A COMPARATIVE-STUDY OF 2 LEVONORGESTREL-CONTAINING HORMONE REPLACEMENT THERAPY REGIMENS ON EFFICACY AND TOLERABILITY VARIABLES

Objective: To compare the effect of two sequential hormone replacement regimens differing in the dose of levonorgestrel on climacteric sympt oms, bleeding pattern and lipid metabolism in postmenopausal women. St udy design: In a multicentre, randomized, double-blind, active-treatme nt-controlled study, 210 postmenopausal women were assessed at the end of treatment cycles 3 and 6. The high-levonorgestrel group was treate d with 2 mg estradiol valerate (days 1-21) sequentially combined with 0.25 mg levonorgestrel (days 12-21). The low-levonorgestrel group rece ived the same estrogen regimen (2 mg estradiol valerate, days 1-21), b ut levonorgestrel was administered sequentially in a dose of 0.15 mg d uring the last 12 days of the cycle (days 10-21). Statistical analysis by Student's t-test for dependent variables (measured values versus b aseline) and independent variables (differences between groups), and t he composite t-test method for comparison of both regimens with respec t to efficacy, was performed. Results: Both groups were statistically comparable. The trial was completed by 137 subjects. Protocol violatio ns occurred in 38 cases. Thirty-five subjects dropped out during the s tudy, 21 of them because of adverse events. Both treatments were equal ly effective in the treatment of climacteric complaints. There were no clinically significant changes in body weight, blood pressure, haemat ological tests, and parameters of clinical chemistry. There was a tend ency towards a reduction in bleeding intensity in both groups in the s econd half of the treatment period. The treatment for six cycles with both regimens significantly (P < 0.05) decreased plasma concentrations of triglycerides (significant in the low-levonorgestrel group only), high-density lipoprotein cholesterol, high-density lipoprotein-3-chole sterol, lipoprotein(a) and apolipoprotein Al. In parallel, the serum c oncentration of total cholesterol increased significantly in both trea tment groups, whereas low-density lipoprotein cholesterol increased si gnificantly in the high-levonorgestrel group only. The changes in high -density lipoprotein-2-cholesterol, and apolipoprotein B did not reach statistical significance. Conclusions: It can be concluded that both sequential combined oral hormone replacement therapy (HRT) regimens we re equivalent with respect to efficacy and tolerability in the treatme nt of women with climacteric complaints. The preparation with the lowe r dose of progestin showed a tendency towards a less unfavourable infl uence on the lipid profile. (C) 1997 Elsevier Science Ireland Ltd.