Testosterone modulation of default mode network and its effects on cognitive function and mood in humans: a systematic review
Daria Malich, Andrii Vasylyshyn
Frontiers in Neuroscience September 14, 2026 DOI: 10.3389/fnins.2026.1901486 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Randomized Longitudinal Peer reviewed |
|---|---|
| Population | Human neuroimaging study participants across 10 included studies |
| Topics | Default mode network |
| Key findings | The authors report that testosterone-related alterations in default mode network connectivity occur across self-referential hubs such as the medial prefrontal cortex, anterior cingulate cortex, precuneus, and angular gyrus. They conclude these effects are highly context dependent, sex-specific, and developmental stage-dependent, with functional consequences mainly in self-referential and affective domains rather than externally oriented cognition. High heterogeneity across studies and limited hormonal profiling constrain causal inference. |
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 registration Identifier: CRD420261368147.