China.^[4]Cision PR Newswire, (2022), Kintor Pharma Announced the Primary Endpoint of Phase II Clinical Study for KX-826’s Treatment of Female Androgenetic Alopecia in China was Met. Available at: … Continue reading 160 female participants were randomly assigned to six treatment groups, including 0.25% pyrilutamide applied once daily, 0.25% applied twice daily, 0.5% applied once daily, and 0.5% applied twice daily, or placebo groups (one group for once daily, and one group for twice daily). The primary measured outcome was the change in hair growth, as measured by target area non-vellus hair count (TAHC). Essentially, the researchers were counting the number of thick, pigmented hairs (or ‘terminal’ hairs) in a given area, as opposed to the number of fine, unpigmented (vellus) hairs.

The researchers determined that the recommended dose for their phase III trial in China is 0.5% once daily, as it increased hairs by 11.39 counts per cm2 from baseline, compared to the placebo group. Furthermore, the researchers said that efficacy was seen as early as the end of week 12 of treatment. When it came to safety, the researchers mentioned that it was well tolerated, with mild adverse events seen that were similar to the placebo. Unfortunately, they do not mention what these adverse effects were.

Study 2

Another 24-week, randomized, double-blind, placebo-controlled, multi-regional study was conducted to evaluate the efficacy and safety of pyrilutamide in 120 men with androgenic alopecia.^[5]Cision PR Newswire, (2023), Kintor Pharma Announces Completion of Subject Enrollment in Phase III Clinical Trial of KX-826 for Treatment of Male Androgenetic Alopecia in China. Available at: … Continue reading For this study, the researchers presented a poster at the 6th National Hair Academic Conference in China and it has since been translated to English online.

The participants were randomized into four groups:

• 0.25% pyrilutamide applied twice daily
• 0.5% pyrilutamide applied once daily
• 0.5% pyrilutamide twice daily
• Placebo (most likely treatment with just the cream or emollient that pyrilutamide is suspended in).

The researchers found that the participants that used 0.5% pyrilutamide twice daily showed improvement in total hair count at the end of the 24 weeks, with an increase of 15.34 hairs per cm2 compared to the placebo-treated groups (Figure 2).^[6]Kintor Pharmaceutical Limited, (2022). Interim Results Announcement for the six months ended 30 June 2022. Kintor Pharmaceutical. 1-50. Available at: … Continue reading

It’s worth noting that the study reports that all the treatment groups demonstrated significant improvement compared to the placebo groups, but it does not provide details on statistical testing or variability in each group.

According to the researchers, the safety profile was good in all dose groups with:

• 5.9% of participants reported pruritus (itchy skin)
• 2.5% of participants reported contact dermatitis
• 2 patients showing hypertriglyceridemia (high volume of fats in the blood)

Study 3

A randomized, double-blind, placebo-controlled, dose-escalation phase 1 trial was completed in the US over 24 weeks to evaluate the safety, tolerability, and pharmacokinetics of different concentrations of pyrilutamide.^[8]Kintor Pharmaceuticals, (2020), Results of Kintor’s Phase 1b Clinical Trials of Pyrilutamide in America. News Center. Available at: https://en.kintor.com.cn/news/129.html (Accessed: 03 May 2023) The participants included 40 healthy male patients, 18-60 years old with androgenic alopecia, who were treated with multiple ascending dose applications of 0.3%, 1.2%, 4.8%, and 9.6% pyrilutamide.^[9]Clinical Trials, (2019), Safety, tolerability, and pharmacokinetics of KX826 in healthy male subjects with androgenetic alopecia following topical single ascending dose administration. NIH. Available … Continue reading

The study showed no “severe” adverse drug events, with all adverse events relating to the drug application being mild contact dermatitis that healed in a short time.^[10]Kintor Pharma, (no date), Developing Novel Drugs and Commercialization Platform. Available at: https://docs.publicnow.com/viewDoc?hash_primary=BFD6444A4669BD4BE0683A8BCC8B5E80F3D7E430 (Accessed: 03 … Continue reading Unfortunately, the amount of time taken to heal was not given. 

Furthermore, the researchers measured the concentration of the drug in the blood to measure the risk of any systemic effects. While we do not have the specific numbers, the researchers do mention that the concentration of pyrilutamide in the blood was low, indicating that the topical concentrations used were not enough to cause a systemic accumulation (i.e., it may not lead to effects around the rest of the body after being topically applied, at these concentrations and frequency).

Study 4

A subsequent phase 2 study was next conducted in the US, with results announced in May 2023. The randomized, double-blind, placebo-controlled, and parallel-group clinical study was conducted in 123 male AGA patients who were classified as stage III vertex, IV, or V using the Hamilton-Norwood scale. 93 patients were randomly assigned to either 0.25% once daily (“QD”), 0.5% QD, and 0.5% twice daily (“BID”) pyrilutamide. 30 patients were randomly assigned to placebo groups for each dose.^[11]Kintor Pharma, (2023). Voluntary Announcement. Successful Completion of Phase II Clinical Trial of KX-826 for Treatment of AGA in the United States. Available at: … Continue reading 

According to Kintor, the 0.5% BID KX-826 group hair count increased by around 10 hairs per cm2 compared to the baseline after 24 weeks, which was statistically significant. An improvement was seen over the placebo. However, this was not found to be statistically significant. Similar to Study 3, a favorable safety profile was observed, with the only adverse events being mild and local scalp sensitivity.

Study 5

After a number of promising results, the next study showed a missed primary endpoint for a phase 3 study. This was a multicenter, randomized, double-blind, placebo-controlled study to evaluate the twice-daily use of 0.5% KX-826 in men with AGA in China.^[12]Kintor Pharma, (2023). Results of KX-826 Phase III Clinical Trial for Treatment of Male AGA in China. Available at: … Continue reading Unfortunately, Kintor did not mention the number of participants in this study.

Pyrilutamide was found to be safe, with no serious adverse events reported. After 24 weeks, the total area hair count was statistically improved compared to the baseline (although no numbers were given), but once again, there was no significant change compared to the placebo. 

A few months later, Kintor announced that the NMPA in China had approved a trial for the combination treatment of pyrilutamide and minoxidil in male AGA patients. We will have to wait and see whether combination treatment leads to better results.

UPDATE SEPTEMBER 2024:
Kintor Pivoted to Selling KX826 as a Cosmetic

Despite not achieving the primary endpoint in their most recently completed trial, Kintor announced in July of 2024 that cosmetic products containing KX-826 were to be launched for sale.^[13]Kintor Pharma, (2024). Cosmetics with KX-826 as the core ingredient launched for sale. News Center. Available at: https://en.kintor.com.cn/news_details/3.html (Accessed: 09 September 2024)

Through Koshine, a subsidiary of Kintor, which was established in 2009, they have released the first of these cosmetics – Koshine 826 Anti Hair Loss Solution. It appears to have been listed on Amazon.com by Koshine Biomedica, although there has not yet been confirmation from Kintor or Koshine that this is the official product.^[14]Amazon, (no date). KX-826 DHT Blocker Hair Thickening,3 Days Oil Control 1-2 Weeks Hair Loss Reduction 4-6 Weeks New Hair Visible, Hair Regrowth Spray for Men and Women -1 Month Supply 60ml. … Continue reading

Koshine 826 is on sale for $69, which buys you a 60ml bottle for a ‘one-month supply’. 1 ml of solution is to be applied each morning and evening, constituting approximately 6-8 sprays from the bottle. The solution should be sprayed onto the exposed scalp within the region of hair loss, followed by a 3-minute scalp massage. Unfortunately, the concentration of KX-826 contained within the product is not stated, so it is not possible to predict how well this product may perform based on clinical studies. However, the product information claims that customers can expect oil control after 3 days of use, reduced hair loss after 1-2 weeks, and visible hair growth after 4-6 weeks.

So, how has Kintor gone from failing the primary endpoint for their most recent study to selling a product containing its KX-826? It all appears to be in the terminology.

To sell a drug in the USA – “articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease” – a company must demonstrate that the product is safe and effective, amongst other factors. This information is generally provided through several rounds of successful clinical trials. However, to sell a cosmetic – “articles intended to be rubbed, poured, sprinkled, or sprayed on, introduced into, or otherwise applied to the human body…for cleansing, beautifying, promoting attractiveness, or altering the appearance” – there is no requirement for FDA approval.^[15]U.S. Food & Drug Administration, (2024). Cosmetics & U.S. Law. Available at: https://www.fda.gov/cosmetics/cosmetics-laws-regulations/cosmetics-us-law (Accessed: 09 September 2024)

In other words, cosmetics need not have proven efficacy because they are not used for ‘treating’ anything. Manufacturers don’t even need to prove the safety of a cosmetic before selling it, with action only taken if the FDA receives reliable information that suggests the product may be unsafe.^[16]U.S. Food & Drug Administration, (2022). Cosmetic Products. Available at: https://www.fda.gov/cosmetics/cosmetic-products-ingredients/cosmetic-products (Accessed: 09 September 2024)

As Koshine 826 is being marketed as a cosmetic, it can be sold despite clinical trials not (yet) showing sufficient evidence to gain FDA approval. This situation will only change if the product is deemed to be unsafe or the FDA believes that Koshine 826 should also be defined as a drug, which would create the need for FDA approval. Only the FDA can truly define which products are cosmetics and which are drugs, and Kintor must be careful with their wording to ensure that Koshine 826 is not also being marketed as a drug. For now, though, Koshine 826 can be sold without the need for FDA approval.

