Objective To assess the long term risks and benefits of hormone
replacement therapy (combined hormone therapy versus placebo, and oestrogen
alone versus combined hormone therapy).
Design Multicentre, randomised, placebo controlled, double blind
Setting General practices in UK (384), Australia (91), and New
Participants Postmenopausal women aged 50-69 years at randomisation.
At early closure of the trial, 56 583 had been screened, 8980 entered
run-in, and 5692 (26% of target of 22 300) started treatment.
Interventions Oestrogen only therapy (conjugated equine oestrogens
0.625 mg orally daily) or combined hormone therapy (conjugated equine oestrogens
plus medroxyprogesterone acetate 2.5/5.0 mg orally daily). Ten years of
Main outcome measures Primary outcomes: major cardiovascular
disease, osteoporotic fractures, and breast cancer. Secondary outcomes: other
cancers, death from all causes, venous thromboembolism, cerebrovascular disease,
dementia, and quality of life.
Results The trial was prematurely closed during recruitment, after a
median follow-up of 11.9 months (interquartile range 7.1-19.6, total 6498 women
years) in those enrolled, after the publication of early results from the
women's health initiative study. The mean age of randomised women was 62.8 (SD
4.8) years. When combined hormone therapy (n=2196) was compared with placebo
(n=2189), there was a significant increase in the number of major cardiovascular
events (7 v 0, P=0.016) and venous thromboembolisms (22
v 3, hazard ratio 7.36 (95% CI 2.20 to 24.60)). There were
no statistically significant differences in numbers of breast or other cancers
(22 v 25, hazard ratio 0.88 (0.49 to 1.56)), cerebrovascular
events (14 v 19, 0.73 (0.37 to 1.46)), fractures (40
v 58, 0.69 (0.46 to 1.03)), and overall deaths (8
v 5, 1.60 (0.52 to 4.89)). Comparison of combined hormone
therapy (n=815) versus oestrogen therapy (n=826) outcomes revealed no
Conclusions Hormone replacement therapy increases cardiovascular and
thromboembolic risk when started many years after the menopause. The results are
consistent with the findings of the women's health initiative study and
secondary prevention studies. Research is needed to assess the long term risks
and benefits of starting hormone replacement therapy near the menopause, when
the effect may be different.
Trial registration Current Controlled Trials ISRCTN 63718836