Table 1.

Studies Which have Investigated Levels of Testosterone in Autism Spectrum Disorder

Testosterone in autism spectrum disorders
Authors	Sample	Study aims	Main findings
Auyeung et al. [2009]	The Childhood Autism Spectrum Test (CAST) and the Child Autism Spectrum Quotient (AQ‐Child) were used to assess ASD traits and were completed by the women about their children (n = 235), ages 6–10 years. Intelligence Quotient (IQ) was measured in a subset of children (n = 74).	To examine the relationship between ASD traits and FT levels in amniotic fluid which was measured during routine amniocentesis.	There was a positive association between levels of FT and higher scores on both the CAST and AQ‐Child, independent of sex which supports the hypothesis that prenatal androgen exposure is associated a greater number of ASD traits in children.
Auyeung et al. [2010]	129 typically developing toddlers (age range = 18 and 24 months, mean age = 19.25 months, SD = 1.52 months).	To investigate whether fetal testosterone (FT) is positively correlated with traits of ASD in toddlers aged between 18 and 24 months. FT levels were measured in the amniotic fluid and compared with autistic traits which were assessed using the Quantitative Checklist for Autism in Toddlers (Q‐CHAT).	Study found sex differences in Q‐CHAT scores, with significantly higher scores found in the boys (suggesting a greater number of autistic traits) compared to girls. Moreover, there was a significant positive relationship between levels of FT and autistic traits
Baron‐Cohen et al. [2015]	Control group (n = 217) and autism group (n = 128). Participants were selected from a population of singleton births between 1993 and 1999 (n = 19,677).	To investigate the prediction that fetal steroidogenic activity is elevated in ASD. Specifically, the study measured concentration levels of Δ4 sex steroids (progesterone, 17α‐hydroxy‐progesterone, androstenedione, and testosterone) and cortisol with liquid chromatography tandem mass spectrometry.	Study found that the autism group had elevated levels of all hormones on this latent generalized steroidogenic factor (Cohen's d = 0.37, P = 0.0009) and this elevation was found to be uniform across ICD‐10 diagnostic label.
Ingudomnukul et al. [2007]	A number of groups including: women with ASD (n =54), mothers of children with ASD (n = 74) and mothers of typically developing children (n = 183)	To examine the rate of testosterone‐related medical conditions in women with ASD and mothers of children with ASD, as part of the “broader autism phenotype.”	Elevated levels of fetal testosterone (FT) show a positive correlation with a variety of ASD traits and an inverse correlation with social development and empathy. Significantly more women with ASD, when compared to controls, were found to have conditions associated with elevated levels of androgen including: hirsutism; bisexuality or asexuality; irregular menstrual cycle; dysmenorrhea; polycystic ovary syndrome; severe acne; epilepsy; “tomboyism” and a family history of ovarian, uterine, and prostate cancers, tumours, or growths. Additionally, compared to mothers of typically developing children, there were significantly more reports of severe acne, breast and uterine cancers, tumors, or growths, and family history of ovarian and uterine cancers, tumours, or growths in the mothers of children with ASD.
Knickmeyer, Baron‐Cohen, Fane et al. [2006]	Sixty individuals with congenital adrenal hyperplasia (CAH) (34 female, 26 male) and 49 unaffected relatives (24 female, 25 male)	To investigate the hypothesis that autistic traits are increased following prenatal exposure to abnormally high levels of testosterone caused by CAH.	Study found a greater number of ASD traits in girls with abnormally high fetal testosterone (FT) levels as a result of CAH compared to their unaffected sisters. These findings have led to the androgen theory of ASD which proposes that elevated levels of FT are a contributory factor in ASD occurrence.
Kosidou et al. [2016]	23,748 ASD cases and 208,796 controls. Children aged 4–17 who were born in Sweden from 1984 to 2007.	A population‐based study to investigate the relationship between maternal diagnosis of polycystic ovary syndrome (PCOS) and the risk of ASD in the offspring.	Study found that maternal PCOS increased the odds of ASD in the offspring by 59%, following adjustment for confounding factors (odds ratio [OR] 1.59, 95% confidence interval [CI] 1.34–1.88). Findings also revealed that the odds of offspring ASD were even greater in mothers with both PCOS and obesity, a condition common to PCOS that is related to more severe hyperandrogenemia (OR 2.13, 95% CI 1.46–3.10). There were no differences in risk estimates between sexes.
Takagishi et al. [2010]	92 healthy, Japanese adults (45 males and 47 females, mean age = 47.9, SD = 12.4; age range = 21–68).	To investigate whether the relationship between testosterone levels and ASD traits found in numerous studies on young children is also supported by data on adults. Indeed, one study examined the relationship between salivary testosterone levels and ASD traits [using the Japanese version of Autism Spectrum Quotient (AQ)] in 92 healthy, Japanese adults.	When males and females were combined into one group, there was a positive correlation between T and AQ. However, this correlation did not occur when correlation analysis by sex was performed. No sex difference in the score of the subscale of attention switching were found in relation to T.
Whitehouse et al. [2012]	184 males (M = 20.10 years; SD= 0.65 years) and 190 females (M = 19.92 years; SD = 0.68 years). Also, umbilical cord blood was collected from 707 children	To investigate, for the first time, the prospective relationship between umbilical cord testosterone concentrations and characteristics of autism.	Findings suggest that testosterone concentrations from umbilical cord blood are unrelated to autistic‐like traits in the general population. Findings do not exclude an association between testosterone exposure in early intrauterine life and ASD.

CAST, the childhood autism spectrum test; AQ‐Child, child autism spectrum quotient; IQ, intelligence quotient; ASD, autism spectrum disorders; FT, fetal testosterone; M, mean; SD, standard deviation; Q‐CHAT, quantitative checklist for autism in toddlers; CAH, congenital adrenal hyperplasia; PCOS, polycystic ovary syndrome; AQ, autism spectrum quotient; T, testosterone.