UPDATE MARCH 2025

Kintor Announces Most Recent Phase 3 Trial Has Met its Primary Endpoint

Kintor Pharma has continued to conduct clinical trials even since launching the product as a cosmetic. The latest? A 16 center open-label trial in China including men and women with AGA.^[17]Kintor Pharma. (2025). Long-Term Safety Phase III Clinical Trial Of KX-826 For The Treatment Of AGA Reached Primary Endpoint. Available at: https://en.kintor.com.cn/news_details/9.html (Accessed: … Continue reading

The primary endpoint was safety (incidence of treatment-emergent adverse events). Secondary endpoints included change in target non-vellus hair counts (TAHC), change in target non-vellus hair width (TAHW) and hair growth assessment (HGA) score.

Participants used 0.5% KX-826 twice daily for 52 weeks.

According to the press release, KX-826 showed good safety and tolerability in a clinical trial, with a low incidence of adverse effects, and no drug-related sexual dysfunction adverse events.

TAHC – At 52 weeks, 46% of patients showed ≥10 hairs/cm2 change from the baseline and 20% showed ≥20 hairs/cm2 change from the baseline.

TAHW – Showed a statistically significant increase from the baseline.

HGA – 53% of male participants and 48.4% of female participants showed an HGA score of ≥1.

Press Releases vs. Peer Reviewed Data, Can We Trust Kintor’s Results?

Kintor has conducted multiple studies to explore the efficacy and safety of KX-826, presenting promising results in press releases. However, none of these findings have been published in peer-reviewed journals, which limits the ability to independently verify the data. Peer-reviewed publications are essential for ensuring transparency, as they subject research to rigorous scrutiny by independent experts. Without this process, the information provided by Kintor reflects only what the company has chosen to disclose, raising concerns about potential biases or omitted data.

In contrast, certain natural supplements have published data, albeit often of limited quality. Even when evidence for supplements is weak, peer-reviewed studies provide a more complete picture by detailing methodologies, statistical analyses, and limitations. This transparency allows readers to critically assess claims and understand their clinical significance. For example, if a supplement claims to improve health outcomes, published studies might reveal whether these improvements are substantial or merely marginal.

Non-peer-reviewed data, such as press releases from pharmaceutical companies like Kintor, should be interpreted with caution for several reasons:

• Lack of Independent Verification: Peer review ensures that findings are evaluated by unbiased experts who can identify flaws or inconsistencies. Without this step, data may be selectively presented to emphasize positive outcomes while downplaying adverse effects or inconclusive results.

• Conflict of Interest Risks: Companies have a vested interest in promoting their products and may prioritize marketing over scientific integrity. This can lead to exaggerated claims or omission of unfavorable data.

• Limited Methodological Transparency: Press releases often lack detailed information about study design, statistical analyses, and participant demographics, making it difficult to assess the robustness of the findings.

While natural supplements are not without issues—such as inconsistent ingredient quality or weak regulatory oversight—they often benefit from published studies that allow for critical evaluation. Until Kintor publishes its findings in reputable journals, it remains challenging to fully trust the reported efficacy and safety of KX-826. Independent peer-reviewed research is important for determining whether the claims made in press releases translate into meaningful clinical benefits.

What’s In the Future For KX-826?

Based on the July press release, Koshine 826 may be the first of many products to use KX-826. Kintor stated that they will continue exploring the use of KX-826 for androgenic alopecia and acne.

In their most recent press release, posted in August 2024, Kintor provided further details regarding the upcoming phase II/III clinical trial of KX-826 in the treatment of androgenic alopecia. Dermatology teams from more than 20 domestic hospitals are set to be involved, with over 750 participants expected to be enrolled. Enrollment will commence in early 2025. The trial itself will treat participants with 1% KX-826, which Kintor claims to have performed significantly better in preclinical studies than 0.5% KX-826. This would be the largest KX-826 trial to date, and if the 1% solution does significantly outperform the 0.5% solution, the results could be one to keep an eye on.^[18]Kintor Pharma. (2024). Starting Again! Pioneer Pharmaceuticals KX-826 Tincture Registrational Clinical Trial Investigators Meeting Successfully Held. Kintor Pharma. Available at: … Continue reading

What are the Side Effects of Pyrilutamide?

As mentioned above, pyrilutamide treatment does not appear to lead to any serious side effects, with mild contact dermatitis being the only adverse event reported by the researchers. However, because we do not have the full study details or outcomes, we do not know if any other side effects were omitted. 

If this is the only side effect, however, pyrilutamide may present an alternative to oral androgen receptor antagonists like flutamide (which you can read about here) that have limited safety profiles in both men and women. Furthermore, because pyrilutamide is a topical treatment instead of an oral treatment this may reduce the risk of systemic effects.

However, as yet, we have no information on whether pyrilutamide can build up in the body and potentially cause systemic effects. Pyrilutamide is an anti-androgen, and therefore it is not unreasonable to hypothesize that,  if present at a high enough concentration, pyrilutamide will be associated with side effects like those of other anti-androgens (like erectile dysfunction and loss of sexual interest).

Is Pyrilutamide Right for Me?

You may want to experiment with pyrilutamide if:

• You accept the risk of potential side effects associated with the use of anti-androgen drugs
• You suffer from male or female pattern hair loss
• Are ok buying a product with no published (in peer-reviewed journals) data available for it
• Want to try a topical androgen receptor antagonist

Where Can I Get Pyrilutamide?

Although this product is still in its clinical trial phase, you can buy it online at certain retailers. However, if you do decide to try it, it will set you back around $100 – $110 for a 2 FL OZ bottle. 

It is also the core ingredient within Koshine 826, a cosmetic product that has recently begun global sales. A one-month supply, 60ml, costs $69.

Final Thoughts

At a dose of 0.5% once daily in women and twice daily in men, topical pyrilutamide appears to be well-tolerated and may lead to an increase in hair number compared to the baseline. However, few of the studies that used a placebo found any statistically significant differences between the two groups. At this point in time, we would recommend not buying this product until more information from the currently ongoing trials is published.

In a recent milestone, a drug called ritlecitinib (brand name Litfulo™) has been approved for treating alopecia areata (AA) in adolescents and adults. Ritlecitinib is a type of drug classified as a kinase inhibitor.^[1]Pfizer, (2023), FDA Approves Pfizer’s LITFULO™ (Ritlecitinib) for Adults and Adolescents with Severe Alopecia Areata. Pfizer. Available at: … Continue reading In this article, we are going to explore how ritlecitinib works, its safety and efficacy, and its implications for treating hair loss. 

Key Takeaways

• Drug. The small molecule ritlecitinib is an inhibitor of Janus-associated kinase 3 (JAK3) recently approved for treating alopecia areata (AA).
• Clinical Data. Clinical trials have demonstrated that ritlecitinib can effectively promote hair regrowth in patients with AA.
  • In a phase 2a study conducted on 142 patients (98 women and 44 men),  ritlecitinib treatments resulted in improved hair growth in a substantial number of patients – 25% of patients showed 90% or more regrowth by the end of the study and 50% of patients showing 30% or more regrowth by the end of this study.^[2]King, B., Guttman-Yassky, E., Peeva, E., Banerjee, A., Sinclair, R., Pavel, A.B., Zhu, L., Cox, L.A., Craiglow, B., Chen, L., Banfield, C., Page, K., Zhang, W., Vincent, M.S. (2021). A phase 2a … Continue reading
  • A phase 2b/3 study conducted on 718 patients (446 women and 272 men), further supported the efficacy of ritlecitinib, with patients who received the 30 mg or 50 mg doses responding to a greater extent than controls.^[3]King, B., Zhang, X., Harcha, W.G., Szepietowski, J.C., Shapiro, J., Lynde, C., Mesinkovska, N.A., Zwillich, S.H., Napatalung, L., Wasjsbrot, D., Fayyad, R., Freyman, A., Mitra, D., Purohit, V., … Continue reading 
  • In a sub-study conducted within these clinical trials, ritlecitinib also reduced the expression of several biomarkers associated with alopecia areata, which correlated with the improvement in disease severity as assessed by SALT scores.^[4]Guttman-Yasky, E., Pavel, A.B., Diaz, A., Zhang, N., Duca, E.D., Estrada, Y., King, B., Banarjee, A., Banfield, C., Cox, L.A., Dowty, M.E., Page, K., Vincent, M.S., Zhang, W., Zhu, L., Peeva, E. … Continue reading
• Safety. Ritlecitinib is FDA-approved for prescription use, so it should be safe if your doctor recommends it. However, some mild side effects are associated with its use, including upper respiratory tract infections, nasopharyngitis, and headaches. Serious side effects were rare in the clinical trials described above. However, there were instances of breast cancer and shingles during the clinical trials (2 out of 718 patients each).
• Evidence Quality: Ritlecitinib scored 76/100 for evidence quality by our metrics.
• Best Practices. Ritlectinib is specifically indicated for severe alopecia areata and is not suitable for other types of hair loss. According to the patient information leaflet, ritlecitinib should be given at dosages of 50 mg once daily. ^[5]LITFULO, (2023). Highlights of prescribing information. LITFULO. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/215830s000lbl.pdf (Accessed: 18 September 2023)

What is Ritlecitinib?

