Hormone Replacement Therapy: An Update
Chester J. Zelasko, Ph.D. | July 23, 2002

Hormone Replacement Therapy (HRT), always a controversial issue anyway, was recently thrust back into the headlines when results from the Women's Health Initiative were published. The study showed that when healthy postmenopausal women take HRT to reduce the risk of coronary artery disease (CAD), cancer, and osteoporosis, the risks outweigh the benefits (1). This Newsletter will try to put the results of the study in perspective.

The purpose of the study was to examine the long-term effects of continued HRT use on healthy postmenopausal women with intact female organs. It did answer that question, but only for women who meet those restrictions and use that form of HRT:

  • The results apply only to the amounts and sources of estrogen and progesterone used in the study.
  • Other combinations of hormones or the use of individual hormones may not produce the same results.
  • The long-term effects of HRT are still unknown for women who are approaching or going through menopause or who have had a hysterectomy.
Most women are prescribed HRT by their physicians for several reasons: continued symptoms of menopause such as hot flashes; risk of CAD; or osteoporosis. Although HRT may benefit women with these symptoms or genetic tendencies, those variables were not included in the published study.

One of the primary problems with the study was that the researchers did not assess initial hormone levels before HRT. It's often true that even though women no longer menstruate, they still produce varying amounts of hormones. It may be that an excess of hormones caused by natural production in addition to HRT had an additive or synergistic effect that resulted in the undesirable outcomes.

While the statistics were accurately reported in the press, percentages do not always give the complete picture. While there was a 26% increase in breast cancer in HRT users, the actual number of cases was 38 versus 30 per 10,000 person-years. What that means is that in a year, 3.8 women out of 1,000 developed breast cancer while taking HRT compared to 3.0 women out of 1,000 who took the placebo. The stats were similar for other outcomes such as heart attack and pulmonary embolisms.

Curiously, there were no differences in mortality (death rate) between the HRT users and placebo group. In fact, the death rate was low at only 2.7% for both the placebo and HRT groups of women with an average of 63.2 years of age.

The study was very well designed and administered. However, it demonstrates the limitations of researching large populations. In spite of the millions of dollars spent and the hours spent collecting and processing data, the results apply to a narrow population. The placebo and HRT group were matched on many characteristics such as age, body mass index, smoking status, initial blood pressure, cholesterol levels, and many more variables--but the study didn't assess initial hormone levels, diet, exercise, and other variables that affect hormone production and thus may have impacted the results. Those variables were not controlled or examined.

What this study really illustrates is that more research should be done on the long-term effects of pharmaceuticals. Pharmaceuticals are appropriate to treat disease, but HRT may not be the best choice as an intervention to prevent disease, as done in this study.

The next class of drugs that may be considered for their potential preventive role are the statin drugs because of the positive effects reported on reducing the risk of several diseases. But it's a long step from using pharmaceuticals to treat disease and using them to prevent disease. That's what this study really proves.

So where does that leave you as someone who either uses HRT or is considering using HRT? Discuss it with your healthcare provider. He or she knows your medical history, your lifestyle, the medications you're taking, and your family history--and it's unlikely you'll be prescribed HRT without a blood test to determine your current hormone levels. Work together to come up with a reasonable plan of action that considers the benefits and potential risks of HRT. There may be lifestyle changes such as weight loss, diet, or exercise that can help reduce the risk of CAD and osteoporosis without relying on pharmaceuticals. You and your provider may decide to use HRT for only a few years, probably during the most uncomfortable phase of menopause or perimenopause.

Headline science is not the best way to make decisions about your health--spend the time collecting all the facts from several sources before making a decision.


  1. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA. 2002. 288(3):321-33.
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