Hormone Replacement Therapy – Saves Lives
by Dr Daisy Mae
HRT, if started early in the postmenopausal period significantly reduced the number of deaths and showed no increase in any cancers, stroke or venous thromboembolism in the treatment group. Read on and see ...
New Research Demonstrates HRT is safe after all!
There was surprisingly little press coverage with the 2012 publication in the British Medical Journal (BMJ) of this paper entitled “Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomised trial,” by Schierbeck et al.1
Hormone Replacement Therapy (HRT) has had a very negative press in recent years. This has largely resulted from publication of The Women’s Health Initiative (WHI 2002),2 and The Million Women Study (MWS 2003),3 both of which concluded that the risks of HRT on cardiovascular disease and breast cancer outweighed the benefits. Widespread panic ensued among women and the medical profession. HRT prescribing fell by 66%.4
WHI Study – the Characteristics of the Study Population
The WHI study was carried out in older women, with an average age of 63, many of whom were obese, smokers and had had previous cardiovascular disease (CVD).
What did the New Research Team do Differently?
In contrast, Schierbeck et al set out to study how taking HRT might affect the risks of CVD, and also the risk of developing cancer, but in healthy women, and who were only newly postmenopausal. This patient group is more representative of the average UK woman using HRT.
The study investigators aimed to discover specifically whether use of hormone replacement therapy (HRT), if started early in the postmenopausal period, had beneficial effects on CVD when taken over a ten year period. This was a randomised, open label study.
They identified a cohort of female patients, already recruited for the Danish Osteoporosis Prevention Study (1990-1993).5 Women were healthy, aged 45-58 years, and had had their last period 3-24 months prior to study entry. Hysterectomised women, aged 45-52, were included if they had had raised serum follicle stimulating hormone (FSH) levels. Exclusion criteria were clearly defined.
2016 patients were recruited. 1006 were randomised to receive either HRT (n=502) or no treatment (n=504). The remaining 1010 were given the choice, and 221 opted for HRT.
What Did the New Study Investigators use as Criteria for the End Points of their Study?
The primary endpoints of the study were death, myocardial infarction or a hospital admission with cardiac failure. Secondary end points were stroke, or hospital admission with venous thromboembolism (VTE).
Women on cyclical HRT took a combined HRT containing 17 β-estradiol 2mg / norethisterone acetate 1mg. Hysterectomised women took 17 β-estradiol 2mg/day only.
The study, due to run for 20 years, was stopped after 10 years, due to the 2002 publication of the Women’s Health Initiative. Study participants therefore discontinued their HRT, but follow up continued for 6 years.
What Were the Findings of this New Study?
This study revealed that use of HRT was highly beneficial. At 10 year follow up, there was a statistically significant reduction in the primary end points - 16 in the HRT treatment group, compared to 33 in the control group (hazard ration 0.48, 95%CI 0.26 to 0.87; P=0.015).
In addition there were statistically significant differences in the numbers of deaths, with 15 deaths in the HRT treatment group and 26 in the control group (0.57, 0.30; P=0.084).
There was no increase in any cancers, breast cancer, stroke or venous thromboembolism in the treatment group. Benefits were maintained in the 6 years after HRT was discontinued.
Can you Explain Why this New Study Showed Better Health Outcomes for HRT Users?
Prior to this study, observational data had suggested that HRT might be beneficial to reduce cardiovascular disease.6 The initial negative findings of the 2002 WHI study were therefore puzzling to specialist physicians. In fact, a 2013 reanalysis of the WHI data, found no extra risk of CVD in women who had started HRT within 10 years of menopause.7
Premenopausal women are protected by their own estrogen from CVD. At menopause, estrogen levels fall, and their CVD risk increases. By starting HRT early in the postmenopausal period, estrogen exerts protective effects on blood pressure, cholesterol and arterial walls, to prevent atherosclerosis. To get optimum benefit, women should use HRT through “the window of opportunity.” 8
Randomisation is the hallmark of a good research strategy. However this study was not double blinded – it was open label – and as such would have been subject to investigator bias.
The study also relied on the accuracy of the Danish Civil Registration system, regarding data on hospital admissions, diagnoses and deaths7 This register is said to have a high level of accuracy and completeness.
Statistical analysis was carried out on an intention to treat basis, however not all women complied with their treatment (although the majority did) and this may have led to some over estimation of HRT benefit.
This is a welcome piece of medical research providing clear evidence for the life saving benefits of HRT. When used in newly menopausal women, for up to 10 years, there were fewer deaths, less CVD and no increase in any types of cancer.
This study further reinforces the advice from the 2015 Menopause Guidelines produced by The National Institute of Care and Excellence (NICE).9
These state clearly that in fact, “women should not suffer in silence,” because the safety of HRT of HRT has - at last - been well established.
Daisy Mae x
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SCHIERBECK, L.L et al.(2012) ‘ Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomised trial’, BMJ, 345 (online) (cited 5th February 2018) Available from <URL https://doi.org/10.1136/bmj.e6409
ROSSOUW, J.E. (2002) ‘Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial’, JAMA, 288:3, 321-33 (cited 5th February 2018) Available from <URL https://www.ncbi.nlm.nih.gov/pubmed/12117397
MILLION WOMEN STUDY COLLABORATORS (2003) ‘Breast cancer and hormone-replacement therapy in the Million Women Study’, The Lancet, 336:962, 419-427 (cited 5th February 2018) Available from <URL https://doi.org/10.1016/S0140-6736(03)14065-2
WOMEN’S HEALTH CONCERN, (November 2017) ‘HRT; Benefits and Risks’ (cited 6th February 2018) Available from <URL https://www.womens-health-concern.org/help-and-advice/factsheets/hrt-know-benefits-risks/
MOSEKILDE, L et al (1999) ‘The Danish Osteoporosis Prevention Study (DOPS): project design and inclusion of 2000 normal perimenopausal women’, Maturitas, 31:3, 207-19 (cited 5th February 2018) Available from <URL https://www.ncbi.nlm.nih.gov/pubmed/10340280
ROSANO,G.M, PANINA, G, (1999) ‘Oestrogens and the heart’, Therapie, 54:3, 381-5 (cited 5th February 2018) Available from <URL https://www.ncbi.nlm.nih.gov/pubmed/10500455
GURNEY, E.P et al. (2014) ‘The Women's Health Initiative trial and related studies: 10 years later: a clinician's view’, Steroid Biochem Mol Biol, 142, 4-11 (cited 5th February 2018) Available from <URL https://www.ncbi.nlm.nih.gov/pubmed/24172877
HODIS, H.H. (2012) ‘The window of opportunity for coronary heart disease prevention with hormone therapy: past, present and future in perspective’. Climacteric, 15:3, 217-228 (cited 5th February 2018) Available from <URL
THE NATIONAL INSTITUTE OF CARE AND EXCELLENCE (2015) Menopause: diagnosis and management. NICE guideline [NG23], (cited 5th February 2018) Available from <URL https://www.nice.org.uk/news/article/women-with-symptoms-of-menopause-should-not-suffer-in-silence