Effects of rosiglitazone on the cardiovascular profile in postmenopausal women without diabetes mellitus: interplay of thiazolidinediones and hormone therapy

Objective: Thiazolidinediones have antiatherothrombotic effects on persons with diabetes. Hormone therapy among postmenopausal women has both positive and negative cardiovascular effects. However, the effects of rosiglitazone with or without concurrent long-term hormone therapy on the cardiovascular profile of nondiabetic postmenopausal women are unknown. Methods: Thirty-eight nondiabetic postmenopausal women were enrolled in this double-blind and placebo-controlled study. Eighteen participants received 4 mg rosiglitazone, and 20 participants took placebo daily for 12 weeks. Global endothelial function and plasma biomarkers were measured. Results: Baseline characteristics and parameters were similar between the groups. Rosiglitazone, but not placebo, significantly reduced leukocyte count and plasma levels of matrix metalloproteinase-9 and inhibited the elevation of plasma levels of plasminogen activator inhibitor-1 and tissue plasminogen activator (P < 0.05 for all). Most of the favorable effects provided by rosiglitazone were still present in participants with concurrent hormone therapy. Increased body weight and waist size as well as elevation of the plasma levels of total and low-density lipoprotein cholesterol were noted after rosiglitazone treatment among participants without concurrent hormone therapy. No significant change in the global endothelial function occurred in response to treatment in either group. Conclusions: Rosiglitazone treatment provided both protective and harmful cardiovascular effects in nondiabetic postmenopausal women. Concurrent hormone therapy resulted in the maintenance of the major beneficial effects while neutralizing the unfavorable effects of rosiglitazone.