Ritlecitinib is a small-molecule inhibitor of the enzyme janus-associated kinase (JAK) that was approved in the US in June 2023. ^[6]Ramirez-Marin & Tosti (2022), Evaluating the Therapeutic Potential of Ritlecitinib for the Treatment of Alopecia Areata. Drug Design, Development and Therapy. 16. 363-374. Available at: … Continue reading Over a year ago, another JAK inhibitor, baricitinib, was approved last year for severe AA. Now, there’s a second FDA-approved drug for this hair loss disorder, and of a similar class for its mechanisms of action.

The recommended dose of ritlecitinib is 50 mg orally once a day with or without food.^[7]{Pfizer, (no date), LITFULO Medical Information. Pfizer. Available at: https://www.pfizermedicalinformation.com/en-us/litfulo/boxed-warning (Accessed: 14 September 2023)

How Does Ritlecitinib Work?

Ritlecitinib comes under a class of drugs called Janus kinase (JAK) inhibitors. This is because it selectively inhibits a specific enzyme in the JAK family called JAK3. JAK3 is part of a cell signaling pathway called the JAK/STAT pathway, which transmits signals from outside the cell to the nucleus to regulate the expression of genes. This pathway is involved in the control of processes such as the maintenance of stem cells, the formation of new blood cells, and the inflammatory response.^[9]Thomas, S.J., Snowden, J.A., Zeidler, M.P., and Danson, S.J. (2015), The role of JAK/STAT signaling in the pathogenesis, prognosis and treatment of solid tumors. British Journal of Cancer. 113. … Continue reading 

The JAK/STAT pathway is activated by a range of growth factors and other signaling molecules, including a group of substances called cytokines. Cytokines are proteins that can modulate the immune system in different ways, depending onthe context.^[10]Broussard, G., Damania, B. (2020), KSHV: Immune Modulation and Immunotherapy. Frontiers in Immunology. 10. 1-8. Available at: https://doi.org/10.3389/fimmu.2019.03084 

In our article on baricitinib, we talk about the JAK/STAT pathway and how cytokine receptors can be described as transmembrane receptors –  the receptors cross the cell membrane and have sections that can be found inside and outside the cell. The binding of the cytokine to the receptor on the outside of the cell causes a protein called JAK to bind to the inside portion of the receptor, leading it to undergo a process called trans-phosphorylation, in which a phosphate group is transferred from the receptor to the JAK protein(Figure 2).^[11]Harrison, J.A. (2012), The JAK/STAT Pathway. Cold Spring Harbor Perspectives in Biology. 4(3). 1-3. Available at: https://doi.org/10.1101/cshperspect.a011205 

These JAK proteins, in turn, activate other pathways by phosphorylating proteins like the STATs (signal transducer and activator of protein transcription). When activated by JAK phosphorylation, STAT proteins undergo a change in shape, which allows them to move to the nucleus (called translocation), where they can then activate or deactivate specific genes involved in several cellular processes.^[13]Awasthi, N., Liongue, C., Ward, A.C. (2021), STAT proteins: a kaleidoscope of canonical and non-canonical functions in immunity and cancer. Journal of Hematology & Oncology. 14(198). 1-17. … Continue reading 

The response to JAK/STAT pathway activation can be different across different types of cells and tissue, depending on the specific type of proteins that make up the pathway and what other signaling pathways are operating in that cell. This provides a contextual element to JAK/STAT signaling.^[14]Harrison, D.A., The JAK/STAT Pathway. Cold Spring Harbor Perspectives in Biology. 4(3). A011205. Available at: https://doi.org/10.1101/cshperspect.a011205

How does JAK/STAT signaling relate to AA?

The short answer: activation of the JAK/STAT pathway leads to hair loss caused by immune system activation.

How does AA develop? Let’s recap. Our hair follicles have something called ‘immune privilege’ – they are less subject to the immune response than most of the other areas of the body. This is thought to be in place to protect the stem-cell-containing area of the hair follicle, known as the bulge,  which is required for new hair follicle growth in the hair cycle.^[15]Azzawi, S., Penzi, L.R., Senna, M.M. (2018), Immune Privilege Collapse and Alopecia Development: Is Stress a Factor. Skin Appendage Disorders. 4(4).236-244. Available at: … Continue reading In AA, something triggers a breakdown of the immune privilege of the hair follicle. The exact cause of this breakdown is not fully understood, but it may involve genetic factors, environmental triggers, or a combination of both. 

When the immune privilege is compromised, a group of immune cells called T cells begin to attack the hair follicle. As mentioned earlier, the JAK/STAT pathway plays a critical role in transmitting signals within cells. When the immune system attacks hair follicles, the JAK/STAT pathway is activated, sending signals instructing cells to participate in the attack. As a result, the cells around the hair follicles respond to these signals by causing inflammation and damaging the hair follicle. This disrupts the normal hair growth cycle and leads to hair loss in the affected areas (Figure 3).^[16]Kumar, N., Kuang, L., Villa, R., Kumar, P., Mishra, J. (2021), Mucosal Epithelial Jak Kinases in Health and Diseases. Mediators of Inflammation. 1-17. https://doi.org/10.1155/2021/6618924

Why target JAK3 specifically?

JAK3 is particularly important in the development and function of T cells.^[18]Sohn, S.J., Forbush, K.A., Nguyen, N., Witthuhn, B., Nosaka, T., Ihie, J.N., Perimutter, R.M. (1998). Requirement for JAK3 in mature T cells: Its role in regulation of T cell homeostasis. The Journal … Continue reading By targeting JAK3, ritlecitinib may help inhibit T cell activity without affecting other immune cells as strongly. This targeted approach may help to reduce the autoimmune response while preserving some aspects of the immune system’s ability to fight infections.^[19]Dai, Z., Sezin, T., Chang, Y., Lee, E.Y., Wang, E.H.C., Christiano, A.M. (2022), Induction of T cell exhaustion by JAK1/3 inhibition in the treatment of alopecia areata. Frontiers in Immunology. 13. … Continue reading 

Furthermore, Targeting JAK3 may provide a more precise therapeutic approach for AA. Since JAK3 is primarily involved in immune responses mediated by certain subsets of T cells, it could potentially lead to fewer off-target effects on other immune system functions. Of course, this precision is desirable to avoid compromising the immune system’s ability to protect against infections. Inhibiting JAK1/2 may have broader effects on the immune system, potentially leading to more significant side effects. For example, JAK1/2 inhibitors might interfere with the body’s response to infections or impact other physiological processes.^[20]Sardana, K., Bathula, S., Khurana, A. (2023), Which is the Ideal JAK Inhibitor for Alopecia Areata – Baricitinib, Tofacitinib, Ritlecitinib, or Ifidancitinib – Revisiting the … Continue reading By specifically targeting JAK3, the goal is to minimize unwanted side effects while still addressing the autoimmune component of the AA disease mechanism.

Is Ritlecitinib Effective at Treating Alopecia Areata?

Several clinical trials have either already been carried out using ritlecitinib or are ongoing. These trials have been conducted in adults, adolescents, and children, either with AA or cicatricial alopecia (which is similar to AA in terms of disease mechanism, although there are important differences). In total, we could find 2 completed clinical trials with a total number of patients included being 789. We will also cover one of the studies that were conducted at the same time as these trials with the same patients. 

The first study was a phase 2a randomized, placebo-controlled study to evaluate the efficacy and safety of ritlecitinib and a similar drug, brepocitinib, in AA.^[21]King, B., Guttman-Yassky, E., Peeva, E., Banerjee, A., Sinclair, R., Pavel, A.B., Zhu, L., Cox, L.A., Craiglow, B., Chen, L., Banfield, C., Page, K., Zhang, W., Vincent, M.S. (2021). A phase 2a … Continue reading 142 participants took part (98 female and 44 male) with an average age of 36. Participants were treated with 200 mg of ritlecitinib or 60 mg of baricitinib once daily for four weeks. Then, they were treated with a maintenance dose of 50 mg (ritlecitinib) or 30 mg (baricitinib) for the next 20 weeks. The results were promising for patients with AA who started the study with over 50% of scalp hair loss. Both medications resulted in significant hair regrowth, with 25% (ritlecitinib group) and 34% (baricitinib group) of patients achieving near-complete hair regrowth as measured by Severity of Alopecia Tool (SALT90) scores compared to the placebo group (Figure 4).

