Hormone replacement therapy (HRT) should not be used to prevent coronary heart disease, experts advise, after a study showed that it does not prevent the disease and almost doubles a woman's risk during the first year of use.
Furthermore, HRT does not slow progression of established coronary artery disease.
These findings come from two studies published in the New England Journal of Medicine.
Dr JoAnn Manson and colleagues reported final results of the arm of the Women's Health Initiative trial that compared combined oestrogen and progestogen treatment with placebo (2003;349: 523-34). The trial, sponsored by the US National Institutes of Health, was stopped in 2002 because the risks of treatment exceeded the benefits (BMJ 2002;325: 61).
“There was no clear heart protection. No subgroup clearly showed evidence of heart disease protection,” said Dr Manson, the principal investigator and chairwoman of preventive medicine at Harvard's Brigham and Women's Hospital.
The authors write, “The treatment should not be prescribed for the prevention of cardiovascular disease.”
Women who took combined HRT had a 24% higher risk of myocardial infarction and death than women who were given a placebo (hazard ratio 1.24 (nominal 95% confidence interval 1.00 to 1.54, 95% confidence interval with adjustment for sequential monitoring 0.97 to 1.60)). The risk was highest in the first year of treatment (hazard ratio 1.81 (1.09 to 3.01)).
“The risk to the individual woman is low. There is still a role for oestrogen in the treatment of menopause,” Dr Manson said. There were 39 cases of coronary heart disease per 100 000 person years for women taking HRT and 33 cases per 100 000 for women taking placebo.
In the combined HRT arm of the trial 16 608 post-menopausal women aged 50 to 79 took a daily dose of Prempro or a placebo. Prempro, the most commonly prescribed HRT in the United States, contains 0.625 mg of conjugated equine oestrogens and 2.5 mg of medroxyprogesterone acetate. The mean age of the women was 63.3 years, and about a third of the women were aged 50-59 years.
Dr Manson said that only about 40% of women stopped taking the pill during the study or changed to a hormone treatment prescribed by their own doctors. Generally, about half of women taking HRT stop within a year.
More than 10 000 women who have had hysterectomies continue in the oestrogen only part of the trial. Results will be reported in 2005.
The second study (2003;349: 535-45), also a double blind, randomised controlled study, looked at the effect of HRT on 226 postmenopausal women who already had coronary artery disease identified by coronary angiography. Their mean age was 63.5 years. They took either micronised 17-β-estradiol alone, 17-β-estradiol with sequential medroxyprogesterone acetate, or usual care. Patients with high concentrations of low density lipoproteins received statins and dietary advice.
The study compared patients' coronary angiograms of stenosis at their entry to the trial with angiograms done about three years later. No treatment produced a significant change in stenosis.
Dr Roger Lobo, an author of the study and professor of obstetrics and gynaecology at Columbia University, New York, said that oestrogen treatment has been shown to lead to a slowing in the thickening of the walls of the carotid artery, an early indicator of atherosclerosis (Annals of Internal Medicine 2001;135: 939-53).