Table 2.
Overview of testosterone assessment methods, DMN findings and cognitive/mood outcomes.
| References | Testosterone assessment/ experimental manipulation methods | Default mode network (DMN)–related findings | Cognitive and mood domains |
|---|---|---|---|
| Westlye et al. (2016) | High (AAS users, essentially synthetic T). Testosterone to epitestosterone T/E ratio elevated | Reduced connectivity between the amygdala and DMN | Increased aggression/violence reported in AAS users |
| Khorashad et al. (2021) | Participants received cross-sex hormone treatment involving testosterone administration | At baseline, both transgender groups showed reduced DMN connectivity (including ACC, mPFC, precuneus, and angular gyrus) compared to cisgender controls; following hormone treatment, partial increases in DMN connectivity were observed in transgender participants, with no significant group differences remaining at follow-up | In the DMN, increased connectivity in the precuneus/posterior cingulate cortex was positively associated with improvements in own body perception, such that greater increases in self-perception ratings corresponded to greater increases in DMN connectivity following treatment |
| Lombardo et al. (2020) | Prenatal (fetal) testosterone (amniotic fluid) | Fetal testosterone (FT) was negatively associated with DMN connectivity in adolescent males, but not in females. This sex-specific relationship remained significant even after controlling for current testosterone levels during adolescence. Current testosterone itself was negatively correlated with DMN connectivity in males only | Dihydrotestosterone (DHT)-dysregulated genes were reported to be enriched for syndromic causes of autism and intellectual disability and to be highly enriched for genes that are spatially expressed in a similar pattern to the cortical midline DMN subsystem |
| Pelletier-Baldelli et al. (2024) | Pubertal testosterone (saliva) | No significant results involving the DMN was reported. The lack of DMN associations across puberty and age outcomes was unanticipated | The role of the DMN in this process was not directly demonstrated. The reported findings indicate that testosterone was uniquely associated with frontoparietal – reward connectivity, whereas perceived pubertal status and age were associated with cingulo-opercular – reward connectivity. No direct link was found between the DMN and cognitive control |
| Wagels et al. (2019) | 50 mg transdermal testosterone gel (single dose) | An enhanced signal was observed in regions that comprise the core hubs of the DMN, namely the precuneus (extending to the posterior cingulate cortex), posterior angular gyrus, and medial prefrontal cortex. Testosterone increases DMN activity in decision periods. Despite of some evidence for testosterone modulating DMN activity, the biological mechanisms behind this were reported to be unclear | Decision-making following provocation is associated with higher DMN activity |
| Khetan et al. (2026) | Salivary testosterone | Testosterone was associated with increased connectivity between the DMN and its posterior subcomponent (retrosplenial temporal network), alongside decreased connectivity between the DMN and both reward-related (nucleus accumbens) and control-related (cingulo-opercular) networks | The authors cautiously proposed that androgens (testosterone and DHEA) may be related to cognitive functioning through their associations with brain structure; however, this interpretation was explicitly presented as speculative. No direct link between testosterone-related neural DMN changes and cognitive outcomes was demonstrated |
| Pletzer et al. (2016) | Users of androgenic oral contraceptives | Users of androgenic but not anti-androgenic OC, showed a significant increase in DMN connectivity compared to naturally cycling women, particularly in the mPFC | Changes in cognitive control were proposed to be influenced by alterations in functional connectivity across brain networks during the luteal phase; however, no direct link was demonstrated in the study |
| Alarcón et al. (2014) | Saliva testosterone (girls ~3.5 pg/mL, boys ~0.3 pg/mL) | During spatial working memory, sex differences in neural activation were observed, with girls showing reduced recruitment of the dorsolateral prefrontal cortex and greater suppression of DMN regions, while boys demonstrated increased frontal activation and less pronounced DMN deactivation | Differences in spatial working memory were not explained by testosterone levels |
| Mertens et al. (2025) | Salivary testosterone | In the current study, greater deactivation of DMN regions, including the anterior cingulate cortex (ACC), during a working memory task was observed in female participants ≤ 21 years and was associated with testosterone levels, whereas no such association was found in adult females | Sex differences were observed in the relationship between testosterone levels and brain activation during working memory task performance in adolescents and young adults |
| Grotzinger et al. (2024) | Serum/Saliva testosterone | Negative associations between testosterone levels and DMN connectivity were observed. These effects were weaker compared to other networks and were more pronounced in males than in females | Total testosterone levels were positively associated with vigor and negatively associated with overall mood disturbance as measured by the Profile of Mood States (POMS), with no other significant relationships between testosterone and mood measures observed after correction for multiple comparisons |