Women's Health Initiative Study: Links to Current Information Updated March 1, 2004

Important Links

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On our site:

- February, 2004 Updates
      Depression & Cardiovascular Sequelae in Postmenopausal Women
      Risk of Peripheral Artery Disease
- Common Questions and Concerns
- Results Concerning Heart Health
- Results Concerning Memory and Cognition
- Links to Information on Menopause

Women's Health Initiative Site

- Homepage with links to information

From American College of Obstetricians and Gynecologists(ACOG):

- Read a statement on the study.
- Questions and Answers on Hormone Replacement Therapy

National Women's Health Information Center

- Menopause and Hormone News

Endocrine Society: Hormone Foundation

- public education website

Common Questions and Concerns

What is the study?

The Women’s Health Initiative (WHI) study is a multi-center study that involves thousands of women from all over the country. The goal is to answer to the question: What can women do to stay healthy longer? The factors being examined in the study are diet, exercise, calcium supplements and hormone replacement therapy.

The press release about hormone replacement therapy that came out this week (July 9, 2002) covers only one part of the study. This part of the study looked at women who have a uterus and were taking either Prempro (a specific estrogen and progesterone) or a placebo pill that contained no active hormone in it. The hypothesis for the study was that taking Prempro would result in a decrease in coronary heart disease. Secondary outcomes were breast cancer, stroke, venous thrombosis, colon cancer and fractures.

The WHI study is very different from most drug studies because it is measuring the long-term effects of the medication. Generally drug studies don’t even consider long-term health effects – but look at immediate side effects and therapeutic value for a given disease. The idea of taking hormones to stay healthy longer is like taking vitamins to stay healthy – we want to be very sure that there is no harm being done. So the WHI study is set up to measure small effects over long periods of time. Incidentally, we don’t have this kind of information on vitamins or calcium.

Why was part of the study stopped early?

Because the study was designed to see if hormone replacement therapy would help women stay heart-healthy longer, it was designed so that as soon as it became clear that the answer was “no,” the study would be stopped. The study investigators agreed to stop the study if a 25 percent increase in breast cancer was demonstrated. This became evident after five years of follow-up, and so the study was stopped. A good way to understand the level of risk that was detected is to consider that if 10,000 healthy, postmenopausal women took Prempro for a year, there would be eight more cases of breast cancer among those women than among 10,000 women (0.08 percent/year) who did not take Prempro.

Looking at the data this way for the other outcomes, the 10,000 women taking Prempro would have eight extra strokes, eight extra pulmonary emboli, and seven extra coronary events. The women taking the Prempro also would have six fewer cases of colon cancer and five fewer fractures. There were no differences in death from any cause between the two groups.

Does this mean that hormones are bad?

The study shows that the two products given to women in the study (Prempro, or conjugated estrogens plus medroxyprogesterone) should not be given to prevent heart disease, strokes, venous thrombosis or breast cancer. It does not mean that they are bad drugs or that they cause these diseases, but they may increase a woman’s risk of developing these problems over time. The study showed that the tested hormones were effective at preventing fractures and colon cancer.

The results can’t be generalized to any other hormone replacement products.

There is another part of the WHI study that has not been stopped. It looks at women who have had hysterectomies and are taking conjugated estrogen alone (no medroxyprogesterone). The data for these women do not, at this point, indicate excess risk. The data for these women will be released in 2005.

Should I stop taking hormones?

If you are taking Prempro therapy purely because you believed it will prevent heart disease, then you should stop taking it. If you are taking another hormone replacement product purely to prevent heart disease, you should talk to your physician.

If you are taking hormone replacement therapy to alleviate menopausal symptoms, this is still the most effective treatment. You may want to address the individual risks and benefits of continuing the therapy when you visit your healthcare provider each year.
If you are taking hormone replacement therapy to prevent osteoporosis and fractures, you should continue, because the WHI study clearly showed that women who took the hormones had fewer fractures.

Should I switch to another drug if I take Prempo, Premarin and Provera?

We don’t know if the results of the WHI study will be the same with other forms of hormone replacement medications. We don’t know if the adverse effects are caused by one of these drugs individually or by both of them. These questions are being investigated. At this time, this is a question that you should ask your healthcare provider. Remember that none of the adverse outcomes in this study happen in the short term. They happen after years of therapy. Take some time to discuss and consider this issue and then make a decision.

If I decide I want to discontinue hormones, how should I do it?

It is best to not stop all at once. You should taper off by taking your hormones every other day for a week, then every third day for a week, then stopping. You may still experience a recurrence of hot flashes and night sweats. These symptoms will most likely disappear over the next one to three months.

WHI Study: Considering Heart Health and HRT

16,000+ Women, aged 50-79, mean study period of five years
PREMPRO 2.5mgs or Placebo

Journal of the American Medical Association July 8, 2002

Results: Number of Occurrences for 10,000 Women in One Year

Important points to consider:

• Does not apply directly to women who have had a hysterectomy.
• Did not study other progesterones or estrogens.
• It did not assess quality-of-life issues.
• Main new finding is effect on cardiovascular disease.
• Decisions must be individualized – requires one-on-one discussion with physician.

Women's Health Initiative Memory Study

Results Descibed and Explained

Dr. Leon Speroff, current Director for the Women's Health Research Unit at Oregon Health & Science University, in an article for the July issue of OB/GYN Clinical Alert, discusses study results as well as what they do and do not tell us about the effects of HRT on memory and cognition such as:

Answered Questions:

1. Will hormone therapy prevent subsequent clinical events in women with existing coronary artery disease?

With a great deal of confidence, we can answer no, based upon the series of secondary prevention trials published over the last few years.

2. Will hormone therapy prevent the appearance and progress of dementia in elderly women?

The results of the WHI and a secondary prevention trial in women with Alzheimer’s disease iindicate that the answer is no.

Unanswered Questions:

1. Will older women who have used hormone therapy for long durations early in their postmenopausal years be protected against dementia?

The WHIMS report recognizes, in the discussion, that this hypothesis cannot be tested in this clinical trial. Nevertheless, the conclusion states that hormone therapy should not be prescribed with the expectation that it will enhance cognitive performance in postmenopausal women. It would have been more accurate to limit that statement to “postmenopausal women 75 years and older.”

2. Will hormone therapy of long duration initiated early in the postmenopausal years have a beneficial impact on cognition?

The WHIMS also cannot answer this question. A prospective study of a homogenous population in Utah (thus minimizing, if not eliminating, the healthy user bias) concluded that a reduction in the risk of Alzheimer’s requires long-term treatment, initiated at least 10 years before symptoms of dementia appear.

3. Will hormone therapy reduce the risk of coronary artery disease when administered in a truly primary prevention fashion (for relatively long durations in women of early postmenopausal age with no clinical evidence of atherosclerosis)?

Indeed, experimental evidence in women and monkeys indicates that as vascular endothelial cells become involved with atherosclerosis, beneficial responses to estrogen diminish.

4. Will the adjudication process produce a shift in cardiac disease case numbers, eliminating the statistical significance of the conclusions already reported by the WHI?

Read the complete article. Requires Adobe Acrobat Reader.

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