Long-term effects of tibolone on the endometrium as assessed by bleeding episodes, transvaginal scan and endometrial biopsy.

Introduction: Period-free hormone replacement therapy (HRT) obliterates the need for withdrawal bleeds. There is a need to ensure that, if these preparations are to be used in the long term, they still achieve amenorrhea.

Aims: To assess the bleeding rates and the endometrial status over 10 years in women who were taking tibolone compared to an age-matched control group.

Methods: A total of 110 recently postmenopausal women were recruited into a prospective, non-randomized, open-label study. Bleeding episodes were assessed by 6-monthly symptomatology questionnaires. Annual transvaginal scans were performed to assess endometrial thickness in all women who gave consent from 1997 onwards. In the tibolone group, endometrial biopsies were performed every year; in the control group, they were performed only if the reported vaginal bleeding and/or endometrial thickness on ultrasound were >5 mm.

Results: Over the entire 10-year period, 39.7% of women in the tibolone group and 12.7% of control subjects experienced vaginal blood loss. However, the rate of amenorrhea in the tibolone group after 1 year of treatment was 86.4%; in the control group, it was 94.1%. At the 10-year visit, the rates of amenorrhea were 60.3% in the tibolone groups and 87.3% in the control group. This is statistically significant, p = 0.001. The mean (+/- standard deviation) endometrial thickness after 10 years was 2.2 mm (+/- 1.2 mm) in the tibolone group vs. 1.8 mm (+/- 0.4 mm) in the control group. These differences were not statistically significant (p = 0.33). Sufficient material from endometrial biopsies could only be obtained in three subjects in the tibolone group. One case of simple hyperplasia was detected.

Conclusion: Tibolone therapy leads to high rates of amenorrhea after 10 years, with minimal evidence of adverse effects on endometrial pathology.