Hormone Replacement Therapy|
|Trials of Hormone replacement therapy (HRT) have cast serious doubts on previous trials that have suggested protective benefits from HRT. Doctors have been aware of a small increased risk of Breast cancer after 5 years of continuous use however many previous trials had suggested a benefit in regard to heart disease and bone protection that was felt to outweigh this risk. This latest trial strongly suggests this is not the case. This latest evidence suggests that the indications for long term use of HRT be reviewed.
The study included more than 16,000 women aged 50-79 taking 1 daily tablet containing 0.625 mg of conjugated equine oestrogen plus 2.5 mg of medroxyprogesterone acetate. The study was published in JAMA on 17 July 2002 and suggest that adverse outcomes began appearing within one or two years of starting combined HRT, and increased risk of breast cancer began after three years. This study does not apply to women taking Oestrogen without Progesterone as may occur after a hysterectomy
- 1.3 fold increase in heart attacks
- 1.26 fold increase in the risk of breast cancer,
- 2 fold increase in the risk of deep vein thrombosis
- 1.22 fold increase in the overall rate of cardiovascular disease
among women taking combined HRT long-term.
This compared to a
- 1.33 fold reduction in hip fractures
- 1.24 fold reduction in total fractures
among the same group.
Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal women. All-cause mortality was not affected during the trial. The risk-benefit profile found in this trial is, however not consistent with the use of HRT to prevent chronic diseases, and the results indicate that this regimen should not be initiated or continued for primary prevention of heart disease.
This trial tested only 1 drug regimen, 0.625 mg of conjugated equine oestrogen plus 2.5 mg of medroxyprogesterone acetate in postmenopausal women with an intact uterus. The results do not necessarily apply to lower dosages of these drugs, to other formulations of oral estrogens and progestins, or to oestrogens and progestins administered through patches.
How should doctors and the millions of women taking an estrogen/progestin combination react to the unexpected results of this study?
Although the trial results are reported primarily in terms of relative risk, which is appropriate for studies of this type, when applying the results to practice, they must be translated into absolute risk. The absolute risk of harm to an individual woman is very small. As the authors point out, the increased risk of the oestrogen/progestin combination means that in 10,000 women taking the drug for a year, there will be
- 8 more invasive breast cancers
- 8 more strokes
- 8 more pulmonary emboli
- 6 fewer colorectal cancers
- 5 fewer hip fractures
Nevertheless, when counting all events over the 5.2 years of the trial, the excess number of events in the active drug group was 100 per 10,000 (or 1 in 100 women). This is still a small risk, and overall there is was no excess “all cause-mortality” between the treatment and non-treatment groups.
The whole purpose of healthy women taking long-term oestrogen/progestin therapy is to preserve health and prevent disease. The results of this study provide strong evidence that the opposite is happening for important aspects of women's health, even if the absolute risk is low. Given these results, we recommend that you take the opertunity to discuss these risks with us at your next visit. The results are for a single dosing regimen (1 daily tablet containing 0.625 mg of conjugated equine oestrogen plus 2.5 mg of medroxyprogesterone acetate) other regimens may have different results, but 3 previous studies with other regimens have also all found an increased risk of breast cancer.
How can women be protected against osteoporosis?
The results from the WHI and from numerous other studies have shown protection with hormone replacement therapy. Fortunately, there are alternative preventive strategies, at least one of which also lowers the risk of breast cancer (although to date, cardiovascular effects are not clear).
What about short-term use for managing menopausal symptoms? The WHI trial does not specifically address this question, but the results suggest short-term use (less than 1 year) of the combination has risks for coronary heart disease and deep vein thrombosis. The possibility of these small absolute risks must be balanced against the severity of symptoms and benefit of treatment.
Common preventive therapies require rigorous evaluation. For hormone replacement therapy, which is used by millions of patients, even rare adverse effects can harm substantial numbers of women. This new trial provides new evidence that seriously questions the value of using oestrogen/progestin to prevent chronic disease.