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Cognitive Problems in Perimenopause: A Review of Recent Evidence

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Abstract

Purpose of Review

To review recent research regarding cognitive problems during perimenopause, including which menopause-related symptoms, demographic variables, stress exposures, and neural biomarkers are associated with cognitive problems and which interventions demonstrate efficacy at improving cognitive performance.

Recent Findings

Cognitive problems are common during perimenopause and have a significant impact on a substantial proportion of women. Evidence continues to indicate that verbal learning and verbal memory are the cognitive functions that are most negatively affected during perimenopause, and new research suggests that perimenopause may also be associated with deficits in processing speed, attention, and working memory. Recent research suggests that the cognitive profiles of women transitioning through perimenopause are heterogenous – with some showing strengths and others demonstrating weaknesses in particular cognitive domains. Depression, sleep problems, and vasomotor symptoms in perimenopause may be associated with cognitive difficulties. Recent neuroimaging studies are identifying changes in activity patterns within brain regions that correlate with cognitive performance in perimenopause, but future causal studies are needed to understand the neural mechanisms of cognitive problems during this time. Although clinical treatment studies for cognitive concerns have historically focused on postmenopause, some small trials in perimenopausal samples have been conducted recently but are frequently underpowered. Current guidelines from the North American Menopause Society do not support the use of hormone therapy at any age for cognitive problems. Animal research demonstrates that estradiol and levonorgestrel combined may alleviate working memory problems.

Summary

Much progress has been made in understanding how perimenopause impacts cognition, and more research is needed to better identify who is at highest risk and how to meaningfully prevent and alleviate cognitive problems during this reproductive stage. Larger-scale randomized intervention trials specifically during perimenopause are urgently needed to address cognitive concerns in this population of women. More consistent reproductive staging, inclusion of covariates, and analyses examining perimenopause specifically would improve study quality and the ability to draw clear conclusions from this research.

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Notes

  1. Defined as having “irregular periods”.

  2. Defined as ≥ 12 consecutive months without spontaneous menstruation, or bilateral ovariectomy ?6 weeks before enrollment (with or without hysterectomy), FSH > 40 IU/L.

  3. Defined as the absence of menstrual periods for the past 12 months or more.

  4. Defined as irregular menstrual cycles, that is, having cycle length differ by 7 or more days between cycles, or having two or more skipped cycles and at least one inter-menstrual interval of 60 days or more.

  5. Defined as regular menstruation.

  6. Defined as irregular menstruation.

  7. Defined as no menstruation for between 1–5 years.

  8. Defined as no menstruation for > 5 years.

  9. Defined as three or more menses in the past 3 months with changes in cycle length, amount of flow or number of days of flow.

  10. Defined as menstruating less frequently than monthly during the past 3 months (< 3 periods in 3 months, potentially including women in early postmenopause.

  11. Defined as menstrual cycles with an average duration of 28 days with only subtle changes in the duration of the cycle (reference interval 22–35 days).

  12. Defined as age older than 40 years and irregular cycles (below or above the reference interval of 22–35 days) or amenorrhea for up to 12 consecutive months.

  13. Defined as older than 40 years and more than 12 consecutive months of amenorrhea.

  14. Definitions were based on STRAW (Soules, 2001), but with the addition of a late premenopause stage. Premenopause was defined as regular menstrual cycles in the 22–35 day range, late premenopause was defined as a change in cycle length of 7 days or more in either direction from the participant’s personal baseline at enrollment in the cohort and observed for at least one cycle in the study, early menopausal transition was defined as changes in cycle length of 7 days or more in either direction from the participant’s personal baseline at enrollment in the cohort and observed for at least 2 consecutive cycles in the study or 60 days amenorrhea, late menopausal transition was defined as more than 60 days to 11 months amenorrhea, and postmenopausal was defined as 12 months or more amenorrhea, excluding hysterectomy.

  15. Defined premenopause as having had no change in predictability of menses; early perimenopause as decreased predictability of menses but no gaps of ≥ 3 months; late perimenopause as no menstrual bleeding for 3–11 months; and postmenopause as absent menses for 12 or more months.

  16. Reproductive stages were defined as premenopausal (menses in the past 3 months with no changes in regularity); early perimenopausal (menses in the past 3 months with change in regularity); late perimenopausal (no menses within the past 3 months but some menstrual bleeding within the past 12 months); and postmenopausal (no menses within the past 12 months).

  17. Defined as FSH levels were between 17 and 25 IU/L and irregular menstrual cycles.

  18. Defined as FSH levels were between 25 and 30 IU/L and occasional menstrual bleeding during the past 3 months.

  19. Defined as FSH > 30 IU/L and no menstrual bleeding during the past 6 months, or FSH > 39 IU/L and no menstrual bleeding during the past 3 months, or FSH > 130 IU/L and possible occasional bleeding.

  20. Defined as a change in ≥ 7 days in either direction from participant personal baseline for at least 2 consecutive cycles or 60 days-11 months of amenorrhea.

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  1. Department of Psychiatry, University of Colorado Anschutz Medical Campus, 1890 N. Revere Court MS F546, Aurora, CO, 80045, USA

    Christina A. Metcalf, Korrina A. Duffy, Chloe E. Page & Andrew M. Novick

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Metcalf, C.A., Duffy, K.A., Page, C.E. et al. Cognitive Problems in Perimenopause: A Review of Recent Evidence. Curr Psychiatry Rep 25, 501–511 (2023). https://doi.org/10.1007/s11920-023-01447-3

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