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.