Effects of lower doses of conjugated equine estrogens and medroxyprogesterone acetate on plasma lipids and lipoproteins, coagulation factors, and carbohydrate metabolism

Abstract

Objective: To determine the effects of lower doses of conjugated equine estrogens (CEE) alone or CEE and medroxyprogesterone acetate (MPA) on lipoproteins, carbohydrate metabolism, and coagulation/fibrinolytic factors.

Design: Randomized, double-blind, placebo-controlled study.

Setting: Multicenter substudy of the Women's HOPE trial.

Patient(s): Seven hundred and forty-nine healthy, postmenopausal women.

Intervention(s): Women were randomized to receive the following doses in milligrams per day: 0.625 CEE; 0.625 CEE/2.5 MPA; 0.45 CEE; 0.45 CEE/2.5 MPA; 0.45 CEE/1.5 MPA; 0.3 CEE; 0.3 CEE/1.5 MPA; or placebo.

Main outcome measure(s): Assessment of lipids, lipoproteins, glucose tolerance, and coagulation/fibrinolytic factors at baseline, cycle 6, and year 1.

Result(s): One year of treatment with any of the CEE or CEE/MPA regimens studied increased high-density lipoprotein cholesterol (HDL-C); the 10% increase in HDL-C for the CEE 0.45/MPA 1.5 group was similar to the CEE 0.625/MPA 2.5 group. Low-density lipoprotein cholesterol was significantly reduced in all of the active treatment groups except the CEE 0.3/MPA 1.5 group at cycle 13. Apolipoprotein A-I and triglyceride levels increased and apolipoprotein B levels decreased in all groups. The lipoprotein (a) level was reduced in the CEE 0.45/MPA 2.5, CEE 0.45/MPA 1.5, and CEE 0.625/MPA 2.5 groups. Minimal changes were observed in carbohydrate metabolism for all groups. Fibrinogen and PAI-1 activity decreased and plasminogen activity increased in all groups. Decreases in antithrombin III and protein S activities were significant for all active treatment groups except the CEE 0.3/MPA 1.5 group.

Conclusion(s): Lower doses of CEE and CEE/MPA induce favorable changes in lipids, lipoproteins, and hemostatic factors with minimal changes in carbohydrate metabolism.