Ultra low dose continuous combined hormone replacement therapy with 0.5 mg 17β-oestradiol and 2.5 mg dydrogesterone: Protection of the endometrium and amenorrhoea rate

The aim of this open, multicentre study was to demonstrate the endometrial safety and assess the bleeding pattern of ultra low dose continuous combined hormone replacement therapy with 0.5 mg 17β-oestradiol and 2.5 mg dydrogesterone in 446 healthy, non-hysterectomised, postmenopausal women with symptoms of oestrogen deficiency. Aspiration endometrial biopsies were performed at baseline and after 1 year of treatment to assess the incidence of endometrial hyperplasia or a more serious endometrial outcome. The only adverse endometrial outcome at the end of the study was one case of simple hyperplasia. This gives an overall incidence of 0.27% (95% CI: 0.01–1.48%) in the per protocol sample (n = 395). The overall rate of amenorrhoea in the full sample (n = 446) was 68% and 14% had only one or two bleeding/spotting episodes. The rate of amenorrhoea in months 10–12 (n = 413) was 88%. The number of bleeding/spotting days per cycle fell during the study. The mean number of bleeding/spotting days was 5.8 and the mean number of days without bleeding was 358.2. Spotting alone was the most prevalent bleeding intensity, whilst heavy bleeding was rare. In conclusion, 2.5 mg dydrogesterone continuously combined with 0.5 mg 17β-oestradiol effectively protects the endometrium in postmenopausal women in accordance with the guidelines of the Committee for Medicinal Products for Human Use (CHMP). It has a favourable amenorrhoea rate and is well tolerated by the majority of women.