Metformin: an old medication of new fashion: evolving new molecular mechanisms and clinical implications in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is now recognized to be the most common endocrinopathy in women of reproductive age with a prevalence of 6.6-6.8%. PCOS, a syndrome of unknown etiology, was initially regarded as a reproductive disorder. However, in the last 15 years the role of insulin resistance (IR) has been identified as a significant contributor to the pathogenesis of PCOS, and the metabolic and cardiovascular sequelae of the syndrome have been increasingly appreciated. The coexistence and interaction of reproductive and cardiometabolic abnormalities in the context of PCOS have created a need for a modified therapeutic management of affected women. Insulin sensitizers, particularly metformin, have been introduced as a pharmaceutical option targeting not only IR, but several other aspects of the syndrome, including reproductive abnormalities. The landscape of the multifaceted actions of metformin evolves to broaden the therapeutic implications of this old drug in a new fashion for patients with PCOS. Most recently, the spectrum of metformin's targets has been expanded, and molecular studies have explored the tissue-specific mechanisms of metformin in the liver, the muscle, the endothelium, and the ovary. The use of metformin in pregnant women with PCOS comprises another scarcely explored, but promising area of research. This review attempts to cover the spectrum of metformin's cellular actions in different tissues and to summarize the current literature regarding the potential medical value of this medication in PCOS. Even if many of these actions are individually modest, they seem to be collectively sufficient to confer therapeutic benefits not only in cardiometabolic aspects but also in reproductive aspects of PCOS.

Hyperreninemia characterizing women with polycystic ovary syndrome improves after metformin therapy.

BACKGROUND: Polycystic ovary syndrome (PCOS) is characterized by chronic anovulation, hyperandrogenemia and insulin resistance. Hyperreninemia is observed in insulin resistance and hyperandrogenemic states. AIMS: To investigate the levels of total plasma renin and their possible relationship with insulin resistance and hyperandrogenemia and to explore the effect of metformin on these parameters in PCOS women. METHODS: 48 PCOS women who were age- and body mass index (BMI)-matched with 21 healthy women were studied. Total renin, aldosterone levels, glucose and insulin levels were measured at basal state and during an oral glucose tolerance test in all subjects. A subgroup of women with PCOS was evaluated 6 months after metformin administration. RESULTS: Total renin levels were significantly higher in PCOS women compared to controls. PCOS women compared to controls displayed higher areas under the curve for glucose, insulin and total renin (AUCREN). Mean AUCREN was correlated significantly with insulin resistance indices and positively with free testosterone levels. Total renin, aldosterone, androgen levels and insulin sensitivity indices were significantly improved after 6 months on metformin treatment. CONCLUSIONS: PCOS women demonstrated an insulin resistance and hyperandogenemia-related increase in serum total renin levels. Metformin treatment was shown to significantly reduce total renin levels.