CYP19A1: Can This Gene Predict Regrowth From Hormone Therapy?

Article Summary

Can your genes predict the effectiveness of hormone therapy for hair loss? The CYP19A1 gene, which encodes the enzyme aromatase, has been linked to hair growth and hair loss, particularly in androgenetic alopecia (AGA). Some studies suggest that certain CYP19A1 variants might influence the effectiveness of hair loss treatments by modulating levels of dihydrotestosterone (DHT). However, the current evidence is not strong enough to make reliable treatment recommendations based on these genetic variations. More research is needed to determine whether CYP19A1 variants can truly guide personalized hair loss treatments.

Full Article

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.