Effects of Estrogen plus Progestin on Cognitive Functioning and the Risk of Developing Dementia - Findings from the Women's Health Initiative Memory Study (WHIMS)

May 2003

Findings Summary

The purpose of the Hormone Program in the Women’s Health Initiative is to study the health benefits and risks of hormone therapy for postmenopausal women. In July 2002, women in the Estrogen Plus Progestin (E-plus-P) part of the Hormone Program were asked to stop taking their study pills because the overall risks of taking combined estrogen plus progestin - including heart attacks, stroke, blood clots, and breast cancers - outweighed the benefits of fewer fractures and colorectal cancers.
Another important question being asked about hormones and women’s health is how estrogen plus progestin or estrogen alone affects women’s cognition, including:
  • Normal cognitive function (thinking abilities like memory, attention, concentration, language, abstract reasoning, and calculation)
  • Mild cognitive impairment (a significant decline or drop in at least one cognitive ability)
  • Dementia (a significant drop in several cognitive abilities, not related to other medical problems, but clearly interfering with day-to-day activities)
The WHI Memory Study (WHIMS) is a sub-study within the WHI Hormone Program that is carefully designed to address these issues using very precise, scientific testing of women’s cognitive function over time. The data from the E-plus-P part of WHIMS have now been analyzed and appear in the May 28, 2003 issue of the Journal of the American Medical Association. The Estrogen-Alone part of the WHI Hormone Program and the WHIMS sub-study continue and results will be available when the E-Alone study is completed.
WHIMS is studying both normal cognitive function and abnormal cognitive decline (mild cognitive impairment and dementia). As described in these two papers, over 4500 E-plus-P participants between the ages of 65 and 79 years agreed to participate in WHIMS and are asked questions once a year to study their cognitive function. Some women also have more detailed testing, including meeting with a specialist who determines whether their cognitive function has declined abnormally and whether mild cognitive impairment or dementia is present.
The results from the E-plus-P part of WHIMS showed that combination estrogen plus progestin does not protect women from normal declines in cognitive function when compared with placebo. Women taking the hormone combination tested slightly worse on the yearly cognitive function questions, although the differences were small and would probably not be noticeable to anyone.
With regard to abnormal cognitive decline, women in the estrogen plus progestin group developed mild cognitive impairment at the same rate as women in the placebo group. This finding indicates that combined hormone therapy does not protect postmenopausal women from the milder type of abnormal cognitive decline.
Women taking estrogen plus progestin were at higher risk for developing dementia than those taking placebo. They were twice as likely to develop this more severe type of abnormal cognitive decline over the course of the study. While this difference is important and clearly shows that estrogen plus progestin increases the risk of developing dementia in postmenopausal women, the actual number of cases of dementia was small. Overall, 61 women in WHIMS were found to have probable dementia -- 40 were taking estrogen plus progestin and 21 were taking the placebo pill. This finding translates into 23 more cases of dementia per year for every 10,000 women 65 and older taking the combination hormone therapy.
These results from WHIMS apply only to women 65 and older who take combined estrogen plus progestin. The Estrogen-Alone part of the WHI Memory Study is continuing, and those results are not yet known.This information has been superceded by the 2004 Hormone Program Update. Furthermore, E-plus-P WHIMS participants continue to be followed, even though they have stopping taking study pills. In this way, scientists can learn more about changes in cognitive function after stopping combination hormone therapy.