TY - JOUR
T1 - Overlap of autism and conditions associated with atypical sex hormone levels or response
T2 - A systematic review and meta-analysis
AU - May, Tamara
AU - Yi, Karen Lee Jing
AU - Loveland, Kate L.
AU - Vollenhoven, Beverley
AU - Williams, Katrina
PY - 2021/2
Y1 - 2021/2
N2 - Background: This review explored any altered risk of Autism Spectrum Disorder (ASD) associated with conditions with a known or postulated atypical exposure to androgens and oestrogens in early fetal development, and conditions associated with atypical hormone levels and responses within an individual. Method: Searches of Ovid Medline, PsychInfo and PubMed were completed until November 2019 with inclusion criteria of cohort, case control or clinical studies exploring the overlap of ASD with hormone-related conditions. Results: Of 2640 studies, 49 met inclusion criteria exploring: Polycystic ovarian syndrome (PCOS), Klinefelter Syndrome, Turner Syndrome, Congenital Adrenal Hyperplasia (CAH), cryptorchidism, hypospadias, hirsutism; ovarian, uterine, testicular, cervical cancer; hypergonadotropic hypogonadism. Half had low risk of bias, with confidence in findings ranging from Very Low to Moderate, with all studies observational. Meta-analyses indicated 5 of 23 analyses had significant associations; with significantly increased odds of ASD in women with PCOS 1.48 [95 % CI 1.21–1.80], ASD in offspring of mothers with PCOS 1.53 [95 % CI 1.37–1.72]; but no increased odds of ASD in women with CAH, hirsutism or cancer. In conditions associated with reduced androgens, meta-analyses found an unexpected increased odds of ASD in hypospadias 1.38 [95 % CI 1.07–1.77], cryptorchidism 1.38 [95 % CI 1.11–1.71], and Klinefelter syndrome 6.39 [95 % CI 4.21–9.71]. Conclusion: The androgen hypothesis was supported by 2 of 25 outcomes with 4 outcomes having opposite findings. Other complex factors are likely involved including genetic influences which may override simple sex hormone associations, as well as confounding pregnancy and birth factors inflating associations in some conditions.
AB - Background: This review explored any altered risk of Autism Spectrum Disorder (ASD) associated with conditions with a known or postulated atypical exposure to androgens and oestrogens in early fetal development, and conditions associated with atypical hormone levels and responses within an individual. Method: Searches of Ovid Medline, PsychInfo and PubMed were completed until November 2019 with inclusion criteria of cohort, case control or clinical studies exploring the overlap of ASD with hormone-related conditions. Results: Of 2640 studies, 49 met inclusion criteria exploring: Polycystic ovarian syndrome (PCOS), Klinefelter Syndrome, Turner Syndrome, Congenital Adrenal Hyperplasia (CAH), cryptorchidism, hypospadias, hirsutism; ovarian, uterine, testicular, cervical cancer; hypergonadotropic hypogonadism. Half had low risk of bias, with confidence in findings ranging from Very Low to Moderate, with all studies observational. Meta-analyses indicated 5 of 23 analyses had significant associations; with significantly increased odds of ASD in women with PCOS 1.48 [95 % CI 1.21–1.80], ASD in offspring of mothers with PCOS 1.53 [95 % CI 1.37–1.72]; but no increased odds of ASD in women with CAH, hirsutism or cancer. In conditions associated with reduced androgens, meta-analyses found an unexpected increased odds of ASD in hypospadias 1.38 [95 % CI 1.07–1.77], cryptorchidism 1.38 [95 % CI 1.11–1.71], and Klinefelter syndrome 6.39 [95 % CI 4.21–9.71]. Conclusion: The androgen hypothesis was supported by 2 of 25 outcomes with 4 outcomes having opposite findings. Other complex factors are likely involved including genetic influences which may override simple sex hormone associations, as well as confounding pregnancy and birth factors inflating associations in some conditions.
KW - Autism spectrum disorder
KW - Congenital adrenal hyperplasia
KW - Cryptorchidism
KW - Hirsutism
KW - Hormones
KW - Hypospadias
KW - Klinefelter syndrome
KW - Polycystic ovarian syndrome
KW - Turner syndrome
UR - http://www.scopus.com/inward/record.url?scp=85098491178&partnerID=8YFLogxK
U2 - 10.1016/j.rasd.2020.101693
DO - 10.1016/j.rasd.2020.101693
M3 - Review Article
AN - SCOPUS:85098491178
VL - 80
JO - Research in Autism Spectrum Disorders
JF - Research in Autism Spectrum Disorders
SN - 1750-9467
M1 - 101693
ER -