The SALT tool is validated for measuring the extent of hair loss in AA with 0% meaning no hair loss, and 100% meaning complete hair loss (with several grades in between).^[22]Wyrwich, K.W., Kitchen, H., Knight, S., Aldhouse, N.V.J., Macey, J., Nunes, F.P., Dutronc, Y., Mesinkovska, N., Ko, J.M., King, B.A. (2020). The Alopecia Areata Investigator Global Assessment Scale: … Continue reading The SALT90 score, however, measures the percentage of people who achieved at least 90% of hair regrowth. 

Adverse events were reported in all three treatment groups, with common events including upper respiratory tract infection, nasopharyngitis, headache, acne, and nausea. Serious adverse events were only noted in the brepocitinib group, which could indicate that it may induce more hair regrowth than ritlecitinib but may not be as safe to use.

So, to summarize, although brepocitinib performed better, ritlecitinib also improved hair regrowth scores in patients with AA and appeared to be better tolerated than brepocitinib. 

This particular clinical trial also contained a further sub-study to further evaluate the efficacy and safety of ritlecitinib and brepocitinib.^[24]Guttman-Yasky, E., Pavel, A.B., Diaz, A., Zhang, N., Duca, E.D., Estrada, Y., King, B., Banarjee, A., Banfield, C., Cox, L.A., Dowty, M.E., Page, K., Vincent, M.S., Zhang, W., Zhu, L., Peeva, E. … Continue reading The study involved taking scalp biopsy samples from patients with AA at baseline and analyzing changes in specific biomarkers between baseline and weeks 12 and 24 of treatment. 

Ritlecitinib significantly shifted gene expression in the scalp towards an improved, non-lesional profile. This improvement exceeded 100% of baseline at week 24, indicating a strong positive response to the treatment. Furthermore, the treatment led to a downregulation of inflammatory markers associated with T cells, T cell activation, and other immune response markers. These changes also correlated with an improvement in the SALT score (Figure 5). 

However, the most recent study (just prior to ritlecitinib becoming FDA approved) was a 48-week phase 2b/3 randomized, double-blind, placebo-controlled clinical trial.^[26]King, B., Zhang, X., Harcha, W.G>, Szepietowski, J.C., Shapiro, J., Lynde, C., Mesinkovska, N.A., Zwillich, S.H., Napatalung, L., Wajsbrot, D., Fayyad, R., Freyman, A., Mitra, D., Purohit, V., … Continue reading The trial was conducted across118 sites in 18 countries, with 718 patients (446 women, 272 men) aged 12 years and older with alopecia areata and at least 50% scalp hair loss – as measured by SALT severity scores. 

The patients were assigned to either an oral ritlecitinib or placebo treatment, given once daily for 24 weeks. Several doses of ritlecitinib were tested, along with a variable 4-week loading dose and were followed by a 24-week extension period, during which the ritlecitinib group continued their treatment, and the placebo-treated group switched to ritlecitinib (Figure 6). 

The researchers found that patients on the 30 mg or 50 mg doses of ritlecitinib exhibited the highest regrowth scores, and including a loading dose resulted in further improvement. Response rates based on a SALT score of 20% or less at week 24 were significantly higher in ritlecitinib groups compared to the placebo (Figure 7A):

• 29.1% difference for 200 mg + 50 mg 
• 20.8% difference for 200 mg + 30 mg
• 21.9% difference for 50 mg
• 12.8% difference for 30 mg

The response rates, based on a SALT score of 10 or less at week 24, were also significantly higher in ritlecitinib groups compared to the placebo (Figure 7B). Furthermore, the proportion of patients with a Patient Global Impression of Change (PGI-C) response of moderately or greatly improved was greater with ritlecitinib treatment compared to placebo at week 24 (Figure 7C). The PGI-C reflects a patient’s belief about the efficacy of a treatment.^[28]Ferguson, L., Scheman, J. (2009). Patient global impression of change scores within the chronic pain rehabilitation program. The Journal of Pain. 10(4). S73. Available at: … Continue reading Regrowth of eyelashes and eyebrows was also observed with ritlecitinib treatment (Figures 7D/7E), with responses continuing up to week 48 in all ritlecitinib groups.

So, to summarize, ritlecitinib was effective in promoting hair regrowth and was generally well tolerated (more on that below) in patients with alopecia areata. There is a longer-term efficacy study currently ongoing called ALLEGRO-LT, which aims to evaluate the safety and efficacy of ritlecitinib over a period of 60 months (5 years).^[30]Clinical Trials (2023) Long-term PF-06651600 for the Treatment of Alopecia Areata (ALLEGRO-LT). NIH. Available at: … Continue reading This trial is due to finish in 2026 and will hopefully provide the long-term efficacy and safety data that is needed.

Is Ritlecitinib Safe?

The overall safety profile was observed throughout the study, and it was determined that ritlecitinib was generally well-tolerated across all doses and showed a favorable safety profile. The most common adverse effects (occurring in at least 10% of patients in any treatment group) included: 

• Upper respiratory tract infection – 8.01% of all patients who took ritlecitinib.
• Nasopharyngitis – 13.01% of all patients who took ritlecitinib.
• Headache – 10.96% of all patients who took ritlecitinib

A total of 16 more serious adverse events were reported in 14 patients. These included:

• Infections (Five serious infections were reported. Notably, one patient experienced empyema (fluid between the lungs) and sepsis, while two cases of shingles occurred.
• Malignancies: Two cases of breast cancer were reported, one of which was deemed related to the treatment by an investigator.
• Other serious events were appendicitis, diverticulitis, and pulmonary embolism.

Treatment with ritlecitinib also led to changes in hematological parameters, including:

• Decrease in hemoglobin levels.
• Transient decrease in platelet count.
• Early decrease in absolute lymphocyte levels, particularly in groups with the 200 mg loading dose.
• Early decreases in natural killer cell counts, most apparent in groups with a 200 mg loading dose.

So 14/718 patients experienced a more serious adverse effect – so roughly 2% of patients, or 1 in 50. While you may consider these ‘good odds’, it is important to consider these potential adverse effects when making a treatment decision and always consult a physician.

Is Ritlecitinib for Me?

Ritlecitinib is an exciting new treatment; however, it is important to remember that it is for the treatment of severe alopecia areata only and will not work for other hair loss types like androgenetic alopecia, as the mechanisms of hair loss are very different.  You may want to try this treatment if:

• You have severe alopecia areata.
• You have tried other treatments with no success.
• You have spoken to your physician, and they have suggested it based on your alopecia severity.

Ketoconazole is a versatile antifungal drug with widespread applications. It is commonly employed to address dandruff issues. It is also utilized off-label as a remedy for hair loss in both men and women, specifically targeting conditions like androgenic alopecia and telogen effluvium that result from an overgrowth of microorganisms on the scalp.

In this guide, we’ll delve into why you might be shedding after using ketoconazole, the difference between normal and abnormal shedding, solutions, and recommendations for those experiencing hair shedding.

What is Ketoconazole?

If you have been using ketoconazole for 1-3 months and are experiencing shedding, it may be because the scalp is still adjusting (and responding) to new treatments. Therefore, it’s possible that some of your shedding is due to a positive treatment response.

Ketoconazole Side Effect

When selecting hair loss treatments, it’s critical to understand how fast your hair loss is progressing, and why the speed your hair loss should influence your treatment choices – particularly for those with rapidly-progressing androgenic alopecia.

In this article, we’ll uncover:

• The average speed of hair loss progression (per year)
• How to estimate your own speed of hair loss (at home)
• Why people with faster hair loss face bigger stakes for treatment failures
• How to minimize these failures by understanding evidence quality

If we have androgenic alopecia, how quickly will we lose hair?

Clinical studies suggest that men with androgenic alopecia will lose 5% hair volume per year. At this rate, it typically takes 15-25 years for a man to go fully bald.^[1]Rushton DH, Ramsay ID, Norris MJ, Gilkes JJ. Natural progression of male pattern baldness in young men. Clin Exp Dermatol. 1991 May;16(3):188-92. doi: 10.1111/j.1365-2230.1991.tb00343.x. PMID: … Continue reading^[2]Sinclair R. Male pattern androgenetic alopecia. BMJ. 1998 Sep 26;317(7162):865-9. doi: 10.1136/bmj.317.7162.865. PMID: 9748188; PMCID: PMC1113949.

However, it’s important to remember that 5% is just the average rate of hair loss.

In other words, 5% is just the mid-point on a bellcurve. Some people will lose hair at a much slower rate than 5% yearly; others will lose hair much faster.

