August 28, 2003
Researchers funded by the National Institute of Child Health and Human Development (NICHD) are seeking volunteers for a study to treat infertility in women with polycystic ovary syndrome (PCOS). The study seeks to enroll 678 women with infertility due to PCOS, who are trying to become pregnant. The study is the largest of its kind that's ever been conducted. The researchers will compare the effectiveness of drugs used to treat infertility to that of metformin, a medication traditionally used to treat type 2 diabetes.
Earlier studies, some funded by the NICHD, have indicated that an abnormality in how the body uses insulin may account for many of the symptoms of PCOS.
In polycystic ovary syndrome, an excess of male hormones interferes with normal ovulation and other body systems. Ovarian cysts form and enlarge the ovaries. In addition to infertility, PCOS symptoms can include irregular menstrual periods, excessive body and facial hair, acne, and obesity, with weight concentrated around the abdomen. Five to 10 percent of women of reproductive age have PCOS. The syndrome begins in childhood, but is often undiagnosed until adulthood, when women fail to become pregnant.
"The objective of this study is to provide a better understanding of PCOS, and help determine how best to treat women with PCOS-related infertility," said Duane Alexander, M.D., Director of the NICHD.
In the long term, women with untreated PCOS are at increased risk for diabetes, heart disease, high blood pressure, and cancer of the endometrium (the lining of the uterus). Current treatments for the condition consist of oral contraceptives, to regulate the menstrual cycle, and weight-loss programs for the accompanying obesity.
The symptom that most often sends women with PCOS to their doctors-infertility-has been difficult to treat successfully, explained Phyllis Leppert, M.D., Ph.D, Chief of NICHD's Reproductive Sciences Branch.
Participants in the study will be assigned to one of three groups and randomly assigned to receive one of three treatments. In one group, women will receive both metformin and clomiphene citrate, a drug that stimulates ovulation. The second group will receive a placebo and metformin, while the third group will receive a placebo and clomiphene citrate. Neither the women in the study nor the researcher will know which medications the women are receiving until the end of the study.
"Metformin has shown promise in treating PCOS associated infertility," said Richard S. Legro, M.D., the study's lead investigator and Professor of Obstetrics and Gynecology at Penn State University College of Medicine. "Our study is large enough to determine if that promise is warranted.
Dr. Legro explained that women with PCOS produce too much insulin, and metformin lowers insulin levels or improves the way the body uses it. This effect may help women ovulate spontaneously.
In addition to testing each drug separately, the study is also testing whether the combination of the two drugs offers women the greatest chance of conceiving.
"The problem is that any single drug we use on women with PCOS tends to have limited effects," said Dr. Legro. "So our theory is that, to help women get pregnant, it's best both to stimulate the ovaries and to lower insulin levels."
Since the study began in November 2002, 179 women have enrolled. The study is being conducted by the Reproductive Medicine Network (RMN), a group of eight academic medical centers funded by the NICHD and additional sites are also participating in the study.
A listing of centers participating in the study is available at http://c2s2.yale.edu/rmn/docs/. Women wishing to volunteer for the study also may call Jamie Ober, R.N., Research Coordinator, at (717) 531-6272.
The study is currently underway at the following sites: Penn State College of Medicine at Penn State in Hershey, Pennsylvania; Baylor College of Medicine in Houston; the University of Pennsylvania in Philadelphia; the University of Alabama at Birmingham; the University of Colorado at Boulder; the University of Medicine and Dentistry of New Jersey at Newark; the University of Texas Southwestern Medical Center at Dallas; Wayne State University in Detroit; the University of California at San Diego; Stanford University in Palo Alto, California; Virginia Commonwealth University in Richmond; , and the University of Pittsburgh in Pennsylvania. Another University is also expected to participate in the study.
Women wishing to take part in the study should:
- Be between the ages of 18-39
- Be seeking to become pregnant
- Have eight or fewer periods a year, or have periods that are 45 or more days apart.
- Have elevated levels of testosterone
Volunteers can expect to participate in the study from 30-32 weeks, to be monitored for possible side effects and for pregnancy while taking the medication. Study participants will receive free of charge all study medications, blood tests performed after enrollment, a physical exam including an ultrasound of the ovaries, a pregnancy test, and, if they become pregnant, an ultrasound test to confirm the pregnancy.
The NICHD is part of the National Institutes of Health (NIH), the biomedical research arm of the federal government. NIH is an agency of the U.S. Department of Health and Human Services. The NICHD sponsors research on development, before and after birth; maternal, child, and family health; reproductive biology and population issues; and medical rehabilitation. NICHD publications, as well as information about the Institute, are available from the NICHD Web site, http://www.nichd.nih.gov, or from the NICHD Information Resource Center, 1-800-370-2943; e-mail NICHDInformationResourceCenter@mail.nih.gov.