Testosterone is a steroid hormone produced by both the testes in males and the ovaries and adrenal glands in females, though typically in much higher concentrations in males. Beyond its well-known roles in reproductive and physical development, testosterone is active in the brain, influencing various cognitive processes. Memory and recall represent complex brain functions, and the relationship with circulating testosterone levels is not a simple linear one. Research indicates that this connection is nuanced, often dependent on an individual’s age and their baseline hormone status.
How Testosterone Interacts with Brain Function
Testosterone influences memory by crossing the blood-brain barrier and interacting with neural tissue. Inside the brain, the hormone binds directly to androgen receptors on neurons. Testosterone also converts into two metabolites that affect brain function. The enzyme 5-alpha reductase converts it into dihydrotestosterone (DHT), while aromatase converts it into the estrogen, estradiol.
These hormones and their receptors are concentrated in brain regions responsible for memory. The hippocampus, the brain’s primary memory center, contains high numbers of both androgen and estrogen receptors. Testosterone and its metabolites support neuroprotection and neurogenesis, the creation of new neurons, within the hippocampus. They also help maintain synaptic plasticity, which is the structural strengthening of connections between neurons that forms the physical basis of learning and memory.
The Impact of Low Testosterone Levels on Recall
A decline in natural testosterone levels, due to hypogonadism or age-related decrease, is associated with reports of cognitive changes. Individuals with low testosterone often report subjective symptoms such as “brain fog,” difficulty concentrating, and issues with mental clarity. This relationship has led researchers to investigate the link between the hormonal drop and measurable cognitive decline.
Population studies show that as men age and their testosterone levels decrease, they exhibit poorer performance on cognitive function tests compared to peers with higher levels. Lower endogenous testosterone has been linked to impairments in both verbal and visual memory. However, this correlation does not establish that low testosterone is the direct cause of all memory problems, as other factors related to aging and overall health also play a significant role.
Cognitive Outcomes of Testosterone Replacement Therapy
Given the correlation between low levels and poor recall, clinical trials have explored whether Testosterone Replacement Therapy (TRT) can improve memory function. Results have been mixed, depending on the patient population and the specific cognitive domain tested. Some smaller studies showed promising results in hypogonadal men, with improvements in spatial memory, verbal memory, and constructional abilities.
However, the large-scale Testosterone Trials (TTrials), which included hundreds of older men with low testosterone and age-associated memory impairment, found different results. The TTrials concluded that one year of treatment did not significantly improve overall cognitive function, including verbal, visual, or spatial ability, compared to a placebo group. The trial also raised a caution, showing that TRT was associated with a greater increase in noncalcified coronary artery plaque volume. This suggests that TRT may not reverse age-associated memory decline in all men and highlights potential cardiovascular risks.
Differences in Memory Types and Biological Sex
The effects of testosterone on memory are not uniform across all cognitive tasks, often showing domain-specific outcomes. The hormone is associated with enhancing spatial memory, which involves navigating and recalling locations, such as in mental rotation tasks. Conversely, evidence suggests that very high levels of testosterone may have a negative impact on verbal memory performance.
This memory specificity is also observed when considering biological sex. Testosterone is a factor in female cognitive health despite much lower circulating levels, and its administration has been shown to improve their performance on spatial tasks. The cognitive effects of testosterone follow a curvilinear, or inverted U-shaped, relationship, meaning both extremely low and extremely high levels can be detrimental to optimal cognitive performance.