Effects on serum lipid profiles of continuous 17beta-estradiol, intermittent norgestimate regimens versus continuous combined 17beta-estradiol/norethisterone acetate hormone replacement therapy

OBJECTIVE: To compare the effects of a daily oral 1-mg dose of continuous 17beta-estradiol (E2) plus intermittent (3 days off, 3 days on) norgestimate (NGM) 90 microg (n = 221), an oral 2-mg dose of continuous E2 plus intermittent NGM 180 microg (n = 219), and an oral 2-mg dose of continuous E2 plus continuous norethisterone acetate (NETA) 1 mg (n = 217) on blood lipids and lipoproteins in postmenopausal women. BACKGROUND: The present study was undertaken because some progestins have adverse effects on lipid profiles, thereby negating the favorable effects of estrogens. METHODS: This was a multicenter, randomized, parallel-group trial that focused primarily on the 2 marketed regimens--E2 1 mg/NGM 90 microg and E2/NETA. Both subjects and investigators were blinded to the intermittent regimens; the continuous combined regimen was administered open-label. After a minimum 12-hour overnight fast, blood samples were collected at baseline and during months 7 and 12 to determine lipid and lipoprotein concentrations using validated methods. RESULTS: E2 1 mg/NGM 90 microg was associated with significant (ie, the 95% CI did not include 0) increases in high-density lipoprotein cholesterol (HDL-C) (6.8% 95% CI = 4.7%, 9.0%] and 4.8% 2.3%, 7.2%] at months 7 and 12, respectively) and high-density lipoprotein 2 cholesterol (HDL2-C) (10.8% 6.2%, 15.3%] and 24.1% 18.9%, 29.4%]) concentrations, and decreases in total cholesterol (-7.7% -9.0%, -6.3%] and -9.2% -10.5%, -7.9%]), low-density lipoprotein cholesterol (-14.3% -16.3%, -12.4%] and -14.9% -16.7%, -13.2%]), and lipoprotein(a) (-30.6% -41.4%, -20.0%] at month 12) concentrations. A significant difference (P < 0.001 by analysis of variance) between the E2 1-mg/NGM 90-microg and NETA regimens was seen for HDL-C and HDL2-C concentrations, which were elevated in subjects receiving E2 1 mg/NGM 90 microg but reduced (-9.1% -11.1%, -7.1%] and -12.3% -14.3%, -10.3%] for HDL-C at months 7 and 12, respectively; -14.2% -18.0%, -10.4%] and -2.5% -7.8%, +2.8%] for HDL2-C at months 7 and 12, respectively) in those receiving E2/NETA. CONCLUSIONS: In the present study, continuous E2 1 mg/NGM 90 microg was associated with beneficial effects on lipids and lipoproteins in healthy postmenopausal women, effects that were greater at least for HDL-C and HDL2-C than those observed with continuous combined E2/NETA. The applicability of the study results to women with preexisting cardiovascular disease or dyslipidemia, or those who are overweight, remains to be investigated.