The cognitive challenges of menopause

Menopause is clinically defined as the discontinuation of menstrual periods for at least 12 consecutive months, while perimenopause is the transition phase lasting four to 10 years prior to menopause.¹ The significant fluctuations in oestrogen and progesterone characteristic of perimenopause are thought to be responsible for many of the symptoms commonly experienced, including cognitive difficulties. ^1,2

Cognitive symptoms

The prevalence of cognitive difficulties is widespread, with almost two-thirds of the 1.5 million women transitioning to menopause each year experiencing cognitive symptoms.^1,3 Specific cognitive difficulties reported by perimenopausal women, in particular, include:

• subjective changes to working and verbal memory (e.g. difficulty remembering words, numbers or reasons for tasks before finishing them)
• complex attention
• language ability
• cognitive processing speed
• increased ‘brain fog’ and forgetfulness.^1,2

While experiencing such cognitive issues can be challenging, they are observed to be more severe in early perimenopause. They also do not appear to affect objective cognitive performance measures, which generally still fall within normal ranges despite the individual’s experience of cognitive symptoms. ^1,3

Proposed causes of cognitive difficulties

The underlying causes of these cognitive difficulties are attributed to the altered endogenous sex steroid hormone environment and the complex and multifaceted roles these hormones play. They are involved in many central nervous system (CNS) structural and functional processes (acting as neurosteroids) through both gene- and non-gene mediated pathways.^2,4

Roles of oestrogen and progesterone

As neurosteroids, oestrogen and progesterone influence CNS structure and function by acting on the many receptors located in the brain and through interactions with neurotransmitters, including acetylcholine, glutamate, noradrenaline and serotonin.^2,4 They both interact with the neurotransmitter synapses at different levels: neurotransmitter synthesis, release and degradation, and neurotransmitter receptor synthesis, activation or inhibition.⁵

Oestrogen also protects cognitive functions and influences emotional and motivational behaviours, by protecting neurons from injury, promoting neuron growth and plasticity, supporting mitochondrial energy synthesis and having antioxidant effects.^2,4,5 In regards to serotonin and dopamine, oestrogen increases their levels by suppressing breakdown and promoting receptor activity and binding. Progesterone also promotes neural cell growth and energy processes. ^2,4

Consequently, changes to oestrogen and progesterone levels during the transition to menopause play a major role in the onset of cognitive symptoms in perimenopausal women. However, recent evidence also found an association between the number of vasomotor symptoms and impaired memory (verbal and delayed logical) that were independent of hormone levels.⁶

The potential effects later in life

An ongoing concern for many women is that they will continue to experience cognitive difficulties later in life with the risk of more serious cognitive impairments. Currently, the evidence indicates that most women will only experience subtle reductions in some cognitive functional processes in the postmenopausal years. However, more research is required to confirm any further long-term cognitive consequences.^3,4

The complexity of the many factors contributing to menopausal cognitive symptoms, and the daily difficulties many women have living with such symptoms, emphasises the need for an empathetic and comprehensive clinical approach during the transition to menopause.

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References:

1. Greendale GA, et al. The menopause transition and cognition. JAMA Insights 2020 March; doi:10.1001/jama.2020.1757.
2. Gava G, et al. Cognition, mood and sleep in menopausal transition: the role of menopause hormone therapy. Medicinia 2019; 55: 668.
3. Santoro N, et al. Menopausal symptoms and their management. Endocrinol Metab Clin N Am 2015; 44: 497-515.
4. Morgan KN, et al. Cognitive changes with reproductive aging, perimenopause and menopause. Obstet Gynecol Clin North Am 2018 Dec; 45 (4): 751-763.
5. Pablo Del Rio J, et al. Steroid hormones and their action in women’s brains: the importance of hormonal balance. Front Publ Health 2018; 6: 141.
6. Maki P, et al. Hot flashes are associated with altered brain function during a memory task. Menopause: J North Am Meno Soc. 2020; 27 (3).