By Peggy O'Farrell
The Cincinnati Enquirer

A widely prescribed diabetes drug helps women afflicted by polycystic ovary syndrome (PCOS) get pregnant and carry their babies to full term, according to a new Cincinnati study.

In the study, risk of miscarriage dropped from 65 percent to 26 percent for women with PCOS who received metformin (marketed as Glucophage), a significant reduction for "otherwise very high-risk women," says Dr. Charles J. Glueck, lead author of the study and director of the Cholesterol Center at Jewish Hospital. The drug also prevents gestational diabetes.

Researchers followed 72 women. Fourteen women suffered first trimester miscarriages, and 63 live births were recorded when the study was wrapped up.

The findings are featured in the November issue of Human Reproduction.

Risk drops significantly

The risk of developing gestational, or pregnancy-induced, diabetes, dropped from 26 percent to 4 percent with the drug. "Four percent is the national average, so these women were brought back to normal levels," Dr. Glueck says.

The possibility of preventing gestational diabetes is important because women who become diabetic during pregnancy are more likely to develop Type 2 diabetes later.

"This in many ways is going to change the way we practice obstetrics and endocrinology," Dr. Glueck says. "The prevention of gestational diabetes, which is part of the picture, may be equally as important as the rest of this."

Polycystic ovary syndrome is the leading cause of infertility among Caucasian women, and affects about 6 to 10 percent of all women. The complex metabolic disorder causes infertility and is linked to insulin resistance, though experts aren't clear on the mechanism that ties the two disorders together, says Dr. Robert Cohen, an endocrinologist at the University of Cincinnati.

Cancer vulnerability

Women with PCOS are prone to diabetes, obesity, acne and excessive body hair. They also may be more vulnerable to certain types of cancer.

Women with PCOS and insulin resistance tend to produce too much insulin to overcompensate for their bodies' inability to properly use insulin to metabolize glucose. The excess insulin stimulates the ovaries to produce excessive amounts of two male hormones - testosterone and androstenedione. The excess insulin also causes the pituitary gland to overproduce a third male hormone, DHEAS.

The excess levels of male hormones, in turn, interfere with signals to the ovaries to produce the two normal female hormones, estradiol and progesterone, which control ovulation and the menstrual cycle.

"You don't ovulate, you don't cycle and you're infertile," says Dr. Glueck.

Insulin resistance also causes the body to hang on to fatty, or adipose, tissue more aggressively, which, in turn, causes obesity and further insulin resistance. It also can interfere with proteins that control blood supply into the placenta, causing miscarriage.

Metformin slows the body's production of glucose and speeds its release from muscle and other tissues, which treats insulin resistance and prevents the metabolic cascade that leads to infertility, Dr. Glueck says.

As a bonus, Dr. Glueck says, none of the babies born to women in the study was unusually large. Fetal macrosomia - birth weight of 10 pounds or more - is fairly common in babies born to women with diabetes or insulin resistance. Very large babies are more prone to a variety of ailments, and the births can cause complications for mothers as well.

None of the babies born to women in the study suffered birth defects or developmental delays as a result of the metformin, Dr. Glueck says.