Overlap of autism and conditions associated with atypical sex hormone levels or response: A systematic review and meta-analysis. (February 2021)

• Record Type: Journal Article
• Authors: May, Tamara; Yi, Karen Lee Jing; Loveland, Kate L.; Vollenhoven, Beverley; Williams, Katrina
• Is Part Of: Research in autism spectrum disorders. Volume 80(2020)
• Publication Date: 2021-02
• Subjects: Autism spectrum disorder -- Hormones -- Polycystic ovarian syndrome -- Congenital adrenal hyperplasia -- Klinefelter syndrome -- Turner syndrome -- Hypospadias -- Cryptorchidism -- Hirsutism; Autism spectrum disorders -- Periodicals; 616.85882005
• DOI: 10.1016/j.rasd.2020.101693
• Languages: English
• ISSNs: 1750-9467

Abstract

Highlights: This review explored an association between conditions associated with altered levels fetal hormones and autism spectrum disorder. This systematic review and meta-analysis identified 49 studies with overall very low to moderate quality evidence. Meta-analyses indicated 5 of 23 analyses had significant associations with two in the direction expected by the androgen hypothesis. Other complex factors are likely involved including genetic influences which may override simple sex hormone associations. Abstract: 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.