Since the Women's Health Initiative study found that long-term therapy with estrogen or estrogen plus progestin may increase the risk of heart attack and stroke, many women have found it difficult to decide whether to take hormone therapy at menopause.

Subsequently, several researchers have speculated that the timing of estrogen treatment may be important for estrogen's effects.

A group of authors therefore designed an animal study to determine if estrogen would be beneficial for females who are going through menopause (perimenopausal) but not for women who are postmenopausal for many years. Since it is not possible to measure "risk" in animal studies, the authors measured severity of stroke injury.

The results were presented Sunday, June 15, at The Endocrine Society's 90th Annual Meeting in San Francisco.

"This study suggests that estrogen treatment is not toxic per se but that its effects on the brain depend on the individual's reproductive age when therapy begins," said one of the study's authors, Farida Sohrabji, PhD, of Texas A & M Health Science Center.

In their study in rats, Amutha Selvamani, a post-doctoral associate and Dr. Sohrabji, found "that estrogen treatment is not beneficial to the brain once the animal is in an acylic state, but is effective when given earlier. This acyclic stage in animals shares similarities with the menopausal stage in women."

Therefore, they compared groups of female rats: mature adults and older, "acyclic" rats that no longer had reproductive cycles. The physiologic status of the older rats resembled that of a postmenopausal woman, and the other rats' status would be more similar to perimenopause, according to Sohrabji. After surgically removing the ovaries of all the rats, the researchers gave them estrogen replacement therapy (estradiol) for 3 weeks. Then they induced a stroke in all the animals. A week later, the rats' brains were studied for tissue damage.

The stroke caused much more tissue damage in the acyclic older females, the authors reported. "Estrogen treatment to this group actually increased the volume of the brain that was damaged," Sohrabji said.

In the mature adult rats, however, estrogen therapy apparently reduced the area of brain damage. After the stroke all rats showed evidence of sensory and motor damage on behavioral testing, but it was more severe in the acyclic rats.

"This study supports the idea that there is a narrow window of time as a woman approaches menopause and immediately afterward where estrogen therapy may provide neuroprotective benefits," Sohrabji said.

The National Institute on Aging funded this study.

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