In 35 postmenarchal adolescent females (17 ± 2 years, range 14-19) with polycystic ovary syndrome (PCOS), in a case-series prospective description, we assessed effectiveness of metformin-diet for 1 year for reduction of weight, insulin, HOMA insulin resistance (IR), cholesterol, triglycerides, and resumption of regular menses. By selection, all 35 girls met the 2003 consensus criteria for diagnosis of PCOS; all 35 had clinical hyperandrogenism, 37% were amenorrheic, and 60% oligomenorrheic. Pretreatment median weight was 82.7 kg, BMI 30.8 kg/m2, and 19 (54%) girls had BMI > the CDC age-gender-specific 95th percentile (overweight). Calories (26% protein, 44% carbohydrate) were targeted to 1,500-1,800/day if BMI was < 25 or to 1,200-1,500/day if BMI was $ 25, along with 2,550 mg metformin. After 1 year on metformin-diet, median weight fell from 82.7 to 79.1 kg (p = .009); the median of the percent change was -5%. In 6 girls (17%) weight loss was $ 10 kg, in 8 (23%) was 5-10 kg, and in 11 (31%) was 0-5 kg. After 1 year on metformin-diet, fasting serum insulin 16.7 to 13.3 uU/mL (p < .0001), HOMA IR 3.41 to 2.74 (p = .0004), total cholesterol 164 to 151 mg/dL (p = .002), and triglyceride 103 to 85 mg/dL (p = .006). After 1 year on metformin-diet, reduction in insulin was associated with reduction in testosterone, R2 = 20%, p = .008. The percentage of cycles with normal menses rose from a pretreatment median of 8% to 100% after 1 year on metformin-diet, p < .0001. In 19/35 girls (54%) serum progesterone was $ 2.3 ng/mL (ovulatory range) at $ 1 of their follow-up visits. Because we did not randomize to diet-placebo vs diet-metformin, we cannot separate metabolic-endocrine benefits attributable to metformin alone or diet alone. The importance of the diagnosis of PCOS in adolescence lies in primary prevention of adult endocrinopathy, obesity, infertility, hyperinsulinemia, hypertriglyceridemia, type 2 diabetes, and increased cardiovascular morbidity-mortality. In adolescents with PCOS, metformin-diet reduces weight, insulin, IR, cholesterol, and triglycerides and facilitates resumption of regular menses. Successful reversal of endocrine and cardiovascular risks associated with PCOS soon after menarche should save the adolescent from the early and late stigmata of the syndrome and emphasizes the importance of the earliest diagnosis and treatment of PCOS in adolescence.
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