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

• Published in: BJOG : an international journal of obstetrics and gynaecology 2007-12, Vol.114 (12), p.1522-1529
• Main Authors: Hammar, ML, Van De Weijer, P, Franke, HR, Pornel, B, Von Mauw, EMJ, Nijland, EA
• Format: Article
• Language: English
• Subjects: Aged; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Clinical outcomes; Clinical trials; Contraceptives, Oral, Synthetic - administration & dosage; Double-Blind Method; Drug therapy; Drug Therapy, Combination; E2/NETA; Estradiol - administration & dosage; Estrogen Receptor Modulators - administration & dosage; Estrogen Receptor Modulators - adverse effects; Estrogen Replacement Therapy - methods; Estrogens - administration & dosage; Female; Gynecology; Gynecology. Andrology. Obstetrics; Hormone replacement therapy; Hot Flashes - etiology; Humans; Medical sciences; MEDICIN; MEDICINE; Menopause; Metrorrhagia - prevention & control; Middle Aged; Norethindrone - administration & dosage; Norethindrone - analogs & derivatives; Norpregnenes - administration & dosage; Norpregnenes - adverse effects; Pharmacology. Drug treatments; Steroids; Tibolone; Tolerability; Vaginal bleeding
• ISSN: 1470-0328; 1471-0528; 1471-0528
• DOI: 10.1111/j.1471-0528.2007.01537.x

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 17β 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.