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WHI Hormone Study and Synthetic HRT Information.

Womens Health Initiative releases Study Findings about Synthetic Progestins, Synthetic Hormone Replacement Therapy

If you are currently trying to make the decision between synthetic hormone replacement therapy and natural hormone replacement, the following results of ongoing WHI studies may help you reach an informed decision.

Following are portions of two press releases from the National Institutes of Health, a division of the U.S. Department of Health and Human Services, along with links to the full text. As released on March 2, 2004--

"National Institute of Health asks Participants in the W.H.I.'s Estrogen-Alone Study to Stop Study Pills, Begin Follow-up Phase".

Statement from Barbara Alving, M.D., Director of the Women's Health Initiative and Acting Director of the National Heart, Lung, and Blood Institute.

The National Institutes of Health (NIH) has instructed participants in the estrogen-alone study of the Women's Health Initiative (WHI), a large multi-center trial, to stop taking their study pills and to begin the follow-up phase of the study.

Letters have been sent to all participants in the estrogen-alone study, 11,000 healthy postmenopausal women who have had a hysterectomy, informing them of a recent NIH review of the study data. After careful consideration of the data, NIH has concluded that with an average of nearly 7 years of follow-up completed, estrogen alone does not appear to affect (either increase or decrease) heart disease, a key question of the study. At the same time, estrogen alone appears to increase the risk of stroke and decrease the risk of hip fracture. It has not increased the risk of breast cancer during the time period of the study.

The increased risk of stroke in the estrogen-alone study is similar to what was found in the WHI study of estrogen plus progestin when that trial was stopped in July 2002. In that study, women taking estrogen plus progestin had 8 more strokes per year for every 10,000 women than those taking the placebo. The NIH believes that an increased risk of stroke is not acceptable in healthy women in a research study. This is especially true if estrogen alone does not affect (either increase or decrease) heart disease, as appears to be the case in the current study...

The WHI estrogen study was designed to assess the effect of long-term use of hormone therapy in healthy postmenopausal women on the prevention of heart disease and hip fractures, and any associated change in risk for breast cancer. It was not designed to evaluate the short-term risks and benefits of hormones for the treatment of moderate to severe menopausal symptoms... The estrogen-alone study involved women ages 50 to 79 years. Study participants were randomly assigned to a daily dose of estrogen-- 0.625 mg/day of conjugated equine estrogen (Premarin(tm))--or a placebo.

The NIH decision to stop the estrogen-alone trial was made on February 2, 2004. In November and December 2003, the WHI Data and Safety Monitoring Board (DSMB), an independent advisory committee which regularly reviews study data and oversees the safety of study participants, reviewed the latest data from the estrogen-alone study. The DSMB was split as to whether the study pills should be stopped or whether the pills should be continued, provided that a letter would be sent to the participants clearly informing them of the stroke risks and other findings. After careful review, the NIH decided that women in the estrogen-alone study should stop taking their study pills..."

For full text of the article,
Click here.

WHI (Womens Health Initiative) study

As released, July 9, 2002

"NHLBI Stops Trial of Estrogen Plus Progestin Due to Increased Breast Cancer Risk, Lack of Overall Benefit

The National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) has stopped early a major clinical trial of the risks and benefits of combined estrogen and progestin in healthy menopausal women due to an increased risk of invasive breast cancer. The large multi-center trial, a component of the Women's Health Initiative (WHI), also found increases in coronary heart disease, stroke, and pulmonary embolism in study participants on estrogen plus progestin compared to women taking placebo pills. There were noteworthy benefits of estrogen plus progestin, including fewer cases of hip fractures and colon cancer, but on balance the harm was greater than the benefit. The study, which was scheduled to run until 2005, was stopped after an average follow-up of 5.2 years.

Participants in this component of WHI, like most women with a uterus who take hormone therapy, were given progestin in combination with estrogen. This practice is known to prevent endometrial cancer. A separate WHI study of estrogen alone in women who had a hysterectomy before joining the WHI hormone program continues unchanged because, at this point, the balance of risks and benefits of estrogen alone is still uncertain.

The report from the WHI investigators on the estrogen plus progestin study findings will be published in the July 17 issue of The Journal of the American Medical Association (JAMA); because of the importance of the information, the study is being released early on Tuesday, July 9, as an expedited article on the JAMA Web site. (Full text version available to all at jama.com.)

