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Early metformin curbs PCOS in at-risk girls

Reuters Health • The Doctor's Channel Daily Newscast

NEW YORK (Reuters Health) – Metformin beginning at the age of 8 years in girls at risk of polycystic ovary syndrome (PCOS) is more effective than a later start, Spanish researchers report in a June 1st on-line paper in the Journal of Clinical Endocrinology & Metabolism.

As Dr. Lourdes Ibanez told Reuters Health by email, “there are groups of young girls — for example, those with a history of a low birthweight and an early appearance of pubic hair — who are long known to be at high risk for PCOS in adolescence and beyond. In these girls, early intervention with metformin starting before puberty reduces the fat stores and delays menarche.”

“In children,” she added, “metformin is extremely well tolerated. In a few cases, it may be accompanied by abdominal pain, but it is easily avoided by starting with half-a-dose during the first days of therapy. In adults, abdominal pain and flatulence seem to be more frequent.”

Dr. Ibanez of the University of Barcelona and colleagues followed 38 girls with low birthweight and precocious pubarche from a mean age of 8 years until they were 15 years old.

At the start of the 7-year open-label study, they were randomized to receive metformin for 4 years and to remain untreated for 3 years or to receive no treatment for 5 years, have metformin for 1 year and to remain untreated in the final year. All completed the study.

At the age of 15 years, the early metformin group was a mean of 4 cm taller and showed lower C-reactive protein and neutrophil levels. They also had less visceral and hepatic fat.

Moreover hirsutism, androgen excess, oligomenorrhea, and PCOS, depending on criteria, were between 2- and 8-fold more prevalent in late- than early-treated girls.

Between girls who did and did not develop PCOS, abdominal adiposity at the age of 8 to 10 years was the first variable to diverge. Circulating androstenedione was the first androgen to diverge.

“PCOS,” continued Dr. Ibanez, “is nowadays the most prevalent hormonal disorder of adolescent girls and young women, often presenting in adolescence with irregular cycles and skin problems… However, the critical years for PCOS development may be those of excessive fat storage in childhood and puberty.”

“These results,” she concluded, “open the perspective that the development of PCOS can be prevented or delayed — at least in selected girls — by adiposity-reducing measures in childhood and puberty.”

J Clin Endocrinol Metab 2011.