Alopecia APIs and Genetic Polymorphisms – New Data on Topical Dutasteride

One of the biggest challenges with topical treatment of alopecia is the trial and error of finding the correct ingredients for best results. Given the time it takes for hair to enter anagen phase and new hair to grow in, it can take months for a given topical treatment to produce results. If the selected active pharmaceutical ingredient (API) or concentration isn’t suitable for the patient, this process would need to be started all over again with a new combination or strength drawing out the process of finding suitable treatment. One technique to try to lessen the amount of trial and error in this process is looking at genetic markers to determine whether a treatment is likely to be efficacious. One of the most well-known examples is minoxidil. Minoxidil is a mainstay of topical and oral alopecia treatment; however, minoxidil itself is a prodrug. Minoxidil must be transformed by sulfotransferase enzyme A1 (SULT1A1) into the active minoxidil sulfate form to have an effect. It is thought that deficiency of SULT1A1 in the skin may be a major contributing factor to why only 40-50% of patients respond to topical minoxidil.¹

Patients with this deficiency who desire to use a topical alopecia product must either use alternative therapy or consider a method to overcome this deficiency either with elevated minoxidil concentrations or with the addition of another ingredient that upregulates SULT1A1. With regards to higher strength, though high strength minoxidil may be associated with an increased risk of topical irritation, some studies have evaluated a high concentration specifically in patients who fail to respond to typical minoxidil concentrations such as 5%. For example, one study in women who had failed to respond to minoxidil 5% evaluated the efficacy of minoxidil 15% over 12 weeks and found clinically significant improvement in 60% of patients  over the course of the study.² However, other studies of high concentration minoxidil, for example, another study that compared 5% minoxidil to 10% minoxidil or placebo in 90 men with androgenetic alopecia found that the higher concentration of minoxidil was not more effective than the standard 5% minoxidil concentration.^3,4  Therefore, it is unclear if taking the approach of dosing every patient with high concentration minoxidil is suitable for managing the risk of SULT1A1 deficiency.  

The other approach if topical minoxidil treatment is desired despite SULT1A1 deficiency is the addition of an ingredient that upregulates existing SULT1A1. Retinoids are known to upregulate SULT1A1 gene transcription. Though there may be benefits associated with other retinoids as well, most of the limited data currently focuses on the impact of tretinoin on minoxidil responsiveness. Studies have evaluated tretinoin at concentrations between 0.01 to 0.1%. One small study that evaluated tretinoin 0.01% with minoxidil 5% vs minoxidil 5% alone did not note statistically significant benefit of the combination over individual therapy, though, studies on higher strengths (0.025%, 0.05%, and 0.1%) did note improved response. These studies are small making comparative data on adverse events difficult to evaluate, though some studies did report numerical increased irritation or contact dermatitis in tretinoin/minoxidil combination groups.^6,7  

Knowing whether a patient is SULT1A1 deficient before initiating treatment could be key for determining whether minoxidil is likely to be beneficial, and, if so, what the desired starting concentration should be or if combination treatment with a retinoid such as tretinoin should be considered at the outset. This particular case is far from the only example of the impact of certain genes on response to alopecia treatment. Another, less well-known example, is the impact on genetic variants in the genes that encode for steroid 5-alpha reductase (SRD5A) and predicted responsiveness to 5-alpha reductase inhibitors such as finasteride and dutasteride.⁸ The enzymes 5-alpha reductase types I and II are responsible for conversion of testosterone to dihydrotestosterone (DHT). DHT is known to cause follicle miniaturization resulting in hair thinning and loss.⁸ Finasteride inhibits only 5-alpha reductase type II whereas dutasteride inhibits both 5-alpha reductase types I and II.⁹ Differences in expression of SRD5A can impact the likelihood of efficacy with 5-alpha reductase inhibitors generally or efficacy of finasteride vs dutasteride.¹² Generally, studies have found oral dutasteride to be more effective at halting hair loss and increasing hair growth than oral finasteride but until recently, the benefit of topical dutasteride has not been studied as topical finasteride has been.¹⁰

Recent studies published in 2025 and 2026 evaluated topical dutasteride compared to both oral finasteride 1mg daily and placebo. One concentration finding study looked at the impact of dutasteride 0.01, 0.02, and 0.05% concentrations. Patients applied 1mL daily for 24 weeks and did not wash the solution off for at least six to eight hours. The study found all studied concentrations to be superior to placebo and the higher concentration (dutasteride 0.05%) superior to 1mg oral finasteride. Additionally, small decreases in systemic DHT and a small increase in testosterone were noted with oral finasteride but not in the dutasteride topical groups, suggests minimal systemic absorption with topical dutasteride treatment.¹¹ This 0.05% concentration was evaluated in another phase 1 study in 2026 that compared daily 0.05% dutasteride lotion to oral finasteride 1mg and found excellent tolerability with dutasteride over 24 weeks. Though the study was focused on tolerability and not on efficacy, improvement in hair count and hair density were noted over the course of the trial. Dutasteride remained undetectable in the serum throughout the trial. There was a numerical decrease in serum DHT, but it did not reach the level of significance.⁹

Interested in learning more about genomics and alopecia? Check out the resources provided by Fagron Genomics regarding TrichoTest. If you’d like to learn more about formulations through Fagron, check out some of our beyond-use date studies here.  

