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.

Author(s): Rozenberg S, Pornel B, Koninckx PR, Palacios S, Christiansen C

Affiliation(s): Department of Obstetrics and Gynaecology, CHU St Pierre, Rue Haute 290, Brussels 1000, Belgium. sergerozenberg@stpierre-bru.be

Publication date & source: 2009-07, Hum Reprod., 24(7):1739-47. Epub 2009 Apr 7.

Publication type: Clinical Trial, Phase III; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't

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.