Abstract
Introduction: There is increasing evidence that steroid hormone levels and, especially, androgen levels are elevated in autism. An overactivity of 17, 20-lyase with a higher production of the testosterone precursors dehydroepiandrosterone (DHEA) and androstenedione/androstenediol seems especially present in autism. Methods: An encompassing literature analysis was performed, searching for altered androgens in children with autism and using preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines. Included were all studies published before 31 March 2021 found using the following electronic databases: PubMed, Google Scholar, Cochrane Library, Scopus, and TRIP. Eight studies with boys and three studies with girls where steroid hormone measurements were performed from either plasma, urine, or saliva were found and analyzed. Analyses were performed for DHEA(-S/-C), androstenedione/androstenediol, and testosterone. Effect sizes were calculated for each parameter between mean concentrations for children with autism versus healthy controls. Results: Higher levels of androgens in autism were detected, with the majority of calculated effect sizes being larger than one. Conclusions: We found higher levels of the main testosterone precursors DHEA, androstenedione, and androstenediol, likely causing an additionally higher level of testosterone, and an increased 17, 20-lyase activity is therefore implied. Medications already used in PCOS such as metformin might be considered to treat hyperandrogenism in autism following further research.
Highlights
There is increasing evidence that steroid hormone levels and, especially, androgen levels are elevated in autism
We present relatively straightforward evidence that DHEA, androstenedione, and testosterone levels are higher in such children and, as a consequence, an increased activity of 17, 20-lyase is present
Oxidative stress has previously been noted numerous times to be involved in the pathogenesis of autism and might yield high androgen levels [50,57]
Summary
There is increasing evidence that steroid hormone levels and, especially, androgen levels are elevated in autism. An overactivity of 17, 20-lyase with a higher production of the testosterone precursors dehydroepiandrosterone (DHEA) and androstenedione/androstenediol seems especially present in autism. The involvement of the HPA axis and cholesterol as precursors of steroid hormones as well as sex hormones, androgens in particular, due to their higher prevalence in boys than in girls, were suggested to be altered in children with autism [1,2]. In addition to studies directly analyzing androgens from urine, saliva, serum/plasma, and amniotic fluid, clear associations between changes in androgen levels and autism have been observed. Xu et al (2013) measured higher testosterone levels in mothers of children with autism [9]. Differences have been found on the level of the hypothalamus [15,16], the pituitary gland [21,23,24,25], and the adrenal gland [5,24]
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