Parental Consanguinity, Spousal Relatedness, and Familial Aggregation as Modifiers of PCOS Severity: Evidence From a 500-Case Clinic Cohort in Pakistan

Abstract

Background: Polycystic ovarian syndrome (PCOS) is a complex endocrine disorder with diverse reproductive and metabolic manifestations. Genetic susceptibility and familial clustering are believed to influence disease severity, particularly in regions with prevalent consanguineous and endogamous marriage patterns. Understanding how intra-familial relationships modify the clinical expression of PCOS may aid in early detection and targeted interventions. Objective: To evaluate the association of parental consanguinity, spousal relatedness, and familial aggregation with reproductive and androgenic severity among women with PCOS. Methods: An analytical cross-sectional study was conducted on 500 women aged 18–40 years diagnosed using Rotterdam criteria. Data were collected on demographic, familial, and clinical parameters. Serum testosterone, Ferriman–Gallwey scores, and reproductive outcomes were compared across familial categories. Multivariable logistic regression adjusted for age, BMI, and residence was applied to assess associations between familial factors and severity indices. Results: Parental consanguinity was present in 61.2% and spousal relatedness in 45.8% of participants. Women with consanguineous parentage had earlier diagnosis (24.3 vs. 26.5 years, p<0.001), higher testosterone (0.82 vs. 0.72 ng/mL, p=0.002), and greater infertility (58.5% vs. 41.6%, OR=1.91, p=0.002). Familial aggregation doubled the odds of combined infertility and hirsutism (OR=2.23, p<0.001). Conclusion: Parental consanguinity, spousal relatedness, and familial clustering independently predict earlier onset and greater severity of PCOS. Family-structure assessment should be integrated into screening and counseling strategies. Keywords: Polycystic ovarian syndrome, Consanguinity, Family history, Spousal relatedness, Hyperandrogenism, Infertility, Genetic predisposition