Early Metformin Therapy Delayed Onset, and Prevention of PCOS

A randomized, open-label, 7-year study revealed a two- to eightfold higher prevalence of hirsutism, androgen excess, oligomenorrhea and PCOS among girls who received brief, delayed metformin therapy compared with those who received treatment earlier and for a longer period of time. All girls had low birth weight and precocious pubarche. Bottom of Form 

The study's lead researcher, Lourdes Ibañez, MD, PhD, professor of pediatrics at the University of Barcelona in Spain, said,  "PCOS often presents in adolescence with irregular menstrual cycles, acne or too much body hair." "But we believe the critical years for PCOS development may be during childhood and puberty when excessive amounts of fat are stored. That excessive weight gain overexposes the ovaries to insulin, causing them to stop ovulating and start releasing male hormones, resulting in PCOS."

In the study, Ibañez and colleagues randomly assigned 38 girls with low birth weight and precocious pubarche to receive 4 years of metformin therapy during ages 8 to 12 years or 1 year of treatment between ages 13 and 14 years. Researchers followed all girls for at least 1 year after discontinuation of treatment.

In addition to lower prevalence of PCOS, at the study's conclusion, girls who received early metformin treatment were approximately 4 cm taller, were in a less proinflammatory state and had less central fat distribution due to decreases of visceral and hepatic fat than girls treated later. They also had lower increments of BMI Z-score, fasting insulin, homeostasis model assessment insulin resistance index, dehydroepiandrosterone sulfate and triglycerides, the researchers said.

Occurring between ages 8 and 10 years, abdominal adiposity was the first variable to diverge between girls with and those without PCOS at age 15 years, while circulating androstenedione was the first androgen to diverge between ages 10 and 12 years.

"Metformin, when given across the potentially critical window of puberty, may have the capacity to preprogram metabolism toward less abdominal and liver fat," Ibañez said. "In the years ahead, the focus of attention should shift from late treatment of PCOS and its complications toward the early and large-scale prevention of PCOS with measures such as diet, exercise and metformin in young girls."

Ibañez L. J Clin Endocrinol Metab. 2011;doi:10.1210/jc.2011-0555.