Obesity Increases Risk of Female Reproductive Disorders

Obesity is associated with uterine fibroids and pre-eclampsia, in addition to polycystic ovary syndrome (PCOS) and heavy menstrual bleeding, according to the results of a recent analysis.

Although obesity has been associated with increased risk of female reproductive disorders, observational estimates of this association may have been biased by confounding environmental and lifestyle factors.

To further explore this association, Oxford University researchers applied logistic regression, generalized additive models, and Mendelian randomization to obesity and reproductive disease data on more than a quarter million women of European ancestry in the UK Biobank and in publicly available genome-wide association studies. Their study also aimed to eliminate bias from confounding environmental and lifestyle factors by estimating the effect of genetically predicted causal associations between obesity and reproductive disorders.

As a result, they found that body mass index (BMI), waist-to-hip ratio, and waist-to-hip ratio adjusted for BMI were observationally associated with uterine fibroids, PCOS, heavy menstrual bleeding, and pre-eclampsia.

Moreover, their results indicated that leptin and insulin mediate the genetic association between obesity and pre-eclampsia. More specifically, leptin, fasting insulin, and insulin resistance each mediate between 20% and 50% of the total genetically predicted association between obesity and pre-eclampsia.

The researchers also found that although inherited genetic variation associated with obesity is also associated with female reproductive disorders, the strength of these associations differed by type of obesity and reproductive disorder.

For example, genetically predicted visceral adipose tissue mass was associated with having pre-eclampsia and heavy menstrual bleeding. Moreover, compared with increased hip circumference, increased waist circumference conferred greater genetic risk of having these disorders and uterine fibroids.

 “Our results suggest the utility of exploring the mechanisms mediating the causal associations of overweight and obesity with gynaecological health to identify targets for disease prevention and treatment,” the researchers concluded.

—Ellen Kurek

Reference:

Venkatesh SS, Ferreira T, Benonisdottir S, et al. Obesity and risk of female reproductive conditions: a Mendelian randomisation study. PLoS Med. Published online February 1, 2022. doi:10.1371/journal.pmed.1003679