Why should we care about how fast (or slow) we’re losing hair?

Because men & women with faster hair loss face a bigger opportunity cost for failed treatments. For these individuals, the cost of failure is much, much higher. Consider the following hypothetical:

Person A is losing hair slowly. They try a nutraceutical product, which is supported by low-quality evidence. It doesn’t work. After 12 months, they quit. They now have 1% less hair compared to a year ago. Their hair basically looks the same.

Person B is losing hair rapidly. They try the same nutraceutical product. It doesn’t work. After 12 months, they quit. They now have 25% less hair compared to a year ago. Their hair loss has significantly advanced.

Clinical studies overwhelmingly suggest it’s easier to stop hair loss than it is to regrow significant amounts of lost hair.^[3]Sinclair R, Torkamani N, Jones L. Androgenetic alopecia: new insights into the pathogenesis and mechanism of hair loss. F1000Res. 2015 Aug 19;4(F1000 Faculty Rev):585. doi: … Continue reading

Therefore, when choosing treatments, time is of the essence. This is especially true for people with rapid-onset hair loss. So if we want to make fully-informed treatment choices, we should know how quickly our hair loss is advancing.

How can we estimate how fast we’re losing hair?

Ask yourself the following question:

In the last 6 months, have you experienced a visual loss in hair density? In other words, during this time, do you feel your hair loss has gotten cosmetically worse?

If no, you’re probably losing hair more slowly. If yes, you’re probably losing hair faster than 5% yearly.

After all, researchers have calibrated mens’ hair density changes with self-perception data, and they concluded: (3)

Long-story short: if you’re weighing your treatment options, do a quick assessment of how fast you’re losing hair.

The slower your hair loss, the more wiggle room you have to experiment. Why? Because the cost of failure might only equate to a 5% loss in hair density.

The faster your hair loss, the more imperative it is to seek treatments with the highest levels of clinical support. Why? Because these treatments tend to maximize your chances of success, and your magnitude of hair regrowth.

We rank some of these treatment options in this video. Moreover, we dive into what constitutes a good study in this article. It’s a deep-dive into how hair loss companies cheat their clinical trials.

Evidence quality example: saw palmetto vs. finasteride

Compare two potential hair loss interventions: saw palmetto and finasteride. One is natural; the other is a drug. Both substances have clinical support for hair growth, particularly for androgenic alopecia. Both substances also work similarly: they help lower the hormone dihydrotestosterone (DHT) in balding regions.

Similar substances. Similar mechanisms. Both clinically supported. But are these truly equal interventions for hair growth? A deeper dive into the evidence on both interventions paints a more nuanced (and dramatically different) picture than what is suggested at face-value.

Saw Palmetto for Hair Loss: 2022 Meta-Analysis

Over nine studies totaling 381 people have shown that saw palmetto might help improve androgenic alopecia.^[4]Evron E, Juhasz M, Babadjouni A, Mesinkovska NA. Natural Hair Supplement: Friend or Foe? Saw Palmetto, a Systematic Review in Alopecia. Skin Appendage Disord. 2020 Nov;6(6):329-337. doi: … Continue reading At face value, this sounds great. But looking closer, many of these studies are what we would call lower quality: most of them lacked a placebo group, some were funded by companies selling saw palmetto, and all had small sample sizes.

This means that, for each study, there’s a higher risk of false-positive results: results due to statistical noise that would’ve washed out with a larger sample size.

This phenomenon happens all the time: early studies on an intervention showing promise, followed by larger, more robust studies showing no effect for that same intervention.

In fact, this happened once before for this same supplement – saw palmetto – but for the indication of prostate enlargement.

In the 1990s, several small studies suggested that saw palmetto extract might help reduce symptoms of an enlarged prostate.^[5]Descotes, J., Rambeaud, J., Deschaseaux, P. et al. Placebo-Controlled Evaluation of the Efficacy and Tolerability of Permixon® in Benign Prostatic Hyperplasia after Exclusion of Placebo … Continue reading These studies inspired better-controlled clinical trials with hundreds of participants over extended periods, in which saw palmetto showed little-to-no effect.^[6]Suzuki M, Ito Y, Fujino T, Abe M, Umegaki K, Onoue S, Noguchi H, Yamada S. Pharmacological effects of saw palmetto extract in the lower urinary tract. Acta Pharmacol Sin. 2009 Mar;30(3):227-81. doi: … Continue reading

Again, study quality, results replication, and sample sizes all inform evidence quality. The lower the evidence quality, the more variance researchers will find between “study results” and “real-world results”. The higher the evidence quality, the less variance between “study” and “real-world” results. In the case of saw palmetto’s effects on prostate enlargement, low-quality data suggested benefit… until higher-quality data came long that brought into question that benefit.

Saw Palmetto Versus Finasteride: Clinical Evidence

When comparing the hair regrowth data on saw palmetto to that of finasteride, the totality of evidence and quality of evidence differ significantly. For instance, finasteride has been studied for 30+ years, in over 30,000 patients, across hundreds of research groups, with dozens of randomized clinical trials – nearly all of which showed significant hair density and hair count increases.

In fact, if you just looked at the treatment arm of one of the randomized, blinded, placebo-controlled studies on oral finasteride, you’d see that the number of participants in a portion of this single study outnumber all participants across all hair growth studies evaluating saw palmetto by a factor of four.^[7]Kaufman KD, Olsen EA, Whiting D, Savin R, DeVillez R, Bergfeld W, Price VH, Van Neste D, Roberts JL, Hordinsky M, Shapiro J, Binkowitz B, Gormley GJ. Finasteride in the treatment of men with … Continue reading^[8]Evron E, Juhasz M, Babadjouni A, Mesinkovska NA. Natural Hair Supplement: Friend or Foe? Saw Palmetto, a Systematic Review in Alopecia. Skin Appendage Disord. 2020 Nov;6(6):329-337. doi: … Continue reading

With this visual, we can really see the relative differences in evidence quality across saw palmetto and finasteride. And this is just one of the dozens of finasteride studies available.

Hierarchy of Evidence & Totality of Evidence

These comparisons illustrate two concepts: the hierarchy of evidence – which evaluates how well studies are designed – and the totality of evidence – which evaluates how much research has been done on any one intervention. The higher the hierarchy of evidence and totality of the evidence, the more likely it is that those study results reflect the real-world experience of people trying it.

We capture these concepts inside our Treatment Metrics: a standardized tool we use to help hair loss sufferers evaluate the science supporting (or not supporting) any hair loss intervention at-a-glance.

Again, for a deep-dive into these concepts, see this article.

This is important because people can use the hierarchy and totality of evidence to rank how hair loss interventions might compare to one another. At the top of the list, there are pharmaceutical options. Toward the bottom of the list, there are natural interventions – which absolutely work for some people. But again, the hierarchy and totality of evidence supporting them are more limited, which means that in real life, there will be higher variability in clinical results versus real-world results.

Here’s how not understanding this can become a problem.

If you’re fighting hair loss, and you’re hit with an advertisement for a product that claims, “clinically proven to regrow hair”, it’s possible this claim is true. But if that claim is also based on a single, small-scale study funded by the company selling you that product, then it’s also true that the evidence supporting that product is not very robust and subject to bias, and that it has a lower likelihood of getting you the hair gains you desire.

In other words, that product probably ranks lower on the hierarchy of evidence and totality of the evidence. So if someone tries it, there are higher odds that the results from that single clinical study won’t reflect their real-world experience.

How Does This All Relate to Hair Loss Speeds?

If you have faster-onsetting hair loss, your opportunity costs for failed treatments are high. In a single year of failed experimentation, you might not lose 5% hair volume; you might lose 20% of your hair or more. There’s a good chance this will be cosmetically significant, which means that people with quickly-progressing hair loss don’t have the same time-freedom as people with slowly-progressing hair loss to play around with interventions that are poorly supported.

So, when considering treatments, one must remember how fast they’re losing hair.

The slower it’s progressing, the better a candidate you are for more experimental, lesser-supported interventions. The faster your hair loss, the more you should consider FDA-approved treatments that rank strongly on the hierarchy and totality of evidence.

Long story short: when fighting hair loss, time is of the essence. The speed of hair loss should always inform candidacy for novel therapies. The slower the hair loss, the better position someone is in to experiment. The faster the hair loss, the more aggressively hair loss should be treated.

Reparex Against Grey Hair is a product that claims to “restore hair color naturally from the inside out, unlike hair dyes”.^[1]Reparex, (no date), Reparex Against Grey Hair. Available at: https://reparexshop.com/usa/reparex-against-grey-hair (Accessed: 30 January 2023 Reparex is owned by a company called BOOS Labs – established in 1991 – which makes many different cosmetic products.

Reparex Against Grey Hair doesn’t have any clinical efficacy and safety data associated with it and there are some inconsistencies in the information provided on their website (more on that below). However, let’s take a look at what mechanistic data might be available for this product (if any) and determine if it is a product that is worth your time and money.

