WEDNESDAY, Feb. 7, 2007 (HealthDay News) -- Women with polycystic ovary syndrome who want to have a baby will probably have better luck if they take the fertility drug clomiphene instead of metformin, an insulin-sensitizing medication that helps induce ovulation in women with the disorder.
That's the conclusion of new research that found the live birth rate was 22.5 percent for women taking clomiphene, compared to just 7.2 percent for those on metformin.
"Many people thought that metformin would be more effective, but it failed on two counts -- either alone or in combination with clomiphene," said the study's lead author, Dr. Richard Legro, professor of obstetrics and gynecology at Penn State College of Medicine.
"Clomiphene alone is the gold-standard way for women with PCOS to achieve pregnancy," he added.
The study, funded by the National Institutes of Health, is published in the Feb. 8 issue of the New England Journal of Medicine. Bristol-Myers Squibb provided the metformin and the placebos used in the study.
Polycystic ovary syndrome (PCOS) is a common endocrinological disorder. It affects as many as 8 percent of American women and may be the cause of most infertility, according to background information in the article. Women with PCOS are often overweight, have excess body and facial hair, reduced insulin sensitivity and irregular menstrual cycles. The root of many of these symptoms is an excess of androgens, or male hormones.
Many women with PCOS are treated with metformin (brand name, Glucophage), a diabetes drug that helps increase the body's response to insulin. This, in turn, reduces the levels of circulating insulin, which reduces the levels of androgens. This often helps restore ovulation and normal menstruation, and possibly helps some women lose weight. Many also believe that metformin could help with PCOS-related infertility, according to the article.
Dr. David Guzick is dean of the School of Medicine at the University of Rochester School of Medicine and Dentistry, in Rochester, N.Y. The author of an accompanying editorial in the journal, he said: "Metformin took hold as a generally accepted treatment. The belief was that because you're addressing the underlying abnormality, you're restoring the system back to normal.
"Clomiphene was viewed as old-fashioned and not reflecting the physiology of PCOS. However, this study found the reverse is true, the old-fashioned way is shown to be preferable," he added.
Guzick said clomiphene works more directly than metformin when it comes to fertility. Clomiphene causes the body to release follicle-stimulating hormone, which stimulates the ovaries to release an egg.
For the new study, the researchers recruited 626 women with PCOS who were infertile. The average duration of infertility, according to Legro, was three years.
The women were randomly assigned to receive clomiphene plus a placebo, metformin plus a placebo, or both metformin and clomiphene for as long as six months.
The combination group had the highest live-birth rate with 26.8 percent. The live-birth rate for the clomiphene group was 22.5 percent, while the metformin group's live-birth rate was just 7.2 percent. The difference between the combination group and the clomiphene group was not statistically significant, the researchers said.
While metformin and clomiphene both caused women to ovulate more, Legro said another interesting finding from this study was that "all ovulations are not alike" and that studies like this one can't stop at looking at the ovulation rate but need to follow through to see how many women actually achieve a pregnancy.
Another concern, Legro said, was that more women on metformin experienced first-trimester pregnancy loss. While the numbers weren't statistically significant in the study, Legro said the finding was troubling, and he would recommend that women stop metformin as soon as they know they're pregnant.
The biggest concern with clomiphene is the increased risk of multiple births, according to Legro. In this study, the rate of multiple births in the clomiphene group was 6 percent, compared to zero percent in the metformin group.
The bottom line, said Legro, is that women with PCOS who want to conceive should get clomiphene as their first-line therapy. "Metformin is not as good as it was hyped to be, but this is not the first time a newcomer has been dethroned," he added.
Guzick said that, aside from medication, one of the most important things women with PCOS can do, both to get pregnant and improve overall health, is to lose weight.
"Even losing just five to 10 pounds can lead to a 50 percent increase in ovulation," said Guzick. And, losing weight prior to conception can also help women lower the risk of some pregnancy complications, he said.
To learn more about polycystic ovary syndrome, visit the U.S. National Women's Health Information Center.