Endometrium protection and acceptability of nasally administered continuously combined hormone therapy: a multicentre, multinational, double-blind trial in post-menopausal women evaluating three regimens of 17beta-estradiol and norethisterone when compared with an orally administered 17beta-estradiol norethisterone regimen.
BACKGROUND
To determine the optimal daily dose of intranasal hormone therapy (HT) in order to achieve adequate endometrial protection.


METHODS
Multicentre, double-blind/double-dummy randomized controlled trial (Phase III) was conducted in 1741 women to compare a daily intranasal dose of 350 microg 17beta-estradiol (E2) together with 50, 175 or 550 microg norethisterone (NET) with the oral administration of 2 mg E2 and 1 mg NET, over a period of 52 weeks. An endometrial biopsy was performed at the end of HT use.


RESULTS
Most women (73-86%) had an 'atrophic and/or inactive' endometrium. Lower doses of NET were associated with a higher incidence of 'proliferative' endometrium. The incidence of vaginal bleeding decreased with time. During the last 4 months of the study, 88.1% of women using the highest dose of NET were in amenorrhoea when compared with 71.7% using the oral comparator (difference 16.5%; 95% confidence interval: 10.9-22.0%) (P < 0.001). Premature discontinuation rates were in the range of 12-17% for the three nasal regimens and 22% for the oral comparator.


CONCLUSIONS
HT using a fixed intranasal dose of 350 microg E2 combined with 550 microg NET is a safe regimen, in relation to 1 year endometrial safety. This regimen is associated with less vaginal bleeding when compared with an oral comparator using 2 mg E2 and 1 mg NET.
Rozenberg
Serge
S
Department of Obstetrics and Gynaecology, CHU St Pierre, Rue Haute 290, Brussels 1000, Belgium. sergerozenberg@stpierre-bru.be
Pornel
Bruno
B
Koninckx
Philippe R
PR
Palacios
Santiago
S
Christiansen
Claus
C
D000281:Administration, Intranasal; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D004717:Endometrium / Q000473:pathology*; D004958:Estradiol / Q000008:administration & dosage* / Q000627:therapeutic use; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D007391:International Cooperation; D008875:Middle Aged; D009640:Norethindrone / Q000008:administration & dosage* / Q000627:therapeutic use; D017698:Postmenopause; D016896:Treatment Outcome
D004958:Estradiol; D009640:Norethindrone