The Hormone Studies The Womens Health Initiative - Hormone Therapy And Disease: Menopause Managing The Change Of Life

Content provided by the Faculty of the Harvard Medical School

The hormone studies: The Women's Health Initiative

How can women best protect themselves against common, chronic diseases such as heart disease, breast and colon cancer, and osteoporosis? The Women's Health Initiative (WHI), a 15-year, multimillion-dollar project, set out to answer this broad question. Begun in the early 1990s by the National Institutes of Health, this far-reaching study involves more than 161,000 women between ages 50 and 79.

The WHI is actually a compendium of several major studies. To date, the most widely publicized is the one involving hormone therapy. Most previous studies of hormone therapy were cohort or observational studies, meaning that researchers compared the medical records and histories of women who used hormones with those who did not. Those studies suggested that over all, hormone therapy seemed to have beneficial health effects. But the most reliable, conclusive evidence comes from randomized clinical trials — like the WHI — in which researchers randomly assign women to take either a drug treatment or a fake pill known as a placebo and compare the two groups after a period of time.

The WHI trial included two parts. The Estrogen-Plus-Progestin (E+P) arm included 16,608 women who had not had hysterectomies and were given either combined hormone therapy (Prempro) or placebo. The Estrogen-Only (E-Only) arm included 10,739 women who had undergone hysterectomies and who were given either estrogen (Premarin) or a placebo. In July 2002, researchers stopped the Prempro trial early, after an average follow-up of 5.2 years instead of the planned 8, when it became clear that hormone users had a higher risk of breast cancer, heart disease, stroke, and potentially fatal blood clots compared with women not taking the hormones. Although hormone users were less likely to fracture a hip or develop colorectal cancer, these positives did not outweigh the negative heath effects. Still, the added risks are quite small (see "Health risks and benefits of Prempro," below).

Two years later, the E-Only arm was also stopped early, after an average of 6.8 years of follow-up instead of 8. Again, the evidence suggested that the hormone treatment's risks outweighed the benefits, although with a somewhat different pattern. Like women who used combination Prempro, estrogen-alone users were more likely to have strokes but less likely to fracture a hip. However, researchers found no significant differences in the risk of heart disease, breast or colon cancer, or blood clots in the lungs between the estrogen and placebo groups.

Since then, researchers have continued to analyze data from both trials. Below are some of the other key findings:

Urinary incontinence. Contrary to conventional wisdom, in the studies, both E-Only and Prempro increased the risk of stress incontinence. This problem — leaking of urine when a person coughs, laughs, sneezes, lifts, stands, or exercises — is the most common form of incontinence. Women with no history of incontinence were more likely to develop the problem if they took hormones. And those with previous incontinence problems tended to develop worse incontinence if they took hormones.

Dementia and cognitive function. Despite expectations that hormones might protect against cognitive problems such as memory loss, the results revealed a slightly higher risk of dementia (including Alzheimer's disease, the most common form of dementia) among older E-Only and Prempro users.

Diabetes. Women who took Prempro had a slightly lower risk of developing diabetes than women not taking the hormones, but experts don't feel this benefit outweighs the other health risks from hormones.

Quality of life. Compared to women taking placebos, women who took Prempro reported slightly higher scores on certain measures of quality of life, such as better physical functioning, less sleep disturbance, and less pain, but only during the first year of the study. After three years, these slight advantages had vanished.

Despite the strengths of this study, it has some limitations. Critics of the WHI point out that the study involved only one form of estrogen and progestogen, Prempro. It's not clear whether other forms of estrogen and progestogen have these same risks or benefits. Also, the average age of participants was 64, which is older than the traditional age of women who've taken hormones in the past, so their risks for certain disease differed from those of younger women. Finally, women with severe menopausal symptoms were discouraged from being in the study.

Researchers will continue to monitor women from these studies until 2010, which will help determine whether the pros and cons from taking hormones continue or disappear over time among women who stopped taking the hormones. Other arms of the WHI are continuing as well. The Dietary Modification component will evaluate how a diet low in fat and high in fruits, vegetables, and grain products affects risk for breast and colon cancers and heart disease. The Calcium/Vitamin D component will evaluate the effect of those nutrients on risk for osteoporosis and colon cancer. Another arm, called the Observational Study, focuses on the relationship between lifestyle, health, and risk factors and specific disease outcomes.

Last updated:	August 13, 2007