Lowering blood sugar could improve fertility in obese women

According to a study published in the Journal of Endocrinology. The study indicates that altered levels of reproductive hormones in a well-established mouse model of obesity can be partially restored by a common type 2 diabetes drug that lowers blood sugar. Many obese women who have fertility issues also have altered levels of reproductive hormones. There is currently no effective therapy to remedy this. Developing a therapy that not only improves women’s metabolic health but also treats obesity-related infertility would be a significant step forward, with the potential to improve the quality of life for many people.

Although fertility problems are well established in obese women, there remains a lack of effective and targeted treatments to address them. Obesity is a growing health epidemic, which means that more and more women are affected by reproductive difficulties. Obesity-related fertility issues are complex, but evidence suggests they may be linked in part to changes in energy metabolism, which lead to altered levels of reproductive hormones which can then disrupt the menstrual cycle and ovulation. Obese people are more at risk of develop type 2 diabetes and often have high blood sugar, along with other metabolic changes.

The MC4R gene knockout (KO) mouse is a well-characterized model of obesity, which also exhibits irregular reproductive cycles with altered hormone levels that lead to reduced fertility. The reproductive cycle of mice is similar to that of humans, in that the profile of changes at the hormonal level is analogous, although much shorter, so the MC4R KO mouse is a good model representative for early investigations of metabolic and reproductive function in obesity.

Dapagliflozin is a drug commonly used to treat type 2 diabetes, where it lowers blood sugar and improves other markers of metabolic health, but its effects on reproductive health and fertility have not yet been studied.

In this study, Professor Chen and colleagues from the University of Queensland in Australia investigated the effects of dapagliflozin treatment on metabolic health and reproductive hormone levels in the MC4R mouse model of obesity. After only 8 weeks of treatment, blood sugar levels were normal, body weight was reduced, the reproductive cycle was normalized, and reproductive and ovulation hormone levels were partially restored, compared to untreated mice.

“We often see low fertility in obese women in clinical practice,” comments lead author Dr. Cui, a visiting scientist at Chengdu Women’s and Children’s Hospital in China, “so this research gives hope of a future effective treatment”.

These data suggest that normalizing blood glucose metabolism with dapagliflozin in obesity may be a promising avenue to at least partially restore reproductive function. It could improve fertility in women for whom no other effective therapy is currently available.”


Professor Chen, University of Queensland, Australia

However, Professor Chen cautions: “While encouraging, these studies were conducted in mice and much more work needs to be done to confirm that these results could be replicated effectively in women. However, people who are obese are at a much higher risk of developing type 2 diabetes, so the known health benefits of blood sugar correction may extend to improving fertility in those affected.

The team now intends to further investigate the therapeutic benefits of using dapagliflozin to improve reproductive function by examining the molecular pathways involved, which could identify better targets for future fertility treatment. in women.

Source:

Journal reference:

Cui, L. et al. (2022) Dapagliflozin partially restores reproductive function in obese female MC4R KO mice. Journal of Endocrinology. doi.org/10.1530/JOE-21-0449.

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