Effect of a HMG-CoA reductase inhibitor combined with hormone replacement therapy on lipid metabolism in Japanese women with hypoestrogenic lipidemia: a multicenter double-blind controlled prospective study

Objectives: Menopause is associated with a rise in serum lipid concentrations. We compared a regimen of pravastatin alone with pravastatin and hormone therapy in postmenopausal women with hyperlipidemia. Methods: We performed a double-blind, randomized, multicenter controlled study in postmenopausal women with hyperlipidemia. The women were randomly assigned to receive pravastatin alone (M group; n =25) or pravastatin and hormone replacement therapy (HRT) (MC group; n =32) for 12 weeks. Serum lipid and estrogen concentrations were measured at baseline and after 4 weeks and 12 weeks of treatment. Results: The two groups were 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% lower at 12 weeks in the M group and 15.1% lower at 4 weeks and 18.3% lower at 12 weeks in the MC group. The low-density-lipoprotein cholesterol (LDL-C) concentration decreased by 25.0% at both 4 weeks and 12 weeks 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 there was no significant difference between the groups in serum lipid concentrations after 12 weeks. Pravastatin combined with HRT was therefore suggested to lower serum lipid concentrations earlier than pravastatin alone. There were no significant differences between the treatment groups in serum high-density-lipoprotein cholesterol concentrations or triglyceride concentrations after the initiation of therapy. In the MC group, there was a significant positive correlation between the percentage change in serum lipid concentrations and that in estrogen concentrations, suggesting that the HRT-induced rise in estrone (E1) as well as that in estradiol (E2) contributed an improved serum lipid profile. TC and E2, and LDL-C and serum E1 had significant negative correlation at 12 weeks and 4 weeks, respectively. Pravastatin had no apparent 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 pravastatin and HRT in the management of hyperlipidemia in postmenopausal women is very useful therapeutically, because it additionally provides the broad benefits of HRT, without compromising the lipid lowering effects of either treatment.