A novel intermittent regimen of norgestimate to preserve the beneficial effects of 17β-estradiol on lipid and lipoprotein profiles

OBJECTIVE: This study was undertaken to evaluate the effects of 3 dosage levels of intermittent norgestimate plus a constant dose of 17 beta-estradiol on blood lipid and lipoprotein concentrations in 236 postmenopausal women. STUDY DESIGN: In this multicenter, double-blind, parallel-group trial the subjects were randomly assigned to receive 1 mg estradiol daily or 1 mg estradiol daily plus intermittent (3 days off and 3 days on) doses of 30 mu g, 90 mu g, or 180 mu g norgestimate for 360 days. RESULTS: The regimens of 1 mg estradiol plus 30 mu g norgestimate and 1 mg estradiol plus 90 mu g norgestimate increased concentrations of high-density lipoprotein cholesterol, HDL2 high-density lipoprotein cholesterol, HDL3 high-density lipoprotein cholesterol (except the regimen of 1 mg estradiol plus 30 mu g norgestimate at 7 months), and apolipoprotein apo A-I. They decreased total cholesterol concentration, low-density lipoprotein cholesterol concentration, low-density lipoprotein/high-density lipoprotein ratio, apolipoprotein apo B concentration, and Lp(a) lipoprotein concentration, and they attenuated estradiol-induced increases in triglyceride concentrations. In contrast, the regimen of 1 mg estradiol plus 180 mu g norgestimate reduced concentrations of high-density lipoprotein cholesterol, high-density lipoprotein HDL3 cholesterol, and apolipoprotein apo A-I at 7 months and increased the low-density lipoprotein/high-density lipoprotein ratio at 7 months. CONCLUSIONS: An intermittent regimen of norgestimate at 30 or 90 mu g daily administered for 3 days off followed by 3 days on preserved the beneficial lipid and lipoprotein changes induced by continuous therapy with 1 mg 17 beta-estradiol daily; however, 180 mu g norgestimate did not do so.