New Study Reveals New Treatment Options for PCOS

Obese women have a well-known risk for infertility, but a new Johns Hopkins Children's Center study has unraveled what investigators there believe is the mechanism that accounts for the risk.
The research, conducted in mice and published online on Sept. 8 in the journal Cell Metabolism, shows that the pituitary gland actively responds to chronically high insulin levels, triggering a cascade of hormonal changes that disrupt ovarian function and impair fertility.

The findings challenge the widely held belief that infertility is a result of insulin resistance -- a body's insensitivity to chronically elevated insulin levels and a hallmark of obesity -- and suggest a new culprit: heightened sensitivity to insulin's effects on the pituitary gland.

"What we propose is a fundamentally new model showing that different tissues respond to obesity differently, and that while cells in the liver and muscle do become insulin resistant, cells in the pituitary remain sensitive to insulin," says principal investigator Andrew Wolfe, Ph.D., of Hopkins Children's.

Scientists traditionally have focused on treating infertility by lowering insulin levels as a way to treat insulin resistance. However, the new model suggests that decreasing the pituitary's sensitivity to insulin could be an important new target for treatment instead.

Insulin resistance, marked by persistently elevated insulin, abnormal regulation of blood sugar and insensitivity to insulin in the liver and muscle cells, occurs in type 2 diabetes, metabolic syndrome and polycystic ovary syndrome (PCOS). PCOS is the most common cause of infertility, affecting up to one in 10 women.

Despite normal hormonal levels and ovulation, the obese mice with missing insulin receptors were not as fertile as lean mice with normal insulin levels. The finding suggests that since the ovaries share partial control of ovulation and fertility with the pituitary, they too may be affected by high insulin levels