Abstract
Background: It has been suggested that autistic patients have elevated blood androgens, and although signs of precocious puberty have been reported in autistic patients, such a relation has not yet been clarified.
Objectives: To assess serum androgen levels in a group of Egyptian male autistic children and adolescents and their relation to disease severity. In addition, the risk for association of androgens with autism was estimated.
Methods: In comparison to 20 controls, 30 male autistic children were studied. All subjects were subjected to clinical evaluation, intelligence quotient (IQ) assessment and measurement of serum free testosterone (FT), dehydroepiandosterone (DHEA) and Δ4-androstenedione (Δ4-A).
Results: Androgens were higher in autistic patients than in controls and increased with increased autistic severity. Of the patients, 11 (36.66%) had high FT, 9 (30%) had high DHEA, 12 (40%) had high Δ4-A and 8 (26.66%) showed elevation of all androgen levels. FT (OR: 38.45, 95% CI: 2.14–688.93, p=0.013) and Δ4-A (OR: 13.6, 95%CI: 2.25–22.89, p=0.04) had a significant risk for association with autism.
Conclusions: Hyperandrogenemia is prevalent in autistic patients and increases with autistic severity. Thus, androgen levels should be assessed in autistic patients with signs of early puberty. Further studies are warranted regarding trials of anti-androgen therapy in such patients.
References
1. Arndt TL, Stodgell CJ, Rodier PM. The teratology of autism. Int J Dev Neurosci 2005;23:189–99.10.1016/j.ijdevneu.2004.11.001Search in Google Scholar PubMed
2. Bailey A, Luthert P, Dean A, Harding B, Janota I, et al. Clinicopathological study of autism. Brain 1998;121:889–905.10.1093/brain/121.5.889Search in Google Scholar PubMed
3. Baron-Cohen S, Knickmeyer R, Belmonte MK. Sex differences in the brain: implications for explaining autism. Science 2005;310:819–23.10.1126/science.1115455Search in Google Scholar PubMed
4. Lutchmaya S, Baron-Cohen S, Raggatt P, Knickmeyer R, Manning JT. 2nd to 4th digit ratios, fetal testosterone and estradiol. Early Hum Dev 2004;77:23–8.10.1016/j.earlhumdev.2003.12.002Search in Google Scholar PubMed
5. Herbert MR, Ziegler DA, Deutsch CK, O’Brien LM, Kennedy DN, et al. Brain asymmetries in autism and developmental language disorder: a nested whole-brain analysis. Brain 2005;128:213–26.10.1093/brain/awh330Search in Google Scholar PubMed
6. Knickmeyer RC, Fane BA, Mathews G, Wheelwright S, Baron-Cohen S, et al. Autistic traits in people with congenital adrenal hyperplasia: a test of the fetal testosterone theory of autism. Horm Behav 2006;50:148–53.10.1016/j.yhbeh.2006.02.006Search in Google Scholar PubMed
7. Ingudomnukul E, Baron-Cohen S, Wheelwright S, Knickmeyer R. Elevated rates of testosterone related disorders in women with autism spectrum conditions. Horm Behav 2007;51:597–604.10.1016/j.yhbeh.2007.02.001Search in Google Scholar PubMed
8. Geier DA, Geier MR. A prospective assessment of androgen levels in patients with autistic spectrum disorders: biochemical underpinnings and suggested therapies. Neuro Endocrinol Lett 2007;28:565–73.Search in Google Scholar
9. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association, 1994.Search in Google Scholar
10. Schopler E, Reichler RJ, Renner BR. The childhood autism rating scale (CARS) for diagnostic screening and classification in autism. New York: Irvington, 1986.Search in Google Scholar
11. Terman LM, Merrill MA. Stanford-Binet intelligence scale: manual for the 3rd Revision Form L-M. Chicago: The Riverside Publishing Company, 1973.Search in Google Scholar
12. Tanner JM, Whitehouse RH, Takaishi M. Standards from birth to maturity for height, weight, height velocity and weight velocity: British children, 1965. Arch Dis Child 1966;41:454–613.10.1136/adc.41.219.454Search in Google Scholar PubMed PubMed Central
13. Tanner JM, Whitehouse RH. Clinical longitudinal standards for height, weight, height velocity, weight velocity and stages of puberty. Arch Dis Child 1976;51:170–9.10.1136/adc.51.3.170Search in Google Scholar PubMed PubMed Central
14. Prader A. Testicular size: assessment and clinical importance. Triangle 1966;7:240–3.Search in Google Scholar
15. Ankarberg-Lindgren C, Norjavaara E. Changes of diurnal rhythm and levels of total and free testosterone secretion from pre to late puberty in boys: testis size of 3 ml is a transition stage to puberty. Eur J Endocrinol 2004;151:747–57.10.1530/eje.0.1510747Search in Google Scholar PubMed
16. Lashansky G, Saenger P, Fishman K. Normative data for adrenal steroidogenesis in a healthy pediatric population: age- and sex-related changes after adrenocorticotropin stimulation. J Clin Endocrinol Metab 1991;73:674–86.10.1210/jcem-73-3-674Search in Google Scholar
