Female reproductive disorders are common conditions affecting the health and well-being of many. However, the role of obesity in the development of female reproductive conditions is under-studied. To investigate the causal associations between obesity, metabolic hormones, and female reproductive disorders, researchers conducted a Mendelian randomization study of 257,193 women of European ancestry aged 40-69. They accessed records from UK Biobank, a large-scale biomedical database containing the medical, environmental, and genetic information of participants. The researchers then created a statistical model to estimate the association of body mass index and waist-to-hip ratio with the risk of numerous female reproductive conditions including endometriosis, heavy menstrual bleeding, pre-eclampsia, and infertility.
The researchers found observational associations between obesity and a range of female reproductive disorders, including uterine fibroids, polycystic ovary syndrome, heavy menstrual bleeding, and pre-eclampsia. They also found that some inherited genetic variation associated with obesity is also associated with female reproductive disorders, but the strength of those associations differed by type of obesity and reproductive condition. The study had several limitations, such as the low prevalence of female reproductive disorders among participants, and a lack of body mass index and waist-hip-ratio data prior to disease onset.
According to the authors, “We provide genetic evidence that both generalised and central obesity play an aetiological 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 gynaecological health to identify targets for disease prevention and treatment.”
ABSTRACT:
What did the researchers do and find?
- In one of the largest publicly available datasets on human health, which includes up to 250,000 women, we saw positive associations between obesity and a range of female reproductive disorders, including uterine fibroids, polycystic ovary syndrome, heavy menstrual bleeding, and pre-eclampsia.
- We found that inherited genetic variation that is associated with obesity is also associated with female reproductive disorders, but the strength of these associations differs by type of obesity and reproductive condition. As genetic variants are randomly assigned at birth, this is a method to estimate the effect of obesity on reproductive conditions unbiased by environmental and lifestyle factors or reverse causation.
- Hormones such as leptin, which is secreted by fat cells, and insulin were found to mediate the genetic association of obesity with pre-eclampsia.
What do these findings mean?
- Genetics-based investigations such as these provide support for the role of obesity in increasing the risk of reproductive conditions, reinforcing the need to address rising obesity rates in the population.
- Increased obesity and insulin resistance are potentially modifiable risk factors, and addressing these risk factors could help mitigate or treat female reproductive disorders, but further research must confirm that their manipulation influences the risk of disease.
Conclusions
“We found that common indices of overall and central obesity were associated with increased risks of reproductive disorders to heterogenous extents in a systematic, large-scale genetics-based analysis of the aetiological relationships between obesity and female reproductive conditions. Our results suggest the utility of exploring the mechanisms mediating the causal associations of overweight and obesity with gynecological health to identify targets for disease prevention and treatment.”
