Obesity Increases Risk of Multiple Reproductive Disorders in Women

A new study from the University of Oxford is providing clinicians with insight into the relationship between obesity and increased risk of female reproductive conditions.

A mendelian randomization study leveraging data from more than 250,000 women of European ancestry from the UK biobank and genome-wide association studies, results detail observational associations between obesity and reproductive disorders, including polycystic ovary syndrome, uterine fibroids, and preeclampsia, as well as shedding light on the etiological link between obesity and female reproductive conditions.

“We provide genetic evidence that both generalized and central obesity play an etiological role in a broad range of female reproductive conditions, but the extent of this link differs substantially between conditions. Our results suggest a need to explore the mechanisms mediating the causal associations of overweight and obesity on gynecological health to identify targets for disease prevention and treatment,” wrote investigators.

With observational data suggesting obesity is associated with increased risk of multiple female reproductive conditions, a team of investigators sought to estimate observational and genetically predicted causal associations between obesity, metabolic hormones, and female reproductive disorders. To do so, investigators designed their study as a Mendelian randomization study of 257,193 women of European ancestry aged 40-69 years from the UK Biobank.

From the UK Biobank cohort, investigators obtained data related to measurements of BMI, waist-to-hip ratio (WHR), waist circumference, and WHR adjusted for BMI, which were used to estimate the general obesity and central obesity within the cohort. Investigators fitted logistic regression models to estimate associations of BMI, WHR, and WHR adjusted BMI with prevalence of endometriosis, heavy menstrual bleeding, infertility, self-reported stillbirth, spontaneous miscarriage, or termination, polycystic ovary syndrome, preeclampsia, and uterine fibroids.

In observational analyses, BMI, WHR, and WHR adjusted for BMI were associated with increased risk of uterine fibroids, polycystic ovary syndrome, heavy menstrual bleeding, and preeclampsia (ORs=1.02–1.87 per 1-SD increase in obesity trait). In analyses assessing genetic associations, results indicated BMI, WHR, and WHR adjusted for BMI were associated with increased risk of uterine fibroids, polycystic ovary syndrome, heavy menstrual bleeding, and preeclampsia (ORs=1.06–2.09).

Further analysis suggested genetically predicted visceral adipose tissue (VAT) mass was associated with the development of HMB (OR per 1 kg increase in predicted VAT mass, 1.32 [1.06–1.64], P=.0130), polycystic ovary syndrome (OR, 1.15 [1.08–1.23], P=3.24×10-05), and preeclampsia (OR, 3.08 [1.98–4.79], P=6.65×10-07). Additionally, results indicated increased waist circumference posed a higher genetic risk for the de elopement of these disorders and uterine fibroids than increased hip circumference (ORs-1.06-1.10).

Investigators pointed out leptin, fasting insulin, and insulin resistance each mediated between 20-50% of the total genetically predicted association of obesity with preeclampsia. Investigators also pointed out reproductive conditions clustered based on shared components of their etiological relationships with obesity.

“Our findings also highlight the importance of hormonal pathways, notably those involving leptin and insulin resistance, as mediating mechanisms and potential targets for intervention in the treatment and prevention of common female reproductive conditions,” wrote investigators.

This study, “Obesity and risk of female reproductive conditions: A Mendelian randomisation study,” was published in PLOS Medicine.