SUN-113 Lean PCOS Unmasked: Can Metformin and Flutamide Transform Metabolism and Fertility?

Abstract Disclosure: V.A. Mendpara: None. S. Sahu: None. B. Padamati: None. K. Navyaja: None. G. Palaniswamy: None. A.J. Augustine: None. P.R. Patel: None. T. Mareedu: None. T. Jain: None. Background: Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder affecting reproductive-age women, characterized by hyperandrogenism, ovarian dysfunction, and metabolic disturbances. While obesity is often linked to PCOS, a distinct subset, lean PCOS, presents without obesity but still experiences metabolic and reproductive complications. The pathophysiology of lean PCOS differs from obese PCOS, making treatment more complex. Despite available pharmacological and lifestyle interventions, their long-term effects remain unclear. This meta-analysis assesses the efficacy of various treatment strategies in lean PCOS by evaluating weight change, insulin sensitivity, ovulation rate, and cardiovascular risk factors. Methods: A systematic search was conducted across PubMed, Scopus, Elsevier, Springer, BMC, and Google Scholar. Inclusion criteria comprised randomized controlled trials (RCTs) and prospective cohort studies assessing pharmacological (e.g., Metformin, Flutamide, oral contraceptives) and lifestyle interventions (e.g., dietary modifications, physical activity) in lean PCOS patients. Studies focusing solely on obese PCOS were excluded. Extracted outcomes included weight change, insulin sensitivity (HOMA-IR or glucose disposal rates), ovulation rate, and cardiovascular risk factors such as blood pressure. A random-effects meta-analysis was conducted to calculate pooled effect sizes with 95% confidence intervals (CIs). Statistical heterogeneity was assessed using the I-squared (I²) statistic. Sensitivity analyses were conducted to assess the reliability of the findings. Results: Five studies encompassing 299 lean PCOS patients were analyzed. The meta-analysis indicated a modest reduction in body weight (pooled effect size 0.40 kg, 95% CI: 0.23 to 0.57), suggesting weight management remains a challenge. Insulin sensitivity improved (SMD 0.36, 95% CI: 0.10 to 0.62), particularly with Metformin. Ovulation rates significantly increased (pooled OR 2.14, 95% CI: 1.30 to 2.98), highlighting reproductive benefits. However, the impact on cardiovascular risk factors was minimal, with blood pressure showing negligible changes (pooled effect size -0.18, 95% CI: -0.38 to 0.02). Moderate heterogeneity (I²: 30-50%) was detected, suggesting some variability across studies. Sensitivity analysis confirmed the reliability of the results. Conclusion: Metformin and Flutamide improve insulin sensitivity and ovulation rates in lean PCOS patients, but their effects on weight reduction and cardiovascular risks remain inconclusive. Further large-scale, long-term RCTs are needed to optimize treatment strategies. Standardized methodologies and well-defined clinical endpoints are essential to establish evidence-based guidelines for lean PCOS management. Presentation: Sunday, July 13, 2025