Insulin sensitizing drugs help thin women as well overweight women with polycystic ovary syndrome

Insulin-sensitizing drugs can help thin women with polycystic ovary syndrome even if they do not appear to be insulin resistant, broadening the range of women who can benefit from the therapy, a Virginia Commonwealth University researcher said in this month’s issue of the journal Fertility and Sterility.

“This is significant because up to 30 percent of women with polycystic ovary syndrome are not overweight, and it has not been clear if such women would benefit from treatment with an insulin sensitizing drug for improving fertility,” said John E. Nestler, M.D., chair of VCU’s Division of Endocrinology and Metabolism, and lead author of the study.

“We now know those women are good candidates for an insulin-sensitizing drug to increase the frequency of ovulation,” said Nestler, who was among the first scientists to recognize insulin as an important reproductive hormone 25 years ago.

Polycystic ovary syndrome is the most common reproductive syndrome in women, affecting between 6 percent and 10 percent of those of childbearing age. Women with PCOS have enlarged ovaries – the organs that produce eggs – that become host to fluid-filled sacs or cysts. PCOS patients have irregular or no ovulation, unwanted facial and body hair, and 70 percent are overweight. Women with PCOS have an increased risk of developing diabetes and heart disease.

Non-obese women with polycystic ovary syndrome, but without clinical or biochemical indications of insulin resistance, ovulate more frequently and experience relief from the overproduction of male hormones when taking insulin-sensitizing drugs, according to the study, which was conducted by scientists from three countries.

The study also offers new insight into the effectiveness of two classes of insulin-sensitizing drugs and whether the two in combination are more potent than treatment with either drug alone.

The study was conducted over six months and involved 128 non-obese women with PCOS, but no clinical indications of insulin insensitivity. Twenty-eight of the women were lost to follow-up initially and received no intervention, while the other 100 women were given either the insulin-sensitizing drugs metformin or rosiglitazone, a combination of the two drugs, or a placebo twice a day.

Frequency of ovulation was higher with both of the insulin-sensitizing drugs compared with the placebo. Frequency of ovulation increased significantly more with metformin than with rosiglitazone and the combination of the two was not more potent, according to the study. Researchers also noted that after treatment, levels of the male hormone testosterone were comparable among the active treatment groups and significantly lower than the placebo group.

The women in the study on active insulin-sensitizing drugs ovulated six to eight times more than the women given the placebo. Researchers concluded that despite apparently normal insulin sensitivity in these PCOS women, insulin-sensitizing drugs exerted multiple beneficial effects.

In addition to Nestler, the research team included Maria J. Iuorno, M.D., from VCU Medical Center, Jean-Patrice Baillargeon, M.D., from the Université de Sherbrooke, Quebec, Daniella J. Jakubowicz, M.D., and Salomon Jakubowicz, M.D., both from the Hospital de Clinicas Caracas, Venezuela.

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