Lowering blood glucose levels could improve fertility in obese women

According to a study published in the publication Journal of Endocrinology† The study indicates that altered levels of reproductive hormones in a well-established mouse model of obesity may be partially restored by a common type 2 diabetes medication that lowers blood glucose levels. Many obese women who experience fertility problems also have altered levels of reproductive hormones. Currently, there is no effective therapy to address this. The development of a therapy that not only improves women’s metabolic health but also treats obesity-related infertility would be a significant advance, with the potential to improve the quality of life for many people.

While 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, meaning more women are affected by reproductive problems. Obesity-related fertility problems are complex, but there is some evidence that they may be linked in part to changes in energy metabolism, leading to altered levels of reproductive hormones that can then disrupt the menstrual cycle and ovulation. Obese people are at greater risk of develop type 2 diabetes and often have high blood glucose levels, as well as 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 leading to declining fertility. The reproductive cycle of the mouse is similar to that of humans in that the profile of changes in hormone level is analogous, although it lasts much shorter, so the MC4R KO mouse is a good, representative model for the first study of the metabolic and reproductive function in obesity.

Dapagliflozin is a drug commonly used to treat type 2 diabetes, where it lowers blood glucose levels and improves other markers of metabolic health, but its effects on reproductive health and fertility have yet to be explored.

In this study, Professor Chen and colleagues from the University of Queensland in Australia examined 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 glucose levels were normal, body weight was reduced, reproductive cycle normalized, and reproductive hormone and ovulation levels were partially restored compared to untreated mice.

“We often see low fertility in obese women in clinical practice,” said lead author Dr. Cui, a guest at the Chengdu Women and Children Hospital in China, “so this research offers hope for future effective treatment.”

These data suggest that normalizing blood glucose metabolism with dapagliflozin in obesity may be a promising pathway for at least partial restoration of reproductive function. This could improve fertility in women where no other successful 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 findings can be effectively replicated in women. However, people who are obese are at much higher risk of developing type 2. developing diabetes, so the known health benefits of correcting blood glucose levels can be extended to improve fertility in those affected.”

The team now plans to further explore the therapeutic benefits of using dapagliflozin to improve reproductive function by investigating the molecular pathways involved, which could identify better targets for future fertility treatments in women.


Reference magazine:

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

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