Metformin for PCOS symptoms: 5 challenging cases
This inexpensive and versatile drug broadens the choices for treating polycystic ovary syndrome. An expert describes its efficacy for common manifestations of PCOS.
No randomized, prospective clinical trials have been performed to address metformin use in pregnancy in women with PCOS. In 1 cohort study, it was associated with an increased risk of preeclampsia and an increased rate of adverse perinatal outcomes.39 While preliminary reports from case series suggest that metformin treatment in pregnancy may reduce the risk of spontaneous abortion and decrease the risk of gestational diabetes, no randomized, prospective trials have established these effects. The studies that have been performed in these areas are provocative, however.
In 1 study of the effects of metformin on early pregnancy loss in women with PCOS, the spontaneous abortion rate was 9% among women receiving metformin (6 of 68 pregnancies) and 42% in women who did not receive metformin (13 of 31 pregnancies).40 Although a similar result was reported by another group,41 it is not clear if the metformin and control groups were well matched on important clinical variables.
It is highly likely that metformin is effective in reducing elevated blood sugar in pregnant women with gestational diabetes. In a study of pregnancy outcome in 33 nondiabetic women with PCOS taking metformin 2,550 mg daily, compared with a control group of 39 nondiabetic women with PCOS who were not taking metformin, gestational diabetes was diagnosed in 3% of the women taking metformin and in 23% of the women not taking metformin.42
A clinical trial is needed to confirm these preliminary findings and better characterize the effects of metformin on the fetus. Based on currently available information, 100 pregnant women with PCOS would need to be treated with metformin to prevent gestational diabetes in 20.
More information also is needed about the characteristics of gravidas most likely to benefit from metformin, as well as the effects of metformin on maternal outcomes. Until high-quality trials supply this data, clinicians and patients need to weigh the known relative risks and benefits of metformin in early pregnancy.
Clinical courseMetformin discontinued
After a thorough discussion of the possible risks and benefits of metformin, the patient discontinues her metformin treatment. She has an uneventful pregnancy, does not develop gestational diabetes, and has a vaginal delivery at term.
Her pre-pregnancy weight loss likely helped to normalize her central metabolism and decrease her risk of developing gestational diabetes. Pre-pregnancy exercise and diet are probably the most effective method for reducing the risk of gestational diabetes in women with PCOS.
CASE 5
Facilitating weight loss
A 40-year-old woman with PCOS and a body mass index of 35 (height 5’ 6”, weight 216 lb) wants to lose weight. The patient has a strong family history of diabetes. In addition, her fasting blood sugar level is 108 mg/dL. She asks if metformin might help her to lose weight.
Metformin is more effective with diet, exercise
Although it is not approved as a weight-loss medication, a number of trials report that metformin plus a low-calorie diet is superior to a low-calorie diet alone in fostering weight loss.1 Metformin (850 mg twice daily) plus a low-calorie diet (1,200 to 1,400 kcal daily) was superior to a low-calorie diet alone in facilitating weight loss both in women with PCOS and obese women who did not have hirsutism and irregular menses.43 In this study, the pretreatment mean weight was 103 kg in the women taking metformin and following a low-calorie diet, and it was 102 kg in the placebo-low-calorie-diet group. After 7 months of treatment, the mean weight was 94 kg and 97 kg, respectively.
Note, however, that metformin treatment without a low-calorie diet or increased exercise is not likely to be associated with significant weight loss,44 although it may decrease hunger and food cravings of patients, especially at daily doses above 1,700 mg.45
Obese adolescents may benefit from metformin. In a clinical trial of 24 hyperinsulinemic, nondiabetic obese adolescents who followed a regimen of metformin (850 mg twice daily) plus a low-calorie diet (1,500 kcal daily for females) or a low-calorie diet alone, the group treated with both interventions lost more weight and body fat than the group treated with a low-calorie diet alone.46 Other investigators have reported similar results.47
The importance of lifestyle interventions in preventing diabetes in high-risk populations—which includes obese women with PCOS—was demonstrated in a large clinical trial.48 Nondiabetic men and women (n = 3,234) with impaired fasting glucose (fasting glucose between 110 and 126 mg/dL) received placebo, metformin (850 mg twice daily), or a lifestyle-modification program with a goal of 7% weight loss and 150 minutes of physical activity per week. The mean age of the cohort was 51 years, and the mean BMI was 34. The average follow-up was 2.8 years.
