title: Tibolone histology of the endometrium and breast endpoints study: design of the trial and endometrial histology at baseline in postmenopausal women.
abstract: OBJECTIVE
  To address the endometrial safety of tibolone.
  
  
  METHODS
  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).
  
  
  METHODS
  Multi-country, multi-center ambulatory care setting.
  
  
  METHODS
  A total of 5,185 subjects were screened, and biopsies were obtained from 4,446 women.
  
  
  METHODS
  Participants were randomized in a 1:1:2 ratio, to tibolone (1.25 or 2.5 mg/d) or CEE-MPA.
  
  
  METHODS
  The one-sided 95% confidence intervals for the incidence of hyperplasia or cancer were evaluated for tibolone compared with CEE-MPA.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Obstetrics and Gynecology, Contraceptive Research and Development Program Clinical Research Center, Eastern Virginia Medical School, Norfolk, Virginia 23507, USA. archerdf@evms.edu
authors.forename: David F
authors.initials: DF
authors.lastname: Archer
authors.forename: Susan
authors.initials: S
authors.lastname: Hendrix
authors.forename: Alex
authors.initials: A
authors.lastname: Ferenczy
authors.forename: Juan
authors.initials: J
authors.lastname: Felix
authors.forename: J Chris
authors.initials: JC
authors.lastname: Gallagher
authors.forename: Janice
authors.initials: J
authors.lastname: Rymer
authors.forename: Sven O
authors.initials: SO
authors.lastname: Skouby
authors.forename: Wil
authors.initials: W
authors.lastname: den Hollander
authors.forename: Victoria
authors.initials: V
authors.lastname: Stathopoulos
authors.forename: Frans A
authors.initials: FA
authors.lastname: Helmond
mesh_terms: D000368:Aged; D001940:Breast; D004311:Double-Blind Method; D004714:Endometrial Hyperplasia; D004717:Endometrium / Q000033:anatomy & histology* / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D009652:Norpregnenes / Q000008:administration & dosage*; D010146:Pain; D017698:Postmenopause / Q000502:physiology*; D014619:Vacuum Curettage
chemical_list: D009652:Norpregnenes; C027385:tibolone