Frequently Asked Questions about Estrogen Plus Progestin and Cognitive Function

Based on findings from the Women’s Health Initiative Memory Study (WHIMS)

May 2003
  1. What is WHIMS?
  2. What is cognitive function?
  3. What is dementia?
  4. What were the main findings about estrogen plus progestin and cognition?
  5. What is the increased risk for women taking estrogen plus progestin?
  6. What are the conclusions from these findings?
  7. What type of hormone treatment did women in the Estrogen plus Progestin study take?
  8. Is there an increased risk of dementia in women taking estrogen alone (without progestin)?
  9. Should I discuss this new information with my health care provider?
  10. I am taking prescription hormones. What should I do?
  11. What if I am under age 65?
1. What is WHIMS?
Answer: WHIMS is a sub-study within the Women’s Health Initiative (WHI). In the past, some studies reported a positive association between use of hormone therapy and cognitive protection, while others failed to find protective effects. Because of these inconsistent results, a large, controlled randomized clinical trial of hormone treatment was needed. Only women who joined the Hormone Program and were 65 years of age and older when they joined, were invited to participate in WHIMS. The purpose of WHIMS was to find out if taking hormones (estrogen alone or estrogen plus progestin) would prevent dementia or slow the decline of cognitive function in postmenopausal women.
2. What is cognitive function?
Answer: Cognitive function includes brain related abilities like attention, concentration, memory, language, abstract reasoning and calculation.
3. What is dementia?
Answer: When cognitive function declines to the point that it interferes a great deal with day-to-day activities, and other medical conditions have been ruled out, a diagnosis of dementia might be given. Different brain diseases can cause dementia. The most well known is Alzheimer’s disease. Other diseases that block the normal flow of blood in the brain can also cause dementia. What causes these diseases and how they progress is not well understood at this time. However, much research is being done to find treatments that can decrease the effects of these diseases on everyday functioning.
4. What were the main findings about estrogen plus progestin and cognition?
Answer: For women age 65 and older who took active estrogen plus progestin pills:
  • More developed dementia compared to women taking placebo (inactive) pills.
  • They had worse scores, on average, on screening tests for dementia compared to women taking placebo.
5. What is the increased risk for women taking estrogen plus progestin?
Answer: A woman is more likely to develop dementia if she is taking estrogen plus progestin. However, the number of women who actually do develop dementia is relatively modest--45 out of 10,000 women taking estrogen plus progestin each year, compared to 22 out of 10,000 women taking placebo each year. While this difference in rates is important, the overall risk remains small.
6. What are the conclusions from these findings?
Answer: Overall, in women age 65 and older, estrogen plus progestin treatment is harmful to cognitive function. For some women, their decline in cognitive function will be so serious that they will be diagnosed as having dementia. Therefore, we recommend that health care providers should not prescribe estrogen plus progestin to enhance or improve cognitive function in postmenopausal women who do not have dementia.
If you are age 65 or older and are having severe menopausal symptoms, you should talk with your health care provider. Your provider can recommend an appropriate treatment based on your personal risk for breast cancer, cardiovascular disease and dementia.
7. What type of hormone treatment did women in the Estrogen plus Progestin study take?
Answer: Women who were randomized to receive active hormones in this study were taking conjugated equine estrogens 0.625 mg each day and medroxyprogesterone acetate 2.5 mg each day (PremPro™). When WHI first began, this was the most commonly prescribed hormonal therapy in the United States for postmenopausal women with a uterus.
8. Is there an increased risk of dementia in women taking estrogen alone (without progestin)?
Answer: WHIMS includes a study of Estrogen-Alone (without progestin) for women who did not have a uterus before they joined WHI. Final results from the Estrogen-Alone study remain uncertain. Participants in the Estrogen-Alone study are asked to continue to take their study pills and to come in for their regular clinical visits. The National Heart, Lung, and Blood Institute, which oversees the WHI, continues to review the study of women receiving estrogen alone and will provide investigators and participants with any new information about the study that might affect their participation.
This information has been superceded by the 2004 Hormone Program Update.
9. Should I discuss this new information with my health care provider?
Answer: Yes. Your WHI clinic has a letter that you may take to your health care provider. Your provider may also want to read the WHIMS scientific paper in the May 28, 2003 Journal of the American Medical Association. Your health care provider may also want to speak with your local WHIMS Principal Investigator about the results.
10. I am taking prescription hormones. What should I do?
Answer: Talk with your health care provider about your individual health risk profile and the hormones you are currently taking.
11. What if I am under age 65?
Answer: Currently, it is not known if the WHIMS findings about cognitive function in women who take estrogen plus progestin apply to women younger than 65 years of age. This question may be answered by future research studies on hormone therapy in younger women.