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Testosterone impacts self-referential and affective domains via default mode network alterationsTestosterone Linked to Changes in Brain Regions for Self Awareness

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Key Takeaway
Note that testosterone impacts self-referential and affective domains via specific default mode network hub alterations.

This systematic review synthesizes evidence regarding the effects of testosterone on the default mode network (DMN) and related cognitive functions. The review focuses on how testosterone influences specific neural hubs and the resulting functional consequences for the user.

The authors conclude that testosterone leads to alterations in key self-referential hubs, specifically the medial prefrontal cortex, anterior cingulate cortex, precuneus, and angular gyrus. These changes appear to impact self-referential and affective domains rather than externally oriented cognition. Secondary outcomes such as mood, affective reactivity, self-referential processing, aggression modulation, and body self-identification were also reviewed.

Limitations noted by the authors include high heterogeneity among the included studies and a lack of broader hormonal profiling in many of the reviewed studies. Due to these factors, causal inferences are constrained. The findings suggest that testosterone's influence on the brain is specifically localized to internal processing domains, though the lack of consistent hormonal profiling across studies limits the certainty of these conclusions.

How this fits prior evidence

This systematic review addresses a gap in understanding the neurological mechanisms of testosterone. While prior evidence has established that testosterone replacement therapy is associated with a significantly increased risk of clinical fractures in hypogonadal men, this review focuses on the neurobiological impact on the default mode network. It provides specific evidence on how testosterone affects self-referential hubs, which is not addressed in the previously covered evidence regarding fracture risk, monitoring methods, or fertility outcomes.

This review looked at how testosterone affects the default mode network, which is a group of brain regions involved in internal thoughts. The researchers looked at several key areas, including the medial prefrontal cortex and the precuneus. They found that testosterone was linked to changes in these specific spots.

These changes seem to affect how people process information about themselves and their emotions. The findings suggest that testosterone impacts internal feelings and self-identity more than it affects general, outward-facing tasks. This means the hormone may play a role in how we perceive our own roles and feelings.

It is important to note that these results come from a review of many different studies. Because the studies were very different from one another and many did not look at a full range of hormones, it is hard to say for certain how much testosterone alone causes these changes. These findings are currently used to help researchers understand the link between hormones and brain function.

What this means for you:
Testosterone is linked to brain changes affecting self-awareness and mood rather than general cognitive skills.

Common questions

What parts of the brain are affected by testosterone?

The review found changes in several key areas of the brain. These include the medial prefrontal cortex, anterior cingulate cortex, precuneus, and angular gyrus. These areas are part of the default mode network and are important for self-referential processing and emotional responses.

Does testosterone affect general thinking or memory?

The findings suggest that the changes linked to testosterone primarily affect internal areas like self-referential processing and emotional reactions. The study did not find that it predominantly affected externally oriented cognition, which involves more general types of thinking.

How certain are these findings about testosterone and the brain?

The evidence is currently limited by the high variety of the studies included in the review. Many studies also did not provide a full profile of other hormones. Because of these factors, it is difficult to make a certain claim about the direct cause of these brain changes.

Study Details

Study typeMeta analysis
EvidenceLevel 1
PublishedSep 2026
View Original Abstract ↓
Testosterone exerts widespread effects on brain structure and function, yet its influence on large-scale neural networks, particularly the default mode network (DMN), remains poorly understood. The role of the DMN in self-referential processing, social cognition, and mood regulation has been demonstrated over the last decade. Neuroimaging studies suggest a link between testosterone and large-scale brain networks, particularly the DMN, in cognitive function and mood domains. A systematic search of the PubMed database was conducted from March to April 2026, restricted to human neuroimaging studies published within the past 15 years, in accordance with PRISMA guidelines. A total of 10 studies were included in this review. Risk of bias was assessed using RoB 2, the Newcastle–Ottawa Scale, the NIH Quality Assessment Tool, and the AXIS tool, selected according to study design. Testosterone-related DMN alterations were observed across key self-referential hubs, including the medial prefrontal cortex, anterior cingulate cortex, precuneus, and angular gyrus. Effects were highly sex-specific, developmental stage-dependent, and sensitive to the form and magnitude of androgen exposure. Testosterone levels were mostly linked to changes in affective reactivity and self-referential processing, including aggression modulation and body self-identification. Overall, testosterone-related modulation of DMN connectivity appears to be highly context dependent, with functional consequences predominantly affecting self-referential and affective domains rather than externally oriented cognition. The high heterogeneity of the included studies, alongside the absence of wider hormonal profiling in many studies, constrains causal inference. Future research should prioritize randomized longitudinal designs with comprehensive hormonal assessment and balanced sex representation to clarify the therapeutic relevance of testosterone-related DMN modulation.Systematic review registrationIdentifier: CRD420261368147.
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