Tibolone histology of the endometrium and breast endpoints study: design of the trial and endometrial histology at baseline in postmenopausal women

Objective To address the endometrial safety of tibolone. Design The Tibolone Histology of the Endometrium and Breast Endpoints Study (THEBES) is a randomized, double-blind, parallel-group trial of tibolone compared with continuous combined conjugated equine estrogen (CEE) and medroxyprogesterone acetate (MPA). Setting Multi-country, multi-center ambulatory care setting. Patient(s) A total of 5,185 subjects were screened, and biopsies were obtained from 4,446 women. Intervention(s) Participants were randomized in a 1:1:2 ratio, to tibolone (1.25 or 2.5 mg/d) or CEE-MPA. Main Outcome Measure(s) The one-sided 95% confidence intervals for the incidence of hyperplasia or cancer were evaluated for tibolone compared with CEE-MPA. Result(s) Endometrial biopsy results at baseline: atrophic (87.29%), inactive (0.25%), proliferative (6.12%), secretory (2.86%), menstrual type (0.40%), and hyperplasia (0.18%). Only subjects with atrophic or inactive endometrium were eligible for this study, and 3% of the women at screening either had no tissue (0.18%) or had an amount of tissue that was insufficient for diagnosis (2.72%). Three thousand two hundred forty postmenopausal women with a mean (±SD) age of 54.4 ± 4.4 years and a mean time since menopause of 4.5 ± 3.6 years were randomized. Conclusion(s) The Tibolone Histology of the Endometrium and Breast Endpoints Study is a prospective, randomized clinical trial, designed to provide evidence of the endometrial safety of tibolone compared with estrogen and progestogen. Screening endometrial histology shows a low prevalence of endometrial hyperplasia (0.18%) and no carcinoma.