Key Takeaways

• Branding. Reparex markets Against Gray Hair products as topically applied alternatives to commercially available hair dyes. Their branding is marketed towards both men and women. 
• What makes it unique? Reparex attempts to differentiate  itself from other hair colorant products by claiming that its product uses a unique mechanism. They state that  “Reparex removes Oxygen from oxidized colorless melanin using the enzyme g-reductase which binds with silver nitrate. This results in the restoration of melanin’s natural color”.^[2]Reparex, (no date), How does it work? Available at: https://reparexshop.com/usa/reparex-against-grey-hair (Accessed: 30 January 2023
• Clinical Support. Currently, no clinical data is available to show us the efficacy and safety of this product.
• Concerns.
  •  The major concern for this product is that there is no mechanistic, efficacy, or safety data (and the explanation they do provide doesn’t make a lot of sense). Basically, this means that we don’t know if this product actually works or whether it’s safe to use for any length of time. 
  • The websites and documents associated with this product include conflicting and sometimes incorrect information. This makes it confusing to navigate or really understand how the product works.
  • The before-and-after photos shown on the website appear to show the same photo for both the before and after shots. Also, in some  photos, it is impossible to actually tell if the after photo is of the same person as the before photo (examples below).
• Recommendations to Reparex. In order to improve their service and reassure potential customers, we would recommend that Reparex do the following:
  • Take a close look at the information they are providing to customers on their websites and correct inconsistencies and mistakes where possible.
  • Conduct long-term, pre-registered, placebo-controlled trials to determine the efficacy and safety of Reparex as a product that can reverse hair graying.
  • Be transparent with their before-and-after photos and encourage people to take multiple photos of different angles of the face so that it is possible to identify them as the same person.
  • Provide mechanistic data so we can understand exactly how Reparex works (in other words, what is the biological mechanism that their product supposedly affects?).
• Our Current Thoughts. Due to the points mentioned above, we cannot recommend Reparex as a product for reversing gray hair. The onus is on Reparex to provide clear information and clinical data to convince us that this product works.

What is Reparex?

Reparex is a brand owned by a company called BOOS Labs that was established in 1991. They create multiple products including the Against Grey Hair product range. Reparex state that Against Grey Hair “Restores your own hair color, bringing back that natural look”.^[3]Reparex, (no date), Reparex Against Grey Hair. Available at: https://reparexshop.com/usa/reparex-against-grey-hair/ (Accessed: 29 January 2023

Reparex says that their product “is an outcome of life-long research made by a well-known biochemist and doctor Oto Sova, M.D, PhD. He developed and created a unique enzymatic formula which fits all people and is 100% safe for the human body”.^[5]Boos Labs, (no date). How it works. Available at: https://forgreyhair.com/how-it-works (Accessed: 30 January 2023

Oto Sova has, according to the website “studied in several scientific centers in Europe and was a student of several Nobel Prize winners”.^[6]For Grey Hair, (no date), For Grey Hair. Available at: https://forgreyhair.au/blog.html (Accessed: 29 January 2023

Who is their target consumer?

Reparex has products aimed at treating gray hair for both men and women. The case studies on their website include 11 men and 6 women.

What products do Reparex offer?

The Reparex range, including prices and volumes, is tabulated below.

Product	Size	Price
Reparex Against Grey Hair for Men	150ml	$54.95
Reparex Against Grey Hair for Women	150ml	$54.95
Reparex Against Gray Hair for Beard and Mustache	150ml	$54.95

Table 1: Prices of Reparex products. Adapted from:^[7]Reparex, (no date), Reparex Shop. Available at: https://reparexshop.com/usa/reparex-against-grey-hair/ (Accessed: 27 January 2023

Reparex also offers anti-dandruff lotions, shampoos, and skin ointments aimed at psoriasis sufferers.^[8]Reparex, (no date), Reparex Shop. Available at: https://reparexshop.com/usa/reparex-against-grey-hair/ (Accessed: 27 January 2023 These however are not part of the Against Grey Hair Range.

How do they claim these offerings are unique?

Reparex claims that their product is not a hair dye as, according to their definition, “hair dye colors your hair from the outside, but Reparex changes the hair color from the inside. It restores the original hair color, just as your hair was before it became gray”.^[9]Reparex, (no date), FAQ. Available at: https://reparexshop.com/usa/faq/ (Accessed: 27 January 2023

Quite what they mean by ‘’…changes hair color from the inside.’’ isn’t clear, and the data to support their claim to this mechanism (not to mention evidence that the product actually changes hair color) is lacking. This makes it difficult to determine whether this product is actually unique.

What is their pricing?

As can be seen above, you’re looking at spending $54.95 a bottle for the specific product you want in the Against Grey Hair series, which should last you around a month.^[10]Reparex, (no date), Reparex Shop. Available at: https://reparexshop.com/usa/reparex-against-grey-hair/ (Accessed: 27 January 2023

As there don’t appear to be other products that claim to do what Reparex does, there is not much to compare the price to. But, compared to standard hair dyes, which can be very cheap at around $10, this is perhaps on the pricier side.

Product Science: Deep Dive

Firstly, let’s give a brief overview of how melanin is formed and cover some reasons why hair might turn gray.

Melanin is a type of material in your hair that gives it its color. There are two types of melanin (eumelanin and pheomelanin) and these are both created by special types of cells called melanocytes. Melanocytes are present in both the skin and hair whose primary job is to create melanin. Eumelanin is a darker pigment and is responsible for darker hair color, and pheomelanin is responsible for lighter hair color. An individual person’s hair color will be based upon a specific amount of each type of melanin and their genetics.^[11]Slominski, A., Wortsman, J., Plonka, P.M., Schallreuter, K.U., Paus, R., Tobin D. (2005). Hair Follicle Pigmentation. Journal of Investigative Dermatology. 124(1), 13-21. Available at: … Continue reading

In the hair follicle, melanocytes undergo a cycle of growth (proliferation) and rest, in tandem with the hair follicle’s own growth (anagen) and non-growing (telogen) cycles. Specialized stem cells called melanocyte stem cells are located in the bulge of the hair follicle, are activated at the start of the hair follicle growing phase, and supply melanocytes to the core part (the matrix) of the hair follicle. Melanocytes then undergo multiple divisions so that there is a  continuous store of melanocytes (and therefore melanin) in the bulb of the hair follicle.^[12]Nishimura, E.K. (2011). Melanocyte stem cells: a melanocyte reservoir in hair follicles for hair and skin pigmentation. Pigment Cell & Melanoma Research. 24(3), 401-410. Available at: … Continue reading 

Melanin is then packaged into a small ‘packet’ called a vesicle (or a melanosome) which is then transferred into the cells that make the actual substance of the hair follicle (matrix keratinocytes).^[13]Schlessinger, D.I., Anoruo, M.D., Schlessinger, J. (2022). Biochemistry, Melanin, In: StatPearls, Treasure Island (FL). StatPearls publishing. Available at: … Continue reading Matrix keratinocytes are cells found in the matrix of the hair follicle, where they are highly proliferative (actively undergo cell division) to form the hair shaft you eventually see as your hair. 

The synthesis of melanin involves specific biochemical reactions (called redox reactions) which are made possible  by a couple of enzymes called tyrosinase and tyrosinase-related protein (TRP). These enzymes are involved at each step of the production of reactive oxygen species (ROS), such as hydrogen peroxide (H2O2) or O2- as can be seen in Figure 2. Redox reactions are chemical reactions in which a compound can either lose an electron (oxidized) or gain an electron (reduced).^[14]Denat, A., Kadekaro, A.L., Marrot, L., Leachman, S, Abdel-Malek, Z.A. (2014). Melanocytes as Instigators and Victims of Oxidative Stress. Journal of Investigative Dermatology. 134(6). 1512-1518 … Continue reading

ROS are chemical compounds that contain oxygen and are therefore highly reactive, so they readily interact with the environment around them. These can cause an environment called oxidative stress which, among other things, can cause damage to melanocytes and other cells in the hair follicle.^[15]NIH, (no date), Reactive oxygen species. Available at: https://cancer.gov/publications/dictionaries/cancer-terms/def/reactie-oxygen-species (Accessed: 30 January 2023

However, the hair follicle has a natural defense against ROS -an enzyme called catalase. Catalase breaks down hydrogen peroxide over a series of chemical reactions (also redox reactions), resulting in the production of water and oxygen, and providing protection against oxidative stress.^[17]Goyal, M.M., Basak, A. (2010). Human Catalase: Looking for Complete Identity. Protein & Cell. 1(10). 888-897. Available at: https://doi.org/10.1007/is13238-010-0113-z

