Why is Autism Spectrum Disorder (ASD) more prevalent in males than females?

Why Autism is More Prevalent in Boys

The higher prevalence of autism in boys results from a combination of biological protective mechanisms in females (the "female protective effect") and diagnostic bias that systematically under-identifies girls with ASD. 1

The True Male-to-Female Ratio

The commonly cited 4:1 male-to-female ratio is inflated. High-quality studies that screen general populations show the actual ratio is closer to 3:1, with diagnostic gender bias causing girls who meet ASD criteria to be disproportionately missed. 2 The reported ratios range from 1.33:1 to 15.7:1 depending on study methodology, with lower ratios found when researchers actively screen populations rather than relying on pre-existing diagnoses. 1, 2

Biological Mechanisms: The Female Protective Effect (FPE)

The most compelling biological explanation is the female protective effect, which suggests specific factors protect females from developing ASD and create a higher threshold for clinical impairment. 1

Evidence Supporting the FPE:

• Females with ASD carry a greater genetic burden than males with ASD, requiring more severe genetic risk to manifest the disorder. 1
• Siblings of female probands show higher autism symptom scores than siblings of male probands, indicating females need more genetic loading to express ASD. 1
• With comparable genetic risk, males are more likely to meet clinical criteria than females—for example, males with SHANK1 microdeletions meet ASD criteria while females with the same mutation show only anxiety. 1

Proposed Mechanisms:

• Sex chromosomes: Either the Y chromosome confers risk or a second X chromosome is protective, supported by increased ASD rates in Turner syndrome (XO) and 47,XYY syndrome. 1
• Sex hormones: Fetal testosterone levels correlate with systematizing traits, social impairments, and reduced empathy; adults with ASD have elevated testosterone metabolites. 1, 3
• Differential gene expression: Sex-specific brain gene expression patterns and synaptic function differences, including excitation/inhibition ratio imbalances, contribute to ASD manifestation. 3

Diagnostic Bias: Why Girls Are Missed

Girls with ASD present with less disruptive, more internalized symptoms that fail to trigger clinical evaluation. 1

Gender Differences in Presentation:

• Boys exhibit externalizing symptoms: aggression, stereotypies, hyperactivity, oppositional defiant disorder, and conduct disorder—behaviors that are readily apparent and disruptive. 1, 4
• Girls exhibit internalizing symptoms: anxiety, depression, and mood disorders that mask ASD features and are less likely to prompt referral. 1, 4
• Girls' behaviors are less overt, meaning only those with severe impairment reach diagnostic attention. 1

The Severity Paradox:

Females with ASD tend to show greater cognitive impairment when diagnosed, with male-to-female ratios approaching 1:1 in severely intellectually disabled populations. 1 Conversely, when girls are identified early through high-risk sibling studies, they show higher cognitive functioning than expected, suggesting many higher-functioning girls remain undiagnosed. 5

Girls diagnosed with ASD deviate further from the female population mean than boys with ASD deviate from the male population mean, indicating diagnosed girls represent a more extreme phenotype. 6

Clinical Implications

Screening Considerations:

• Screen for sex-specific comorbidities: Look for internalizing disorders (anxiety, depression) in girls and externalizing disorders (ODD, conduct disorder) in boys. 1, 4
• Use sex-specific comparison norms when evaluating autistic traits, as girls may meet criteria when compared to female norms but not male-based diagnostic thresholds. 6
• Evaluate girls with less obvious presentations, particularly those with anxiety or social difficulties without overt disruptive behaviors. 1

Common Pitfalls:

• Assuming the 4:1 ratio reflects true prevalence rather than diagnostic bias leads to under-identification of girls. 2
• Using male-typical symptom profiles as the diagnostic standard misses girls whose ASD manifests differently. 1
• Failing to screen for comorbid internalizing conditions in girls that mask core ASD symptoms. 1, 4

Treatment Implications:

Target sex-specific symptom profiles therapeutically: address externalizing behaviors in boys and internalizing symptoms in girls, though no hypothesis-driven treatment studies have specifically targeted females with ASD to date. 1