Oestrogen and cognition in the perimenopause and menopause

Key Points

  • Women commonly report memory or cognition changes associated with the menopause transition and menopause. Women may refer to this as ‘brain fade’ or ‘brain fog’.
  • However, the contributing roles of menopause related to oestrogen decline, aging, effect of co-morbidities, psycho-social functioning and menopauserelated symptoms such as insomnia and hot flushes need clarification.
  • Cognitive changes associated with the menopause transition include reduced processing speed and reduced verbal memory. Verbal memory is defined as the ability to encode words and it is influenced by circulating oestradiol.
  • MHT has positive or neutral effects of cognitive function in younger peri- or postmenopausal women. The age of the woman, MHT preparation and baseline cognitive function influence this effect.
  • Cognitive testing is not indicated unless the symptoms are progressive and interfere with work performance or relationships.

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Memory loss in the menopause

Memory loss associated with menopause comprises poor recollection of recent events (recent recall) or of a while ago (delayed recall). This may manifest as:

These are not related to normal cerebral functioning such as learning, deduction and reasoning.

The incidence of memory problems in the menopause transition is reported by up to two thirds of women. It is thought these are transient and do not become chronic postmenopausal issues. There is no evidence that these functional deficits are indicative of dementia or precede neurodegenerative disease1.

Memory problems associated with menopause are multifactorial. The process of menopause transition takes 5-8 years with symptoms described consistently in observation studies (Study of Woman Across the Nation (SWAN) 2. 50-80 % of women experience vasomotor symptoms (hot flushes, night sweats). Hot flushes are associated with hyperintensities on brain imaging and changes in brain function on fMRI. Cognitive symptoms are associated with depression which may also be increased during the perimenopause. Observational studies indicate an increased risk of memory deficits and Alzheimer’s disease associated with premature surgical oophorectomy.

Effects of oestrogen on the brain

There are three common physiological oestrogens (oestradiol, oestrone and oestriol) of which oestradiol (E2) is seen to decline rapidly over the menopausal transition. This decline in E2 has been associated with a number of changes in the brain including cognitive changes, effects on sleep and effects on mood (see AMS Information Sheet: Sleep disturbance and the menopause). The role of oestrogen in cognition is indicated by:

Effect of oestrogen therapy

Studies indicate mixed effects regarding oestrogen therapy and cognitive function with the hypothesis of a “window of opportunity” postulating that younger age or fewer years since menopause may be associated with positive effects of oestrogen whereas commencement of oestrogen therapy in later years is associated with an increased risk of dementia. The evidence suggests increased harm when oestrogen is given to women with poor baseline cognitive function. The evidence is summarised below:

Effect of other therapeutics

Advice to women

Further Information



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2. Kravitz HM, Janssen I, Bromberger JT, et al Sleep Trajectories before and after the final menstrual period in the study of women’s health across the nation (SWAN) Curr sleep Med Reports 2017; 235-250.

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16. Resnick, S.M., Maki, P.M., Rapp, S.R., et al. Effects of combination estrogen plus progestin hormone treatment on cognition and affect. J Clin Endocrinology Metab 2006, 91:1802- 10

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22. Henderson, VW, St. John, JA, Hodis, HN.,et al. Cognitive effects of estradiol after menopause. Neurology. 2016 Aug 16; 87(7): 699–708.

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24. Georgakis MK, Beskou-Kontou TB, Theodoridis, I. et al. Surgical menopause in association with cognitive function and risk of dementia: A systematic review and meta-analysis. Psychoneuroendocrinology. 106: 9-19.

25. Weber MT, Maki PM, McDermott MP. Cognition and mood in perimenopause: a systematic review and meta-analysis. J Steroid Biochem Mol Biol. 2014;142:92-98. Doi:101016/j.jsbmb.2013.06.00.

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28. Wagner LL, Gray RJ, Sparao JA. et al. Patient-reported cognitive impairment among women with early breast cancer randomly assigned to endocrine therapy along versus chemoendocrine therapy: results from TAILORx. J Clin Onc. 2020;38:1-19. Doi.org/10.1200/JCO.19.01866.

29. Branigan GL, Soto M, Neumayer L et al. Association between hormone-modulating breast cancer therapies and incidence of neurodegenerative outcomes for women with breast cancer. JAMA netw Open 2020;3(3):e201541.doi10.1001/jamanetworkopen.2020.1541.

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Content updated July 2020