Menopause Has Variable Effect on Memory Decline in Women Interview with:
Jill M. Goldstein, Ph.D.

Director of Research for the Connors Center for Women’s Health and Gender Biology
Brigham and Women’s Hospital and
Professor of Psychiatry and Medicine at Harvard Medical School What is the background for this study?

Response: Maintaining intact memory function as we age is one of the primary public health challenges of our time. In fact, women are at almost twice the risk for Alzheimer’s disease and it is not only because women live longer. Thus, it is incumbent upon us to understand this sex difference and incorporate the knowledge into the development of sex-dependent therapeutics.

Our study focused on beginning this investigation by understanding how memory circuitry and memory function change over the menopausal transition, when we believe that sex differences in memory aging emerge. By understanding healthy aging, we will better understand how the brain goes awry with age differently in men and women and who might be at highest risk for Alzheimer’s disease later in life. What are the main findings?

Response: The current study included a community sample of 200 early midlife (ages 47-55 years) pre-, peri- and postmenopausal women and aged matched men who underwent clinical and cognitive assessments and functional and structural brain imaging while performing working and encoding memory tasks. We used more challenging memory performance tasks in order to identify changes in healthy people as they aged.

There was a sex difference in memory performance with women having an advantage over men regarding all verbal memory measures. We further refined this by demonstrating that, among the women, there was an attenuation of the female advantage after menopause. However, not all women undergoing menopause perform the same. There was substantial variability in how memory performance changed over the menopausal transition, regardless of age itself, and that estradiol (the primary form of estrogen that impacts the brain) was critical in maintaining memory performance. Although all women eventually experience ovarian decline, women differ in how they maintain so-called “estrogenicity” in the brain. What should readers take away from your report?

Response: Although all women eventually experience ovarian decline, women differ in how they maintain so-called “estrogenicity” in the brain. What recommendations do you have for future research as a result of this study?

Response: We must continue to understand the factors that drive maintaining intact memory function by incorporating an understanding of sex differences in this process.

One of those factors may be hormonal adjunctive therapeutics. We need to systematically re-invigorate the study of hormonal therapeutics, including:

• what should be the mode of transport (transdermal patch, oral);
• what should be the hormonal content (i,e, type, dosage, etc);
• under what conditions should they be taken, and, if taken, for how long;
• what types of synthetic forms could be developed that may not affect other tissues in the body like the breast and uterus; and
• what other “downstream” effects do these hormones have and how could we capitalize on discovering these in order to develop other forms of therapeutics, given that hormone replacements are unsafe for some women and we know that hormones are not the only answer. Thank you for your contribution to the community.


Sex differences in episodic memory in early midlife: impact of reproductive aging.
Rentz, Dorene M. PsyD; Weiss, Blair K. BS; Jacobs, Emily G. PhD; Cherkerzian, Sara ScD; Klibanski, Anne MD; Remington, Anne MA; Aizley, Harlyn MEd; Goldstein, Jill M. PhD
November 7, 2016
doi: 10.1097/GME.0000000000000771

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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Last Updated on November 12, 2016 by Marie Benz MD FAAD