Systemic and local effects of metformin administration in patients with polycystic ovary syndrome (PCOS): relationship to the ovulatory response

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Abstract
Several data have demonstrated the efficacy of metformin in inducing ovulation in patients with polycystic ovary syndrome (PCOS), however, the exact mechanism by which this drug acts remains unknown. The aim of the present study was to evaluate whether the efficacy of the drug in patients with PCOS is related to a systemic hormonal–metabolic improvement, or to a local action on the ovary. Twenty-four normal weight patients with PCOS, who were treated with metformin, were enrolled. Of these, 12 subjects were anovulatory (Group A1), whereas the other 12 were ovulatory but had failed to conceive (Group A2). A further 24 untreated subjects who were scheduled for laparoscopic surgery were enrolled as controls, 12 anovulatory patients with PCOS scheduled for laparoscopic myomectomy (Group B1) and a further 12 non-PCOS participants were scheduled for diagnostic laparoscopy (Group B2). Clinical assessments and biochemical evaluations in blood and antral follicular fluid were performed in each participant. In 1/12 and 9/12 participants from Groups A1 and A2, respectively, the ovarian morphology was changed, and a significant (P < 0.05) reduction in the ovarian dimensions was observed only in Group A2. In both of these groups, and without difference between them, serum androgens and indices of insulin resistance improved significantly (P < 0.05) after metformin treatment. On the other hand, significant differences (P < 0.05) between the two groups were detected with respect to the same biochemical parameters in antral follicular fluid. In Groups A1 and A2, levels of androgens and indices of insulin resistance in the antral follicular fluid were significantly (P < 0.05) better than in Group B1, but worse than in Group B2. Irrespective of its systemic effects, the efficacy of metformin in the induction of ovulation is probably due to a direct action on the ovary, and the ovulatory response to the drug seems to be related to local sensitivity or resistance to the drug.

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