Long-term safety and tolerability of continuous-combined hormone therapy in postmenopausal women: results from a seven-year randomised comparison of low and standard doses

Abstract

Objective: To establish the long-term safety profile of four oestradiol valerate/medroxyprogesterone acetate (E(2)V/MPA) regimens.

Study design: 419 postmenopausal women in parallel treatment groups started treatment with 1 or 2 mg E(2)V with either 2.5 or 5 mg MPA for 84 cycles of 28 days in a randomised, comparative study. The first 24 month double-blind efficacy period has been previously reported. This report focuses on the open safety period after the first two years until completion of 84 treatment cycles.

Results: A total of 275 women (65.6%) completed the seven-year study. All regimens provided good bleeding control and endometrial protection, with no cases of endometrial hyperplasia or cancer diagnosed. All regimens were well tolerated with a low frequency of adverse effects, mostly occurring within the first two years. The most common drug-related adverse events included breakthrough bleeding, headache/migraine, abdominal pain and mood changes. Very few women (n = 4) receiving the lowest dose option (1 mg E(2)V + 2.5 mg MPA) reported adverse effects (p<0.009 vs other groups). No serious cardiovascular events occurred in any of the groups, the incidence of strokes was lower than the national incidence for the age group and the incidence of breast cancer was comparable with the national incidence (95% CI). In the lowest dose group, no women had to stop therapy prematurely due to serious adverse events.

Conclusions: The results support the use of lower doses for longterm hormone therapies.