Oral ultra-low dose continuous combined hormone replacement therapy with 0.5 mg 17β-oestradiol and 2.5 mg dydrogesterone for the treatment of vasomotor symptoms: results from a double-blind, controlled study

Abstract

Objectives: Guidelines recommend using the lowest effective dose of oestrogen for the management of vasomotor symptoms in postmenopausal women. The primary aim of this double-blind, multi-centre, randomised study was to assess the efficacy of oral ultra-low dose continuous combined hormone replacement therapy with 17β-oestradiol and dydrogesterone.

Study design: 313 women with ≥50 moderate to severe hot flushes during the previous week were randomised to 0.5 mg 17β-oestradiol/2.5 mg dydrogesterone (E 0.5 mg/D 2.5 mg), 1mg 17β-oestradiol/5mg dydrogesterone (E 1mg/D 5 mg) or placebo for 13 weeks. The placebo group then switched to E 0.5 mg/D 2.5 mg for a further 39 weeks, whilst the other groups continued on the same treatment.

Results: After 13 weeks, the reduction in the number of moderate to severe hot flushes/day in the E 0.5 mg/D 2.5 mg group was greater than in the placebo group (-6.4 vs. -4.9, p<0.001) and comparable to that in the 1/5 mg group (-6.3). E 0.5 mg/D 2.5 mg and E 1mg/D 5 mg significantly improved the total Menopause Rating Scale score. The number of bleeding/spotting days was lower with E 0.5 mg/D 2.5 mg than with E 1 mg/D 5 mg. The overall amenorrhoea rate with E 0.5 mg/D 2.5 mg was 81%; this increased to 91% in months 10-12.

Conclusions: Continuous combined 0.5 mg 17β-oestradiol and 2.5mg dydrogesterone was effective in alleviating vasomotor symptoms and improving quality of life, and was associated with a high amenorrhoea rate and a good tolerability profile.