Ultra-low-dose continuous combined estradiol and norethisterone acetate: improved bleeding profile in postmenopausal women.
OBJECTIVE
To evaluate the effect of two ultra-low-dose hormone treatments containing estradiol (E2) 0.5 mg and norethisterone acetate (NETA) 0.1 or 0.25 mg on the endometrium and bleeding.


METHODS
A prospective, randomized, placebo-controlled trial of 6 months. Local Ethics Committee approval and informed consent were obtained prior to initiation and enrollment. Out of 577 postmenopausal women randomized, 575 took E2/NETA 0.1 (n = 194), or E2/NETA 0.25 (n = 181) or placebo (n = 200). Endometrial bleeding was monitored by daily diary cards and endometrial thickness by transvaginal ultrasound at baseline and on completion. An endometrial biopsy was obtained when indicated clinically.


RESULTS
In months 1-6, the amenorrhea rates with E2/NETA 0.1 were 89%, 89%, 86%, 85%, 89% and 89%, respectively and the no-bleeding rates were correspondingly high: 95%, 94%, 93%, 90%, 95% and 95%. The amenorrhea and spotting-only rates were similar with both ultra-low-dose combinations. The withdrawal rates due to bleeding were very low and the same in all three treatment arms (n = 1; 1%). There was a slight increase in the mean endometrial thickness in all three groups, which remained less than 5 mm.


CONCLUSIONS
The ultra-low-dose combination of E2/NETA 0.1 or E2/NETA 0.25 resulted in a high incidence of amenorrhea and no bleeding in postmenopausal women, and a corresponding high level of compliance. Overall, there was no significant change in mean endometrial thickness during 6 months of active treatment or placebo.
Sturdee
D W
DW
Department of Obstetrics and Gynecology, Solihull Hospital, Solihull, West Midlands, UK.
Archer
D F
DF
Rakov
V
V
Lang
E
E
D000328:Adult; D000368:Aged; D000568:Amenorrhea / Q000139:chemically induced* / Q000453:epidemiology; D003280:Contraceptives, Oral, Synthetic / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004717:Endometrium / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009640:Norethindrone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077563:Norethindrone Acetate; D017698:Postmenopause; D011446:Prospective Studies; D014463:Ultrasonography; D014592:Uterine Hemorrhage / Q000139:chemically induced* / Q000453:epidemiology
D003280:Contraceptives, Oral, Synthetic; D004958:Estradiol; D000077563:Norethindrone Acetate; D009640:Norethindrone