MIND : MENTAL HEALTH STUDYING A TIE BETWEEN ESTROGEN, ALZHEIMER'S.

Byline: Jane E. Brody The New York Times

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. The evidence, derived from experimental animals and from women after menopause taking estrogen supplements, has prompted two major studies to assess the effectiveness of estrogen replacement in currently 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 a recent international Alzheimer's conference in Osaka, Japan, 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 disease and other dementias in women who took estrogen after menopause; clinical studies that found less severe symptoms of senility in Alzheimer's 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 brain involved in Alzheimer's disease.

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