Hormone replacement therapy (HRT) is a common practice for post-menopausal women. The
secretion of estrogen and progesterone are greatly reduced at the onset of menopause, leading to symptoms like hot flushes. Initially, physicians only administered estrogen. However, when it was realized that estrogen use alone leads to increased risk of endometrial (uterine) cancer, it became common practice for HRT to consist of the combination of estrogen and progesterone (trade name-progestin). The progestin has a protective effect against endometrial cancer.
Observational studies previously indicated potential benefits from the use of hormone replacement therapy. The studies indicated that long-term use may reduce the risk of bone fractures due to osteoporosis, and may reduce the risk of cardiovascular disease. Observational studies have their limitations in terms of bias. The selection of women who receive HRT is left to the judgment of the physician. It may have turned out that women receiving the treatment were healthier to begin with. Likewise, the clinical outcome of the women may have been due to factors other than the treatment. These issues were reviewed in my article.
Estrogen is well known to have a growth stimulatory effect on breast tissue, and is a factor in the development of cancer. In order to address this concern, a large meta-analysis study that was conducted in 1997; however, this study focused on estrogen use only. A meta-analysis combines the data from a large number of individual studies (in this case 51) in order to conduct an overall statistical analysis. The report concluded that there was a 30% increased risk of breast cancer in women who had used HRT for a period of 5 years, while 15 or more years of HRT was associated with a 60% increased risk.
The Women's Health Initiative was a very large clinical trial that was undertaken to address the questions raised from previous studies, and to come to some more definitive conclusions. It is known as a double blind randomized controlled clinical study. This means that neither the patients nor the physicians treating them were aware of the treatments that the patients received. Randomized means that both treatment groups were equalized as much as possible by patient characteristics, so that the differences in development of cancer or other medical conditions between groups is more directly attributable to the treatments administered. The findings, therefore, were considered more credible and convincing to the scientific community than observational studies. There were two main parts to the study. The larger study, reported herein, involved 16,608 women who were relatively healthy, ages 50 to 79, post-menopausal, with an intact uterus, and no prior history of breast cancer. They were randomized into two groups, and received either Prempro pills or an identical-appearing inactive placebo pill. Prempro is a product of Wyeth-Ayerst, and consists of estrogen and progestin. The primary goals of the study were to evaluate if HRT would increase or decrease the risk of breast, endometrial or colon cancers, reduce the risk of fractures due to osteoporosis, and to see the effect on cardiovascular disease. Strict criteria were defined that had to be met before a study could be terminated early. As the study progressed, risk-benefit analyses were conducted on the data, and if the overall risks exceeded the benefits, the study was terminated. This indeed occurred for this trial.
