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Title: Metformin Shows Promise in Preventing Miscarriage in Polycystic Ovary Syndrome
URL: http://www.pslgroup.com/dg/214C6E.htm
Doctor's Guide
February 27, 2002


BETHESDA, MD -- February 27, 2002 -- The anti-diabetes drug metformin appears to reduce the likelihood of early miscarriage in women with a common form of female infertility, according to a study funded by the National Institute of Child Health and Human Development (NICHD).
The study appears in the February issue of the Journal of Clinical Endocrinology and Metabolism.

The drug, metformin, increases the body's sensitivity to insulin and is used to treat non-insulin-dependent diabetes. Metformin also has proven successful in treating some of the symptoms of Polycystic Ovary Syndrome (PCOS), the most common form of female infertility in which women fail to ovulate.

"This is a very promising lead," said Duane Alexander, MD, Director of the NICHD. The next step is to confirm these results in a larger, randomised trial."

PCOS affects from 5 to 10 percent of American women of reproductive age (as many as five million in all), explained the study's senior author, John E. Nestler, MD, chairman of endocrinology at the Medical College of Virginia at Virginia Commonwealth University in Richmond. Dr. Nestler's group is part of NICHD's Specialized Cooperative Centers Program in Reproduction Research.

The ovaries of women with PCOS appear to be filled with numerous small cysts, Dr. Nestler added. The cyst-like appearance results from an accumulation of immature ovarian follicles, the bubble-like structures which, upon maturation, rupture and release the egg.

The features of PCOS may include failure to ovulate or menstruate, abnormally high levels of insulin, obesity, high blood pressure, hardening of the arteries, and high triglyceride levels. PCOS patients also have high levels of the male hormone testosterone, which may cause them to grow excess facial or body hair. Also, PCOS patients have a higher than normal risk of developing non-insulin-dependent, type 2 diabetes.

In the article, the study authors noted that women with PCOS often have a history of recurrent miscarriage. In earlier studies, Dr. Nestler's group had shown that metformin reduces the high testosterone levels of PCOS patients and also increases the chances that they can become pregnant. Similarly, other research by the group showed that, in women with PCOS, metformin increases blood flow to the uterus and brings about changes in the lining of the uterus that make it more capable of supporting a fetus.

In the current study, Dr. Nestler and his co-workers evaluated a group of women under the care of Venezuelan endocrinologist, Daniela J. Jakubowicz. Dr. Nestler's group had earlier learned that it was Dr. Jakubowicz's practice to prescribe metformin during the pregnancies of patients under treatment for PCOS. After analysing records of patients treated by Dr. Jakubowicz, Dr. Nestler and his coworkers found that of the 68 pregnancies that were treated with metformin, six pregnancies (8.8 percent) ended in miscarriage. By comparison, of the 31 pregnancies in the group that did not receive metformin, 13 pregnancies (41.9 percent) ended in miscarriage.

Only one child born in the metformin group had a birth defect. This child had achondrodysplasia, a genetic disorder in which the limbs fail to keep pace with the growth of the body. More studies would need to be conducted to confirm the current study's results and assess the drug's safety for use during pregnancy.

The study results do not mean that physicians should begin treating PCOS patients with metformin during their pregnancies, said the project officer for NICHD's Specialized Cooperative Centers in Reproduction Research, Dr. Louis DePaolo. Although metformin has not been shown to cause any problems during pregnancy in animal studies, its use throughout pregnancy has not been rigorously studied in human beings.

SOURCE: National Institutes of Health

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