Mouse study suggests that with HRT, timing counts

WASHINGTON (Reuters) - An estrogen study in mice suggests that hormone replacement therapy may benefit women if started right at the time of menopause, researchers reported on Monday.

While the researchers stress that more studies need to be done in women, they said their findings offer hope to women who want to safely relieve the symptoms of menopause.

"When you treat animals immediately with estradiol (a form of estrogen) therapy, it protects the brain against injury due to stroke and this correlates with an ability of estradiol to suppress the inflammatory response. It is a very potent anti-inflammatory agent," said Dr. Phyllis Wise of the University of Washington in Seattle, who led the study.

For their study, published in the Proceedings of the National Academy of Sciences, Wise and colleagues first tried to make a mouse "model" of human menopause by taking out the ovaries of female mice.

"Then we replaced it with estrogen therapy that mimics the dose of human estradiol in the blood," Wise said in a telephone interview.

Estradiol is the form of estrogen involved in the human reproductive cycle.

A big study called the Women's Health Initiative found in 2002 that hormone replacement therapy raised the risk of blood clots, heart attacks and breast cancer.

Women stopped taking HRT in droves. But controversy arose immediately, because the women in the study were years past menopause, with an average age of 63, and they took just one brand of HRT that was made using estrogen taken from horses.

Experts wondered if the results would be different among women who began using HRT as soon as they entered menopause, and using formulations of estrogen that more closely resembled human estrogen.

Studies are ongoing among women who still choose to take HRT, but researchers such as Wise want to break down the actual biological mechanisms involved.

STOPPING INFLAMMATION

Estrogen reduces inflammation, which is involved in heart disease, cancer, Alzheimer's disease and other conditions.

Wise's team caused menopause in mice, and gave half of them estradiol right away and some got estradiol later. Then they induced strokes in both groups of mice.

The mice given estradiol right away had much less stroke damage than mice given estradiol 10 weeks later -- the equivalent of 5 to 10 years in a human.

Wise believes that menopause changes cells, so that they can no longer use estrogen in the same way that cells in younger women can. This in turn explains why young women have lower rates of stroke and heart attack than men or older women.

The changes occur in receptors -- molecular locks and keys that allow various compounds to act on cells. In a young woman with normal estrogen levels, and in normal mice, a receptor called estrogen receptor alpha becomes very active, or "upregulated."

"If you wait for 10 weeks (in a mouse), the estrogen receptor is not upregulated and therefore the key mediator of estrogen's ability to influence the inflammatory state is not there," Wise said.

"The lock isn't there. Even if you give back the estrogen, the key can't open the door because the lock isn't there any more."

Wise notes that mice do not age in the same way as human women. But she hopes her study sheds some light on how menopause affects a woman's tendency to heart disease and stroke and how HRT might help prevent some of these effects.