Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Viewpoint
  • Published:

The timing of estrogen therapy after ovariectomy—implications for neurocognitive function

Nature Clinical Practice Endocrinology & Metabolism volume 4, pages 494–495 (2008)Cite this article

Removal of the ovaries and uterus before the natural onset of menopause results in acute declines in the circulating levels of the ovarian steroid hormones, estrogen and progesterone, as well as reduced testosterone levels. The effect of surgical menopause on cognitive function has been a topic of great clinical interest since 1988, when Barbara Sherwin published a randomized clinical trial demonstrating that women (mean age ∼45 years) who underwent surgical menopause experienced a decline in verbal memory from a premenopausal, presurgery baseline to a postsurgery follow-up 3 months later.1 Of particular interest, there was statistically significant cognitive benefit from treatment with 10 mg intramuscular estradiol valerate per month and/or an androgen immediately after surgery when compared with placebo.1

This early report remains arguably the most influential finding to date on the role of ovarian steroids in cognitive function. Women have an advantage over men in their ability to recall words, stories, and other types of verbal information from standardized memory tests. Sherwin and others have suggested that verbal memory could be particularly sensitive to abrupt changes in the levels of ovarian steroid hormones. This line of thinking raises an interesting question—do high circulating estrogen levels confer an advantage in verbal memory ability, and if so, should we treat women undergoing surgical menopause with estrogen to maintain cognitive function?

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Sherwin BB (1988) Estrogen and/or androgen replacement therapy and cognitive functioning in surgically menopausal women. Psychoneuroendocrinology 13: 345–357

    Article  CAS  Google Scholar 

  2. Shumaker SA et al. (2004) Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women's Health Initiative Memory Study. JAMA 291: 2947–2958

    Article  CAS  Google Scholar 

  3. Espeland MA et al. (2004) Conjugated equine estrogens and global cognitive function in postmenopausal women: Women's Health Initiative Memory Study. JAMA 291: 2959–2968

    Article  CAS  Google Scholar 

  4. Resnick SM et al. (2006) Effects of combination estrogen plus progestin hormone treatment on cognition and affect. J Clin Endocrinol Metab 91: 1802–1810

    Article  CAS  Google Scholar 

  5. Gibbs RB and Gabor R (2003) Estrogen and cognition: applying preclinical findings to clinical perspectives. J Neurosci Res 74: 637–643

    Article  CAS  Google Scholar 

  6. Dumas J et al. (2008) Estradiol interacts with the cholinergic system to affect verbal memory in postmenopausal women: evidence for the critical period hypothesis. Horm Behav 53: 159–169

    Article  CAS  Google Scholar 

  7. Maki PM (2006) Hormone therapy and cognitive function: is there a critical period for benefit? Neuroscience 138: 1027–1030

    Article  CAS  Google Scholar 

  8. Henderson VW and Sherwin BB (2007) Surgical versus natural menopause: cognitive issues. Menopause 14: 572–579

    Article  Google Scholar 

  9. Rocca WA et al. (2007) Increased risk of cognitive impairment or dementia in women who underwent oophorectomy before menopause. Neurology 69: 1074–1083

    Article  CAS  Google Scholar 

  10. Simon J et al. (2005) Testosterone patch increases sexual activity and desire in surgically menopausal women with hypoactive sexual desire disorder. J Clin Endocrinol Metab 90: 5226–5233

    Article  CAS  Google Scholar 

Download references

Author information

Author notes

  1. Center for Cognitive Medicine, University of Illinois at Chicago, 912 South Wood Street, Chicago, IL 60612, USA pmaki@psych.uic.edu

Authors and Affiliations

  1. PM Maki is an Associate Professor of Psychiatry and Psychology in the Center for Cognitive Medicine, University of Illinois at Chicago, IL, USA.,

    Pauline M Maki

Authors
  1. Pauline M Maki
    View author publications

    You can also search for this author in PubMed Google Scholar

Ethics declarations

Competing interests

Pauline M Maki has received consulting fees, research funding, and speaking honoraria from Wyeth Pharmaceuticals.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Maki, P. The timing of estrogen therapy after ovariectomy—implications for neurocognitive function. Nat Rev Endocrinol 4, 494–495 (2008). https://doi.org/10.1038/ncpendmet0901

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncpendmet0901

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing