HRT increases cardiovascular and thromboembolic risk when started many years after menopause.

According to data from WISDOM, a RCT of HRT (Hormone Replacement Therapy) in postmenopausal women, treatment started many years after the menopause increases cardiovascular and thromboembolic risk.

This multicentre, randomised, double blind study involved postmenopausal women aged 50-69 years, from general practices in UK (384), Australia (91), and New Zealand (24). The participants were randomised to 10 years of treatment with oestrogen only therapy (conjugated equine oestrogens 0.625 mg OD) or combined HRT (conjugated equine oestrogens plus medroxyprogesterone acetate 2.5/5.0 mg OD). The primary outcomes were major cardiovascular disease, osteoporotic fractures, and breast cancer. Secondary outcomes included other cancers, death from all causes, venous thromboembolism (VTE), cerebrovascular disease, dementia, and quality of life. After a median follow-up of 11.9 months, the trial was prematurely closed during recruitment, after the publication of early results from the women's health initiative study. At that stage, 56,583 had been screened, 8980 entered run-in, and 5692 (26% of target of 22,300) had started treatment.

When combined HRT (n=2196) was compared with placebo (n=2189), there was a statistically significant increase in the number of major cardiovascular events (7 v 0, p = 0.016) and VTE (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, cerebrovascular events, fractures and overall deaths. There were also no significant differences in outcomes between combined or oestrogen only HRT.
The study concluded that these findings are consistent with those of the women's health initiative study and secondary prevention studies. In addition, the researchers call for further study of the long term risks and benefits of starting HRT near the menopause, when the effect may be different.

BMJ, published early online 11 July 2007; doi:10.1136/bmj.39266.425069.AD (link to abstract)