Association Between 5α-Reductase Inhibitor Use for Dermatologic Conditions and the Risk of Breast or Gynecologic Cancers

5α-reductase inhibitors (5ARIs), such as finasteride and dutasteride, are commonly indicated for the treatment of benign prostatic hyperplasia and androgenetic alopecia in males, with finasteride prescription rates among men older than 25 years increasing by 200% over the past 7 years. Although there are no official guidelines regarding 5ARI use in women, these medications have been increasingly prescribed to treat alopecia, including androgenetic and frontal fibrosing alopecia, as well as hirsutism and acne. 5ARIs have shown promise in managing alopecia and hirsutism; however, evidence regarding their effectiveness in the management of acne currently remains limited.

Prior studies have demonstrated favorable safety profiles of 5ARIs in female patients. However, 5ARI use may occasionally be associated with sexual dysfunction and breast tenderness and, like oral minoxidil, is contraindicated during pregnancy. These medications may offer an alternative for women unresponsive to oral minoxidil, those experiencing adverse effects such as fluid retention or postural hypotension, or those with pre-existing cardiovascular conditions.

This retrospective cohort study evaluated the risk of estrogen-mediated malignancies, such as breast and gynecologic cancers, in 13,853 adult female patients with female pattern hair loss, acne, hirsutism, and/or lichen planopilaris who were treated with 5ARIs. The study used data from the TriNetX database, which includes de-identified data from more than 300 million patients across 220 healthcare organizations across more than 30 countries. An active comparator design was used to examine the risk of malignancy among patients treated with 5ARIs versus spironolactone. Covariate analysis was performed based on age, comorbidities, family history, medication history of hormone-based therapies, and healthcare utilization. In this study, patients receiving 5ARIs did not have an increased risk of new-onset breast, uterine, ovarian, or cervical cancers.

The study is limited by its retrospective nature, absence of stratification by 5ARI dosage and treatment duration, and a lack of covariate analysis of additional risk factors for breast and gynecologic malignancy (eg, BMI, radiation history, and alcohol use). Furthermore, TriNetX captures data only when patients receive care at healthcare organizations in their network, and their database primarily relies on ICD coding, which may be limited by excluding free text data or miscoding.

However, the results of this study are consistent with those of prior studies, demonstrating that oral and topical 5ARIs can provide an appropriate treatment alternative for women with alopecia and/or hyperandrogenism. Dermatologists can consider using these agents in patients who have failed other treatment modalities or have contraindications to medications such as spironolactone or oral minoxidil.