Increased absolute risk per
10 000 w/y
Increased absolute benefit per
10 000 w/y
|Risk / benefit||41||11|
W/y=women per year
Interpretation of results:
Conclusions are only valid for continuous combined HRT, and not for unopposed ERT.
Conclusions are not valid for other hormone regimes or different drugs.
Conclusions may not be valid for low dose HRT.
Although the trial was stopped primarily because the risk of incident breast cancer crossed a predetermined value, this is surprising as the increased incidence was consistent with available epidemiological studies (2). Breast cancer in patients on HRT is generally accepted as having a better prognosis than cases diagnosed in non-users. This may happen as a result of oestrogen promoting growth in pre-existing cancers and thus allowing earlier diagnosis and treatment. Tumours in the WHI study have not yet been analyzed in this regard. The results are consistent with two recent trials indicating risk only when progestin is added. The WHI results do not significantly change present thinking on breast cancer risk.
The lack of cardiovascular protection in a primary prevention study is the most significant finding of this study. As in HERS, the increased risk of cardiac events was mostly confined to the first year of treatment. Increases in thromboembolism though occurred during all 5 years of the study. As myocardial infarction is the main cause of death in menopausal patients, the WHI results are very significant for long-term use of HRT.
The WHI paper is the first trial with definitive data to support the ability of HRT to significantly prevent osteoporotic fractures. The magnitude of this effect will obviously be much greater in a population at high risk for fracture.
WHI is the first large study to support the beneficial effect as seen in observational studies
When assessing the risk/benefit ratio of HRT use, it is important to note that the WHI study did not include the following proven HRT benefits:
Alleviation of menopausal vasomotor symptoms.
Overall quality of life assessment.
Effects on cognitive function and brain dementia
Conclusion reached by the authors
In healthy asymptomatic postmenopausal women with an intact uterus, this particular regime of HRT should not be initiated or continued for the sole purpose of primary prevention of CHD.
Suggested clinical guidelines
It is important to understand that there is no need for panic. Patients must be assured that they can continue with their present medication, but be encouraged to consult their health care provider, when convenient, to assess their individual indication for HRT. This should be reassessed annually.
Although the risk and benefits of HRT given for the treatment of acute menopausal symptoms were not addressed in this study, there is still good reason to suspect that risk in the first 5 years after menopause is small. Undisputed scientific evidence supports the fact that only ERT/HRT is successful in the alleviation of vasomotor symptoms. There is no evidence to support the use of alternate medication such as phyto-oestrogens. It is concluded that present practice as regards the management of acute symptoms of menopause be unchanged.
A decision to continue with HRT after 5 years will have to be based on an individual assessment of risk and benefit. The WHI results make this task easier than before. The difficult part remains the value placed on the improvement of quality of life. This has not been quantified and will differ between individuals. For many patients at present, this constitutes the only reason why they persist with the use of HRT. The patient must understand that the absolute risks as found in the WHI study. It is expected that patients will be most concerned by the breast cancer results. It is important to be prepared to spend some time to explain that the increased diagnosis does not necessarily imply causality. Furthermore, neither in this nor in other studies has mortality been shown to be increased.
The suggestion not to use HRT for the sole purpose of prevention of CHD should be strictly observed. The beneficial effect of lifestyle changes on the prevention of CHD must be stressed. Optimal medical treatment of hypertension, diabetes and hypercholesterolemia must be assured.
There is evidence from observational data to suspect that the results of the ERT arm of WHI study may differ significantly. This issue will be resolved in 2005. In the meantime, it is recommended that the results of this WHI study and suggested guidelines be applied to ERT and HRT users. The medical profession must put pressure on companies providing other drugs and routes of administration of HRT to undertake appropriate clinical trials. Without such evidence, we simply have no other choice but to apply the results of the WHI study to all methods of prescribing ERT/HRT when assessing the need of individual patients. This is recommended not only on a scientific basis, but also from a medico-legal point of view.