Summary
This Mendelian randomisation study of up to 257,193 UK Biobank women of European ancestry investigated causal relationships between obesity, metabolic hormones, and female reproductive conditions. Body mass index, waist-to-hip ratio, and visceral adipose tissue mass showed significant genetic associations with uterine fibroids, polycystic ovary syndrome, heavy menstrual bleeding, and pre-eclampsia, with leptin, fasting insulin, and insulin resistance mediating 20–50% of the obesity–pre-eclampsia association. The findings suggest that central adiposity (waist circumference) poses greater genetic risk than peripheral adiposity (hip circumference) for these reproductive disorders.
UK applicability
This study was conducted in a UK-based population (UK Biobank) and is therefore directly applicable to understanding reproductive health risk in the United Kingdom. The findings may inform clinical assessment and management of reproductive disorders in women with obesity in UK healthcare settings, though generalisation to non-European ancestry populations remains limited.
Key measures
Odds ratios per 1-SD increase in obesity trait; odds ratios per 1-kg increase in predicted visceral adipose tissue mass; mediation proportions for leptin, fasting insulin, and insulin resistance
Outcomes reported
The study estimated observational and genetically predicted causal associations between obesity measures (BMI, waist-to-hip ratio, visceral adipose tissue), metabolic hormones, and five female reproductive conditions (PCOS, uterine fibroids, heavy menstrual bleeding, endometriosis, pre-eclampsia, infertility, and abnormal uterine bleeding). Mediation analysis quantified the proportion of obesity's effect on reproductive disease attributable to leptin, fasting insulin, and insulin resistance.
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