17. Tordjman S, Ferrari P, Sulmont V, Duyme M, Roubertoux P. Androgenic activity in autism. Am J Psychiatry 1997;154:1626–27.10.1176/ajp.154.11.1626-aSearch in Google Scholar
18. Majewska MD, Hill M, Urbanowicz E, Rok-Bojko P, Namyslowska I, et al. Different levels of salivary steroids in autistic and healthy children. Eur Neuropsychopharmacol 2010;20(suppl 2):S615–6.10.1016/S0924-977X(10)70941-XSearch in Google Scholar
19. Ruta L, Ingudomnukul E, Taylor K, Chakrabati B, Baron-Cohen S. Increased serum androstenedione in adults with autism spectrum conditions. Psychoneuroendocrinology 2011;36:1154–63.10.1016/j.psyneuen.2011.02.007Search in Google Scholar PubMed
20. Takagishi H, Takahashi T, Yamagishi T, Shinada M, Inukai K, et al. Salivary testosterone levels and autism spectrum quotient in adults. Neuro Endocrinol Lett 2010;31:837–41.Search in Google Scholar
21. Moilanen AM, Karvonen U, Poukka H, Janne OA, Palvimo JJ. Activation of androgen receptor function by a novel nuclear protein kinase. Mol Biol Cell 1998;9:2527–43.10.1091/mbc.9.9.2527Search in Google Scholar PubMed PubMed Central
22. Van Honk J, Schutter DJ, Bos PA, Kruijt AW, Lentjes EG, et al. Testosterone administration impairs cognitive empathy in women depending on second-to-fourth digit ratio. Proc Natl Acad Sci USA 2011;108:3448–52.10.1073/pnas.1011891108Search in Google Scholar PubMed PubMed Central
23. Auyeung B, Baron-Cohen S, Ashwin E, Knickmeyer R, Taylor K, et al. Fetal testosterone and autistic traits. Br J Psychol 2009;100:1–22.10.1348/000712608X311731Search in Google Scholar PubMed
24. Knickmeyer R, Baron-Cohen S, Raggatt P, Taylor K. Fetal testosterone, social relationships, and restricted interests in children. J Child Psychol Psychiatry 2005;46:198–210.10.1111/j.1469-7610.2004.00349.xSearch in Google Scholar PubMed
25. Krajmer P, Spajdel M, Kubranska A, Ostatnikova D. 2D:4D finger ratio in Slovak autism spectrum population. Bratisl Lek Listy 2011;112:377–9.Search in Google Scholar
26. Chakrabarti B, Dudbridge F, Kent L, Wheelwright S, Hill- Cawthorne G, et al. Genes related to sex steroids, neural growth, and social-emotional behavior are associated with autistic traits, empathy, and Asperger syndrome. Autism Res 2009;2:157–77.10.1002/aur.80Search in Google Scholar PubMed
27. Zhou R, Bird IM, Dumesic DA, Abbott DH. Adrenal hyperandrogenism is induced by fetal androgen excess in a rhesus monkey model of polycystic ovary syndrome. J Clin Endocrinol Metab 2005;90:6630–37.10.1210/jc.2005-0691Search in Google Scholar PubMed PubMed Central
28. Dorn LD, Hitt SF, Rotenstein D. Biopsychological and cognitive differences in children with premature vs. on-time adrenarche. Arch Pediatr Adolesc Med 1999;153:137–46.Search in Google Scholar
29. Vargas DL, Nascimbene C, Krishnan C, Zimmerman AW, Pardo CA. Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol 2005;57:67–81.10.1002/ana.20315Search in Google Scholar PubMed
30. Strous RD, Golubchik P, Maayan R, Mozes T, Tuati-Werner D, et al. Lowered DHEA-S plasma levels in adult individuals with autistic disorders. Eur Neuropsychopharmacol 2005;15: 305–9.10.1016/j.euroneuro.2004.12.004Search in Google Scholar PubMed
31. Tanaka T, Hibi I, Kato K, Saito S, Shimizu N, et al. A dose finding study of a super long-acting luteinizing hormone-releasing hormone analog (leuprolide acetate depot, TAP-144-SR) in the treatment of central precocious puberty. The TAP-144-SR CPP Study Group. Endocrinol Jpn 1991;38:369–76.10.1507/endocrj1954.38.369Search in Google Scholar PubMed
32. Bhathena RK. Therapeutic options in the polycystic ovary syndrome. J Obstet Gynaecol 2007;27:123–9.10.1080/01443610601113797Search in Google Scholar PubMed
33. Farquhar C, Lee O, Toomath R, Jepson R. Spironolactone versus placebo or in combination with steroids for hirsutism and/or acne. Cochrane Database Syst Rev 2003;4:CD000194.Search in Google Scholar
34. Zhang X, Zhang Z, Cheng W, Mou X, Reynolds GP. The effect of chronic antipsychotic treatment on sexual behavior, hormones and organ size in the male rat. J Psychopharmacol 2007;21:428–34.10.1177/0269881106068702Search in Google Scholar PubMed
35. Berria R, Gastaldelli A, Lucidi S, Belfort R, De Filippis E, et al. Reduction in hematocrit level after pioglitazone treatment is correlated with decreased plasma free testosterone level, not hemodilution, in women with polycystic ovary syndrome. Clin Pharmacol Ther 2006;80:105–14.10.1016/j.clpt.2006.03.014Search in Google Scholar PubMed
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