Polycystic Ovary Syndrome and Cardiometabolic Health Across Generation: Insights from 25 Years of the Tehran Lipid and Glucose Study (TLGS)

Context: Polycystic ovary syndrome (PCOS) affects an increasing number of reproductive-aged women and has been progressively associated with a spectrum of metabolic disturbances. Understanding its long-term cardiometabolic consequences, both in affected women and in their offspring, is critical for informing early prevention and targeted intervention strategies. This study provides a comprehensive synthesis of published data from the Tehran lipid and glucose study (TLGS) on women with PCOS, offering insights into epidemiological patterns, risk factors, and potential intergenerational impacts in this population. Evidence Acquisition: This narrative review provides a comprehensive summary of TLGS-based publications addressing cardiometabolic disorders associated with PCOS. Relevant studies were identified through a comprehensive search of PubMed (including Medline), Web of Science, and Scopus. Results: Data from the TLGS indicate a rising prevalence of PCOS over approximately a decade, increasing from 8.5% based on the National Institutes of Health (NIH) criteria to 13.6% (NIH), 17.8% (androgen excess (AE)-PCOS Society), and 19.4% (Rotterdam criteria). Women with PCOS in early adulthood demonstrated elevated levels of insulin resistance (IR) as reflected by higher HOMA-IR and fasting insulin values, and subsequently experienced a heightened likelihood of developing type 2 diabetes mellitus (T2DM), hypertension, metabolic syndrome (MetS), and obesity, with adjusted hazard ratios ranging from approximately 0.58 to 2.08 across multiple publications. Notably, the prevalence of certain cardiometabolic disorders appeared to decline after the age of 40 years. Longitudinal data showed that trajectories of HOMA-IR and fasting insulin differed depending on obesity status in women with PCOS, and that cardiometabolic risk burden varied across diagnostic phenotypes. Interestingly, PCOS was not associated with an increased risk of silent coronary artery disease. Nevertheless, the Framingham risk score (FRS) showed good predictive performance for cardiovascular disease (CVD) in the PCOS population, with a 38% increase in CVD risk per 1-unit increment in FRS among affected women. Intergenerational analyses further highlighted that the offspring of women with PCOS carry a higher predisposition to metabolic disorders. Daughters of affected women were found to have increased risks of T2DM, overweight, and MetS. At the same time, sons exhibited significantly elevated risk of pre-diabetes mellitus, with adjusted hazard ratios ranging from approximately 1.3 to 2.4. These findings underscore both the individual and transgenerational cardiometabolic disorders of PCOS. Conclusions: Publications from the TLGS provide consistent evidence that PCOS is associated with a spectrum of early cardiometabolic disturbances in affected women with potential adverse impacts extending to their offspring. These observations underscore the importance of implementing age-specific metabolic screening and preventive interventions for women with PCOS and their offspring. Furthermore, they highlight the need for long-term, prospective follow-up studies to elucidate underlying causal pathways and identify targeted strategies for timely intervention.