Background Obese women with the polycystic ovary syndrome arerelatively unresponsive to the induction of ovulation by clomiphene.We hypothesized that reducing insulin secretion by administeringmetformin would increase the ovulatory response to clomiphene.
Methods We performed oral glucose-tolerance tests before andafter the administration of 500 mg of metformin or placebo threetimes daily for 35 days in 61 obese women with the polycysticovary syndrome. Women who did not ovulate spontaneously werethen given 50 mg of clomiphene daily for five days while continuingto take metformin or placebo. Serum progesterone was measuredon days 14, 28, 35, 44, and 53, and ovulation was presumed tohave occurred if the concentration exceeded 8 ng per milliliter(26 nmol per liter) on any of these days.
Results Twenty-one women in the metformin group and 25 womenin the placebo group were given clomiphene because they didnot ovulate spontaneously during the first phase of the study.Among the 21 women given metformin plus clomiphene, the mean(±SE) area under the serum insulin curve after oral glucoseadministration decreased from 6745±2021 to 3479±455µU per milliliter per minute (40.5±12.1 to 20.9±2.7nmol per liter per minute, P=0.03), but it did not change significantlyin the 25 women given placebo plus clomiphene. Nineteen of the21 women (90 percent) who received metformin plus clomipheneovulated (mean peak serum progesterone concentration, 23.8±3.4ng per milliliter [7.6±10.9 nmol per liter]). Two ofthe 25 women (8 percent) who received placebo plus clomipheneovulated (P<0.001). Overall, 31 of the 35 women (89 percent)treated with metformin ovulated spontaneously or in responseto clomiphene, as compared with 3 of the 26 women (12 percent)treated with placebo.
Conclusions The ovulatory response to clomiphene can be increasedin obese women with the polycystic ovary syndrome by decreasinginsulin secretion with metformin.
Source Information
From the Departments of Medicine at the Medical College of Virginia, Virginia Commonwealth University, Richmond (J.E.N.); Hospital de Clinicas Caracas, Caracas, Venezuela (D.J.J.); the University of Virginia, Charlottesville (W.S.E.); and the University of Bologna, Bologna, Italy (R.P.).
Address reprint requests to Dr. Nestler at the Medical College of Virginia, P.O. Box 980111, Richmond, VA 23298-0111.
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