Treatment-induced cyclic variations in serum lipids, lipoproteins, and apolipoproteins after 2 years of combined hormone replacement therapy: exaggerated cyclic variations in smokers.

Abstract

To study the long-term effect of cigarette smoking on cyclic variations in serum lipids, lipoproteins, and apolipoproteins following combined hormone replacement therapy. One hundred eighteen healthy, early postmenopausal women were followed for 2 years in a randomized, placebo-controlled study. Four treatment groups received estradiol, either sequentially combined with levonorgestrel (75 micrograms), medroxyprogesterone acetate (10 mg), or desogestrel (150 micrograms), or continuously combined with cyproterone acetate (1 mg). Two groups received placebo. Serum lipids, lipoproteins, and apolipoproteins were measured at well-defined times. Information on smoking habits was elicited by questionnaire. We found statistically significant cyclic variations in apolipoprotein A1 in the levonorgestrel group (6.7%; 95% confidence interval [CI] 1.1-12.7%) and the desogestrel group (7.4%; 95% CI 2.9-12.1%). The cyclic variations in high-density lipoprotein (HDL) cholesterol were highly statistically significant in the levonorgestrel group (24.9%; 95% CI 10.2-39.2%). When women from sequential regimens were combined, further analysis showed that smokers had significantly larger cyclic variations in HDL cholesterol (P less than .01) and apolipoprotein A1 (P less than .05) than non-smokers. Sequentially combined hormone replacement therapy produces cyclic variations in HDL cholesterol and apolipoprotein A1 for at least 2 years. In addition, cigarette smoking is associated with an exaggeration of the cyclic effect of treatment on these indices.