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.


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.
Archer
David F
DF
Department of Obstetrics and Gynecology, Contraceptive Research and Development Program Clinical Research Center, Eastern Virginia Medical School, Norfolk, Virginia 23507, USA. archerdf@evms.edu
Hendrix
Susan
S
Ferenczy
Alex
A
Felix
Juan
J
Gallagher
J Chris
JC
Rymer
Janice
J
Skouby
Sven O
SO
den Hollander
Wil
W
Stathopoulos
Victoria
V
Helmond
Frans A
FA
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
D009652:Norpregnenes; C027385:tibolone