Safety of hormone replacement therapy
3 July 2007
Women's Health Concern press statement
Prepared by:
John C Stevenson, Consultant Metabolic Physician, Royal Brompton Hospital, and Chairman, Women's Health Concern, and
Richard Farmer, Emeritus Professor of Epidemiology, University of Surrey
In the light of further results from the Women's Health Initiative (WHI), we believe it is timely to reappraise the situation concerning the safety of hormone replacement therapy (HRT).
WHI studied 16,608 postmenopausal women with uterus randomised to combined oestrogen/progestogen HRT or placebo over 5.2 years, and 10,739 postmenopausal women with hysterectomy randomised to oestrogen-alone HRT or placebo over 6.8 years. The women were aged between 50 and 79 years, and the effects on various clinical outcomes were documented.
- The initial report from the combined HRT arm of the study was published in 2002, and claimed that HRT caused an increase in heart attacks, strokes, blood clots and breast cancer.
- The publication of the oestrogen-alone arm of the study in 2004 reported that there were non-significant decreases in heart attacks and breast cancer, although there were still increases in strokes.
- The publication of the total results from combining the arms of the studies in 2007 showed that there were clear effects of age and time since menopause on the adverse outcomes. Women starting HRT aged below 60 years or within 10 years of their menopause had no significant increase in heart attack or stroke, and a decreased total mortality compared with placebo. This contradicts the statement in 2002 of the lead author of the study, who categorically stated that the adverse effects of HRT applied to all women, irrespective of age.
- A further report in 2006 from the combined HRT arm showed that the increase in breast cancer with HRT was not significant when the values were correctly adjusted for known confounding variables. The increase was significant only in women who had previously used HRT prior to entering the study.
- Moreover, the recent claim from the USA that breast cancer rates fell when the use of HRT fell should not be interpreted as indicating that there was a causal relationship. Rates fell amongst middle-aged menopausal women, but also amongst women aged over 75. The most likely explanation for the reduction in diagnosed breast cancer is the 7% fall in mammography which occurred at that time. There was no reduction in the number of new cases of breast cancer in England after a similar reduction in the use of HRT.
The effect of the initial publications of the WHI, and also the Million Women Study (MWS), resulted in a decline in HRT use of around 50% in the UK. Based on the current evidence, we conclude that women starting on HRT below age 60 years are not at increased risk of adverse events other than a slight increase in risk for blood clots amongst users of combined HRT. This risk could be decreased by the use of the new low-dose HRT preparations. For women aged below 60 years there is a decreased total mortality and a decrease in fractures. HRT should be considered first-line therapy for relief of menopausal symptoms, and for prevention of osteoporosis in women of this age with increased risk for the disease. It is not possible to predict from current randomised trials the effect of long-term HRT use in these women, but it would certainly appear to be free from significant risk for at least 7 years. The increase in coronary disease, osteoporosis and deaths resulting from the drop in use of HRT will only become apparent in future years, but should be considered in discussions of benefit and risk. These findings should reassure women entering the menopause and their healthcare providers about using HRT when indicated.
For interviews with Dr Stevenson or Professor Farmer or other media enquiries please contact:
Patrick Shervington
Chief executive
or telephone 07974 384 254
