Estrogen-only study halted: Hormone therapy promise deflates to symptom control

The most recent round of findings regarding the effectiveness and risks of hormone therapy -- this time estrogen only -- appears to put the idea of HT's powers of prevention down for the count.

"There's no preventive role for hormones of any type, and we really should limit their use as much as we can," said Monisha Seth, MD, an internist and director of women's services at Florida Hospital in Orlando.

The knockout punch came earlier this month when the National Institutes of Health announced that letters had been sent to the more than 11,000 study participants in the estrogen-only arm of the Women's Health Initiative, advising them to stop taking their pills. Data gathered from an average of seven years of follow-up indicated that this formulation did not prevent heart disease but did increase the risk of stroke.

"We have stopped the study in the interest of patient safety," said Barbara Alving, MD, director of the WHI, a 15-year examination of interventions to prevent cardiovascular disease, osteoporosis and cancer involving more than 160,000 healthy, postmenopausal women. "The NIH advises women to continue to follow the [Food and Drug Administration] guidance regarding hormone therapy and use it at the lowest doses for the shortest period of time."

Halting this WHI arm marked the end of an era. Specifically, it piled on more information dispelling earlier beliefs that HT should be taken almost as readily as vitamins. HT is now only recommended for limited use for very specific indications.

"Estrogen-plus-progestin and estrogen-alone therapy remain important and effective therapies for relief of menopausal symptoms," said Victoria Kusiak, MD, vice president of clinical affairs at Wyeth Pharmaceuticals, the company that manufactured the hormones used by the WHI. "[These drugs] need to be prescribed on an individual basis appropriately and with clearly defined treatment goals."

Various formulations have been used for decades, usually for the alleviation of symptoms such as hot flashes. But patients generally stayed on the regimen for years because of the notion HT was good for women's overall wellness.

This concept was turned on its ear with the July 2002 WHI announcement ending the estrogen-plus-progestin arm of the study. It found a significant populationwide increase in risks for developing breast cancer and cardiovascular disease. Women pitched their pills and placed panicked calls to their physicians.

This time around, the response has been calmer. The decision to use HT had already shifted from a simple, almost automatic prescription to one that involved significant time and discussion between physicians and their women patients. Now, nearly every appointment with a patient who is on any hormones includes a conversation about whether to continue.

"The decision needs to be very individualized," said Mitchell Miller, MD, a family physician in Virginia Beach, Va. "Some women are willing to accept some risk, especially if the symptoms are affecting their quality of life, but others aren't."

Meanwhile, although nearly everyone has adopted the mantra that hormones are good but only at the lowest dose possible for the shortest amount of time, physicians are left with many unanswered questions.

The definition of "short-term" remains particularly elusive, and there is also the question of how to stop. Many women want off hormones, and some have done well quitting cold turkey. But there are few good protocols to help those who have trouble.

"The myth is that women get over their menopausal symptoms while they're on the estrogen," said Ann Honebrink, MD, clinical assistant professor of obstetrics and gynecology at the University of Pennsylvania in Philadelphia. "We know real well now that for most women those symptoms come back when they go off the estrogen. We've spent the last three years trying to figure out how to get women off with the least amount of aggravation to them."

For those who decide to continue to take HT, there is the question of how to manage risks. Physicians also have to navigate alternatives to hormones, including both prescription medications and natural supplements, for which there is even less data.

"There isn't any other medication that has this level of study of long-term risks and benefits," said Dr. Honebrink. "We're saying don't take this medicine that we know a lot about and we're putting people on drugs that we really don't know a lot about long-term risks and benefits."

For many experts, however, the WHI's true take-home message is one about how to make decisions regarding what to recommend based on what kind of data. HT was used by millions of women primarily based on observational data. For most physicians, this method will no longer be enough of a foundation for such widescale recommendations.

"This is a wake-up call for those who have questioned the importance of evidence-based medicine," said Michael Fleming, MD, a family physician based in Shreveport, La., and president of the American Academy of Family Physicians. "For years and years, we went with experiential data saying that this was preventive and what women needed and now we know it wasn't so."

Final data from the estrogen-only arm will be published in April, and the FDA is considering how the drug labeling needs to be changed. Meanwhile, arms of the WHI examining dietary modifications and vitamin D supplementation will continue.