Hormone could halt senility Health: Possibility that estrogen may help prevent or delay Alzheimer's disease catches eyes of researchers.

August 20, 1996|By Jane E. Brody | Jane E. Brody,NEW YORK TIMES NEWS SERVICE

As the number of patients with Alzheimer's disease continues to climb, researchers are studying the possibility that a common and already approved drug estrogen may help to prevent or delay it, and even reverse some of its symptoms.

Though far from conclusive, the evidence so far is highly suggestive.

Just last week, researchers at Columbia-Presbyterian Medical Center in New York City announced that in a study of 1,124 elderly women, only 5.8 percent of women who had taken estrogen developed Alzheimer's, compared with 16.3 percent of women who had not used the hormone.

With each passing year of the five-year study, only 2.7 percent of the women who had used estrogen developed Alzheimer's, as against 8.4 percent of those who had not used it.

Moreover, the longer the women took estrogen, the lower their risk.

The evidence has prompted two major studies to assess the effectiveness of estrogen replacement in healthy older women and in those in the early stages of the disease.

Although no comparable studies are planned for men, who are less likely than women to develop Alzheimer's disease, there are hints that older men may benefit from supplements of testosterone, which is converted to estrogen in the brain.

Dr. Stanley Birge, a geriatrician at the Washington University School of Medicine in St. Louis, called the estrogen work "terribly exciting, the most promising thing that's happened so far in Alzheimer's disease," the most common form of dementia.

If the early findings are supported by the new clinical trials, he said, "estrogen has the potential to prevent two-thirds of Alzheimer's cases."

At an international Alzheimer's conference in Osaka, Japan, last month, Dr. Sally Schumacher described the first large-scale study of whether estrogen can prevent or delay dementia, using the products Premarin or Prempro, the hormone-replacement therapy already being taken by millions of postmenopausal women.

Premarin, a mixture of about 10 different estrogenic hormones, gets its name from pregnant mare's urine, from which it is derived. Prempro is a combination of Premarin and a progesterone, used to prevent Premarin from overstimulating and causing cancer in the uterus.

Schumacher, a psychologist at Bowman Gray School of Medicine in Winston-Salem, N.C., who is directing the prevention study in healthy older women, said "most people in the field are quite excited" about estrogen's role in Alzheimer's.

But she cautioned against jumping to premature conclusions. She said many questions remained to be answered, including whether Premarin's promise would hold up in the trial against a dummy drug, whether its benefits would outweigh its risks and whether progesterone in the combined pill might negate estrogen's effects on the brain.

Other questions to be resolved include estrogen's precise mode of action in the brain and, if it is proved effective, at what age to start therapy. Schumacher pointed out that while the symptoms of Alzheimer's disease usually did not become apparent until the late 60s or 70s, the disease process in the brain often started before menopause.

In the Journal of the American Geriatrics Society in July, Birge summarized the diverse findings that support a role for estrogen as a preventive and treatment for dementia.

These include population studies that show a reduced incidence of Alzheimer's and other dementias in women who took estrogen after menopause; clinical studies that found less severe symptoms of senility in Alzheimer patients who happened to be on hormone replacement, and studies in laboratory animals demonstrating estrogen's ability to stimulate nerve-cell growth and branching in the critical regions of the brains involved in Alzheimer's.

Estrogen also improves circulation in the brain, which can foster continuing health of brain neurons.

Perhaps most intriguing is growing evidence that specific subcomponents of Premarin may have a more potent effect on brain neurons than the drug itself but would be free of the potential risks to the uterus and breast associated with the combination of estrogens in Premarin.

Birge, who directs the university's Older Adult Health Center, said he was most excited by the prospect of developing a custom-designed estrogenic molecule that stimulated growth of brain neurons but not cells in the uterus and breast, which can raise the risk of cancer in these organs.

These unwanted effects are associated with the estrogens naturally produced by women before menopause as well as with Premarin, the most widely used estrogen replacement in postmenopausal women.

Dr. Roberta Brinton, a molecular pharmacologist at the University of Southern California in Los Angeles, reported at the Osaka meeting that one of the hormones found in Premarin, equilin, was even more effective than estrogen in stimulating nerve-cell growth and branching in the brain. The greater the number of connections between brain cells, the better this organ can process information.

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