Menopause: Effects of Sex Hormones on Cognition and Mood

Dr. Victor W. Henderson MD Professor of Health Research and Policy and of Neurology and Neurological Sciences Stanford University, Stanford, CA Interview with:
Dr. Victor W. Henderson MD
Professor of Health Research and Policy and of Neurology and Neurological Sciences
Stanford University, Stanford, CA 94305 What are the main findings of the study?

Dr. Henderson: Estrogen or hormone therapy effects on some health outcomes differ by age, harmful at one age and beneficial at another.

This difference is sometimes referred to as the “critical window” or “timing” theory. It is controversial whether the so-called critical-window applies to memory or other cognitive skills.

In assessing the critical window hypothesis, we found that the relation between blood levels of estrogen and memory or reasoning skills is the same in younger postmenopausal women as in older postmenopausal women.  Essentially, there is no association at either age. Were any of the findings unexpected?

Dr. Henderson: Our findings for estradiol were different from what we had predicted from the critical window hypothesis, and from other studies that suggest there should be a relation between blood levels of estradiol and memory. What should clinicians and patients take away from your report?

Dr. Henderson: Our research did not look directly at effects of hormone therapy, but the findings seem to imply that there is no reason for younger postmenopausal women to rush into hormone therapy with the goal of improving memory or enhancing reasoning abilities. Conversely, the these results imply there is no reason to avoid hormone therapy solely because of concerns about impairing memory or reasoning.

Clearer answers will be available when results of two large, recently completed hormone therapy trials are analyzed and published.  One of these, the KEEPS trial, looked only at younger postmenopausal women.  The other, the ELITE trial, compared effects of hormone therapy in younger and older postmenopausal women.  KEEPS data have been analyzed but not yet published.  ELITE data are in the process of being analyzed. What recommendations do you have for future research as a result of this study?

Dr. Henderson: The most important recommendation is to see what KEEPS and ELITE trials reveal about hormone therapy effects in younger postmenopausal women.

Also, in younger postmenopausal women, our analyses suggested a positive relation between blood levels of progesterone, a different sex steroid hormone, and memory and global cognition.  However, we did not predict the progesterone association ahead of time, so I am a bit more concerned that this might still be a chance finding. Very few human studies have considered progesterone effects on cognition in this age group.  I think results should first be replicated before perhaps moving on to consider potential clinical implications.


Victor W. Henderson, Jan A. St. John, Howard N. Hodis, Carol A. McCleary, Frank Z. Stanczyk, Roksana Karim, Donna Shoupe, Naoko Kono, Laurie Dustin, Hooman Allayee, and Wendy J. Mack

Cognition, mood, and physiological concentrations of sex hormones in the early and late postmenopause PNAS 2013 ; published ahead of print November 25, 2013, doi:10.1073/pnas.1312353110

Last Updated on March 19, 2014 by Marie Benz MD FAAD