Hormone therapy in women in the menopause transition. Randomised, double-blind, placebo-controlled trial of effects on body weight, blood pressure, lipoprotein levels, antithrombin III activity, and the endometrium

Abstract

Objective: To determine whether hormone treatment of women during the menopause transition induces changes in body weight, blood pressure, lipoprotein levels, antithrombin III activity, and the endometrium.

Design: Prospective, randomised, placebo-controlled, double-blind, 12-month study, with crossover at 6 months.

Setting: Outpatient clinic of a city hospital.

Participants: 105 apparently healthy women in the menopause transition (40-52 years), with menstrual function, who were experiencing minor menopausal symptoms, were selected from the general population by advertising.

Interventions: Active arm--oral conjugated oestrogens (0.625 mg daily) and cyclic medroxyprogesterone acetate (10 mg daily) on Day 14-27 of each menstrual cycle; placebo arm--placebos of both medications.

Main outcome measures: Excess change from baseline associated with active compared with placebo treatment for all variables; effect of order of treatment.

Results: Baseline biochemical values were similar for both treatment-order groups, but baseline blood pressures and body weights were higher in the group receiving placebo first. With treatment, there were no differences in overall values for body weight and blood pressure (P > 0.4), and order of treatment had no significant influence (P > 0.3). There were no differences in total and low density lipoprotein cholesterol levels, overall or with order of treatment. Active treatment increased high density lipoprotein (HDL) cholesterol levels (overall and when placebo was given first; P = 0.001), and triglyceride levels (when active treatment was given first; P = 0.03). There was no overall treatment effect, but a significant order-of-treatment effect, on antithrombin III activity (mean levels were decreased by active treatment to a greater extent when it was given first; P = 0.02). The endometrium showed only physiological changes regardless of treatment.

Conclusions: The lack of significant excess change in anthropometry, lipoprotein levels, antithrombin III activity, and endometrial histology in women given hormone treatment compared with placebo is reassuring. The increase in HDL cholesterol level is an extra benefit. Our study provides conclusive evidence that hormone treatment does not produce weight gain in women during the menopause transition.