References:

1. Ramos, P., 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 loss. Journal of the European Academy of Dermatology & Venereology, 35(1), e24-e26. https://doi.org/10.1111/jdv.16765

2. McCoy J, Goren A, Kovacevic M, Shapiro J. Minoxidil dose response study in female pattern hair loss patients determined to be non-responders to 5% topical minoxidil. J Biol Regul Homeost Agents. 2016 Oct-Dec;30(4):1153-1155. PMID: 28078868.

3. Shreya Singh, Anant Patil, Nika Kianfar, Anna Waśkiel‐Burnat, Lidia Rudnicka, Rodney Sinclair, Mohamad Goldust, Does topical minoxidil at concentrations higher than 5% provide additional clinical benefit?, Clinical and Experimental Dermatology, Volume 47, Issue 11, 1 November 2022, Pages 1951–1955, https://doi.org/10.1111/ced.15338

4. Goldust M. Minoxidil 15% solution versus minoxidil 5% solution in the treatment of androgenetic alopecia. Br J Dermatol  2020; 183(Suppl): 91 (abstract BH107

5. Ghonemy, S., Alarawi, A., & Bessar, H. (2021). Efficacy and safety of a new 10% topical minoxidil versus 5% topical minoxidil and placebo in the treatment of male androgenetic alopecia: a trichoscopic evaluation. Journal of Dermatological Treatment, 32(2), 236–241. https://doi.org/10.1080/09546634.2019.1654070

6. Maas D, Spindler A, Zappi I, Maas K, Brody A, Tucci C, Garza-García L, Patrocínio J, Shapiro J, Lo Sicco KI. Efficacy of Topical Tretinoin and Topical Minoxidil Cotherapy in Androgenetic Alopecia: A Review. Skin Appendage Disord. 2026 Jun 18. doi: 10.1159/000553018. Epub ahead of print. PMID: 42535115; PMCID: PMC13423365.

7. Ferry JJ, Forbes KK, VanderLugt JT, Szpunar GJ. Influence of tretinoin on the percutaneous absorption of minoxidil from an aqueous topical solution. Clin Pharmacol Ther. 1990 Apr;47(4):439-46. doi: 10.1038/clpt.1990.55. PMID: 2328551.

8. Vila-Vecilla L, Russo V, de Souza GT. Genomic Markers and Personalized Medicine in Androgenetic Alopecia: A Comprehensive Review. Cosmetics. 2024; 11(5):148. https://doi.org/10.3390/cosmetics11050148

9. Lyakhovitsky A, Shemer A, Koren A et al. A novel dutasteride lotion (FOL100) for male pattern baldness in Isreali men. Dermatologic Therapy. 2026; DOI: 10.1155/dth/8300136

10. Almudimeegh A, AlMutairi H, AlTassan F, AlQuraishi Y, Nagshabandi KN. Comparison between dutasteride and finasteride in hair regrowth and reversal of miniaturization in male and female androgenetic alopecia: a systematic review. Dermatol Reports. 2024 Apr 12;16(4):9909. doi: 10.4081/dr.2024.9909. PMID: 39749123; PMCID: PMC11694415.

11. Panuganti VK, Kumar Madala P, Ramalingayya Grandhi V, Varma Alluri C, Mohammad J, Rao Kssvv S, Reddy Dundigalla M. A Randomized, Double-Blind, Placebo and Active Controlled Phase II Study to Evaluate the Safety and Efficacy of Novel Dutasteride Topical Solution (0.01%, 0.02%, and 0.05% w/v) in Male Subjects With Androgenetic Alopecia. Cureus. 2025 Aug 3;17(8):e89309. doi: 10.7759/cureus.89309. PMID: 40909044; PMCID: PMC12405733.

12. Escamilla-Cruz M, Magaña M, Escandón-Perez S, Bello-Chavolla OY. Use of 5-Alpha Reductase Inhibitors in Dermatology: A Narrative Review. Dermatol Ther (Heidelb). 2023 Aug;13(8):1721-1731. doi: 10.1007/s13555-023-00974-4. Epub 2023 Jul 11. PMID: 37432644; PMCID: PMC10366043.

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