HRT Dosing May Determine Risks, Benefits

Rodent study finds higher levels of estrogen replacement proved more dangerous

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HRT Dosing May Determine Risks, Benefits

HealthDay Reporter

MONDAY, April 7, 2008 (HealthDay News) -- In the continuing search to uncover the benefits and risks of hormone therapy for women, a new study suggests that the amount of hormone a woman takes may determine whether it helps or harms her.

The study, done with mice, found that lower doses of estrogen were safer, while moderate and high doses increased the risk of kidney and heart problems.

And although the findings were in rodents, they may provide a glimmer of insight for humans as well.

"It brings to our attention the fact that HRT [hormone replacement therapy] is not something we totally have to dismiss," said Dr. Suzanne Steinbaum, director of Women and Heart Disease at Lenox Hill Hospital in New York City. "There might be a way to give this more safely to women."

The findings were expected to be presented April 7 at the American Physiological Society annual meeting, part of the Experimental Biology 2008 scientific conference, in San Diego. The study was conducted by researchers at the Hypertension and Vascular Research Division of Henry Ford Hospital in Detroit.

A section of the original 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 hormone therapy 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 progestin, another female hormone.

At the time the trial started, older women at high risk of cardiovascular disease or who already had a diagnosis were commonly taking hormone therapy to reduce their future risk.

Since the halting of the WHI, however, it has become increasingly clear that hormone therapy has different benefits and risks, depending on several different factors.

"Now we're finding nuances and intricacies," Steinbaum said.

The new study was designed to look at the effect of different doses of estrogen. Mice that had had their ovaries removed (and therefore could no longer produce estrogen) were given replacement estrogen for 60 days in one of four doses: very low (0.001 micrograms per day), low (0.42 micrograms), moderate (4.2 micrograms), or high (28.3 micrograms).

According to Rajat Sethi, assistant professor of pharmaceutical sciences at the Texas A&M Health Science Center Irma Lerma Rangel College of Pharmacy in Kingsville, these doses seem to be in a range comparable to those that women would be taking.

Both the moderate and the high doses resulted in a 4.5-fold increase in blood estrogen levels in the mice. This, in turn, was linked with fluid retention in the uterus, protein in the urine and dilated kidneys. These doses also increased atrial natriuretic peptide (ANP), a hormone that is a marker of severity of heart failure.

Low doses of estrogen, on the other hand, put blood estrogen levels back to those seen in control rodents -- those not receiving replacement estrogen. The low-dose mice didn't experience fluid retention, kidney damage or changes in ANP levels.

Sethi said it makes sense that different dosages may result in different outcomes. "That's why I think it's very important when women talk to their doctors that they ask, 'Is the time right?' And I think the amount of medication you take should be kept to a minimum."

Previous studies have shown less cardiovascular risk in women under 60 who take HRT.

Doctors now typically recommend that women looking to hormone replacement therapy to counter menopausal symptoms take the lowest possible dose for the shortest amount of time.

More information

Visit the U.S. National Heart, Lung, and Blood Institute for more on hormone therapy and the Women's Health Initiative.

SOURCES: Suzanne Steinbaum, D.O., director, Women and Heart Disease, Lenox Hill Hospital, New York City; Rajat Sethi, Ph.D., assistant professor of pharmaceutical sciences at the Texas A&M Health Science Center Irma Lerma Rangel College of Pharmacy, Kingsville; April 7, 2008, presentation, American Physiological Society annual meeting, part of the Experimental Biology 2008 scientific conference, San Diego

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