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A diabetes drug given to girls at age eight might prevent future infertility

Dominika Osmolska Psy.D.'s picture

A new study concludes that girls who are at risk for developing infertility caused by PCOS can be helped by taking the drug metformin, used to control type 2 diabetes. If the girls take metformin at age 8, their odds of preventing future infertility are remarkably increased.

PCOS, or polycystic ovary syndrome, is one of the most common conditions responsible for female infertility, accounting for 5% to 10% of the cases in women of reproductive age. The main features of the syndrome are a tendency to become overweight, excessive hair growth (particularly in areas of the body more typical of male hair growth), insulin resistance (which may result in diabetes or pre-diabetes), acne and irregular periods – periods which may be absent, irregular and/or very light.

Even though the tender age of eight might seem like an awfully early time to diagnose a potential condition, it turns out that PCOS is often heralded during a girl’s prepubescent years. Girls at risk for developing PCOS later in life develop pubic hair growth very early. Most of them also had a very low birth weight. By age eight, they may already show a predisposition towards insulin resistance and excessive hair growth.

PCOS is commonly treated with metformin in adult women, but researchers asked whether the drug might not help girls before they develop the condition. Since PCOS is essentially an endocrine disorder directly associated with insulin regulation, researchers wondered if correcting insulin regulation in girls might prevent the development of dysfunctional ovaries.

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Study researcher Dr. Lourdes Ibáñez, an endocrinologist at the University of Barcelona, said that his team used the drug in a preventive instead of a therapeutic way.

"What we have done is chosen an at-risk group and treated them before they have clinical signs of the syndrome," he said. Ibáñez and his colleagues recruited 38 girls who fit that profile. Half of these girls took metformin daily from age 8 to 12. The other half took metformin for only a year, beginning at age 12.
The girls who took the earlier and longer course of the drug were as much as eight times less likely to develop PCOS by age 15 as the other group, the researchers found. Ibáñez’s team will now follow the girls up to the age of 18 to see if the results of the study hold up over time. The initial study is published in the August issue of the Journal of Clinical Endocrinology and Metabolism.

PCOS begins early in life but remains invisible for many years and is very much a lifelong condition. As an infertility syndrome, it is not a disease per se. Rather, it is a cluster of symptoms with a definable outcome. It is triggered primarily by an excess of insulin. When the ovaries are exposed to too much insulin, their hormone production is altered, resulting, through a complex endocrine pathway, in excess circulating androgens, or male hormones. This is why many women with PCOS are afflicted with excess hair and why many deposit excess fat around their middle – more typical of the male pattern.

Metformin treats the insulin imbalance that's a driving cause of PCOS. By returning insulin levels to normal, the ovaries can produce hormones at a healthy rate. In addition to women already struggling with infertility, the drug is also offered to girls who have developed signs of PCOS. The new study suggests that earlier treatment would be even more effective.

As a diabetes drug, metformin is already approved for children age 10 and older. There are few side effects. The challenge will be to identify girls who truly are at risk for developing the syndrome, as not all women who have PCOS were necessarily of low birth weight or developed pubic hair early. Likewise, some women with PCOS do not necessarily display excessive hair growth or lack of menstrual cycles.