Absent correlation between vaginal bleeding and oestradiol levels or endometrial morphology during tibolone use in early postmenopausal women.
OBJECTIVE
To investigate a potential correlation between vaginal bleeding and oestradiol (E2) levels/endometrial morphology in early postmenopausal women using tibolone (Livial(R)).


METHODS
A 2-year randomised placebo-controlled study of 94 healthy women, 1-3 years after spontaneous menopause, receiving either placebo (n=23), 1.25 mg/day (n=36) or 2.5 mg/day (n=35) tibolone. Episodes of vaginal bleeding throughout the 2-year study period were recorded. Age, age of menopause, months since menopause and body mass index were recorded. Serum E2 levels were assessed at baseline and at 3-month intervals throughout the study period. In case of vaginal bleeding, endometrium morphology was assessed by Vabra Curettage.


RESULTS
Fifty-one percent (n=18, P<0.05) of women in the 2.5 mg/day tibolone group and 44% (n=16, P=0.07) in the 1.25 mg/day tibolone group presented with at least one period of vaginal bleeding, compared with 22% (n=5) in the placebo group. The women who bled in the placebo group were younger (P<0.01), had menopause at an earlier age (P<0.05), had a shorter duration since menopause (P<0.05) and had a higher median E2 serum level prior to bleeding (P<0.05). In contrast, in both tibolone groups, no determinants could be found for the vaginal bleeding. Ninety percent of the first bleedings occurred within 9 months after starting the treatment. At Vabra endometrium sampling, there was no evidence of endometrial stimulation.


CONCLUSIONS
In the present study, early postmenopausal women using 1.25 or 2.5 mg/day tibolone are 2-2.5 times more likely to present with vaginal bleeding compared with placebo (P<0.05) without evidence of higher serum E2 levels or endometrial stimulation.
Berning
B
B
Division of Reproductive Medicine, Department of Obstetrics and Gynecology, Dr. Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands.
van Kuijk
C
C
Bennink
H J
HJ
Fauser
B C
BC
D015519:Bone Density / Q000187:drug effects; D004717:Endometrium / Q000187:drug effects* / Q000473:pathology; D004958:Estradiol / Q000097:blood*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009652:Norpregnenes / Q000009:adverse effects / Q000494:pharmacology*; D017698:Postmenopause; D014592:Uterine Hemorrhage / Q000139:chemically induced*
D009652:Norpregnenes; D004958:Estradiol; C027385:tibolone