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Timing, Dosage of HRT Affect Chances of Heart Trouble

Large study found younger women taking it for a longer time did have higher risk

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HealthDay Reporter

WEDNESDAY, Oct. 1, 2008 (HealthDay News) -- The largest observational study of hormone replacement therapy since the landmark Women's Health Initiative finds that how and when women take hormone replacement therapy affects their heart attack risk.

Younger women had a higher risk of heart attacks, especially younger women who took hormone replacement therapy (HRT) for a long time, Danish researchers found. Certain formulations also lead to different results.

"For women with an intact uterus, cyclic combined therapy (causing menstrual bleedings) should be preferred instead of continuous combined therapy (not causing menstrual bleedings)," said Dr. Ellen Lokkegaard, lead author of the study published online Oct. 1 in the European Heart Journal. "And for women without a uterus, dermal application via gel or patch is associated with a lower risk."

"The regimen and route of administration should be considered carefully when HRT is administered," concluded Lokkegaard, who is a gynecologist at the Rigshospitalet in Copenhagen, Denmark.

A section of the U.S. government-sponsored Women's Health Initiative (WHI), which was designed to look at health issues in postmenopausal women, was halted in 2002, when U.S. researchers found that HRT led to an increased risk of adverse events that included heart attack, stroke, breast cancer and blood clots. The risk depended on whether the woman was taking estrogen alone or estrogen plus progesterone, another female hormone.

Since that time, however, a more complex picture has emerged with various factors, including amount of hormone as well as timing of use, determining the exact nature of risks and benefits.

Previous research indicated that HRT might have a negative effect on cardiovascular health in women who started therapy long after menopause, versus women taking it sooner after menopause.

Before the WHI, many women took HRT in the belief that it would reduce their risk for heart disease.

These researchers looked at almost 700,000 healthy Danish women aged 51 to 69 who were followed for six years. There was no information on whether the women were postmenopausal or not, although the authors stated that most of even the younger women participating were probably postmenopausal given the age range.

Overall, there was no increased risk of a heart attack in women who were currently using HRT compared with women who had never used HRT. There was, however, a 24 percent increased risk in younger women (aged 51 to 54) and a heightened risk in younger women taking the prescribed medications for a longer period of time.

There was no correlation between long-term use of HRT in older women and an elevated heart attack risk. Nor was there an increased risk with estrogen alone.

A combination of estrogen and progesterone administered continuously resulted in a 35 percent increased risk of heart attack compared with women who had never used HRT. But estrogen taken alone, followed by estrogen plus progesterone (a cyclical regimen) actually resulted in a reduced risk of heart attack as compared to women who had never taken HRT. The same reduced risk was also seen with the synthetic hormone tibolone.

Estrogen taken via patch (on the skin) or gel (in the vagina) reduced the risk of heart attack by 38 percent and 44 percent, respectively.

"Overall biological evidence suggests the findings are plausible," Lokkegaard said. "But the finding of significant lower risk among women using vaginal estrogen was very surprising and needs to be investigated further before clinical recommendations can be given."

The results were essentially similar to those from the Women's Health Initiative.

However, one expert added a caveat.

"We have learned from observational data in the past that it is not an appropriate scientific approach to draw conclusions about the benefits or risks of hormone therapy in women," said Dr. Lori Mosca, director of preventive cardiology at New York-Presbyterian Hospital/Columbia University Medical Center and founder and director of the Columbia Center for Heart Disease Prevention in New York City. "These data are interesting, but in no way definitive," Mosca said.

More information

The National Heart, Lung, and Blood Institute has more on the original findings of the Women's Health Initiative.

SOURCES: Ellen Lokkegaard, M.D., gynecologist, Rigshospitalet, Copenhagen, Denmark; Lori Mosca, M.D., director, preventive cardiology, New York-Presbyterian Hospital/Columbia University Medical Center, and founder and director, Columbia Center for Heart Disease Prevention, New York City; Oct. 1, 2008, European Heart Journal

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