BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with metabolic and hormonal abnormalities. This study aimed to evaluate the comparative efficacy of pharmacological interventions on these outcomes. METHODS: We conducted a systematic review and network meta-analysis of randomized controlled trials (RCTs) assessing pharmacological treatments for PCOS. Searches in PubMed, MEDLINE, Embase, and Web of Science were conducted up to October 20, 2023. Eligible studies were RCTs with at least 12 weeks of follow-up and outcomes including body weight (BW), body mass index (BMI), waist circumference (WC), testosterone, sex hormone-binding globulin (SHBG), lipid profiles, HOMA-IR, fasting blood glucose (FBG), and fasting insulin (FINS). RESULTS: Twenty-nine RCTs with 1476 participants were included. The combination of standard therapy with GLP-1 receptor agonists significantly reduced BW (MD= -3.44
95% CI= -6.20 to -0.67), BMI (MD= -2.05
95% CI= -3.55 to -0.55), and WC (MD= -4.39
95% CI= -6.75 to -2.02) compared to standard therapy alone. Orlistat significantly lowered testosterone (SMD= -2.16
95% CI= -3.84 to -0.48) and increased HDL-C levels (SMD = 0.90
95% CI = 0.02 to 1.79) compared to placebo. The combination therapy also reduced HOMA-IR (MD= -1.29
95% CI= -2.38 to -0.21) and FBG (SMD= -1.80
95% CI= -3.04 to -0.55) compared to placebo. CONCLUSION: Combining standard therapy with GLP-1 receptor agonists offers superior efficacy in improving metabolic and hormonal outcomes in women with PCOS. Orlistat effectively reduces androgen levels. These findings support the use of combination pharmacotherapy for comprehensive management of PCOS.