Anti-androgen therapy in polyendocrine metabolic ovary syndrome (PMOS, formerly PCOS): efficacy, safety, and phenotype-oriented clinical decision-making

Polyendocrine metabolic ovarian syndrome (PMOS, formerly polycystic ovary syndrome [PCOS]), hereinafter referred to as PMOS/PCOS, is the most prevalent endocrine metabolic disorder among women of reproductive age. It is characterized by a self-perpetuating cycle in which hyperandrogenemia (central in several, but not all, phenotypes) acts as the primary driver, exacerbating reproductive dysfunction, metabolic disturbances, and psychological distress. Anti-androgen therapy remains an important treatment for alleviating hyperandrogenism-related clinical signs, including hirsutism, acne, and female-pattern hair loss. In this review, we provided a comprehensive molecular analysis of hyperandrogenism in PMOS/PCOS, systematically evaluated the efficacy of key anti-androgen agents, including combined oral contraceptives, spironolactone, cyproterone acetate, finasteride, and emerging therapies, and assessed their safety profiles concerning metabolic, reproductive, and general adverse effects. We further examine integrated management strategies combining pharmacotherapy, lifestyle modifications, insulin sensitizers such as metformin, and emerging integrative approaches. Special considerations for adolescents, women planning pregnancy, and individuals with obesity are highlighted. This review also addressed current controversies, including uncertainties regarding long-term cardiovascular safety, optimal treatment duration, and the lack of predictive biomarkers, outlining future research priorities. Finally, we proposed a practical phenotype-guided framework for the stratified clinical management of hyperandrogenic PMOS/PCOS.