Estrogen Fails Test As Alzheimer's Treatment

Researchers from Taiwan gave estrogen to 25 postmenopausal women with mild or moderate symptoms of Alzheimer's disease and determined that after 12 weeks, the patients scored no better on tests of attention, concentration, memory, and other mental abilities than did 25 patients who had been taking a placebo (inactive pill). Physician evaluations of the patients' disease progression also failed to find differences between the two groups.

"This is the third study this year that showed that estrogen had no effect in the treatment of postmenopausal women with Alzheimer's disease," said Karen Marder, MD, a neurologist at Columbia University in New York and co-author of an editorial accompanying the article. "All three studies were randomized, controlled clinical trials, the gold standard when examining a treatment's effectiveness."

In the Taiwanese trial, patients were assigned at random to receive either estrogen or a placebo, and neither the patient nor the physician knew whether the patient was receiving the drug.

Earlier studies had suggested that postmenopausal Alzheimer's patients might benefit from estrogen replacement therapy, but these trials either had few patients enrolled or were "open-label" studies, studies in which the patients and physicians knew when the patient was receiving estrogen.

The problem with open trials was pointed out by the present study, in which even the patients taking placebo showed mild improvement in some test scores. The authors suggest that this may simply reflect that the patients were already familiar with the tests.

These results are disappointing, but they will still not put scientists off the track of estrogen in the treatment or prevention of Alzheimer's, said both Marder and the authors of the study. There is too much evidence from basic research that shows estrogen combats destructive cellular processes that are the main suspects in the disease.

"Although we had more subjects than previous studies, 50 is probably not enough," said Hsiu-Chih Liu, MD, a neurologist at the Neurological Institute of the Taipei Veterans General Hospital in Taiwan and senior author of the study. "Moreover, it may require a longer period, such as one year, to produce a significant effect."

Liu also questions whether the standard tests of memory and other mental functions used in the study are sensitive enough to detect subtle improvements. Marder adds that estrogen still needs to be tested in conjunction with other drugs, on other dosing regimens, and with other routes of administration, such as a skin patch.

More information is also needed on whether estrogen taken before the onset of Alzheimer's can delay or prevent the disease. Several large scale studies of menopausal and postmenopausal women taking estrogen will begin to yield data in several years on whether estrogen has helped those women avoid Alzheimer's.

Estrogen is known to protect women against osteoporosis and cardiovascular disease and it may yet prove to be helpful in counteracting Alzheimer's. "In my opinion, postmenopausal women should take estrogen and progesterone unless there are contraindications or intolerable side effects," said Liu.