Hormones and Cognition

Overview

• The term cognitive function refers to the brain’s ability to process information and encompasses several processes, including thinking, memory, recall, mental flexibility, problem solving and learning. Without all these functions operating properly, people can show abnormalities that may be diagnosed as diseases or disorders.
• Hormonal fluctuations are one of the key factors for optimal cognitive function, and various changes in hormone levels may lead to defects in cognitive function.
• Estrogen and progesterone regulate physiology and reproductive behaviour.
• Progesterone is the main hormone regulated at three different stages: the maintenance of the uterus; the development of oocytes, and sexually responsive behaviour in the brain.
• Loss of endogenous estrogen has been associated with mitochondrial dysfunction and decline in genomic maintenance processes, loss of synapses in the brain, brain inflammation etc.
• Estrogen has been investigated as a hormone with the potential ability to act as a neuro-protector, which may selectively benefit certain cognitive tasks such as memory-forming, mediated by the hippocampus and frontal lobe.
• Results are contradicting as the opposite effects have also been reported.
• The testosterone hormone, which is predominantly higher in males than females, is believed to be one of the sex hormones that may reduce cognitive performance, as its levels decrease with aging.
• Despite the occurrence of the same hormones (estrogen and testosterone) in males and females, the amount, potency, tempo, tissue specificity, and biophysiological activity differ considerably, creating different functional outcomes.
• It has been a challenge to disentangle the role of steroid hormones on brain function because they broadly influence physiology and behavior, making it difficult to characterize direct versus indirect effects.

Cognitive Function

The term cognitive function refers to the brain’s ability to process information and encompasses several processes, including thinking, memory, recall, mental flexibility, problem solving and learning. Without all these functions operating properly, people can show abnormalities that may be diagnosed as diseases or disorders. There is ample evidence that alterations in brain structure and function are intimately tied to alterations in cognitive function, however, these relationships can be speculative due to the complexity of neural and cognitive functions, which make exact mapping between brain and behavior extraordinarily difficult. The good news is, we can test these associations! This is exactly what cognitive neuroscientists do! Nevertheless, the two domains – brain structure/function and cognition, will ultimately always be related, regardless of the dynamic relationship between the two. Cognitive function is impacted by numerous factors (i.e., genetics, aging, lifestyle, environment), but also, an abundance of research has found that hormonal fluctuations are one of the key factors for optimal cognitive function, and various changes in hormone levels may lead to defects in cognitive function.

Just as age-related changes in brain structure and function are not uniform across the whole brain or across individuals, age-related changes in cognition are not uniform across all cognitive domains or across all older individuals. Deficits in cognitive function are identified through a neuropsychological assessment that comprises language, attention, conceptual reasoning, memory and processing speed. Beyond typical changes with aging, some cognitive deficits are pathological. Some examples of pathological cognitive impairment are mild cognitive impairment (MCI), deficits associated with Alzheimer’s disease and dementia, and deficits associated with neuropsychiatric disorders.

Hormones

Hormones are modulated from the beginning of life in utero, as the differentiations of gender begin in utero. The sexual/gonadal hormones such as testosterone, estrogen and progesterone are continuously produced by gonads and are regulated throughout adolescence and adulthood. The sex steroidal hormone mechanism begins once the hormone binds to a receptor on the target tissue and the hormone-receptor complex enters he nucleus by translocating through membranes. Then, the complex structure interacts with chromatin inside the nucleus and changes the DNA (deoxyribonucleic acid) structure of chromatin for the gene transcription process. The steroid hormones interact with the chromatin, causing an increase in ribonucleic acid (RNA) synthesis, which allows the synthesis of protein. However, this process, and therefore hormone levels, may not remain well-maintained when certain triggers cross their pathways, such as aging and pregnancy.

