A Danish study reported this week in the British Medical Journal has concluded that after 10 years of follow-up, women receiving HRT early after menopause had a significantly reduced risk of mortality, heart failure, or myocardial infarction, with no apparent increase in risk of cancer, stroke, or blood clot.
1,006 healthy women aged 45 to 58 who were recently menopausal were randomly allocated to receive HRT or placebo. Intervention was stopped after 11 years, but follow-up continued for up to 16 years.
The beneficial effects of taking HRT in this randomized trial, agree with data from observational studies which have consistently indicated a reduced risk of heart disease with the use of HRT. Confusion has arisen over the last decade following publication of results of HERS and WHI trials, which both suggested an increased risk of heart disease with the use of HRT. However, most women in these trials were older than 60 years and more than 10 years postmenopausal when starting HRT as part of the trials. Re-analyses of these and other randomized trials have now shown that heart disease and total mortality are reduced when HRT is initiated in women aged less than 60 years, or within 10 years of the menopause. This new Danish trial reinforces the message of a “window of opportunity” for cardiovascular benefit with HRT, while reassuringly emphasizes the safety of HRT in terms of no significant risks even when used for more than 10 years.
Commenting on behalf of Women’s Health Concern and the British Menopause Society, Dr John Stevenson:
“Its main importance is the absolute safety of HRT with long term use. Because of the young age of the women, the numbers of events are very small, …but the trends are clear – a reduction in Coronary Heart Disease and in all-cause death, a significant reduction when these endpoints are combined (which was the planned primary endpoint of the study), no increase in stroke, VTE or any cancer, and a non-significant reduction in breast cancer (i.e. no increase). The strength of this study is the long duration of use. The safety concerns generated 10 years ago by biased reporting and mis-interpretation of HRT studies have been steadily assuaged by further analyses and reappraisals of those studies. This latest study totally reinforces this. The mantra “use HRT at the lowest dose for the shortest time” was never evidence-based, and this is now evidence against it. The other mantra that HRT must be stopped on safety grounds after 5 years duration should be blown out of the water!”
Surely now both women and healthcare professionals can again take and prescribe HRT when required for control of menopausal symptoms, or for treatment or prevention of osteoporosis without undue concern about risk and with reassurance about heart benefit when started early.
Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomized trial. Schierbeck L L, Rejnmark L, Tofteng C L, et al. BMJ 2012;345:e6409
KEEPS trial results
Results of the Kronos Early Estrogen Prevention Study (KEEPS), presented at the North American Menopause Society annual conference last week, has shown that HRT started soon after the menopause appears safe and relieves many menopausal symptoms, as well as improving mood and cardiovascular risk markers.
KEEPS was a 4 year randomized, placebo controlled trial of low dose oral or estrogen patch and cyclical progesterone in women aged 42 to 58 who were within 3 years after the menopause at randomization.
Many beneficial effects of HRT were found with improvements in hot flushes, night sweats, mood, sexual function and bone density, with no differences in adverse events such as breast cancer, endometrial cancer, myocardial infarction, stroke or blood clot. Regarding cardiovascular effect, some measures showed slight evidence that HRT may be cardioprotective in this age group.
These results should provide reassurance for the many women who are considering taking HRT, or are already taking HRT, for control of menopausal symptoms in the early menopausal years, and for the healthcare professionals who may be unsure about prescribing HRT.
Good news for HRT – now lets go forwards!
Nick Panay 11th October 2012
The new data from the Danish and KEEPS trials reaffirms the belief of many of our members, from their experience of prescribing for many decades, that HRT is not only safe and efficacious but also confers primary prevention benefits to long term users. However, the data from these new studies are only of use if these messages are conveyed effectively to menopausal women and their primary carers.
The merger of BMS with our patient arm Women’s Health Concern will certainly help to get the key messages directly to women, as will informative websites such as Menopause Matters. However, it is imperative that all health professionals involved in the care of women in the menopause have ready access to correct, contemporary information such as the data from the Danish and KEEPS studies.
The key aim of our ongoing liaison of the BMS with the Royal College of General Practitioners is to optimize training in post reproductive health in primary care. The BMS is also striving, through its recommendations on menopause, to lobby for resources from the secretary of state for health. This will enable every woman approaching the menopause to have the opportunity to engage in a discussion about her general health, HRT and alternatives. The current level of funding and resourcing in primary care is restricting access of women to their GPs and nurses for the purposes of women’s midlife health and in the meantime, menopause and HRT remain taboo subjects.
The Department of Health, through the Medicines and Healthcare products Regulatory Agency (MHRA) should reconsider the information from the new studies as a matter of urgency and revise the stringent guidelines on HRT prescribing i.e. minimum effective dosage for the shortest duration. In particular, HRT should be reinstated as a first line intervention for osteoporosis prevention, as per the recommendations of all the menopause societies and the Royal Osteoporosis Society. It could even be argued that there are now sufficient data to consider granting HRT a cardiovascular disease prevention indication for women who commence treatment early in the “Window of Opportunity”.
In conclusion, all the aforementioned strategies should be actioned without delay if we are to restore the rational management of the menopause, where HRT is perceived by all prescribers and their women as being a safe and effective tool to manage their symptoms and maintain their long term health.