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.

Objective. To establish the long-term safety profile of four oestradiol valerate/medroxyprogesterone acetate (E2V/MPA) regimens.Study design. 419 postmenopausal women in parallel treatment groups started treatment with 1 or 2 mg E2V 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 (...