Estrogenic effects of 5-alpha-reductase inhibitors in male androgenetic alopecia patients

Summary: Androgenetic alopecia (AGA) is commonly treated with 5-alpha-reductase inhibitors (5ARIs), which inhibit the conversion of testosterone to dihydrotestosterone. However, these medications may shift hormone pathways, potentially increasing estrogen levels and raising concerns about estrogen excess. This study investigates conditions associated with estrogen excess in male AGA patients treated with 5ARIs. TriNetX Research Network was queried for AGA males (ICD-10: L64, L65.8, L65.9) treated with finasteride or dutasteride from 2004–2024, with 5ARI-naïve AGA males used as controls. Propensity score matching was applied based on age, race/ethnicity, obesity/overweight, alcohol use disorder, and hormone replacement therapy. Outcome risks ≥1 day post-5ARI prescription were assessed for gynecomastia (ICD-10: N62), infertility (ICD-10: N46), and erectile dysfunction (ED) (ICD-10: N52). Patients with outcomes prior to 5ARI initiation were excluded. We included 49,937 5ARI-treated and 49,937 5ARI-naïve AGA males. Mean age at index was 39.0 vs. 39.4 years for 5ARI-treated patients vs. controls, respectively, with a majority White identifying (70.9% vs. 69.2%, respectively). Baseline characteristics were clinically similar between cohorts (standardized mean differences <0.04). Compared to controls, 5ARI-treated AGA males had higher risk of gynecomastia (RR: 1.402 [95% CI: 1.218–1.615]) and ED (RR: 1.613 [95% CI: 1.533–1.699]), but no association with infertility (RR: 1.130 [95% CI: 0.976–1.309]) was observed. Our findings indicate increased risk of gynecomastia and ED in 5ARI-treated AGA males, suggesting possible testosterone aromatization contributing to estrogenic effects. The observed associations underscore the need for physicians to consider the potential hormonal side effects when prescribing 5ARIs for male AGA and to discuss these risks with patients as part of shared decision-making. Michael Ong¹, Amit Singal², Shari Lipner³ 1. MD Program, Weill Cornell Medicine, New York, NY, United States. 2. Rutgers New Jersey Medical School, Newark, NJ, United States. 3. Department of Dermatology, Weill Cornell Medicine, New York, NY, United States. Clinical Research: Epidemiology and Observational Research