RESUMO
OBJECTIVE: To assess the effects of continuous administration of conjugated estrogen combined with sequential administration of medrogestone on lipid profiles, climateric symptoms and endometrial tolerance. METHODS: This multicenter open study was conducted for one year to assess the effects of a hormone replacement therapy (HRT) regimen using Premarin (0.625 mg/day 28d/28) combined with medrogestone 5mg for 12 days (d17-d28 of each 28-day cycle) on lipid profiles, climateric symptoms and cycle control in 228 post menopausal women with an intact uterus. The subjects were recruited in 23 centers in 7 countries in Europe and Asia. Serum lipid/lipoprotein levels were determined at baseline and at cycles 3, 6, 13; endometrium biopsies were performed at screening then at cycle 13. Climateric symptoms and bleeding patterns were recorded by the patients from daily diaries cards collected at baseline and at visits during cycle 3, 6, 9, and 13. RESULTS: By cycle 3, the conjugated estrogen-medrogestone combination induced significant modifications of the lipid profile which were judged favorable. These modifications were maintained throughout treatment. All the baseline values were within normal limits. Mean variations compared with baseline values (expressed in mmol/l) after cycles 3, 6, and 13 were -0.46, -0.54, and -0.46 for total cholesterol (p<0.05), + 0.053, + 0.057, and + 0.078 for HDL-cholesterol (p<0.05) and -0.556, -0. 542, and -0.493 for LDL-cholesterol (p<0.001) respectively. VLDL-cholesterol levels were unchanged. Triglycerides increased significantly though moderately: + 0.12, + 0.15, and + 0.15 mmol/l at cycles 3, 6, and 13 respectively. Endometrial biopsies obtained at cycle 13 (n=195) did not reveal any endometrial hyperplasia. Withdrowal bleeding was predictable for a 6 to 7.4 day interval. The incidence of irregular bleeding varied from 7 to 33% and decreased progressively over the 13-cycle treatment. The incidence of amenorrhea increased from 14 to 52% over the 12 months studied. Finally, at each cycle, menopausal symptoms (mean number of hot flushes/day and Küpperman score) were significantly improved compared with the baseline. As expected, modifications were more pronounced after cycle 1, but improvements were maintained throughout the study. CONCLUSION: Continuous administration of Premarin in combination with sequential administration of medrogestone was found to be an effective treatment for menopausal symptoms. It was associated with favorable modifications of the lipid profile and was safe for the endometrium.
