Can hormones be used to enhance cognitive brain function in healthy individuals?

Hormones for Cognitive Brain Function in Healthy Individuals

While steroid hormones play important roles in brain function, current evidence does not support the use of hormone therapy to enhance cognitive function in healthy individuals. 1

Current Evidence on Hormone Effects on Cognition

• Steroid hormones have significant actions in the brain, with estrogen and progesterone regulating oxidative metabolism in brain mitochondria and influencing neuroplasticity 1
• Estrogen receptors in the human forebrain are associated with neuroprotective mechanisms and may influence cognitive function 1
• Estradiol stimulates dendritic spine production and enhances neuroplasticity, possibly via enhancement of brain-derived neurotrophic factor (BDNF) 1

Evidence Against Hormone Use for Cognitive Enhancement

• Higher-quality guidelines from Scotland and Germany specifically recommend against using hormone replacement therapy to treat cognitive symptoms in women 1
• Austrian guidelines recommend against using androgens such as testosterone to treat cognitive symptoms in men 1
• The Women's Health Initiative Memory Study found that hormone therapy with conjugated equine estrogens with or without medroxyprogesterone acetate did not protect against cognitive decline but actually increased the risk of dementia in women over 65 2
• Cognitive decline was greater in women aged 65 years and older receiving hormone therapy compared to those receiving placebo 2

Specific Cognitive Domains and Hormone Effects

• In studies of postmenopausal women, hormone therapy showed no benefits for overall cognitive function or verbal memory compared to non-users 3
• Some limited evidence suggests that current hormone users may perform better on tests of verbal fluency, but this does not translate to better overall cognitive function 3
• A meta-analysis of observational studies suggested hormone replacement therapy might be associated with decreased risk of dementia, but these studies had important methodological limitations including possible biases and lack of control for potential confounders 4

Special Considerations

• In transgender individuals receiving gender-affirming hormone treatment, current evidence does not support an adverse impact on cognitive function, with some studies showing enhancement of visuospatial ability in birth-assigned females 5
• The effects of hormone therapy may differ based on age, with some evidence suggesting possible benefits in younger postmenopausal women but detrimental effects in older women 6
• Estrogen alone may have different cognitive effects compared to estrogen combined with progestin, with some evidence suggesting that combination therapy may have more detrimental effects on verbal memory 6

Potential Mechanisms

• Estrogen offers antioxidant effects that can reduce reactive oxygen species-induced mitochondrial damage 1
• Estradiol influences dendritic spine production and enhances neuroplasticity through BDNF-related mechanisms 1
• Decreased estradiol concentrations may reduce N-methyl-D-aspartate receptor concentrations and down-regulate BDNF expression 1
• Reduction in testosterone may impair neprilysin function, which could affect amyloid β clearance 1

Conclusion

• Current clinical guidelines do not support the use of hormones for cognitive enhancement in healthy individuals 1
• The potential risks of hormone therapy, including increased risk of dementia in older women, outweigh any potential cognitive benefits in healthy individuals 2
• More research is needed on the long-term effects of hormone therapy on cognition, particularly in younger individuals where data is more limited 5