UC San Diego

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of reproductive age. The etiology of this disease is poorly understood, and there is also no known cure. PCOS features both reproductive and metabolic dysfunction and can have devastating and long-term health consequences. Further research is needed to better understand this disease and to develop new therapeutic approaches for treating this disorder.

Because many women who have PCOS also have some degree of insulin resistance, we investigated possible contributors to insulin resistance in a letrozole-induced PCOS-like mouse model. We found that hyperandrogenism from dihydrotestosterone (DHT) treatment or estrogen deficiency from ovariectomy (OVX) was not sufficient to induce insulin resistance in female mice. However, mice that received both DHT and OVX became insulin resistant, suggesting that a combination of elevated androgen levels and lowered estrogen levels may be necessary for the development of insulin resistance in PCOS.

The gut microbiome has been implicated in various diseases such as metabolic syndrome and PCOS. More specifically, multiple studies have demonstrated that changes in the gut microbiome are associated with PCOS in humans and rodent models, and studies in mice have demonstrated that altering the gut microbiome can alleviate PCOS pathology. We investigated whether dietary supplementation with a prebiotic, resistant fiber was protective against the development of PCOS reproductive and metabolic phenotypes in a letrozole-induced PCOS-like mouse model. We found that 5% resistant fiber supplementation was not sufficient to protect against development of PCOS phenotypes, suggesting that the effect of supplementation with a greater percentage of dietary fiber or different types of dietary fiber should be explored further.