Association of leukocyte telomere length alteration with polycystic ovary syndrome in Pakistani population: a case-control study with meta-analysis

Telomere shortening has been implicated in cellular aging and may play a role in the pathophysiology of polycystic ovary syndrome (PCOS). The main objective is to investigate the relationship between leukocyte telomere length (LTL) and polycystic ovary syndrome (PCOS) in a Pakistani population and to contextualize findings through a meta-analysis of existing literature. This case-control study included 280 participants (120 PCOS patients and 160 age-matched healthy controls). Biochemical and hormonal profiles were assessed. Telomere length was measured by qPCR. Correlation and multiple regression analyses were conducted. A meta-analysis (8 studies) with sensitivity and meta-regression analyses was performed. PCOS patients had significantly higher BMI, total cholesterol, triglycerides, LDL, and VLDL (p < 0.001), and lower HDL (p < 0.001). LH, FSH, and prolactin levels were significantly elevated (p < 0.05), with no significant difference in testosterone. LTL was significantly shorter in PCOS women (p = 0.007). LTL correlated negatively with BMI (r=–0.157, p = 0.035) and LH (r=–0.192, p = 0.001). Regression analysis showed a significant association between PCOS and LTL (p = 0.006) after adjusting for age and BMI. A PCOS×BMI interaction was significant (β=-0.241, p = 0.001). Meta-analysis revealed a non-significant trend towards a shorter LTL (SMD = 1.21, p = 0.123), high heterogeneity (I²=99.6%), and no publication bias (Egger’s p = 0.975). Removal of one study altered significance (p = 0.002). Meta-regression found no moderating effects of age or BMI. Shorter LTL in PCOS may reflect underlying metabolic and hormonal dysregulation, particularly influenced by obesity. The meta-analysis findings remain inconclusive due to extreme heterogeneity and limited power, and should be considered exploratory, underscoring the need for larger, standardized longitudinal studies.