Effect of Weight Loss Interventions on the Symptomatic Burden and Biomarkers of Polycystic Ovary Syndrome : A Systematic Review of Randomized Controlled Trials.

Background: Polycystic ovary syndrome (PCOS) is common in women of reproductive age and is associated with obesity. Clinical guidelines recommend weight loss, but the impact on the clinical manifestations of PCOS is unclear.

Purpose: To quantify the effect of weight loss interventions on clinical features of PCOS, compared with usual care.

Data sources: MEDLINE, Embase, PsycINFO, CINAHL, Cochrane, Web of Science, and trial registries were searched from inception through June 2024.

Study selection: Randomized controlled trials comparing interventions aiming to reduce weight against usual care, including lower-intensity weight loss interventions in people with PCOS. Conversations with people with PCOS informed the outcomes.

Data extraction: Pairs of independent reviewers screened studies, extracted data, and assessed risk of bias (RoB). Outcomes included glycemic control (Homeostasis Model Assessment for Insulin Resistance [HOMA-IR], fasting insulin and glucose), hormonal markers (free androgen index [FAI] and other sex hormones), menstrual frequency, hirsutism, and PCOS-related quality of life (QoL). Pooled mean differences were obtained from random-effects meta-analysis with Knapp-Hartung adjustment.

Data synthesis: Primary analyses included 29 comparisons with 1529 participants: 13, 12, and 4 comparisons were judged as high, some, or low RoB, respectively. Twelve used behavioral interventions, 9 used glucagon-like peptide-1 (GLP1) agonists, and 8 used other weight loss medications. Weight loss interventions were associated with significantly greater improvements in HOMA-IR (mean difference, -0.45 [-0.75 to -0.15]; I ² = 24%), FAI (mean difference, -2.03 [-3.0 to -1.07]; I ² = 48%), and menstrual frequency (mean difference, 2.64 [0.65 to 4.63]; I²  = 43%). There was no evidence that weight loss interventions were associated with clinically or statistically significant improvements in hirsutism, QoL, or other sex hormones, which may be due to the limited power of the available data.

Limitation: There was high statistical heterogeneity in the interventions, comparators, and outcomes, largely unexplained by sensitivity and subgroup analyses.

Conclusion: Weight loss interventions were associated with improvements in some important features of PCOS and should be considered as a routine treatment option for people with PCOS.

Primary funding source: National Institute for Health and Care Research School for Primary Care Research. (PROSPERO: CRD42022367488).