Estrogen and Progesterone

Estrogen and progesterone regulate physiology and reproductive behaviour. Progesterone is the main hormone regulated at three different stages: the maintenance of the uterus; the development of oocytes, and sexually responsive behaviour in the brain. Estrogens are a family of important steroid hormones, exerting many reproductive and non-reproductive physiological roles in the body and brain. Endogenous estrogens have antioxidant properties, meaning that estrogen found in the brain contributes to a stable ratio of antioxidants. Loss of endogenous estrogen has been associated with mitochondrial dysfunction and decline in genomic maintenance processes, loss of synapses in the brain, brain inflammation etc. These effects may play a role in memory, cognition and spatial tasks. There are estrogen receptors at multiple sites of brain regions: the hippocampus, the amygdala and the cerebral cortex. These three regions are responsible for the critical functioning of emotions, memory consolidation and retrieval, and cognitive processes in general. 

When menopause occurs in women, endogenous estrogen levels are depleted, causing a range of symptoms. Exogenous estrogen in the form of hormone replacement therapy is a widely used therapeutic intervention for women in mid-life. Estrogen has been investigated as a hormone with the potential ability to act as a neuro-protector, which may selectively benefit certain cognitive tasks such as memory-forming, mediated by the hippocampus and frontal lobe. The results however are quite contradicting! Estrogen hormone therapy is being selectively suggested for menopausal women who are experiencing a decline in cognitive function, due to conclusions from some studies suggesting that this type of therapy may reduce the risk of getting dementia and Alzheimer’s disease. Other studies suggest the opposite effect, where exogenous estrogen is associated with declines in certain functions. Some neuroimaging findings lend support to hormone therapy’s ability to act as a neuroprotector for menopausal women, by preventing the aging-related risk of brain atrophy, specifically in the frontal lobe and hippocampal cognitive area, while other studies suggest that hormonal therapy may accelerate age-related declines and contribute to an increased rate of brain atrophy.

Testosterone

The testosterone hormone, which is predominantly higher in males than females, is believed to be one of the sex hormones that may reduce cognitive performance, as its levels decrease with aging. Testosterone production is stimulated by the gonadotropin-releasing hormone (GnRH) in the hypothalamus and activation of the pituitary gland to secrete certain levels of testosterone into the bloodstream. However, the claim of cognitive memory deficits due to testosterone is still debatable, as some studies have found that cognition and testosterone levels have a positive linear relationship, while some studies have found contradicting effects. Most people have some idea about how testosterone regulates male behavior or how too little of it might cause a decrease in libido and too much might cause aggressive and irritable behavior. Turns out, no one yet knows how testosterone really does all that! It is known that androgen hormones like testosterone, have effects on neurons, but the mechanisms behind this are largely unknown. What is noteworthy is that despite the occurrence of the same hormones (estrogen and testosterone) in males and females, the amount, potency, tempo, tissue specificity, and biophysiological activity differ considerably, creating different functional outcomes.

It has been a challenge to disentangle the role of steroid hormones on brain function because they broadly influence physiology and behavior, making it difficult to characterize direct versus indirect effects. However, there is substantial research currently being undertaken in the field of neuroendocrinology, which will definitely enrich our current understanding of the links between steroid sex hormones and healthy brains!

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References

Ali, S., Begum, T., & Reza, F. (2018). Hormonal Influences on Cognitive Function. Malaysian Journal Of Medical Sciences, 25(4), 31-41. https://doi.org/10.21315/mjms2018.25.4.3

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Erickson KI, Colcombe SJ, Raz N, Korol DL, Scalf P, Webb A, et al. Selective sparing of brain tissue in postmenopausal women receiving hormone replacement therapy. Neurobiol Aging. 2005;26:1205–1213.

Harada CN, Natelson Love MC, Triebel K. Normal cognitive aging. Clin Geriatr Med. 2013;29(4):737–752. doi: 10.1016/j.cger.2013.07.002.

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Luine VN. Estradiol and cognitive function: past, present and future. Horm Behav. 2014;66(4):602–618. doi: 10.1016/j.yhbeh.2014.08.011.

Mahmoud R, Wainwright SR, Galea LA. Sex hormones and adult hippocampal neurogenesis: regulation, implications, and potential mechanisms. Front Neuroendocrinol. 2016;41:129–152. doi: 10.1016/j.yfrne.2016.03.002.

Featured Image Credit: Cesar M. Romero / Shutterstock

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