A multicentre randomised trial to compare uterine safety of raloxifene with a continuous combined hormone replacement therapy containing oestradiol and norethisterone acetate.
BJOG
; 110(2): 157-67, 2003 Feb.
Article
em En
| MEDLINE
| ID: mdl-12618160
ABSTRACT
OBJECTIVE:
To compare the uterine effects of 60 mg of raloxifene with a continuous combined hormone replacement therapy, a preparation of 2 mg 17beta-oestradiol (E(2)) 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 OUTCOMEMEASURES:
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.
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Base de dados:
MEDLINE
Assunto principal:
Doenças Uterinas
/
Osteoporose Pós-Menopausa
/
Cloridrato de Raloxifeno
/
Congêneres da Progesterona
/
Estradiol
/
Antagonistas de Estrogênios
/
Noretindrona
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article