Acceptability and patterns of endometrial bleeding in estradiol-based HRT regimens: a comparative study of cyclical sequential combinations of trimegestone or norethisterone acetate.
OBJECTIVE
This randomized, double-blind, multicenter study was planned to compare the efficacy and tolerance of a novel oral regimen containing estradiol (2.0 mg) sequentially combined with trimegestone, at a daily dose of either 0.25 mg or 0.5 mg, with a standard hormone replacement therapy containing estradiol and norethisterone acetate (E2 + NETA) in the treatment of climacteric symptoms.


METHODS
The study was conducted over 13 cycles, each of 28 days, and involved 487 subjects, of whom 349 completed the study.


RESULTS
All three treatments were equally effective in alleviating hot flushes and showed a progressive and significant reduction in the value of the Kupperman index. The treatments diminished equally effectively urogenital signs and symptoms. All treatments were well tolerated and the incidences of adverse events associated with each treatment were similar across the treatment groups. The duration of expected withdrawal bleeding was shorter in the estradiol + trimegestone 0.5 mg group than in the estradiol + trimegestone 0.25 mg or E2 + NETA group.


CONCLUSIONS
All treatments were effective and well tolerated, providing significant relief from climacteric symptoms. Treatment with estradiol + trimegestone 0.5 mg provided the most favorable bleeding pattern.
al-Azzawi
F
F
Gynaecology Research Group, Department of Obstetrics and Gynaecology, Faculty of Medicine and Biological Sciences, University of Leicester, UK.
Wahab
M
M
Thompson
J
J
Pornel
B
B
Hirvonen
E
E
Ylikorkala
O
O
van der Mooren
M J
MJ
Dillon
J
J
Magaril
C
C
D001118:Argentina; D004311:Double-Blind Method; D004717:Endometrium / Q000187:drug effects / Q000473:pathology; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D015914:Estrogen Replacement Therapy; D005060:Europe; D005260:Female; D019584:Hot Flashes / Q000188:drug therapy*; D006801:Humans; D008875:Middle Aged; D009640:Norethindrone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D000077563:Norethindrone Acetate; D017060:Patient Satisfaction; D011397:Promegestone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D014592:Uterine Hemorrhage / Q000503:physiopathology*
C050319:trimegestone; D004958:Estradiol; D000077563:Norethindrone Acetate; D011397:Promegestone; D009640:Norethindrone