Two women walking in park

Taking the hormones estrogen and progestin does not protect memory and increases the risk for developing dementia in older, post-menopausal women according to the Women's Health Initiative Memory Study published in the May 28 issue of the Journal of the American Medical Association.

The results are the latest evidence that hormone therapy is no magic pill. As with the Women's Health Initiative's (WHI) Estrogen and Progestin study and the subsequent Quality of Life study, the results surprised menopausal women and the study investigators alike.

"We used to think that hormone therapy was helpful in improving memory, but from the data, we see that it has an adverse effect on cognitive function," said Jennifer Hays, Ph.D., an associate professor of medicine and director of the Center for Women's Health at Baylor College of Medicine. "This proves conclusively that women shouldn't start taking combination hormone therapy in their 60s."

Hormone study makes history

The Women's Health Initiative Estrogen and Progestin study was halted in May of 2002 for increased risk of breast cancer. The study also showed that combination hormone therapy increased risk of heart attack, stroke and blood clots. Hays was principal investigator of the WHI's Quality of Life study published in March of this year. That study added to the controversy over hormone therapy when it found that hormone therapy had no significant effects on perceived general health, vitality, social functioning, mental health, depression, cognitive functioning or sexual satisfaction.

What is dementia?

  • Dementia is a progressive loss of intellectual functions such as thinking, remembering and reasoning. The symptoms of dementia eventually become so severe that they interfere with everyday life. The most well known type of dementia is Alzheimer's disease, which affects 10 percent of people 65 years old, and nearly 50 percent of people age 85 and older. An estimated four million Americans have Alzheimer's.
  • Strokes and vascular disorders can also cause dementia. Other causes include brain injury, Parkinson's disease, hydrocephalus, Pick's disease, Lewy body disease, Creutzfeldt-Jakob disease, Huntington's disease and depression.
  • Scientists are still not certain what causes Alzheimer's disease, but believe the malfunction and death of nerve cells contributes to the progression of the disease. Studies on the disease focus on biochemical processes and pathways in nerve cells, effects of inflammation and the influence of genes.

The WHI Memory Study, led by Sally Shumaker, Ph.D. at Wakeforest University, went further. It sought to determine whether taking combination hormones would prevent dementia or slow the decline of cognitive function in postmenopausal women. Hays was a co-author on WHI's paper on cognitive function.

Investigators at 39 WHI sites, including Baylor, studied a subset of 4,532 women over the age of 65 enrolled in the Women's Health Initiative Estrogen Plus Progestin study. Women between the ages of 50 and 64 were not included in the memory study, since women over the age of 65 are most at risk for dementia and cognitive decline. Participants took written and verbal tests to assess their cognitive abilities and were later examined by a clinician for signs of cognitive impairment. Investigators referred participants with possible dementia for a brain computerized tomography and laboratory blood tests. The results were sent to a board of WHI specialists to confirm the diagnosis.

A matter of memory

Of the 4,532 women in the trial, 61 participants were diagnosed with dementia. Of those with a dementia diagnosis, 66 percent or 40 participants in the estrogen plus progestin group were diagnosed with possible dementia, compared to 34 percent or 21 patients in the placebo group.

"We gave participants an exam that contained some simple questions that tested their cognitive ability," Hays said. ""Kinds of questions like, 'Who is the president,' that if you missed them, you would be embarrassed and not miss it again the next time you took it. A learning effect would usually occur in most people.

"We saw a learning improvement in the women on the placebo. We didn't see any improvement in the women on combination hormone therapy. We also saw more women below the cutting off point for dementia, where we referred them for further neuropsychiatric testing," Hays continued.

Hormone therapy and Alzheimer's

A woman

Researchers have also studied hormone therapy as a treatment for the disease. Past studies of women taking hormone therapy showed that it helped improve memory and protect against dementia. The theory was that estrogen helped reduce the loss of neurons in the brain and reduce cholesterol in the blood vessels in the brain, which improved blood flow.

But other studies, including a multi-center trial conducted at Baylor published in 2000 in JAMA, did not yield the same results.

"We found that estrogen did not slow the progression of Alzheimer's or improve mental function in women with mild to moderate Alzheimer's," said Rachelle Doody, M.D., Ph.D., director of the Alzheimer's Disease Research Center and an associate professor of neurology at Baylor.

Putting it in perspective

Both Doody and Hays stress the need for further study of the effect of hormone therapy on younger women.

"We don't know from this study whether there still could be a beneficial effect of hormone therapy in women that took it earlier in life or for shorter periods," Doody said.

The study does not apply to younger women who are taking short-term combination hormone therapy to ease the symptoms of perimenopause, or for women with severe symptoms of menopause, since they were not included in the study group.

"The results do not alter the WHI's recommendations on hormone use," Hays said. "Hormone therapy should only be used to treat the symptoms of menopause, not for long-term prevention of other health conditions."