Longitudinal metabolic observation of metformin effects during pregnancy in hyperinsulinemic women with polycystic ovary syndrome: a case report.

Obese hyperinsulinemic women with polycystic ovary syndrome (PCOS) present a markedly increased risk of developing glycaemic alterations during pregnancy, commonly recognized as a "diabetogenic" condition. This risk seems to be safely reduced by the administration of metformin during gestation. We analyzed the metabolic changes in two hyperinsulinemic PCOS women, who became pregnant after 8 weeks of metformin therapy and continued taking the drug till delivery. An oral glucose tolerance test and an euglycemic hyperinsulinemic clamp were performed at baseline and, during metformin therapy, in pre-conceptional state and at each trimester of gestation. A pronounced decrease in peripheral insulin sensitivity occurred as the pregnancies proceeded (at the third trimester 51.7% and 41.1% of pregestational values in patient 1 and 2 respectively), along with an increase in stimulated insulin secretion (at the third trimester 120% and 50.6% of pregestational values in patient 1 and 2 respectively). Despite these findings, none of the studied subjects developed gestational diabetes or impaired glucose tolerance. This confirms that metformin may exert a protective role against such disturbances in hyperinsulinemic PCOS patients, probably by avoiding the gestational physiologic changes leading to a loss of the metabolic balance achieved by these subjects out of pregnancy.