Metformin May Prevent or Delay Polycystic Ovary Syndrome

Laurie Barclay, MD

July 01, 2011

July 1, 2011 — Metformin may prevent or delay the development of polycystic ovary syndrome (PCOS) in adolescence, according to the results of a randomized, open-label study published online June 1 in the Journal of Clinical Endocrinology & Metabolism.

"PCOS often presents in adolescence, with irregular menstrual cycles, acne, or too much body hair," lead study author Lourdes Ibáñez, MD, PhD, professor of pediatrics at the University of Barcelona in Spain, said in a news release. "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."

The study goal was to compare the efficacy of early vs late metformin treatment to prevent adolescent PCOS in girls at high risk of developing PCOS because of a combined history of low(-normal) birth weight (LBW) and precocious pubarche (PP).

At a university hospital, 38 LBW-PP girls were followed-up from 8 years to 15 years of age and were assigned to receive early metformin (study year, 1 - 4; age, 8 - 12 years) or late metformin (study year, 6; age, 13 - 14 years). The study endpoints were evaluated after study year 7, when all participants had been untreated for 1 year or more. These endpoints included height; weight; hirsutism score; menstrual cycle; fasting endocrine-metabolic screening, measured in the follicular phase; C-reactive protein; body composition, measured by absorptiometry; abdominal fat partitioning, as determined by magnetic resonance imaging; ovarian morphology, as imaged by ultrasound; and PCOS by National Institutes of Health and Androgen Excess Society definitions.

Retention rate in the study was 100%. Girls randomly assigned to receive early metformin were 4 cm taller at age 15 years than those girls assigned to receive late metformin, and they also had less of a proinflammatory state and less central fat because of reductions in visceral and hepatic fat. Compared with early-treated girls, late-treated girls had 2-fold to 8-fold more hirsutism, androgen excess, oligomenorrhea, and PCOS. At age 8 to 10 years, abdominal adiposity was the first variable to differ in girls who did vs those who did not have PCOS at age 15 years.

"In LBW-PP girls, early metformin therapy was found to prevent or delay the development of hirsutism, androgen excess, oligomenorrhea and PCOS more effectively than late metformin," the study authors write. "The time window of late childhood and early puberty may be more critical for the development — and thus for the prevention — of adolescent PCOS than the first years beyond menarche."

Limitations of this study include its small sample size.

"Metformin, when given across the potentially critical window of puberty, may have the capacity to reprogram metabolism toward less abdominal and liver fat," Dr. Ibáñez 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."

The research of 3 of the study authors is supported by the Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas, Instituto de Salud Carlos III, Madrid, Spain, where they serve as clinical investigators. Another author's research is supported by the Fund for Scientific Research I3, Ministry of Education and Science, Spain. Another author is an investigator of the Clinical Research Council of the University Hospital Leuven, Belgium. The study authors have disclosed no relevant financial relationships.

J Clin Endocrinol. Published online June 1, 2011. Abstract

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