Women With PCOS, Siblings Have Same Gene Defect

August 19, 2002

Women With PCOS, Siblings Have Same Gene Defect

CHICAGO— Siblings of women with polycystic ovary syndrome (PCOS) have metabolic and hormonal abnormalities that are linked to the same gene defect that causes PCOS, a disorder associated with irregular periods, infertility, excessive body hair, and increased risk for diabetes.

These new findings came from the $6 million National Institutes of Health–funded National Centers Program for Infertility Research. The study was led by Northwestern University researcher Andrea Dunaif, MD, Charles F. Kettering Professor, chief of endocrinology and metabolism, and professor of medicine at Northwestern University’s Feinberg School of Medicine, and collaborators at Pennsylvania State University and the University of Pennsylvania.

Dr. Dunaif and co-investigators believe the location of the PCOS gene mutation is on chromosome 19, near the insulin receptor gene, which plays a key role in allowing insulin to enter cells and metabolize sugar. This marker, called allele 8 of D19S884, was associated with risk factors for diabetes in PCOS women and their brothers.

In recently published studies, approximately 50 percent of the sisters of PCOS women had elevated androgen (so-called “male hormones” that are present in both men and women) levels while the other half of the sisters were unaffected. Of the high-androgen group, half (or 25 percent of the sisters) had PCOS and insulin resistance, while the other 25 percent were insulin resistant but showed no PCOS symptoms and had normal menstrual periods.

The PCOS sisters and those with high androgen levels were more obese than unaffected sisters.

The PCOS brothers also had significantly elevated levels of the androgen DHEAS, which correlated with the high androgen levels in their sisters with PCOS.

These results strongly suggest that the same gene defect is responsible for PCOS and the hormonal abnormalities and other symptoms found in the siblings of PCOS-affected women, but further studies are required, Dr. Dunaif said.

PCOS is a complex disorder that affects nearly 10 percent of premenopausal women and is associated with elevated levels of androgens, as well as irregular menstrual periods and reproductive problems. Other symptoms of PCOS include obesity, excess hair on the face and body, male-pattern baldness, and severe, chronic acne.

Many women with PCOS are insulin-resistant, a condition that raises the level of insulin circulating in the body and is a precursor to Type 2 diabetes. In fact, women with PCOS have seven times the risk of other women for developing adult-onset diabetes, which in turn greatly increases their chance of having cardiovascular disease, stroke, and kidney problems. Dr. Dunaif’s research also has shown that PCOS is an important risk factor for the adult form of diabetes in teenaged girls.

Dr. Dunaif’s co-investigator on the NIH grant is Richard L. Legro, MD, Pennsylvania State University. Also collaborating on the PCOS gene research are Margrit Urbanek and Ralph Kazer, MD, professor of obstetrics and gynecology and chief of reproductive endocrinology, The Feinberg School of Medicine, Northwestern University; and Richard S. Spielman and Jerome F. Straus III, University of Pennsylvania. Kazer also is co-director of the PCOS Center at Northwestern.