Testosterone and the Brain: From Cognition to Autism

Abstract

Sex and gender matter in all aspects of life. Humans exhibit sexual dimorphism in anatomy, physiology, but also pathology. Many of the differences are due to sex chromosomes and, thus, genetics, other due to endocrine factors such as sex hormones, some are of social origin. Over the past decades, huge number of scientific studies have revealed striking sex differences of the human brain with remarkable behavioral and cognitive consequences. Prenatal and postnatal testosterone influence brain structures and functions, respectively. Cognitive sex differences include especially certain spatial and language tasks, but they also affect many other aspects of the neurotypical brain. Sex differences of the brain are also relevant for the pathogenesis of neuropsychiatric disorders such as autism spectrum disorders, which are much more prevalent in the male population. Structural dimorphism in the human brain was well-described, but recent controversies now question its importance. On the other hand, solid evidence exists regarding gender differences in several brain functions. This review tries to summarize the current understanding of the complexity of the effects of testosterone on brain with special focus on their role in the known sex differences in healthy individuals and people in the autism spectrum.

Sex and gender difference in cognitive and behavioral studies in developmental age: An introduction

“…Studies in nonhuman animals and in infant/children show that sex differences in empathy have origin in biology and not only in social and cultural influences, for example the fetal testosterone can negatively affect the neural mechanisms responsible for social development (Lutchmaya et al., 2001). An elevated fetal steroidogenic activity can behave as epigenetic fetal programming mechanisms, interacting with other pathophysiological factors to determine ASD (Baron‐Cohen et al., 2015; Ostatnikova et al, 2020). A rat animal study found that prenatal hyperandrogen exposure could decrease social sounds in pups and impair social interaction in females, with a negative correlation between length of social relationship and maternal serum testosterone levels in pregnancy, so that maternal hyperandrogenism during pregnancy may represent a possible factor to consider for monitoring children at risk to develop ASD (Xu et al., 2015).…”

Prenatal Sex Hormone Exposure Is Associated with the Development of Autism Spectrum Disorder

“…For instance, there have been studies suggesting that testosterone per se does not affect the body and brain development and behavioral alterations; instead, androgen or estrogen receptors to which testosterone binds are responsible [89]. Hodosy et al demonstrated that the effects of endogenous testosterone are blocked when rats are treated with a competitive inhibitor of the androgen receptor, supporting the hypothesis that the effects are not directly caused by testosterone.…”

Transgender man receiving testosterone treatment became pregnant and delivered a girl: A case report

“…Thus, it is important to be aware of the effects that hormone therapy can have on fetuses. For example, multiple reports discuss the exposure to testosterone of female babies because of their mothers' polycystic ovarian syndrome (PCOS), and others show that congenital adrenal hyperplasia raises their likelihood of having what have traditionally been considered male/boy‐oriented tastes and behaviors, 5 increasing their risk of developing PCOS 6 and the risk of autism 7 . Indeed, the female child in the present case has shown some characteristic symptoms of autism, so careful follow‐up is ongoing.…”