Effects of pharmacological, lifestyle, and combined interventions on body composition and metabolic health in women with excess adiposity and polycystic ovary syndrome: a systematic review and network meta-analysis of randomised controlled trials

Summary Background Polycystic ovary syndrome (PCOS) is a common endocrine disorder often accompanied by excess adiposity, which exacerbates metabolic and reproductive complications. We aimed to compare the effectiveness of lifestyle interventions, pharmacological therapies, and their combination in women with PCOS and overweight or obesity. Methods In this systematic review and meta-analysis, we searched Embase, MEDLINE, CENTRAL, PsycINFO, and PubMed from inception of each database to July 8, 2025, for randomised controlled trials assessing lifestyle and pharmacological interventions for women with PCOS and excess adiposity published in English. Frequentist random-effects network meta-analyses were conducted based on a six-node framework: control (placebo, no treatment, or standard care), lifestyle interventions (ie, structured diet, exercise, or both), metabolic and weight-loss pharmacotherapies (pharm-MWT), hormonal pharmacotherapies (pharm-HT), and a combination of lifestyle interventions and pharmacotherapy (COM-MWT and COM-HT). Primary outcomes were body composition measures, including BMI, waist circumference, and waist-to-hip ratio (WHR). The study protocol was registered with PROSPERO (CRD42024607409). Findings We included 66 studies in the systematic review and 52 (3644 participants) studies in the networked meta-analysis. In the primary analysis, COM-MWT was the most effective strategy compared with control, significantly improving body composition: BMI (mean difference –1·99 kg/m2 [95% CI –2·80 to –1·17]), waist circumference (–5·92 cm [–8·60 to –3·25]), and WHR (–0·05 [–0·10 to –0·01]). Compared with control, significant improvements were also observed for COM-HT (BMI –1·37 kg/m2 [–2·64 to –0·09]; waist circumference –5·39 cm [–10·05 to –0·72]; and WHR –0·03 [–0·10 to 0·04]) and lifestyle interventions alone (BMI –1·14 kg/m2 [–1·64 to –0·64]; waist circumference –3·64 cm [–5·35 to –1·94]; and WHR –0·03 [–0·06 to 0·00]). Pharm-MWT (BMI –0·63 kg/m2 [–1·39 to 0·13]; waist circumference –1·84 cm [–4·49 to 0·81]; and WHR –0·02 [–0·05 to 0·02]) and pharm-HT (BMI 0·10 kg/m2 [–0·75 to 0·94]; waist circumference –1·34 cm [–5·07 to 2·38]; and WHR 0·00 [–0·07 to 0·07]) did not yield statistically significant improvements. Interpretation Combination therapies, especially those pairing lifestyle interventions with medications targeting metabolic dysfunction and weight loss, offer the most comprehensive benefits for women with excess adiposity and PCOS. This integrated approach improves body composition and metabolism more than lifestyle alone. Although widely used to manage reproductive symptoms, oral contraceptive pills provide minimal benefits for body composition and metabolic health. Future work must focus on refining these combined regimens to further enhance clinical guidelines and patient results. Funding Initiation Grant for Faculty Niche Research Area (grant number 160300) and Tier 1 Research Start-up Grants, Hong Kong Baptist University, Hong Kong Special Administrative Region, China.