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A multicentre randomised trial to compare uterine safety of raloxifene with a continuous combined hormone replacement therapy containing oestradiol and norethisterone acetate

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Neven, Patrick Lunde, Tore Benedetti-Panici, Pierluigi Tiitinen, Aila Marinescu, Bogdan Fatela, Ana

Objective: To compare the uterine effects of 60 mg of raloxifene with a continuous combined hormone replacement therapy, a preparation of 2 mg 17β-oestradiol (E2) and 1 mg norethisterone acetate for a duration of 12 months. Design: A randomised, double-blind trial. Setting: Multicentre: Europe, Israel, South Africa. Population: Asymptomatic postmenopausal women with risk factors for osteoporosis or cardiovascular disease who had an endometrial thickness of less than 5 mm. One thousand and eight women were randomised for the six month core; of these 420 were invited to continue into a six month extension period. Methods: Randomisation to either raloxifene or continuous combined hormone replacement therapy. Patients, recruiters and assessors were blinded to the treatment used. Main outcome measures: The frequency of vaginal spotting/bleeding as recorded in a diary, endometrial thickness and uterine volume as measured by transvaginal ultrasonography at baseline and after 6 and 12 months. Results: After six months of therapy with raloxifene, the rate of women on raloxifene reporting vaginal bleeding and spotting (6.8%) was similar to the rate in the lead-in phase (8.3%) but increased from 7.0% to 55.1% in the continuous combined hormone replacement therapy group. Raloxifene treatment was not associated with a significant change from baseline to endpoint in mean endometrial thickness (P = 0.11), whereas continuous combined hormone replacement therapy treatment was associated with an increase in this value of mean (SD) of 1.2 (2.2) mm (P < 0.001). Compared with raloxifene, mean endometrial thickness for women on continuous combined hormone replacement therapy was significantly increased at endpoint [4.6 (2.1) mm vs 3.5 (1.7) mm; change from baseline P < 0.001]. In the raloxifene group, there was a trend towards a decrease from baseline in uterine volume [from 31.4 (20.3) to 30.3 (16.2) mm; P = 0.37]; in the continuous combined hormone replacement therapy group, there was a significant increase in uterine volume [from 31.3 (16.3) to 54.0 (36.1) mm; P < 0.001], and the difference in the effect of both compounds on change in uterine volume at endpoint reached statistical significance (P < 0.001). Statistically significant differences between the treatment groups were sustained for all parameters during the extension period. Early discontinuation rates, both overall and due to adverse events, were significantly lower (P < 0.001) in the raloxifene group after 6 and 12 months. Conclusion: Compared with continuous combined hormone replacement therapy, 6 and 12 months of raloxifene treatment do not lead to vaginal bleeding/spotting, are not associated with increased endometrial thickness or uterine volume and result in a significantly lower rate of early treatment discontinuations in asymptomatic women receiving treatment to prevent long term postmenopausal health risks.

Document type Article de périodique (Journal article) – Article de recherche
Publication date 2003
Language Anglais
Journal information "BJOG : an international journal of obstetrics and gynaecology" - Vol. 110, no. 2, p. 157-167 (2003)
Peer reviewed yes
Publisher Wiley-Blackwell Publishing Ltd.
e-issn 1471-0528
issn 1470-0328
Publication status Publié
Links
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Bibliographic reference Neven, Patrick ; Lunde, Tore ; Benedetti-Panici, Pierluigi ; Tiitinen, Aila ; Marinescu, Bogdan ; et. al. A multicentre randomised trial to compare uterine safety of raloxifene with a continuous combined hormone replacement therapy containing oestradiol and norethisterone acetate. In: BJOG : an international journal of obstetrics and gynaecology, Vol. 110, no. 2, p. 157-167 (2003)
Permanent URL http://hdl.handle.net/2078.1/164513