Pioglitazone Improves Outcomes in Women With POS

The thiazolidinedione pioglitazone is as effective as metformin in reversing insulin sensitivity and hyperandrogenism in obese women with polycystic ovary syndrome (PCOS), but metformin is safer.

Dr. Carlos Ortega-Gonzalez from Instituto Nacional de Perinatologia, Mexico City, Mexico, stated that, "The key metabolic feature in women with PCOS is insulin resistance and, thus, hyperinsulinemia, whether or not they are obese." "Thus, from a theoretical point of view the amelioration of insulin resistance and hyperinsulinemia should be observed also in lean PCOS women using pioglitazone."

Dr. Ortega-Gonzalez and colleagues studied 52 obese women with PCOS and insulin resistance who were previously untreated with drugs intended to improve insulin sensitivity.

Treatment for 6 months with pioglitazone resulted in significant decreases in fasting serum insulin levels, AUC-insulin during the 2-hour oral glucose tolerance test, and insulin resistance index, the authors report. Metformin treatment brought similar results, the report indicates, but the AUC-insulin was significantly lower in the pioglitazone group than in the metformin group.

Decreases in serum concentrations of androgens and LH were similar with both drugs, the researchers note. Unlike metformin treatment, pioglitazone treatment was associated with significant increases in body weight, body mass index, and waist to hip ratios.

Eight pregnancies (5 on pioglitazone and 3 on metformin) occurred during the study, but only 4 pregnancies proceeded to delivery (two mothers on each drug). According to the report, all 4 newborns had normal weights for gestational age, were clinically healthy, and encountered no perinatal complications.

"These results suggest that pioglitazone is as effective as metformin in improving insulin sensitivity and hyperandrogenism, despite an increase in body weight, body mass index, and the waist to hip ratio associated with pioglitazone," the authors conclude.

"We are working to study the changes in body composition in PCOS women associated with the use of either drug, looking at two issues," Dr. Ortega-Gonzalez said. "First, whether or not there is indeed a ‘beneficial’ shift from intraabdominal to subcutaneous fat in PCOS women using pioglitazone, as occurs in patients with type 2 diabetes. Second, because fat mass is not the only important compartment of the body, we will also look at possible changes in lean body mass, especially in the face of significant reduction in hyperandrogenism induced by these drugs."

"If the chief complaint of a women with PCOS is sterility, then the use of pioglitazone may represent a potential risk if the diagnosis of pregnancy at an early stage is missed," Dr. Ortega-Gonzalez cautioned. "This is because pioglitazone may cause intrauterine growth retardation. Thus, metformin is a much safer drug."
J Clin Endocrinol Metab 2005;90:1360-1365