Endocrine Abstracts

Background: Observational and genetic Mendelian randomisation (MR) data has demonstrated the association of adulthood overweight/obesity with development of polycystic ovary syndrome (PCOS). However, the contribution of early life (i.e. childhood/adolescence) body composition on incident PCOS is unclear. This study determines the influence of body composition on the likelihood of developing PCOS.

Methods: We conducted a 2-sample Mendelian randomisation study to determine the impact of body composition and metabolic parameters (fasting serum insulin or sex-hormone binding globulin) on the odds of PCOS. PCOS genome-wide association study meta-analysis data (from 10,074 people with PCOS, 103,164 controls) was interrogated using the inverse-variance weighted method. Furthermore, we conducted a systematic review (71 studies) and meta-analysis (63 studies) of the role of overweight, obesity and central obesity (defined via waist circumference / waist-hip ratio) on odds of PCOS in adults and adolescents.

Results: From Mendelian randomisation, significant associations were shown between body composition and odds of PCOS. For every standard deviation increase in BMI (a BMI increase of 4.8 kg/m²), odds of PCOS increased significantly (OR: 2.76, 2.27 - 3.35). Similar associations were demonstrated between body fat percentage (OR: 3.05 per 8.5%, 2.24 - 4.15), whole-body fat mass (OR: 2.53 per 9.6 kg, 2.04 - 3.14), fasting insulin (OR: 6.98 per 0.79 pmol/l, 2.02 - 24.13) and sex-hormone binding globulin (OR: 0.74 per 28 nmol/l, 0.64 - 0.87). Genetically determined childhood body size increased odds of PCOS after adjusting for adult body size (OR: 2.56, 1.57 - 4.20). From meta-analysis, women with overweight (OR 3.80, 2.87- 5.03)), obesity (OR 4.99, 3.74 – 6.67) and central obesity (OR 2.93, 2.08 – 4.12) had increased odds of PCOS. For adolescents with overweight and/or obesity the PCOS odds were greater than for adults (adult vs adolescent: overweight: OR 3.57 and 5.32; Obese: OR 4.66 and 7.86).

Conclusions: Using two complementary epidemiological techniques we demonstrate a clear relationship between markers of body composition, indicative of excess body fat accumulation, and odds of developing PCOS, especially in childhood and adolescence. MR reports that genetically determined childhood body composition increases PCOS likelihood independent of adult body composition. From meta-analysis, women with overweight, obesity and central obesity had increased odds of PCOS, with odds even higher in adolescents with overweight and obesity. Overall, this study has implications for the prevention and treatment of obesity and the importance of effective weight maintenance from early years and beyond.