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No overall increase in all cause mortality with HRT, study finds

BMJ 2017; 358 doi: (Published 12 September 2017) Cite this as: BMJ 2017;358:j4230
  1. Jacqui Wise
  1. London

The results of 18 years of follow-up should provide reassurance that there is no long term increase in all cause mortality or mortality from specific causes, such as cardiovascular disease or cancer, among women who received hormone replacement therapy (HRT) for five to seven years.1

The results of the study, published in JAMA, show that it is appropriate to offer HRT to women experiencing menopausal symptoms such as hot flushes and night sweats. However, the study found no long term reductions in all cause mortality among women who used HRT, so the results do not support using it for the prevention of cardiovascular or other chronic disease.

The effect of HRT on cancer mortality, especially breast cancer mortality, has been a subject of debate and has generated concern among women and a reluctance to prescribe among some GPs. The latest findings support the current NICE guidance published in 2015 which say that for most women with menopausal symptoms, the benefits of HRT outweigh the risks.2 These guidelines were criticised by some, partly because they failed to focus on alternatives to HRT.3

The study assessed mortality outcomes among the 27 347 women who took part in the Women’s Health Initiative hormone therapy trials. In one trial, women were randomised to receive conjugated equine oestrogen (0.625 mg/d) plus medroxyprogesterone acetate (2.5 mg/d) or placebo for a median of 5.6 years and in the other, women were randomised to receive oestrogen alone or placebo for a median of 7.2 years. The trials were stopped early because of an increased risk of breast cancer and stroke.

Health outcomes from the two trials have previously been reported but this study is the first to focus on all cause and cause specific mortality. The authors of the study say that, because of the complex interplay of hormone therapy with different health outcomes, all cause and cause specific mortality provide an important summary measure to help women and doctors with decision making.

The analysis included postmenopausal women aged 50 to 79 years who were enrolled in the trials between 1993 and 1998 and followed up through to 2014. Mortality follow-up data was available for more than 98% of the women. During 18 years there were a total of 7489 deaths: 1088 during the intervention phase and 6401 during the post intervention follow up. There was no significant difference in all cause mortality between those women who had taken any hormone therapy and those given placebo (27.1% v 27.6%; hazard ratio 0.99; 95% confidence interval 0.94 to 1.03).

For cardiovascular disease mortality rates were 8.9% in the pooled hormone therapy group compared with 9% in the placebo group (hazard ratio 1.00; 95% CI, 0.92 to 1.08). During the 18 years of follow up there were 2207 deaths from cancer in the overall pooled cohort and cancer mortality rates were almost identical between hormone users and non-users (8.2% compared with 8%, hazard ratio 1.03; 95% CI 0.95 to 1.12).

Study leader JoAnn E Manson, from Brigham and Women’s Hospital, Boston, said: “These findings may be helpful to clinicians in decision making. The results suggest that current guidelines are correct in that it is reasonable to treat women with moderate to severe hot flashes and night sweats as they may derive benefit from HRT at least in early menopause.” But she added: “Hormonal treatment for prevention of cardiovascular disease or other chronic disease would not be advisable in view of no evidence of benefit in terms of all cause mortality.”

One limitation of the study is that it focused on a single dose and formulation that was commonly used at the time so it is not certain that the results can be extrapolated to other hormone preparations.

Heather Currie, spokesperson for the Royal College of Obstetricians and Gynaecologists and the British Menopause Society, said: “We welcome these results which show that hormone therapy use in women who experienced menopause was not associated with an increased risk of all cause, cardiovascular, or cancer death. The question around the possibility of decreased mortality for women who start hormone therapy within 10 years of the menopause is not tackled by this report but is gaining strength from other evidence. These findings should be helpful to both women and doctors.”

Currie added: “Even though not every woman requires hormone therapy, they should have accurate information about menopause and treatment options. Hormone therapy can be a safe and effective treatment for menopausal symptoms, particularly the management of hot flushes. For each woman, however, the risks and benefits are different.”


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