A double-blind, randomised trial comparing the effects of tibolone and continuous combined hormone replacement therapy in postmenopausal women with menopausal symptoms

Objective To compare the effects of two postmenopausal regimens on menopausal symptoms, bleeding episodes, side effects and acceptability. Design Double-blind, randomised controlled trial. Setting Twenty-nine sites in Denmark, nine in Norway and six in Sweden. Participants Four hundred and thirty-seven postmenopausal women with menopausal complaints. None of these women had had a hysterectomy. Interventions Daily treatment with tibolone 2.5 mg (n = 218) or 17 beta-oestradiol 2 mg plus norethisterone acetate 1 mg (E-2/NETA) (n = 219). Main outcome measures Hot flushes, sweating episodes, vaginal dryness, assessment of sexual life and bleeding patterns; at baseline and after 4, 12, 24 and 48 weeks. Results Treatment with either preparation significantly reduced mean scores for hot flushes, sweating episodes and vaginal dryness. The overall discontinuation rate was 28% (tibolone 25%, E-2/NETA 31%; P = 0.14), mostly during the first six months. There was a markedly lower cumulative incidence of bleeding or spotting episodes with tibolone compared with E-2/NETA (P < 0.0001), mainly during the first six treatment cycles. Conclusions Both tibolone and E-2/NETA effectively alleviate menopausal symptoms. However, tibolone caused significantly fewer bleeding or spotting episodes, which were reflected by lower overall rates of bleeding, as well as lower drop-out rates due to bleeding.