Do Pleiotropic Effects of Spironolactone in Women with PCOS Make it More than an Anti-androgen? Evidence from a Systematic Review and Meta-analysis

Background: Spironolactone use as a treatment for hirsutism and other dermatological conditions among polycystic ovary syndrome (PCOS) and idiopathic hirsutism shows varied results. Objective: This study thus summarizes the entire evidence to better define its impact on Ferriman-Gallwey (FG) score in addition to other derangements associated with PCOS. Methods: PubMed, Embase, Scopus and bibliographies of relevant articles were searched. Randomized controlled trails (RCTs) investigating the efficacy of spironolactone in PCOS and idiopathic hirsutism were included. Pooled mean difference (MD) was calculated using random effects model and relevant subgroup analysis was done. Potential heterogeneity and publication bias was assessed. Results: Of 1041 retrieved studies, 24 RCTs were included. Spironolactone (100 mg/daily) exhibited a significant reduction in FG score in idiopathic hirsutism compared to finasteride (MD: -2.43; 95% C.I: -3.29, -1.57) and cyproterone acetate (MD: -1.18; 95% C.I: -2.10, -0.26), however, no significant difference was found among PCOS subjects in comparison to flutamide and finasteride. A lower dose of spironolactone (50 mg/day) exhibited no significant difference relative to metformin on FG Score (MD: -0.61; 95% C.I: -1.76, 0.54, I² = 57%), serum total testosterone (MD: -0.61; 95% C.I: -1.76, 0.54), I² = 57% and HOMA-IR (MD: 1.03; 95% C.I: -1.22, 3.29), I² = 60% among PCOS women. The main side effects reported by the studies were menstrual irregularity, mild nausea, vomiting and diarrhea. Conclusion: Spironolactone is well tolerated among idiopathic hirsute and PCOS women. The drug significantly improved hirsutism in the former group and shows a positive trend in the latter women, however, displays no effect on FSH, LH, menstrual cyclicity, BMI, and HOMA-IR in PCOS women.