NCT05811507

Evaluation of Serum Adrenal Androgens Among Prepubertal and Pubertal Boys With Autism Spectrum Disorder

Status unknown Last updated 12 April 2023

What this trial tests

trial testing serum total testosterone, serum androsterone, serum androstenedione and serum dehydroepiandrosterone sulfate in Autism Spectrum Disorder in 100 participants. Status unknown.

Timeline

1 April 2023

Primary endpoint
1 April 2024

1 April 2024

Quick facts

Lead sponsor	Sohag University
Status	Status unknown
Study type	OBSERVATIONAL
Enrollment	100
Start date	1 April 2023
Primary completion	1 April 2024
Estimated completion	1 April 2024
Sites	1 location across Egypt

Drugs / interventions tested

• serum total testosterone, serum androsterone, serum androstenedione and serum dehydroepiandrosterone sulfate
• The Childhood Autism Rating Scale (CARS)
• DSM-5 Diagnostic Criteria for ASD
• Assesment of IQ: The Stanford-Binet V (Stanford-Binet Intelligence Scales):

Conditions studied

• Autism Spectrum Disorder — all drugs for Autism Spectrum Disorder →

Sponsor

Sohag University

Who can join

Adults 6 to 18, male only, with Autism Spectrum Disorder.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• serum total testosterone level.
  Time frame: baseline
  serum total testosterone level will be measured in (nglml).
• serum dehydroepiandrosterone sulfate (DHEAS) level
  Time frame: baseline
  serum dehydroepiandrosterone sulfate (DHEAS) will be measured in (mcgldl)
• serum androsterone level
  Time frame: baseline
  serum androsterone level will be measured in (nglml)
• serum androstenedione level
  Time frame: baseline
  serum androstenedione level will be measured in (nglml)
• Assessment of severity of autism
  Time frame: baseline
  Assessment of severity of autism by Childhood Autism Rating Scale (CARS)

Sponsor's own description

Autism spectrum disorder (ASD) is a neurodevelopmental disorder of unclear etiology. There are theories depicting the importance of sex steroid hormones in autism, since the prevalence of the disorder is male-biased. What makes boys more vulnerable to achieve the diagnosis of autism remains unclear. One of the theories strengthens the importance of fetal organizational effect of testosterone on brain development. Baron Cohen with coworkers showed that elevated fetal levels of several androgens including testosterone were high in male-fetuses who later in postnatal life achieved the diagnosis of autism and fetal testosterone levels were positively correlated with autistic traits in general population.

Females with conditions of abnormal prenatal exposure to testosterone and its sex steroid precursors, such as congenital adrenal hyperplasia and polycystic ovary syndrome, were found to have higher rate of autistic traits as well as their children were of higher risk of developing autism. However, the exact mechanism by which these hormones influence the manifestation of autistic traits remains undiscovered. Another model explaining higher prevalence of ASD in males is a female protective model which suggests that multiple genetic factors contribute to the development of ASD and that higher threshold of genetic liability is required in females compared to males. Zhang et al. demonstrated genetic evidence of sex differences in ASD confirming female protective model, employing investigation of de novo mutations, common variants of ASD candidate genes and their co-expression in male and female brain.

During infancy: The Gonadotropin releasing hormone (GnRH) pulse generator is reactivated by 6 to 10 days after birth. This period, termed the mini puberty of infancy, was first described in the 1970s. During mini puberty, luteinizing hormone (LH) levels approximate pubertal concentrations, reaching a peak between 16 and 20 days of life. Serum testosterone levels rise in response to rising concentrations of LH, paralleling an increase in Leydig cell number and testicular testosterone concentrations. Serum testosterone levels peak from 1 to 3 months (210 ± 130 ng/dL or 7.28 ± 4.51 nmol/L on day of life 30) and decline by roughly 50% per month reaching prepubertal levels by 7 to 12 months of age. Dihydrotestosterone (DHT) concentrations parallel the rise in testosterone, reaching pubertal values during the early postnatal period.

During puberty: Testosterone is produced primarily by the testes, though a small amount is also made in the adrenal gland. Gonadarche refers to the onset of sex steroid production from the gonads and occurs in response to pulsatile production of GnRH from the hypothalamus, which in turn stimulates production of LH and Follicle stimulating hormone (FSH) from the pituitary gland. LH stimulates the Leydig cells to produce testosterone, whereas FSH stimulates the Sertoli cells to proliferate and initiate spermatogenesis.

Active androgens are synthesized via two alternative pathways. The first of them is known as the classic "frontdoor" pathway with pregnenolone serving as androgen precursor, which underwent a conversion to DHEA and subsequently to androstenediol. These metabolic steps are catalyzed by CYP17A1 (in the C17,20-lyase step) and (mostly adrenal) AKR1C3 enzyme, respectively. Dehydroepiandrosterone (DHEA) and androstenediol are readily sulfated by SULT2A1 in adrenal cortex and their sulfates serve as the stock pool for the production of active androgens of the adrenal origin as the production of androgens in early childhood of boys is limited to extra-gonadal tissues, such as adrenal, skin, etc. These sulfated primary androgens may be subsequently deconjugated and metabolized by HSD3B1 and HSD3B2 isoforms to androstenedione and Total testosterone (TST) and then to 5α/β-reduced 17-oxo- and 17β-androgens, respectively. In addition, the androstenedione may be readily converted to testosterone by adrenal AKR1C

Publications & conference data

No peer-reviewed publications indexed yet for this trial.