Uterine physiology in hyperandrogenism: Can Metformin avoid the effects of androgens?

ELIA EVELIN MARIEL

Simposio; XV Annual Symposium of the Frontiers in Reproduction; 2012

Polycystic ovary syndrome (PCO) is one of the most frequent endocrine diseases that affect women in their childbearing age. This syndrome is characterized by hyperandrogenism that shows detrimental effects on the endometrial function, contributing to the high rates of pregnancy loss, hyperplasia and endometrial cancer. Metformin in the treatment of PCO shows numerous benefits although there is controversy about its effectiveness to improve pregnancy rates. In addition, many patients do not respond to Metformin-treatment and in those patients better results are obtained when Metformin is administered together with Rosiglitazone. The aim of the present work was to study the mechanisms by which the hyperandrogenism alters the uterine function and the capacity of Rosiglitazone and/or Metformin-treatment/s to prevent such alterations. We found that the hyperandrogenism altered the uterine histology, the balance between apoptosis/cell proliferation, the arachidonic acid metabolism, the activation of the transcription factors PPAR and increased the oxidative stress. Administration of Metformin avoided many of these alterations except the oxidative stress. The combination Metformin plus Rosiglitazone improved the antioxidant defenses. We conclude that this would be one of the reasons because of the fact that the combined therapy would give better results in the treatment of PCOS women, especially in those who do not respond optimally to Metformin.