Risk of Estrogen-Driven Malignancies in Females on 5-alpha Reductase Inhibitors

Abstract Importance: It is hypothesized that 5α-reductase inhibitors (5aRI) increase aromatase-mediated conversion of testosterone to estrogen, which may facilitate development of estrogen-driven malignancy. Previous studies in male patients receiving 5aRI treatment failed to demonstrate an increased risk of breast cancer; however, similar data in females are lacking. Methods We utilized the TriNetX Global Collaborative Network, which provides access to electronic medical records from ~ 145 million patients. Both cohorts included females with an ICD-10 diagnosis of androgenetic alopecia (AGA), non-scarring hair loss, or cicatricial alopecia and excluded patients with prior diagnoses of estrogen-driven malignancies. The study cohort included patients with at least 6 months of finasteride of dutasteride use, while the control cohort excluded any-time use of these medications. A 1:1 matched propensity score analysis was performed for confounding risk factors. Results After matching, there were 5,156 patients in each cohort (median age 57.8 ± 14.3). Ten years after first medication use, patients taking 5aRI had a 27.6% decreased risk of having a breast cancer diagnosis compared to controls (95% CI: 0.532–0.985, p = 0.0389). The study cohort had a 31.9% decrease in lifetime breast cancer risk compared to the control patients (95% CI: 0.503–0.923; p = 0.0126). Between the 5aRI and control groups, there was no significant difference in risk of developing ovarian or endometrial cancer (95% CI: 0.317–1.605; p = 0.4126 and 95% CI; 0.025–1.13; p = 0.09367 respectively). Conclusions The data show that there is no increased risk of estrogen-driven malignancies for women taking 5aRI for alopecia, and that 5aRI use may be protective against breast cancer.