Tibolone and low-dose continuous combined hormone treatment: vaginal bleeding pattern, efficacy and tolerability.
OBJECTIVE
The primary objective was to compare the vaginal bleeding pattern during administration of tibolone and low-dose continuous combined estradiol plus norethisterone acetate (E2/NETA). The secondary objectives were efficacy on vasomotor symptoms and vaginal atrophy.


METHODS
A randomised, double-blind, double-dummy, group comparative intervention trial.


METHODS
Multicentre study executed in 32 centres in 7 European countries.


METHODS
Five hundred and seventy-two healthy symptomatic postmenopausal women, aged 45-65 years.


METHODS
Participants were randomised to receive 2.5 mg tibolone or 1 mg 17beta estradiol plus 0.5 mg norethisterone acetate (E2/NETA) daily for 48 weeks.


METHODS
Prevalence of vaginal bleeding, hot flushes and adverse events.


RESULTS
The incidence of bleeding was significantly lower in the tibolone group during the first 3 months of treatment (18.3 versus 33.1%; P < 0.001) when compared with the E2/NETA group. This effect on the bleeding pattern was sustained throughout the study, although reaching statistical significance again only in 7-9 months of treatment (11 versus 19%; P < 0.05). In both treatment groups, vasomotor symptoms and vaginal atrophy were significantly reduced to a similar extent when compared with baseline. The prevalence of breast pain/tenderness was significantly lower with tibolone compared with E2/NETA (3.2 versus 9.8%; P < 0.001).


CONCLUSIONS
Tibolone reduces menopausal symptoms to a similar extent as conventional low-dose continuous combined hormone therapy but causes significant less vaginal bleeding in the first 3 months of treatment. This constitutes an important argument for woman adherence to therapy.
Hammar
M L
ML
Division of Obstetrics and Gynecology, Department of Molecular and Clinical Medicine, Faculty of Health Sciences, Linköping University Hospital, Linköping, Sweden.
van de Weijer
P
P
Franke
H R
HR
Pornel
B
B
von Mauw
E M J
EM
Nijland
E A
EA
D000368:Aged; D003280:Contraceptives, Oral, Synthetic / Q000008:administration & dosage; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004958:Estradiol / Q000008:administration & dosage; D020847:Estrogen Receptor Modulators / Q000008:administration & dosage* / Q000009:adverse effects; D015914:Estrogen Replacement Therapy / Q000379:methods*; D004967:Estrogens / Q000008:administration & dosage; D005260:Female; D019584:Hot Flashes / Q000209:etiology; D006801:Humans; D008796:Metrorrhagia / Q000517:prevention & control*; D008875:Middle Aged; D009640:Norethindrone / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077563:Norethindrone Acetate; D009652:Norpregnenes / Q000008:administration & dosage* / Q000009:adverse effects
D003280:Contraceptives, Oral, Synthetic; D020847:Estrogen Receptor Modulators; D004967:Estrogens; D009652:Norpregnenes; D004958:Estradiol; D000077563:Norethindrone Acetate; C027385:tibolone; D009640:Norethindrone