Autism spectrum disorder involves challenges in social communication and restricted, repetitive behaviors. Historically, males have received autism diagnoses at comparatively high rates, prompting an underrepresentation of females in research and an incomplete understanding of sex-specific symptom presentations and comorbidities. This review examines sex differences in the prevalence of common comorbidities of autism to inform tailored clinical practices. These conditions include attention deficit hyperactivity disorder, anxiety disorders, conduct disorder, depression, epilepsy, intellectual disability, and tic disorders. Attention deficit hyperactivity disorder is prevalent in both sexes; however, females may more frequently exhibit the inattentive subtype. Anxiety disorders display inconsistent sex differences, while conduct disorder more frequently impacts males. Depression becomes more common with age; some studies indicate more pronounced symptoms in adolescent girls, while others suggest greater severity in males. Epilepsy is more prevalent in females, especially those with intellectual disabilities. Despite displaying a male predominance, intellectual disability may exacerbate the severity of autism to a greater degree in females. No clear sex differences have been found regarding tic disorders. Overall, contributors to sex-based differences include biases stemming from male-centric diagnostic tools, compensatory behaviors like camouflaging in females, genetic and neurobiological differences, and the developmental trajectories of comorbidities. Recognizing these factors is crucial for developing sensitive diagnostics and sex-specific interventions. Inconsistencies in the literature highlight the need for longitudinal studies with large, diverse samples to investigate autism comorbidities across the lifespan. Understanding sex differences could facilitate earlier identification, improved care, and personalized interventions, thus enhancing quality of life for individuals with autism.

Neurodevelopmental disorders, which emerge early in development, include a range of neurological phenotypes and exhibit marked differences in prevalence between sexes. A male predominance is particularly pronounced in autism spectrum disorder (ASD). Although the precise cause of ASD is still unknown, certain genetic variations and environmental influences have been implicated as risk factors. Preclinical ASD models have been instrumental in shedding light on the mechanisms behind the sexual dimorphism observed in this disorder. In this review, we explore the potential processes contributing to sex bias by examining both intrinsic differences in neuronal mechanisms and the influence of external factors. We organize these mechanisms into six categories: 1) sexually dimorphic phenotypes in mice with mutations in ASD-associated genes related to synaptic dysfunction; 2) sex-specific microglial activity, which may disrupt neural circuit development by excessively pruning synapses during critical periods; 3) sex steroid hormones, such as testosterone and allopregnanolone, that differentially influence brain structure and function; 4) escape from X chromosome inactivation of the O-linked-N-acetylglucosamine transferase gene in the placenta; 5) sexually dimorphic activation of the integrated stress response pathway following maternal immune activation; and 6) immunological responses that are differentially regulated by sex. Understanding these mechanisms is essential for deciphering the underlying causes of ASD and may offer insights into other disorders with notable sex disparities.