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Early initiation of HRT ‘halves risk of death or CVD’

GPs should aim to initiate hormone replacement therapy as early as possible after menopause, as it can halve a woman’s risk of death or a serious cardiovascular event, say researchers.

The ten-year study found that initiating HRT less than two years after women have stopped menstruating resulted in a significant 52% reduction in death, heart failure or myocardial infarction compared to women not receiving treatment.

The study adds support to the ‘timing hypothesis’ for HRT – a theory that differences in cardiovascular outcome are explained by the time between menopause and the start of HRT.

Danish researchers followed 502 women aged 45-58 whose last menstrual bleed was three to 24 months prior to study entry or had perimenopausal symptoms in combination with recorded postmenopausal serum FSH values for ten years.

They compared them with 504 controls who were randomised to no hormone therapy.

They found a 43% decreased risk of death, an 86% decrease in heart failure risk and a 75% reduced likelihood of myocardial infarction in the HRT group compared with those not receiving treatment, though these were non-significant.

There was no significant difference between the two groups for cancer occurrence – 36 cases in the HRT group compared with 39 in the control group. Breast cancer rates were also non-significant between the two groups – 10 in the intervention arm compared with 17 in the controls.

The results from the Danish Osteoporosis Prevention Study conflict with the Women’s Health Initiative study published in 2010.

This study found combined HRT was associated with a 25% increase risk of invasive breast cancer in a group of women aged 50-79 years, compared to those not taking HRT in 2010, but it involved elderly women who were post-menopausal for a number of years before receiving HRT.

Study lead Dr Louise Lind Schierbeck, registrar in endocrinology at Hvidovre Hospital in Denmark, said their study showed the timing of HRT initiation was important.

She said: ‘Our findings suggest that initiation of HRT in women early after menopause significantly reduces the risk of the combined endpoint of mortality, MI or heart failure.

‘Importantly, early initiation and prolonged HRT did not result in an increased risk of breast cancer or stroke.’

Dr Fiona Cornish, a GP in Cambridge and president of the Medical Women’s Federation, said the study was good news for GPs.

She said: ‘HRT is so effective for treating menopausal symptoms, yet we have felt apprehensive about promoting it because of the perceived risks of cardiovascular events.

‘Personally, I have always been baffled by the apparent change of position from beneficial to risky, and this study looking at the specific issues of starting time and age, seems to clarify the situation and allow us to make use of HRT to the great benefit of women. ‘

But Dr Sally Hope, honorary research fellow in women’s health at Oxford University and retired GP, felt that the study needed a larger cohort.

She said: ‘This is an interesting study. However, I think it is too small a study to make any firm conclusions either way. I wish they’d done a several orders of magnitude bigger study.’

Risk reduction with HRT

SymptomRisk reduction
Death, heart failure, MI combined52%
Heart failure86%

BMJ 2012, available online 9 October


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