Viewpoint: Can Metformin Help Teenagers With PCO?

Charles P. Vega, MD, FAAFP


April 19, 2006

Randomized Placebo-Controlled Trial of Metformin for Adolescents With Polycystic Ovary Syndrome

Bridger T, MacDonald S, Baltzer F, Rodd C
Arch Pediatr Adolesc Med. 2006;160:241-246

Summary and Viewpoint

One of the privileges of practicing family medicine is being able to provide care for conditions that can span the periods from childhood to adulthood. We are in a unique position to provide care for patients who benefit from our experience -- not only providing care for the problem at hand, but also knowing the best means for management of that problem in the future. As the rates of obesity increase among children and adolescent patients, polycystic ovary syndrome (PCOS) is certainly one of these conditions suited for family medicine.

PCOS has been associated with health consequences that are important to physician and patient alike. In a study of the natural history of PCOS among 122 young women, 35% of subjects had an impaired glucose tolerance, and 10% had overt type 2 diabetes.[1] A subset of these women was followed for a mean of 2.4 years, and repeat testing indicated overall worsened glucose tolerance with time in this study cohort.

The mean age of women in the above study was 25 years, but the metabolic abnormalities associated with PCOS can be detected even during adolescence. One study compared girls with an average age of 12 years who had PCOS to a group of obese, nonhyperandrogenic girls who were matched for age, percent body fat, and abdominal fat.[2] Girls with PCOS were found to have an approximate 50% reduction in peripheral tissue insulin sensitivity compared with controls, and they also exhibited evidence of hepatic insulin resistance and compensatory hyperinsulinemia.

It makes sense to consider metformin for adolescents with PCOS. Previously, metformin in combination with low-calorie diet was demonstrated to promote greater weight loss and decrease in body fat compared with low-calorie diet alone among a cohort of adolescent girls.[3] In addition, girls receiving metformin experienced superior outcomes in terms of glucose sensitivity, plasma leptin levels, and lipid values after only 8 weeks of treatment.

One study has compared pre- and post-intervention outcomes of metformin among 15 adolescents with PCOS.[4] Following 3 months of treatment, glucose tolerance testing and free testosterone levels improved. Moreover, the authors noted that metformin suppressed levels of androstenedione and 17-hydroxyprogesterone after an ACTH stimulation test, and they called for randomized, placebo-controlled trials of metformin for adolescents with PCOS to confirm their findings.

The current research offers precisely this type of analysis. However, its results are somewhat disappointing. Although the researchers demonstrated that metformin could reduce testosterone levels and improve the return of menses, metformin failed to significantly improve outcomes important to the patient (eg, weight loss, hirsutism) and the physician (eg, insulin sensitivity, lipid profile beyond HDL-cholesterol).

Why the discrepancy between the findings of the current study and previous research on metformin? First, the current study examined a small cohort of patients, and nearly half of the girls in the active intervention group were not adherent to therapy. If participants had been more compliant in taking metformin regularly, the improvement recorded in insulin sensitivity in the metformin vs control groups might have gained statistical significance. At the same time, it is not necessarily surprising that teenagers would have difficulty maintaining compliance with taking a medication twice daily, particularly one associated with gastrointestinal side effects. So, the high rate of noncompliance in this small sample might best reflect clinical practice.

Second, it is important to note that diet was not controlled in this study of metformin, which may explain the negligible effects on weight in the metformin vs placebo groups. Also, the study duration was only 3 months, which may have precluded a significant effect on weight and almost certainly precluded the possible effect of metformin on hirsutism.

A larger randomized trial of metformin in adolescents with PCOS with a longer follow-up period would be welcome to determine whether metabolic and anthropometric outcomes could be improved with treatment. Using metformin for PCOS is attractive because this medication is known to improve these variables among adults with PCOS. In addition, compared with clomiphene citrate, metformin improves other conditions that are more important to young women than to adolescents, including ovulation, pregnancy rate, and rate of spontaneous abortion.[5] Currently, metformin appears to offer some benefit to adolescents with PCOS, but greater evidence of benefit in this population would put family physicians in an excellent position to expose young women to the benefits of this therapy even as the goals of treatment may evolve with the patient's age.



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