Dr. Holley Allen, a pediatric endocrinologist at Baystate Medical Hospital in Springfield, Mass., said that a metaanalysis of case-control studies published in 2005 showed a twofold increased risk of both MI and ischemic stroke in women who took OCs. The risk may be higher in women with PCOS, since they likely start at a higher baseline risk and take OCs for long periods of time, she said.
Still, she said she views the concerns about OCs' impact on insulin resistance and cardiovascular disease as “potential but unproven.”
And the “question is, whether she'll take a pill for the next 30 years that doesn't make her lose weight, doesn't do much for her facial hair or acne, and tastes like dead fish,” she said.
Dr. Lebinger, who spoke with Dr. Allen, acknowledged there are “inadequate data [on metformin use] in adolescents—only small studies and not many [that are] placebo controlled.”
Still, the literature consistently demonstrates either normalization or significant improvements in glucose intolerance, insulin resistance, and menstrual irregularities, said Dr. Lebinger, who practices in New Rochelle, N.Y. Her adolescent patients on metformin also have improvements in their acne and frequently lose weight.
“We're making recommendations based on what we know today. I present all the options—it's the patient's decision,” she said. Regarding OCs and insulin resistance, “most of us observe that if you take a patient with type 1 diabetes and give them OCs, they usually require more insulin,” Dr. Lebinger said.
Dr. Nestler disclosed to the ADA that he is on the speakers' bureau for Sanofi-Aventis and is a stock/shareholder of the Bristol-Myers Squibb Co. and Pfizer Inc.
Metformin OK for Infertile Patients
If time is not critical, metformin is also an appropriate front-line drug for patients with PCOS whose primary concern is infertility, Dr. Nestler said at the annual meeting of the American Diabetes Association.
“If a woman comes to me with PCOS who wants to get pregnant, I usually tell her I'd like to put her on 3–6 months of metformin coupled with diet and exercise. This way we can try first for the singleton pregnancy [without clomiphene],” Dr. Nestler said. “If at the end of 6 months she doesn't become pregnant, I send her to the endocrinologist.”
The authors of a 2003 review by the Cochrane Collaboration concluded that women with PCOS who take metformin are almost four times as likely to achieve ovulation, compared with women receiving placebo, he said.
In a study of 68 infertile women treated at his institution with metformin, Dr. Nestler and his colleagues found that 78% had improvements in menstrual cyclicity and ovulation, with the frequency of cycles increasing threefold. Approximately 44% had normalized cycles—the “optimal” outcome, he said.
Results from a National Institutes of Health-sponsored, multicenter, randomized study of metformin, clomiphene, or both for treating infertility in PCOS patients will be announced in October, he mentioned.