Absent correlation between vaginal bleeding and oestradiol levels or endometrial morphology during tibolone use in early postmenopausal women

Abstract

Objective: To investigate a potential correlation between vaginal bleeding and oestradiol (E2) levels/endometrial morphology in early postmenopausal women using tibolone (Livial®). Methods: A 2-year randomised placebo-controlled study of 94 healthy women, 1–3 years after spontaneous menopause, receiving either placebo ( n=23), 1.25 mg/day ( n=36) or 2.5 mg/day ( n=35) tibolone. Episodes of vaginal bleeding throughout the 2-year study period were recorded. Age, age of menopause, months since menopause and body mass index were recorded. Serum E2 levels were assessed at baseline and at 3-month intervals throughout the study period. In case of vaginal bleeding, endometrium morphology was assessed by Vabra Curettage. Results: Fifty-one percent ( n=18, P<0.05) of women in the 2.5 mg/day tibolone group and 44% ( n=16, P=0.07) in the 1.25 mg/day tibolone group presented with at least one period of vaginal bleeding, compared with 22% ( n=5) in the placebo group. The women who bled in the placebo group were younger ( P<0.01), had menopause at an earlier age ( P<0.05), had a shorter duration since menopause ( P<0.05) and had a higher median E2 serum level prior to bleeding ( P<0.05). In contrast, in both tibolone groups, no determinants could be found for the vaginal bleeding. Ninety percent of the first bleedings occurred within 9 months after starting the treatment. At Vabra endometrium sampling, there was no evidence of endometrial stimulation. Conclusions: In the present study, early postmenopausal women using 1.25 or 2.5 mg/day tibolone are 2–2.5 times more likely to present with vaginal bleeding compared with placebo ( P<0.05) without evidence of higher serum E2 levels or endometrial stimulation.