Estrogen Doesn’t Fight Alzheimer’s, Study Says

Estrogen is not useful in the treatment of mild to moderate Alzheimer’s disease in older women, according to a UC Irvine study, the largest and longest examination to date of a possible therapeutic role for the hormone.

The results, published today in the Journal of the American Medical Assn., run counter to previous studies that have shown some benefits to the hormone treatment. But those were of short duration and involved smaller numbers of women of varying ages.

“Several studies have suggested that estrogen helped improve the cognitive impairment of Alzheimer’s disease,” said study director Ruth Mulnard, associate director of UCI’s Institute on Brain Aging and Dementia. “But we were surprised that over the long run, patients did not benefit from estrogen.”

For one year, researchers at UCI’s College of Medicine followed 120 women over age 60, all of whom had had hysterectomies. Doctors have been prescribing estrogen specifically to benefit Alzheimer’s patients, but Mulnard said the study now suggests that this “was clinical practice preceding the scientific evidence.”

Researchers, however, drew no conclusions about whether estrogen may prevent Alzheimer’s. Nor did it study possible treatment benefits for those in the very earliest stages of the disease, the so-called onset phase. Studies in both areas are underway elsewhere, as is research on women who have an intact uterus.

Alzheimer’s is a complex disease with multiple stages, and drug therapies that are ineffective at one phase may be useful at an earlier one, experts said.

“It still may be correct that [some categories of] women taking estrogen may be at a lower risk,” said Neil Buckholtz, chief of the Dementias of Aging Branch at the National Institute on Aging. “That is why it is important to study onset stages of Alzheimer’s and healthy women to see if this is a benefit.”

The authors of the current study cautioned that their findings should not deter women with Alzheimer’s who are on estrogen replacement therapy for other reasons, such as to prevent osteoporosis or heart disease, Mulnard said.

There had been indications that estrogen offered protective benefits to neurons in laboratory cultures. Estrogen also is known to benefit several body systems--particularly the heart, bones and bladder. Some small-scale studies over the past 15 years of women with Alzheimer’s also had shown improvement in cognition over a period of eight weeks of estrogen therapy.

The UCI study showed a similar improvement in one indicator of mental acuity at two months, but determined that the benefits were not long-term.

The subjects taking the estrogen showed short-term improvement in their ability to perform certain cognitive skills on the mental skills exam. The test assesses skills such as the ability to copy a simple drawing and spell the word “world” backward. But the subjects showed no improvement in mood, memory, motor skills or other measurements.

Mulnard and other researchers emphasized that the findings are limited and more study is needed into its possible benefit in reducing risk for healthy patients or slowing the disease’s progress for those in the earliest stage.

The research was praised for its thoroughness in an accompanying JAMA editorial by Drs. Sally and Bennett Shaywitz of the Yale University School of Medicine.

“The study gives a very clear answer: Estrogen doesn’t work in Alzheimer’s disease once you already have it,” said Dr. Bennett Shaywitz. “It answers a very specific question and answers it very clearly. But it is a narrow question.”

He and others said there had been great hope, based on earlier indicators, that the results would demonstrate efficacy.

“It is real surprising, and almost all the investigators thought it would be effective,” said the NIA’s Buckholtz.