While there are in-built mechanisms in place for reducing oxidative stress, these can be dysregulated by old age, radiation, inflammation, and psychological/emotional stress. It has been found that there is an increase in oxidative stress and death (apoptosis) of melanin-producing cells (melanocytes) in individuals with gray hairs, as well as a reduction of key protectors against oxidative stress, such as Bcl-2 (and catalase which we will go into further below) and growth factors involved in melanocyte growth such as c-Kit. This reduction in melanocytes subsequently leads to less melanin in hair shafts, giving hair a gray appearance (Figure 3).^[18]Arck, P.C., Overall, R., Spatz, K., Liezman, C., Handjiski, B., Klapp, B.F., Birch-Madin, M.A., Peters, E.M.J. (2006). Towards a “free radical theory of graying”: melanocyte apoptosis in the … Continue reading 

A further study compared isolated growing hair follicles, dermal papilla cells (DPCs), and other specialized hair follicle cells from gray- and brown-haired donors.^[20]Wood, J.M., Decker, H., Hartmann, H., Chavan, B., Rokos, H., Spencer, J.D., Hasse, S., Thornton, S.J., Shalbaf. M., Paus, R., Schallreuter, K.U. (2009). Senile hair graying: H2O2-mediated oxidative … Continue reading The researchers showed that catalase and other enzymes responsible for maintaining a healthy redox balance within the hair follicle are reduced in graying hair, leading to a negative cycle of imbalance and subsequent oxidative stress. In addition to this, hydrogen peroxide was also found to be present in the graying hair follicle whereas it was not present in the brown hair follicle. Furthermore, the researchers found that tyrosinase activity, the enzyme essential for facilitating the synthesis of melanin, was reduced after melanocytes were incubated with increasing doses of hydrogen peroxide (Figure 4).

So, it is generally thought that oxidative stress can build up through different stressors in addition to the reactive oxygen species naturally produced through the synthesis of melanin. When oxidative stress builds up, it can reduce the activity of melanocytes and even induce them to die. In these circumstances as there is no longer enough melanin produced to provide keratinocytes with the natural pigment and hairs become gray.

But what does all this have to do with Reparex?

Reparex states that “as we get older hair turns gray due to a natural build-up of hydrogen peroxide in the hair follicles, which causes oxidative stress which oxidizes melanin and consecutively causes graying”. Then they claim that “Reparex removes Oxygen from oxidized colorless  melanin using the enzyme g-reductase which binds with silver nitrate. This results in restoration of melanin’s natural color”.^[22]Reparex, (no date), How does it work? Available at: https://reparexshop.com/usa/reparex-against-grey-hair (Accessed: 29 January 2023

While the statement above is an attempt to explain the mechanism of action of the Against Grey Hair products, it does not seem to fit with the current theories that state that we lose melanin rather than have colorless melanin within our hair. Additionally,  the information on their website is quite confusing and inconsistent,  so the only thing we can do is try to break the product down and see how it might work.

The two main ingredients in Reparex’s Against Grey Hair products are silver acetate and glucuronate reductase. Reparex claims that “glucuronate reductase…was able to remove the oxygen from hair melanine [sic] and gives it to silver nitrate”.^[23]Boos Labs, (no date), Product Information File. Available at: https://www.forgreyhair.co.uk/wp-content/uploads/sites/12/2022/09/PIF-FGH.pdf (Accessed: 27 January 2023 

So, let’s see what these ingredients might do…

Silver acetate…or is it silver nitrate?

Reparex uses the terms silver acetate and silver nitrate interchangeably throughout its website. While they are superficially similar chemical names, they are certainly not the same chemical. In their reasoning for including these chemicals, Reparex state that when they just used the glucuronate reductase by itself it “…took away the oxygen and the hair darkened, but after a while, the hair turned gray again, because the enzymes had no place to transfer the taken oxygen and so they put it back in the hair…therefore it was necessary to engage some ‘oxygen scavenger’ and thus the addition of a minimum amount of silver acetate. As a result, For Grey Hair has become fully functional and usable”.^[24]Boos Labs, (no date), The single best treatment for gray hair invented by Oto Sova. Available at: https://forgreyhair.com.au/httpswwwforgreyhaircombest-treatment-for-grey-hair.c128.html (Accessed: 30 … Continue reading

However, with regard to silver acetate, we weren’t able to find any evidence to suggest that it can bind to oxygen or react with oxygen. Furthermore, there does not appear to be any precedence for using silver acetate in hair products. 

Silver nitrate, however, can react with oxygen. Furthermore, it has been used as a hair colorant.  used daily, it slowly darkens or lightens the hair. So, perhaps there is some rationale for including silver nitrate ^[25]Guerra-Tapia, A., Gonzalez-Guerra, E. (2014). Hair Cosmetics: Dyes. Actas Dermo-Sifiliográficas (English Edition). 105(9), 833-839. https://doi.org/10.1016j.adengl.2014.02.003

Glucuronate Reductase

Glucuronate reductase is an enzyme that belongs to a family of oxidoreductases. Oxidoreductases are enzymes that facilitate redox reactions.^[26]Legesse, H.B., Assefa, B.E. (2021). Biological Application and Disease of Oxidoreductase Enzymes. Oxidoreductase. Available at: https://doi.org/10.5772/intechopen.93328 With regard to  Reparex, we can hypothesize that it might work by facilitating a redox reaction in which hydrogen peroxide present in graying hair gets broken down, therefore clearing it from the hair. Perhaps this would reduce oxidative stress and prevent damage to melanocytes. Even if this was the case, would this mechanism still work to replenish already lost melanocytes? Perhaps not.

In any case, as there is no actual mechanistic data, all we can do is speculate and hypothesize, but is there any clinical information about whether this product actually works?

Does Reparex work as a hair treatment?

Unfortunately, there is no clinical data associated with this product that can tell us whether it actually works. There are some case study before-and-after photos presented on the Reparex website; however, some of these appear to actually be just the same photo twice, and it’s impossible to tell if some of the before-and-after photos are the same person, even if there are some notable changes. 

Additionally, Reparex offers “2 Free Reparex products of your choice for and before and after photos from our customers”.^[27]Reparex, (no date), Reparex Against Grey Hair. Available at: https://reparexshop.com/usa/reparex-against-grey-hair (Accessed: 30 January 2023 The problem with only having before-and-after photos and an incentive to provide them, is that it’s more likely that only people who have positive responses to the treatment will post their results. Furthermore, it’s possible that there are a number of people who saw no improvement, that Reparex may have chosen not to show. This can be avoided with pre-registered clinical trials with disclosed patient numbers, as they will need to show details for all the participants regardless of whether they show a response to the treatment or not.

So, there is no clinical data and no mechanism of action data, meaning that if we did want to use it, we have to trust Reparex and its unconvincing before-and-after photos. But can we actually trust them?

Other than the confusing information on the website about their own product, Reparex also has some somewhat shaky information in their FAQs which leads us to question their overall knowledge about hair. An example is:

“Q: Does REPAREX reduce hair loss?

A: According to latest scientific research, hair loss is caused by a lack of elements such as nickel and iron. We cannot say which one of these is particularly missing for each individual therefore REPAREX cannot help your hair to grow again but we can assure you that it will not cause hair loss to start nor make it worse if you are already suffering from hair loss. Our product has no effect on hair loss.”^[30]Reparex, (no date), FAQs. Available at: https://reparexshop.com/usa/faq/ (Accessed: 29 January 2023

While vitamin and mineral deficiency can certainly contribute towards hair loss, in reality, it’s not the only way that hair loss can develop.^[31]Almohanna, H.M., Ahmed, A.A., Tsatalis, J.P. (2019). The Role of Vitamins and Minerals in Hair Loss: A Review. Dermatology and Therapy. 9, 51-70. Available at: … Continue reading For example, androgenetic alopecia (AGA) can be caused by an overproduction or oversensitivity to androgens (such as dihydrotestosterone); telogen effluvium can be caused by multiple triggering events, including pregnancy; alopecia areata can be caused as a function of autoimmune dysregulation (to name a few).^[32]Alessandrini, A., Bruni, F., Piraccini, B.M., Starace, M. (2020). Common causes of hair loss – clinical manifestations, trichoscopy and therapy. Journal of the European Academy of Dermatology and … Continue reading

Is Reparex Against Grey Hair safe?

Reparex states that “REPAREX has been carefully tested according to the latest EC regulations for cosmetic products; this includes testing for heavy metal content, skin irritation, and any general harm. It has also been evaluated by independent Cosmetic Product Safety Assessors. Furthermore, REPAREX has also been registered at the Central Registration of Cosmetic Products in Brussels and according to its status as harmless it was released to the EU market as harmless and 100% legal.”^[33]Reparex, (no date) FAQ. Available at: https://reparexshop.com/usa/faq/ (Accessed: 29 January 2023

However, to our knowledge, there has been no published efficacy or safety data for this product, so we cannot say with certainty that this product is safe to use long-term. It’s also worth noting there are dozens of examples whereby short-term (i.e., 1-2 year) data suggested that a natural substance might be safe, only for long-term (i.e., 5-10+ year) data to show the exact opposite. One example: the effects of vitamin E and selenium supplements on prostate cancer. Short-term data suggested benefit, while long-term data showed these supplements doubled the rates of prostate cancer in men with already-adequate vitamin E and selenium levels.

