Recent data suggest that treatment with metformin during
late childhood or early puberty may impede or prevent the development of
polycystic ovary syndrome in girls at high risk for the disease.
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.
“PCOS often presents in adolescence with irregular
menstrual cycles, acne or too much body hair,” the study’s lead
researcher, Lourdes Ibañez, MD, PhD, professor of pediatrics at
the University of Barcelona in Spain, said in a press 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.”
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.”
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Disclosure: The researchers report no relevant financial