"We have long sought the answer to the question: Does postmenopausal hormone therapy prevent heart disease and, if it does, what are the risks? The bottom-line answer from WHI is that this combined form of hormone therapy is unlikely to benefit the heart. The cardiovascular and cancer risks of estrogen plus progestin outweigh any benefits--and a 26 percent increase in breast cancer risk is too high a price to pay, even if there were a heart benefit. Similarly, the risks outweigh the benefits of fewer hip fractures," said NHLBI Director Claude Lenfant, M.D.

"Menopausal women who might have been candidates for estrogen plus progestin should now focus on well-proven treatments to reduce the risk of cardiovascular disease, including measures to prevent and control high blood pressure, high blood cholesterol, and obesity. This effort could not be more important: heart disease remains the number one killer of American women," added Lenfant.

The estrogen plus progestin trial of the WHI involved 16,608 women ages 50 to 79 years with an intact uterus. An important objective of the trial was to examine the effect of estrogen plus progestin on the prevention of heart disease and hip fractures, and any associated change in risk for breast and colon cancer. The study did not address the short-term risks and benefits of hormones for the treatment of menopausal symptoms.

About 6 million women in the U.S. are taking estrogen plus progestin for a variety of reasons, including symptom relief, because their doctors advised it, or for long-term health.

"Women with a uterus who are currently taking estrogen plus progestin should have a serious talk with their doctor to see if they should continue it. If they are taking this hormone combination for short-term relief of symptoms, it may be reasonable to continue since the benefits are likely to outweigh the risks. Longer term use or use for disease prevention must be re-evaluated given the multiple adverse effects noted in WHI," said Jacques Rossouw, M.D., acting director of the WHI.

According to Rossouw, the adverse effects of estrogen plus progestin applied to all women, irrespective of age, ethnicity, or prior disease status.

"When the estrogen-only trial is completed, a comparison of the results of these two trials may provide a better idea of the roles of estrogen, compared to estrogen plus progestin, in health and disease," said Marcia Stefanick, Ph.D., chair of the WHI Steering Committee and Associate Professor of Medicine, Stanford University, Palo Alto, California.

Women enrolled in the estrogen plus progestin study were randomly assigned to a daily dose of estrogen plus progestin (0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate) or to a placebo. Participants were enrolled in the study between 1993 and 1998 at over 40 clinical sites across the country.

In 2000 and again in 2001, WHI investigators complied with a recommendation from the study's Data and Safety Monitoring Board (DSMB) to inform participants of a small increase in heart attacks, strokes, and blood clots in women taking hormones. The DSMB, an independent advisory committee charged with reviewing results and ensuring participant safety, found that the actual number of women having any one of these events was small and it did not cross the statistical boundary established to ensure participant safety. Therefore, the group recommended continuing the trial due to the still uncertain balance of risks and benefits.

Then, at the DSMB's regularly scheduled meeting on May 31, 2002, the data review revealed for the first time that the number of cases of invasive breast cancer in the estrogen plus progestin group had crossed the boundary established as a signal of increased risk.

"In designing the trial and following the results, the safety of the patients was of the utmost importance," said Garnet Anderson, Ph.D., a biostatistician who led the analysis at the Fred Hutchinson Cancer Research Center, Seattle, Washington. "Because breast cancer is so serious an event, we set the bar lower to monitor for it. We pre-specified that the change in cancer rates did not have to be that large to warrant stopping the trial. And the trial was stopped at the first clear indication of increased risk," she added. She also noted that, at that point, there was no indication of increased risk for breast cancer in the estrogen-only group.

The DSMB's May 31 recommendation to stop the trial was based on the finding of increased breast cancer risk, supported by the evidence of overall health risks exceeding any benefits. Following the NHLBI's decision to stop the study, the Institute and the investigators have worked intensively to develop information materials for participants. On July 8, participants started receiving letters informing them about the results and telling them that they should stop study medications. Participants will be contacted by their clinical centers for further counseling and will continue to have clinic visits so that their health outcomes can be followed...

Specific study findings for the estrogen plus progestin group compared to placebo include:* A 41 percent increase in strokes* A 29 percent increase in heart attacks* A doubling of rates of venous thromboembolism (blood clots)* A 22 percent increase in total cardiovascular disease* A 26 percent increase in breast cancer* A 37 percent reduction in cases of colorectal cancer* A one-third reduction in hip fracture rates* A 24 percent reduction in total fractures* No difference in total mortality (of all causes)"...

For full text of this press release, along with a full list of other related findings, go here.

Disclaimer: This information is not intended to diagnose, treat or cure any disease or other medical condition. This information is provided for educational and informational purposes only. Please consult with your doctor should you have specific health questions or concerns.