SRD5A2 and emerging therapies in androgen-driven disorders

Benign prostatic hyperplasia (BPH) is one of the most prevalent urological disorders in ageing men. Medical therapies are widely used to treat BPH, but truly effective long-term treatments remain limited. Among the most commonly prescribed drugs are 5α-reductase inhibitors (5ARIs), which alleviate symptoms and slow disease progression by inhibiting steroid 5α-reductase (SRD5A) enzymes, particularly the SRD5A1 and SRD5A2 isoforms. SRD5A2, the dominant isoform in the prostate, has a pivotal role in androgen metabolism by converting testosterone into dihydrotestosterone, a potent driver of prostate growth. Proper regulation of SRD5A2 is essential to maintain the balance between androgenic and oestrogenic signalling, thereby supporting healthy prostate physiology. Emerging evidence links SRD5A2 alterations, such as genetic polymorphisms, epigenetic silencing and inflammation-induced changes to disease risk and progression, positioning these factors as promising biomarkers for personalized therapy. Beyond BPH, SRD5A2 has also been implicated as a potential therapeutic target in prostate cancer and androgenic alopecia. Thus, SRD5A2 has clinical relevance in BPH, prostate cancer and other androgen-mediated conditions. However, limitations of SRD5A2-targeted therapies need to be overcome for future strategies to enhance the efficacy of 5ARI-based treatments.