Articles

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

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

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

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

Single Nucleotide Polymorphisms (SNPs)

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

In coding regions of genes, SNPs can be:

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

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

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

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

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

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

Angiotensin-converting enzyme (ACE)

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

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

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

Read our ACE gene article here.

Biotinidase (BTD)

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

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

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

Read our BTD gene article here.

Collagen Type 1 Alpha 1 Chain (COL1A1)

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

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

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

Read our COL1A1 gene article here.

CRAPB2

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

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

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

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

Read our CRABP2 gene article here.

CYP19A1

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

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

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

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

Read our CYP19A1 gene article here.

GPR44

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

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

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

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

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

Read our GPR44 gene article here.

IGF1R

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

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

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

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

Read the full IGF1R gene article here.

NR3C1

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

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

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

Read more about the NR3C1 gene here.

PGTFR

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

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

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

Read the PGTFR gene article here.

PTGES2

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

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

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

Read the PTGES2 gene article here.

SRD5A1 & SRD5A2

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

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

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

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

Read the full SRD5A1 and SRD5A2 gene article here.

SULT1A1

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

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

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

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

Should We Be Targeting Genes for Hair Loss Treatment Efficacy?

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

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

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

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

Key Takeaways

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

What Is Progesterone?

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

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

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

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

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

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

Can Progesterone Improve Hair Loss Outcomes?

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

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

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

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

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

Progesterone Formulations

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

Oral

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

Topical

Topical progesterone has a few potential benefits, including:

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

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

Injection

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

Micronized

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

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

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

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

Synthetic Progesterone

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

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

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

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

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

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

Cyproterone Acetate

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

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

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

Drospirenone

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

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

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

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

Dosing Considerations

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

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

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

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

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

Best Practices

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

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

Final Thoughts

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

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

What is CRABP2?

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

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

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

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

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

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

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

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

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

What is the Evidence for Targeting CRABP2 for Hair Loss?

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

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

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

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

What Do Your Genetic Results Mean?

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

What Relevance Does CRABP2 Have for Hair Loss Treatment?

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

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

This score is a rating based on evidence quality.

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

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

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

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

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

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

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

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

Total Score = 1

Final Thoughts

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

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

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

What Is COL1A1?

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

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

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

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

What is the Evidence for Targeting COL1A1 For Hair Loss?

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

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

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

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

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

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

What Do Your Genetic Results Mean?

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

What Relevance Does COL1A1 Have for Hair Loss Treatment?

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

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

This score is a rating based on evidence quality.

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

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

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

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

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

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

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

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

Total Score = 1

Final Thoughts

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

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

What Is CYP19A1?

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

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

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

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

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

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

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

What Is The Evidence for Targeting CYP19A1 For Hair Loss?

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

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

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

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

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

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

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

What Do Your Genetic Results Mean?

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

What Relevance Does CYp19A1 Have For Hair Loss Treatment?

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

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

This score is a rating based on evidence quality.

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

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

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

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

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

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

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

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

Total Score = 1

Final Thoughts

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

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

What is ACE?

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

Can Targeting ACE Help Hair Loss?

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

Evidence Supporting Targeting ACE  Polymorphisms For Hair Loss

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

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

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

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

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

Evidence Against Targeting ACE Polymorphisms For Hair Loss

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

Your Genetic Results

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

Treatment Relevance

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

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

This score is a rating based on evidence quality.

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

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

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

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

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

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

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

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

Total Score = 0

Final Thoughts

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

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

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

What is NR3C1?

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

What is the Evidence for Targeting NR3C1 for Hair Loss?

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

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

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

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

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

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

What is the Evidence Against Targeting NR3C1 for Hair Loss?

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

What Do Your Genetic Results Mean?

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

What Relevance Does NR3C1 Have For Hair Loss Treatment?

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

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

This score is a rating based on evidence quality.

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

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

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

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

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

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

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

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

Total Score = 1

Final Thoughts

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

The 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.

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.

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.

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.

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.