EFFECT OF A HMG-COA REDUCTASE INHIBITOR COMBINED WITH HORMONE REPLACEMENT THERAPY ON LIPID-METABOLISM IN JAPANESE WOMEN WITH HYPOESTROGENICLIPIDEMIA - A MULTICENTER DOUBLE-BLIND CONTROLLED PROSPECTIVE-STUDY

Objectives: Menopause is associated with a rise in serum lipid concent rations. We compared a regimen of pravastatin alone with pravastatin a nd hormone therapy in postmenopausal women with hyperlipidemia. Method s: We performed a double-blind, randomized, multicenter controlled stu dy in postmenopausal women with hyperlipidemia. The women were randoml y assigned to receive pravastatin alone (M group. n = 25) or pravastat in and hormone replacement therapy (HRT) (MC group; n = 32) for 12 wee ks. Serum lipid and estrogen concentrations were measured at baseline and after 4 weeks and 12 weeks of treatment. Results: The two groups w ere similar with respect to baseline demographic characteristics such as age, height, and body weight. As compared with baseline, the total cholesterol (TC) concentration was 15.0% lower at 4 weeks and 17.7% lo wer at 12 weeks in the M group and 15.1% lower at 4 weeks and 18.3% lo wer at 12 weeks in the MC group. The low-density-lipoprotein cholester ol (LDL-C) concentration decreased by 25.0% at both 4 weeks and 12 wee ks in the M group and by 26.8% at 4 weeks and 30.0% at 12 weeks in the MC group. Serum TC and LDL-C concentrations were significantly lower in the MC group than in the M group after 4 weeks of treatment, but th ere was no significant difference between the groups in serum lipid co ncentrations after 12 weeks. Pravastatin combined with HRT was therefo re suggested to lower serum lipid concentrations earlier than pravasta tin alone. There were no significant differences between the treatment groups in serum high-density-lipoprotein cholesterol concentrations o r triglyceride concentrations after the initiation of therapy. In the MC group, there was a significant positive correlation between the per centage change in serum lipid concentrations and that in estrogen conc entrations, suggesting that the HRT-induced rise in estrone (El) as we ll as that in estradiol (E2) contributed an improved serum lipid profi le. TC and E2, and LDL-C and serum El had significant negative correla tion at 12 weeks and 4 weeks, respectively. Pravastatin had no apparen t effect on endogenous estrogen levels and was not associated with any side effects, which confirmed that pravastatin is safe, either alone or in combination with HRT. Conclusions: The combination of pravastati n and HRT in the management of hyperlipidemia in postmenopausal women is very useful therapeutically, because it additionally provides the b road benefits of HRT, without compromising the lipid lowering effects of either treatment. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.