Polycystic ovary syndrome (PCOS) is one of the most common hormonal disorders in women of reproductive age. It can cause irregular periods, infertility, weight gain, insulin resistance, and elevated male hormone levels. Current treatments mainly focus on managing symptoms rather than addressing underlying causes.
Recent studies have linked PCOS to gut bacteria and bile acid signaling. FXR is a receptor activated by bile acids that helps regulate metabolism and hormones. However, drugs that activate FXR throughout the body have shown mixed results and safety concerns.
To address this, researchers from Fudan University tested fexaramine (Fex) , a compound that stays mainly in the intestine after oral administration. By activating only intestinal FXR, Fex may avoid the risks of conventional systemic drugs.
In the new study, researchers used two different mouse models of PCOS to investigate whether the gut-targeted drug could improve both metabolic and reproductive problems.
Using two PCOS mouse models, the team found that Fex treatment markedly improved metabolic health . Treated mice gained less weight, showed better glucose tolerance, and exhibited substantially improved insulin sensitivity.
Importantly, the benefits extended beyond metabolism . Fex restored disrupted reproductive cycles, reduced the number of abnormal ovarian follicles, increased corpus luteum formation associated with ovulation, and lowered circulating testosterone and androstenedione levels. The treatment also normalized several reproductive hormones commonly disrupted in PCOS, including luteinizing hormone and anti-Müllerian hormone.
Transcriptomic analysis further confirmed that Fex altered gene pathways associated with follicular development, steroid hormone production, inflammation, and glucose and lipid metabolism. Several genes linked to ovarian function and insulin sensitivity were reversed toward healthier expression patterns following treatment.
"Fex improved both the metabolic and reproductive features of PCOS," said the authors. "The drug works only in the intestine and is not processed by the liver, so we are less concerned about its safety.”
The findings suggest that intestinal FXR signaling may serve as a key communication hub between the gut and reproductive system, supporting the emerging concept of a “gut–ovary axis” in PCOS.
The authors note that while the results are promising, further research is needed to understand the exact mechanisms by which intestinal FXR activation improves ovarian function. They also acknowledge that mouse models do not fully replicate human PCOS, and clinical studies will be necessary before any conclusion about human application can be drawn.
The study was published in Reproductive and Developmental Medicine.
Reproductive and Developmental Medicine
Experimental study
Gut-restricted farnesoid X receptor agonist fexaramine improves abnormal metabolic and reproductive phenotypes in polycystic ovary syndrome model mice
26-Mar-2026