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A genetic analysis led by BDI researchers indicates that both overall and central obesity directly increases the risk of many female reproductive conditions.

Obese woman

Female reproductive disorders are common, yet relatively understudied, conditions which have a large impact on the health and overall wellbeing of many women. These conditions include uterine fibroids, polycystic ovary syndrome, heavy menstrual bleeding, and pregnancy complications such as infertility, pre-eclampsia and miscarriage.

Previous studies have found obesity to be associated with an increased risk of female reproductive disorders, but it is not clear if obesity itself directly causes these diseases. Potentially, obesity may increase the risk of female reproductive disorders through insulin-resistance, dysregulated sex hormones, or increased production of leptin (a hormone secreted by adipocytes). Alternatively, the association between obesity and reproductive disorders may instead be driven by weight gain caused by these diseases or their treatments, as well as confounding environmental and lifestyle factors.

To investigate the role of obesity in female reproductive disorders, a new study led by BDI researchers used a genetic approach using data from participants of the UK Biobank Study. The results have been published today in PLOS Medicine.

The analysis was based on medical, environmental and genetic data for 257,193 women of European ancestry aged 40-69. The researchers searched for genetic variations known to predispose people to a higher overall body mass index (BMI)*, or greater fat deposition around the middle (central obesity). People with these gene variations are more likely to become overweight or obese because they inherit these genes. These gene variants are randomly assigned at birth, therefore they provide a method to estimate the effect of obesity without bias from lifestyle and environmental factors, or reverse causation.

The researchers then created a statistical model to estimate the association between overall and central obesity with the risk of numerous female reproductive conditions.

Key findings:

  • There was a positive observational association between obesity (measured as BMI at recruitment) and most of the female reproductive disorders, including uterine fibroids, polycystic ovary syndrome, heavy menstrual bleeding, and pre-eclampsia.
  • The genetic analysis revealed that having a higher genetically predicted risk for obesity was also associated with an increased risk of developing many female reproductive disorders, but the strength of these associations differed by the type of obesity and reproductive condition. The strongest association was between overall obesity and pre-eclampsia.
  • For some disorders, the association with obesity was driven mainly by fat deposition over all the body (eg heavy menstrual bleeding and miscarriage), whilst for others the association was driven only by central obesity (eg infertility and endometriosis). In some cases, both overall and central obesity appeared to play a role (eg pre-eclampsia and uterine fibroids).
  • For both overall and central obesity, the positive association with pre-eclampsia was found to be partly driven by insulin resistance and increased levels of leptin.

According to the researchers, the findings indicate that insulin resistance could be a potential target for treating and preventing some female reproductive disorders driven by obesity, since affordable and safe treatments are available to improve insulin sensitivity.

Lead author Samvida Venkatesh, a PhD student at the BDI, said: ‘Our research shows  that both overall and central obesity play a role in causing a broad range of female reproductive conditions, but the extent of this link differs substantially between conditions. Our results suggest a need to explore what is causing the associations between overweight and obesity and gynaecological conditions to identify targets for disease prevention and treatment.’

*Body mass index (BMI) is a measure of weight relative to a person’s height. It is calculated by dividing a person’s weight (in kilograms) by the square of their height (in metres). A BMI between 18.5 and 24.9 kg/m² is considered a healthy weight; a BMI between 25 and 29.9 kg/m² is classed as overweight; and a BMI greater than 30 kg/m² is classed as obese.