Metformin reduces miscarriages in women with polycystic ovary syndrome
Från Experimental Biology Meeting 2000.

    Metformin therapy reduces the risk of miscarriages in women with polycystic ovary syndrome (PCOS) by reducing levels of plasminogen activator inhibitor, according to a presentation made here this week at the Experimental Biology 2000 meeting. Dr. Charles Glueck of Jewish Hospital, Cincinnati, Ohio, said that he has found that metformin reduces the first-trimester miscarriage rate from 45% to 9%, with 9% to 13% being the US average.

    Now his group has discovered that the miscarriage rate is so high because, in addition to high insulin levels and an abundance of male sex hormones, women with PCOS have high levels of plasminogen activator inhibitor, which causes placental blood clots. Metformin reduces the risk of miscarriage by reducing plasminogen activator inhibitor levels, Dr. Glueck said.

    Noting that "there's no other biologic system that we know of that fails 13% of the time in healthy people," he said that he and his colleagues determined that many miscarriages are due to abnormalities in placental blood clotting. Women who are homozygous for a particular version of the plasminogen activator inhibitor gene or who have inherited coagulation disorders are at particular risk.
- Once you know that in a woman who's had a miscarriage, then you can identify the genetic disorder and treat with low-molecular-weight heparin throughout the pregnancy, Dr. Glueck said. His group is recommending that all women be tested for coagulation ability before conception.
- We suspect we could identify women prone to miscarriage, he said. He noted that a year's supply of metformin would cost about $700, while fertility treatments, which are ineffective for PCOS, cost about $30,000 and are not covered by insurance.

Noting that metformin induced an average weight loss of 16 kg in women with PCOS, Dr. Glueck's group also examined the ability of metformin to induce weight loss in 22 morbidly obese men and women who had significant insulin resistance but were not diabetic. In an open-label study, they treated patients with metformin daily for 24 weeks without any change in their regular diet.

    Metformin caused a 6% weight loss and reduced weight and hip circumference by 3 inches. The fasting insulin also fell from high to normal levels, and surprisingly, levels of low-density lipoprotein cholesterol also fell significantly.
- Treatment with metformin may prevent the development of type 2 diabetes in these patients, Dr. Glueck said.

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