Most girls at age 8 aren't worried about having children of their own. But that may be the perfect time to protect them against future infertility problems, a new study concludes.
Girls that age who had a high risk of developing a condition that leads to infertility were treated for four years with metformin, a commonly used diabetes drug, and were found to be less likely to develop the condition later.
While 8-year-olds don’t show any outward signs of polycystic ovary syndrome, which is the top cause of infertility in women in the U.S., physiological precursors to PCOS are already present in their bodies, the researchers said. Metformin is already used to treat PCOS in older women, but hadn't previously been tested as a means of preventing the condition in patients at such a young age.
"What we have done is chosen an at-risk group and treated them before they have clinical signs of the syndrome," said study researcher Dr. Lourdes Ibáñez, an endocrinologist at the University of Barcelona. "It's using the drug in a preventive way instead of a therapeutic way."
An at-risk population
Girls who were born with a very low birth weight and begin developing pubic hair at a very early age are at high risk of developing PCOS. So 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.
Those 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.
The earliest symptoms of PCOS include weight gain, irregular menstruation, acne and excessive hair growth caused by disproportionate levels of male hormones. Eventually, PCOS can lead to subfertility and infertility.
"Now we are trying to follow patients until age 18 to see whether our preliminary results hold true as these girls grow up," Ibáñez said. The initial study is published in the August issue of the Journal of Clinical Endocrinology and Metabolism.
Why a diabetes drug?
Although the visible symptoms of PCOS emerge in puberty, research over the past decade has revealed that PCOS develops silently for years before that.
"It is clear from all of the data on PCOS that this is a lifelong condition," said Kathleen Hoeger, an endocrinologist and PCOS expert at the University of Rochester Medical Center. "It just doesn't become recognizable — because it's reproductively defined — until the adolescent period."
PCOS begins with an excess of insulin in the body — similar to Type 2 diabetes. When the ovaries are exposed to too much insulin, their hormone production is altered. As the small amounts of male hormones that all females produce begin to build up, they affect the rest of a girl's body, and she develops the typical outward signs of PCOS.
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.
Currently, metformin is given to women of childbearing age who are struggling with infertility, as well as girls who have developed symptoms of PCOS. But 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 and no reason to think that using it in PCOS-prone girls would be risky, Ibáñez said.
The challenge is identifying who to treat, said Hoeger, who was not involved with the study. The patients chosen by Ibáñez's team were a very narrow slice of girls, she said.
"What we need is a large, longitudinal study that tells us who in the population is really at risk for PCOS," Hoeger said. "Then we would know who to treat early."
Pass it on: Prescribing metformin to prepubescent girls at risk of polycystic ovary syndrome lowers their chances of developing the disorder.