Tibolone and low-dose continuous combined hormone treatment: vaginal bleeding pattern, efficacy and tolerability.

Author(s): Hammar ML, van de Weijer P, Franke HR, Pornel B, von Mauw EM, Nijland EA, TOTAL Study Investigators Group

Affiliation(s): Division of Obstetrics and Gynecology, Department of Molecular and Clinical Medicine, Faculty of Health Sciences, Linkoping University Hospital, Linkoping, Sweden.

Publication date & source: 2007-12, BJOG., 114(12):1522-9.

Publication type: Research Support, Non-U.S. Gov't

OBJECTIVES: The primary objective was to compare the vaginal bleeding pattern during administration of tibolone and low-dose continuous combined estradiol plus norethisterone acetate (E2/NETA). The secondary objectives were efficacy on vasomotor symptoms and vaginal atrophy. DESIGN: A randomised, double-blind, double-dummy, group comparative intervention trial. SETTING: Multicentre study executed in 32 centres in 7 European countries. SAMPLE: Five hundred and seventy-two healthy symptomatic postmenopausal women, aged 45-65 years. METHODS: Participants were randomised to receive 2.5 mg tibolone or 1 mg 17beta estradiol plus 0.5 mg norethisterone acetate (E2/NETA) daily for 48 weeks. MAIN OUTCOME MEASURES: Prevalence of vaginal bleeding, hot flushes and adverse events. RESULTS: The incidence of bleeding was significantly lower in the tibolone group during the first 3 months of treatment (18.3 versus 33.1%; P < 0.001) when compared with the E2/NETA group. This effect on the bleeding pattern was sustained throughout the study, although reaching statistical significance again only in 7-9 months of treatment (11 versus 19%; P < 0.05). In both treatment groups, vasomotor symptoms and vaginal atrophy were significantly reduced to a similar extent when compared with baseline. The prevalence of breast pain/tenderness was significantly lower with tibolone compared with E2/NETA (3.2 versus 9.8%; P < 0.001). CONCLUSION: Tibolone reduces menopausal symptoms to a similar extent as conventional low-dose continuous combined hormone therapy but causes significant less vaginal bleeding in the first 3 months of treatment. This constitutes an important argument for woman adherence to therapy.