Endometrial effects of tibolone.
OBJECTIVE
The Tibolone Histology of the Endometrium and Breast Endpoints Study is a multicenter, randomized, double-blind study designed to address the conflicting reports in the literature about the endometrial safety of tibolone (1.25 or 2.5 mg/d). Tibolone was compared with continuous combined conjugated equine estrogen (CEE) plus medroxyprogesterone acetate (MPA) (0.625 + 2.5 mg/d).


METHODS
Subjects were randomized in a 1:1:2 ratio to tibolone 1.25 mg/d, 2.5 mg/d, and CEE/MPA, respectively. The one-sided 95% confidence interval (CI) has been evaluated for the incidence of abnormal endometrial histology (hyperplasia or carcinoma) and hyperplasia and carcinoma separately for each of the two treatment groups and the treatment groups combined after 1 and 2 yr of treatment with tibolone, compared with CEE/MPA.


RESULTS
A total of 3240 women were randomized, with 3224 receiving at least one dose of study medication. The incidence and upper one-sided 95% CI for the incidence of abnormal endometrium (hyperplasia or carcinoma), and hyperplasia and carcinoma separately, were calculated at end point, yr 1, and yr 2. The incidence (upper one-sided 95% CI) of abnormal endometrium at end point was 0.0 (0.5), 0.0 (0.4), and 0.2 (0.5) in the tibolone 1.25 mg, 2.5 mg, and CEE/MPA groups, respectively. During the entire treatment period, amenorrhea was reported more frequently with tibolone 1.25 mg (78.7%) and 2.5 mg (71.4%) than CEE/MPA (44.9%).


CONCLUSIONS
The Tibolone Histology of the Endometrium and Breast Endpoints Study results confirm previous findings that tibolone does not induce endometrial hyperplasia or carcinoma in postmenopausal women, and it is associated with a better vaginal bleeding profile than CEE/MPA.
Archer
David F
DF
CONRAD Clinical Research Center, 601 Colley Avenue, Norfolk, Virginia 23507, USA. archerdf@evms.edu
Hendrix
Susan
S
Gallagher
J Chris
JC
Rymer
Janice
J
Skouby
Sven
S
Ferenczy
Alex
A
den Hollander
Wil
W
Stathopoulos
Victoria
V
Helmond
Frans A
FA
D000368:Aged; D002277:Carcinoma / Q000139:chemically induced / Q000453:epidemiology; D015331:Cohort Studies; D004311:Double-Blind Method; D004338:Drug Combinations; D004714:Endometrial Hyperplasia / Q000139:chemically induced / Q000453:epidemiology; D016889:Endometrial Neoplasms / Q000139:chemically induced / Q000453:epidemiology; D004717:Endometrium / Q000187:drug effects*; D015914:Estrogen Replacement Therapy / Q000009:adverse effects; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage; D005260:Female; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage; D008875:Middle Aged; D009652:Norpregnenes / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D010146:Pain / Q000139:chemically induced; D014592:Uterine Hemorrhage / Q000139:chemically induced / Q000453:epidemiology
D004338:Drug Combinations; D004966:Estrogens, Conjugated (USP); D009652:Norpregnenes; D017258:Medroxyprogesterone Acetate; C027385:tibolone