Should I use Reparex?

You may consider trying out this product if:

• You are unhappy with your gray hair
• You do not want to use other hair dyes
• You are happy using products that have no efficacy or safety data
• You are ok buying a product from a company that has confusing and incorrect information on their website

You may be better placed however to just use a standard hair dye, which you can buy for a fraction of the price.

Recommendations to the company

We would recommend that Reparex look at the information that they are showing on their websites and make sure that it is consistent with (1) the actual ingredients in the product and (2) current scientific data. Furthermore, we recommend that Reparex conduct some mechanistic and long-term pre-registered clinical trials to determine the efficacy and safety of Reparex as a product that can reverse hair graying. Additionally, Reparex should address the issues with their before-and-after photos and make sure that they are not the same photos, and that people can be clearly identified as the same person.

Final thoughts

If you are comfortable trying products with zero published clinical or mechanistic data, and you do not want to use hair dyes, then Reparex might be something you could consider experimenting with. Otherwise, we do not recommend using this product in its current state.

Ketoconazole is used off-label to treat androgenic alopecia and telogen effluvium. While it is well-studied in men, there is a significant lack of clinical data showing its efficacy in women. In this guide, we will explore the evidence supporting the use of ketoconazole in androgenic alopecia, as well as answer whether it is suitable for use in women.

What is Ketoconazole?

Ketoconazole, primarily an antifungal drug, is commonly employed to combat diverse fungal infections within the body. Interestingly, it also finds application in addressing hair loss issues, including androgenic alopecia (AGA) and telogen effluvium (TE), typically through topical formulations and shampoos. Certain products containing ketoconazole for hair loss are accessible without a prescription, like shampoos containing 1% ketoconazole. Medical practitioners might advise or provide more potent ketoconazole treatments in specific cases.

How Does Ketoconazole Work?

Ketoconazole functions as an antifungal agent by disrupting the cell membranes of fungi, impeding their growth and replication. Its antifungal properties are beneficial for addressing scalp conditions by reducing fungal activity and inflammation. In hair loss conditions like AGA and TE, ketoconazole contributes to a healthier and less inflamed scalp, creating a more conducive environment for growth.

Moreover, recent studies have suggested that ketoconazole shampoo may lower dihydrotestosterone (DHT) levels by inhibiting five alpha-reductases. Combined with treatments like finasteride, this can offer a more comprehensive approach to addressing these conditions.^[1]Perez, B.S.H. (2004). Ketoconazole as an adjunct to finasteride in treating androgenetic alopecia in men. Medical Hypotheses. 62(1). 112-115. Available at: … Continue reading

What Evidence is there for Ketoconazole in Hair Loss?

The effectiveness of ketoconazole in treating hair loss, particularly in conditions such as AGA and TE is supported by various clinical studies. These studies have explored the impact of ketoconazole not only as a standalone treatment but also in combination with other hair loss therapies.

Study One

This study involved 39 male participants exclusively with androgenic alopecia (AGA); the effects of 2% ketoconazole shampoo were compared to those of regular shampoo over 21 months. 27 men used the ketoconazole shampoo, while 12 used a regular shampoo. Additionally, 22 individuals without AGA served as controls, half using ketoconazole and the other half using regular shampoo. The results revealed a significant difference between the two groups.

Results

Among the non-AGA control participants, the choice of shampoo had no discernable impact on their AGA pilary index (defined as the product of the percentage of hairs in the growth (anagen) phase and average diameter (in micrometers) of the hair shaft).

Conversely, among the participants with AGA who used an unmedicated shampoo, there was a gradual linear decline in their AGA pilary index over time. In contrast, the group using the ketoconazole shampoo exhibited a progressive increase in their AGA pilary index, and this effect became noticeable after six months. The increase seemed to plateau after approximately 15 months of using the ketoconazole shampoo.^[2]Piérard-Franchimont, C., De Doncker, P., Cauwenbergh, G., Piérard, G.E. (1998). Ketoconazole shampoo: effect of long-term use in androgenic alopecia. Dermatology. 196(4). 474-477. Available at: … Continue reading

Study Two

Another study involved 150 male participants experiencing TE-related to AGA with associated dandruff. During the study, 150 male participants were split into three groups, and each group was given a different shampoo to use. One group used a shampoo containing 1% ketoconazole, another group used a shampoo with 1% piroctone olamine, and the third group used a shampoo with 1% zinc pyrithione.

The researchers measured hair shedding, hair density, the percentage of anagen (growth phase) hair, the average diameter of proximal hair shafts, and sebum excretion rates to evaluate the effectiveness of each shampoo.

Results

The study results indicated that all three shampoo formulations promptly addressed pruritus (itching) and dandruff symptoms, leading to rapid clearance. No significant changes were observed in any of the three shampoo groups regarding hair density.

However, there was a noteworthy reduction in all three groups regarding hair shedding. The ketoconazole group experienced a 17.3% decrease, the piroctone olamine group saw a 16.5% reduction, and the zinc pyrithione group had a 10.1% decrease in hair shedding.

Furthermore, the percentage of anagen hair increased in all three shampoo groups. The ketoconazole group exhibited a 4.9% rise, the piroctone olamine group showed a 7.9% increase, and the zinc pyrithione group demonstrated a 6.8% increase.

All groups showed a decrease in sebum secretion rates, with the ketoconazole group experiencing a 4.8% reduction, the piroctone olamine group showing a 2.9% decrease, and the zinc pyrithione group recording a 5.5% decline.^[3]Piérard-Franchimont, C., Goffin, V., Henry, F., Uhoda, I., Braham, C., Piérard, G.E. (2002). Nudging hair shedding by antidandruff shampoos. A comparison of 1% ketoconazole, 1% piroctone olamine, … Continue reading

Other Studies

Two other studies evaluated the efficacy of ketoconazole in combination with other hair loss treatments like finasteride and minoxidil in men with AGA. They found it works well as a combination therapy and can even improve AGA in men with atopic and/or seborrheic dermatitis.

So, clinical evidence shows that ketoconazole can improve hair loss outcomes. However, all these studies suffer from a significant limitation; they have only included male subjects. Let’s find out if there is evidence for using ketoconazole in women.

Clinical Evidence for Ketoconazole for Women

There is currently no published evidence for using ketoconazole shampoo in women. However, one study did compare the efficacy of a 2% ketoconazole solution to 2% minoxidil in female pattern hair loss. The study involved 40 female pattern hair loss patients. 20 were in Group A using 2% topical minoxidil, and 20 were in Group B treated with 2% topical ketoconazole. Both groups received treatment for six months, with changes to the Ludwig scale and trichoscopic (magnified images of the scalp, typically used for counting hairs) outcomes evaluated.

Results

The results showed that both groups experienced improved hair growth (Figure 1 & 2), but the minoxidil group responded faster. In contrast, the ketoconazole group had a delayed response, which became significant at the 6-month. Side effects were also less common in the ketoconazole group (10% vs. 55% in the minoxidil group), and patient satisfaction did not significantly differ between the two groups.^[4]El-Garf, A., Mohie, M., Salah, E. (2019). Trichogenic effect of topical ketoconazole versus minoxidil 2% in female pattern hair loss: a clinical and trichoscopic evaluation. Biomed Dermatol. 3(8). … Continue reading

 

 

The study indicates that applying ketoconazole topically can facilitate hair regrowth in women with fewer side effects than minoxidil. Ketoconazole is probably as effective for women as it is for men. However, additional research is necessary to obtain a more comprehensive understanding of its efficacy and safety.

Can I Use Ketoconazole If I am Pregnant or Breastfeeding?

We always recommend a trip to the doctor before using any product if you are pregnant or breastfeeding. While certain patient informational leaflets suggest ketoconazole shampoo can be used during pregnancy and breastfeeding, the ketoconazole dilutions in those leaflets only reference products with 20 mg per gram of ketoconazole.^[7]Nizoral, (no date). Nizoral Anti-Dandruff Shampoo Ketoconazole. Nizoral. Available at: https://www.medicines.org.uk/emc/files/pil.6456.pdf (Accessed: 03 November 2023) Be sure to check with your doctor to confirm your dilution of ketoconazole shampoo matches that of 20 mg/gram, and that your doctor also agrees with these recommendations.

Can I Use Ketoconazole Alongside Other Hair Loss Medications?

Researchers have observed that combining ketoconazole with other treatments works best in treating AGA in humans. This is because ketoconazole has different mechanisms of action than minoxidil, microneedling, and finasteride. Targeting multiple mechanisms generally leads to better results. If you’re interested in seeing a real-life example of hair regrowth achieved using ketoconazole in combination with other treatments, you can find it here.