VCU news

By Lorraine Cichowski, John Nestler, Valerie Gliem and Phyllis Leppert

Nov. 21, 2002 — Virginia Commonwealth University and Penn State Milton S. Hershey Medical Center have announced the launch of a new research study for women with polycystic ovary syndrome (PCOS) who want to become pregnant. 

Recruitment is underway at 13 medical centers across the country for this National Institute of Child and Human Development (NICHD) – National Institutes of Health (NIH) study under the leadership of Richard S. Legro, M.D., associate professor of obstetrics and gynecology, Penn State College of Medicine, and John E. Nestler, M.D., professor and chair of VCU’s Division of Endocrinology and Metabolism. Legro and Nestler, along with the steering committee of the NIH’s Reproductive Health Network, developed the protocol.

In all, the study could enroll as many as 678 women, aged 18-39, who suffer from PCOS, a disorder of the endocrine system that causes hormone imbalances, leading to irregular menstrual cycles, excess facial and body hair, weight gain and adult acne. PCOS is a leading cause of female infertility, affecting as many as 10 percent, or five million, women.

“The goal is to test a combination of medications to bring about ovulation in women with infertility due to polycystic ovary syndrome,” Legro said. “This investigation is important because few studies ever focus on pregnancy as an outcome due to the liability and ethical issues. It would have never been initiated without NIH support.”

Women with PCOS who meet the inclusion criteria for the study will be assigned at random to one of three medication groups comparing 1) metformin XR (a sustained-release version of metformin) and placebo – an inactive pill; 2) clomiphene citrate (the standard treatment for infertility in women with PCOS) and placebo, and 3) metformin XR and clomiphene citrate. Each arm of the study thus will contain at least one active medication that improves the chance for ovulation and, ultimately, pregnancy. Metformin XR was provided by Bristol-Myers Squibb.

“We want to determine definitively what is the preferred drug or preferred combination of drugs for producing ovulation and pregnancy in women with PCOS,” Nestler said. “What’s wonderful about this study is that there are so many women involved and so many sites involved. Whatever answer it gives us will have a lot of statistical power and will strongly influence the kind of treatment administered in the future to infertile women with PCOS.

In the 1980s, Nestler was among the first scientists in the world to suggest that insulin was an important reproductive hormone. His pioneering work to induce ovulation through the use of such insulin-sensitizing drugs as metformin has led to the common use of metformin to treat infertility in women with PCOS. In 1998, in an article in the New England Journal of Medicine, Nestler's research team was the first to publish findings on the combination therapy of metformin and clomiphene to promote ovulation.

Legro has conducted numerous studies of insulin resistance and its sequelae in women with PCOS as well as in their family members, looking for its genetic roots. He has received multiple awards for his research including the Outstanding Service Award from the patient support group, Polycystic Ovarian Syndrome Association, Inc. He has also edited a book for women with PCOS, “Living with PCOS” (Addicus Books, 2000). His collaboration with Nestler on the protocol arose from mutual interests in the role of insulin in the etiology of the syndrome. This study is part of an NIH cooperative agreement. Both investigators hold multiple NIH grants in other areas.

Those who qualify for the study and choose to participate will receive the following free of charge: all study medications, cost of blood tests performed after enrollment in the study, a physical exam including an ultrasound of the ovaries, a pregnancy test and, if they become pregnant, an ultrasound to confirm it.

Although the study’s primary goal is to determine rates for live births, it also will examine whether multiple births result from use of the drugs – a known problem with clomiphene – and if any of the therapies reduce the possibility of early miscarriage, also a problem for women with PCOS.

The study has been approved by the Institutional Review Board under FDA regulations at Penn State College of Medicine and at Virginia Commonwealth University. It is being conducted by the Reproductive Medicine Network, a group of eight academic medical centers that have received NIH funding to study reproductive medicine issues. The RMN is sponsored and overseen at the NIH by the National Institute of Child Health and Human Development. This research is supported by NIH grant 5 U10 HD38992.

In addition to Penn State College of Medicine at Penn State Milton S. Hershey Medical Center, the other RMN hospitals participating are: Baylor College of Medicine in Houston, Hospital at the University of Pennsylvania, University of Alabama at Birmingham, University of Colorado, University of Medicine and Dentistry of New Jersey at Newark, University of Texas Southwestern Medical Center, and Wayne State University in Detroit. 

The following participating hospitals are part of the Specialized Cooperative Centers Program in Reproductions Research funded by the NIH: University of North Carolina at Chapel Hill, Virginia Commonwealth University, Stanford University, University California of San Diego, and University of Pittsburgh. The landmark participation of these two programs was arranged by program officials at NICHD.

Virginia Commonwealth University is ranked by the Carnegie Foundation as one of the nation’s top research universities. Located on two campuses in Richmond, VA., VCU enrolls 26,000 students in more than 160 undergraduate, graduate, professional, doctoral and post-graduate certificate degree programs at 11 schools and one college. Sixteen graduate and professional programs have been ranked by U.S. News & World Report as among the best of their kind in the nation.  The VCU Health System is one of the leading academic medical centers in the country. VCU recently launched VCU Life Sciences, a comprehensive undergraduate and graduate program involving academic and medical faculty. In addition, the university is developing the Virginia Biotechnology Research Park in collaboration with business, civic and government leaders. For more information, visit www.vcu.edu

Founded in 1963 with a gift from The Milton S. Hershey Trust, today, Penn State Milton S. Hershey Medical Center is one of the leading teaching hospitals in the country. The 504-bed Medical Center is staffed by more than 200 specialty physicians who offer world-class medical care and a full spectrum of advanced medical and surgical diagnostics, procedures and treatments. Located at the Medical Center, Penn State Children’s Hospital – central Pennsylvania’s only children’s hospital – offers the region’s only pediatric trauma center, the region’s most advanced Neonatal Intensive Care Unit and Pediatric Intensive Care Unit and more than 150 pediatric medical and surgical specialists. For more information about the Medical Center and the Penn State College of Medicine, visit www.pennstatehershey.com