Obesity linked to reproductive disorders like preeclampsia

Obesity was associated with an increased risk for reproductive disorders among women, according to findings published in PLoS Medicine.

“Our understanding is that the causal role of obesity in female reproductive disorders is heterogeneous in its effect and may be driven by different types of obesity,” Samvida S. Venkatesh, a doctoral student in genome sciences and genetics at the University of Oxford, told Healio. “For example, an increase in BMI of 5 kg/m² is associated with double the risk for preeclampsia, a 20% increase in risk for uterine fibroids, but has no association with infertility or endometriosis. Conversely, an increased waist-to-hip ratio independent of BMI, which is a measure of abdominal obesity, increases the risk of endometriosis and infertility.”

In a Mendelian randomized study, Venkatesh and colleagues used data from the U.K. Biobank to evaluate the association of BMI and waist-to-hip ratios (WHR) with the risk for reproductive conditions, including endometriosis, uterine fibroids, polycystic ovary syndrome, heavy menstrual bleeding, preeclampsia, stillbirth or miscarriage and infertility. The researchers also used data from publicly available genome-wide association studies to determine genetic associations. The analysis included 257,193 women of white European ancestry aged 40 to 69 years.
Overall, 57.8% of participants did not have any reproductive disorder. Among these individuals, the mean age was 57.22 years, the mean BMI was 26.89 kg/m² and the mean WHR was 0.82 cm.

Among the reproductive disorders experienced by the remaining participants, the most common were stillbirth, miscarriage or termination of pregnancy (31.5%), uterine fibroids (7.46%) and heavy menstrual bleeding (6.7%), according to Venkatesh and colleagues. The mean age of women who had experienced a stillbirth, miscarriage or pregnancy termination was 55.84 years; the mean BMI was 27.1 kg/m² and the mean WHR was 0.82 cm. Among women with uterine fibroids, the mean age was 56.86 years, the mean BMI was 27.63 kg/m² and the mean WHR was 0.82 cm. The mean age of women who had ever experienced heavy menstrual bleeding was 52.52 years, the mean BMI was 27.86 kg/m² and the mean WHR was 0.82 cm.

The researchers reported that BMI, WHR and WHR adjusted for BMI were observationally (ORs = 1.02-1.87 per 1-SD increase in obesity trait) and genetically (ORs = 1.06-2.09) associated with uterine fibroids, PCOS, heavy menstrual bleeding and preeclampsia. Also, genetically predicted visceral adipose tissue mass was associated with heavy menstrual bleeding (P = .013), PCOS (OR = 1.15; 95% CI, 1.08-1.23) and preeclampsia (OR = 3.08; 95% CI, 1.98-4.79). A larger waist circumference was associated with a higher genetic risk (ORs = 1.16-1.93) for the development of these specific disorders in addition to uterine fibroids compared with a larger hip circumference (ORs = 1.06-1.1), according to Venkatesh and colleagues.

They reported that leptin, fasting insulin and insulin resistance mediated 20% to 50% of the total genetically predicted association of obesity with preeclampsia. Genetic variation associated with obesity was also linked to reproductive disorders. However, these associations varied by type of obesity and type of disorder, the researchers said. The strongest disorder associated with obesity was preeclampsia. Endometriosis was the only disorder inconsistently linked to obesity, according to the researchers.

Since the analyses included an overrepresentation of women of European ancestry, the results “may not be transferable to those of other genetic ancestries,” Venkatesh said.

She added that, since there were no associations between BMI and infertility, yet higher abdominal obesity increases the risk for infertility, “there may be nonlinear effects of body weight on infertility.”

Based on the findings and previous studies, “there is currently no evidence that physicians should be recommending weight loss to women who want to get pregnant,” Venkatesh said.