After HRT, Some Health Risks Remain

Researchers Examine Pros and Cons of Hormone Replacement Therapy

Medically Reviewed by Louise Chang, MD on March 04, 2008
From the WebMD Archives

March 4, 2008 -- For postmenopausal women who stop their hormone replacement therapy (HRT), there is good news, bad news, and surprising news from a new study that followed women for about two and a half years after they stopped the regimen.

On the plus side, some risks associated with the use of the combined estrogen and progestin therapy disappear after the regimen is stopped, including the increased risks of heart disease, stroke, and blood clots in the lungs, the researchers found. Unfortunately, the protective effects the hormones provide for hip fracture and colorectal cancer also disappear once women quit the regimen.

Even two and a half years later, former HRT users still have an increased risk of breast cancer, which was discovered in the original study, called the Women's Health Initiative (WHI). The increased risk after stopping the hormones, however, was not statistically significant. And, in a surprise finding, former HRT users also have a higher overall risk of getting cancers of many types compared to nonusers, the researchers found.

Despite the new findings, including the surprise finding about cancer, "the bottom line hasn't changed," says study researcher Gerardo Heiss, MD, professor of epidemiology in the School of Public Health at the University of North Carolina, Chapel Hill. The standard advice still applies, Heiss tells WebMD.

And that is for women to take the lowest possible dose of HRT for the shortest amount of time if they need it to quell bothersome symptoms such as hot flashes.

The study is published in the March 5 issue of The Journal of the American Medical Association.

HRT and Health Risks: Study Details

Heiss and his colleagues followed up 15,730 of the 16,608 women who participated in the original study, the WHI, designed to examine the health effects of taking estrogen plus progestin in older women. The WHI study was halted in 2002, after an average of 5.6 years of treatment, when researchers found an increased breast cancer risk among those who took the hormone therapy vs. those who took a placebo.

During the trial, they also found hormone users were at higher risk of heart disease, stroke, and blood clots than were nonusers but at lower risk of colorectal cancer and fractures.

In the new follow-up study, conducted from July 2002 to March 2005, Heiss' team looked at the effect that stopping the hormones had on six outcomes: heart disease, stroke, blood clots in the lungs (pulmonary embolism), invasive breast cancer, colorectal cancer, and hip fracture.

HRT and Health Risks: Findings

"We have some good news," says Rowan T.Chlebowski, MD, PhD, a medical oncologist at the Los Angeles Biomedical Research Institute in California and another study researcher. "The cardiovascular disease risk really ended once you stopped the hormones."

The risk for cardiovascular problems, including heart attacks, strokes, and lung blood clots, was comparable for the former users and the nonusers. While former HRT users had 343 such "events," nonusers had 323.

After the HRT was stopped, the risk of fractures was similar among former users and nonusers, indicating the protective effect of the hormones disappeared once they were stopped. The rates of colorectal cancer didn't differ in a significant way between the two groups, either, indicating the protective effects found with HRT against colorectal cancer disappeared, too.

The risk of breast cancer stayed elevated during the follow-up. "Women on HRT had a 27% increased risk" of breast cancer compared to nonusers, Chlebowski says. While 79 former HRT users developed breast cancer during the follow-up, 60 nonusers did. However, the differences are not statistically significant, Chlebowski says.

When looking at the breast cancer risk, say Heiss and Chlebowski, it may have been a bit too soon for the breast cancer risk to decline. "We do see a tendency toward the breast cancer risk going down," Heiss tells WebMD.

The other troubling cancer finding: "Women on HRT had a 24% greater risk of all [invasive types of] cancer compared to women on placebo," Heiss says. While 281 of the former HRT users developed cancer during the follow-up, 218 nonusers did. Still, Heiss says, "that is not overly alarming."

Chlebowski says the finding is "concerning" and warrants more study. Why other cancers, including lung cancer, were more common among former HRT users than nonusers is a mystery, he says.

Another Expert Weighs In

The new study does have some good news, says James Liu, MD, chairman of obstetrics and gynecology at MacDonald Women's Hospital, Case Medical Center, University Hospitals, Cleveland, who reviewed the findings for WebMD. Until 2001, Liu was one of the principal investigators for the Women's Health Initiative.

"The good news is that the effects for the vast majority of side effects appear to reverse," he says. "The breast cancer issue may take longer to resolve."

HRT and Health Risks: Advice for Former Users

Women who took HRT should pay close attention to cancer screenings such as mammograms and colorectal cancer screening, Chlebowski says.

Women who are still taking HRT should re-evaluate their need for it with their doctor periodically, Liu says. "If they are still on it, I think they need to ask the question, why are they still on it? If they are still symptomatic [with menopausal symptoms] they need to continue their breast [cancer] surveillance."

The findings apply only to the combined HRT; results of the follow-up of women who took estrogen-only are expected later.

Pharmaceutical Company Views

The hormone regimen used in the WHI study is quite different than the typical regimen prescribed these days, according to representatives speaking at a teleconference sponsored by Wyeth Pharmaceuticals, which makes the HRT used in the WHI study. The typical duration of treatment has declined, according to Wyeth, and the doses are typically lower than those used in WHI.

Currently, HRT is prescribed to women younger than those in the WHI study, according to Wyeth. The average age of WHI participants was 63 at the start of the study. The risks associated with older women are not the same as in younger women, according to Gary Stiles, MD, chief medical officer and executive vice president of Wyeth Pharmaceuticals in Philadelphia.

The study results, according to Wyeth, should be reassuring to women who use hormone therapy during the "hard" stages of menopause, when symptoms are most bothersome.

WebMD Health News



Gerardo Heiss, MD, professor of epidemiology, University of North Carolina School of Public Health, Chapel Hill.

Rowan T.Chlebowski, MD, PhD, medical oncologist, Los Angeles Biomedical Research Institute, Los Angeles.

James Liu, MD, chairman of obstetrics and gynecology, MacDonald Women's Hospital, Case Medical Center, University Hospitals, Cleveland.

Heiss, G. TheJournal of the American Medical Association, March 5, 2008: vol 299: pp1036-1045.

Gary L. Stiles, MD, executive vice president and chief medical officer, Wyeth Pharmaceuticals.

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