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Testosterone in ADHD


Testosterone in ADHD

1. Case studies: Testosterone as an effective ADHD medication in single cases

In three male Caucasian ADHD sufferers with ADHD-C aged 24, 37, and 43, ADHD symptoms improved with testosterone monotherapy within one week and remained so permanently (10-60 mg testosterone/day as a skin gel).1
Winter depression and sleep problems also improved.
Before testosterone treatment, patients’ serum levels were 12 - 16 nmol/L (age-specific reference range: 10.4 - 32.6 nmol/L).
The testosterone/sex hormone-binding globulin ratio was low in two patients (0.32 and 0.34; age-specific reference range: 0.38-1.1), indicating low free serum levels of testosterone.
With testosterone treatment, serum testosterone levels and the ratio of testosterone to sex hormone-binding globulin increased but remained within reference values.
Only the youngest of the three subjects had a loss of libido while on MPH.
Testosterone treatment did not result in any strong side effects for the subjects, especially no increase in aggressiveness.
In the case of testosterone therapy, it is recommended to regularly monitor:

  • Polycythemia
  • Plasmalipids
  • Liver function
  • Prostate function
  • Heart function
  • Blood pressure
  • Sleep apnea
  • Irritability
  • Mood swings.

Moderately decreased serum levels of free testosterone appear to contribute to ADHD symptoms in some adult male ADHD patients.
Testosterone treatment could be beneficial for these patients.
Nevertheless, these case studies do not allow a generalization that testosterone would be a generally effective drug for ADHD. ADHD has hundreds, if not thousands, of different causes. The fact that a treatment is effective in individual sufferers does not allow any conclusion to be drawn as to how often this would also be the case in other sufferers.

2. MPH and testosterone

One study found no effect of 4 weeks of MPH use on testosterone levels in ADHD.2
A 12-month study of ADHD sufferers (mean: 8.9 years) found significant serum level changes due to MPH:

  • reduced:
    • SHBG
    • Progesterone
  • increased:
    • LH
    • FSH
    • free testosterone.

Duration, formulation, and dosage of MPH did not affect gonadal hormone development or Tanner stage.3
A group of 7 case studies reported a correlation between MPH use and premature puberty. Basal hormone levels (luteinizing hormone [LH], follicle-stimulating hormone, and estrogen/testosterone) were within the normal range.4
A large cohort study found no correlation between MPH use and testicular dysfunction in boys with ADHD.5

A correlation between MPH intake and decline in serum testosterone was found in a long-term treatment in macaque monkeys6 and in two case studies in humans.78
In rats, a small study found an increase in testicular weight and sperm count due to MPH. The authors concluded that subchronic MPH exposure in adolescent rats could have a trophic effect on testicular growth and a negative influence on testosterone metabolism.9

3. AMP and steroids

Lisdexamfetamine and d-amphetamine significantly increased plasma levels of in a randomized double-blind placebo-controlled study in healthy subjects:10

  • adrenocorticotropic hormone
  • Glucocorticoids (here similar to MPH)
    • Cortisol
    • Cortisone
    • Corticosterone
    • 11-Dehydrocorticosterone
    • 11-Desoxycortisol
  • Androgens
    • Dehydroepiandrosterone
    • Dehydroepiandrosterone sulfate
    • Δ4-Androstene-3,17-dione [androstene dione]
  • Progesterone (only in men)

Unchanged were the plasma levels of vion

  • Mineralocorticoids
    • Aldosterone
    • 11-Desoxycorticosterone
  • of the androgen testosterone

4. Other about testosterone in ADHD

In prepubertal ADHD sufferers, serum testosterone levels and serum androstenedione levels correlated with measures of autistic traits, whereas serum oxytocin levels were significantly higher.11

Two studies found significantly increased ADHD symptoms in users of anabolic (androgenic) steroids (AAS) in weight training. AAS are testosterone derivatives.1213 The authors conclude that there is a risk potential of AAS for ADHD symptoms. Against the background described above, it is equally conceivable that the use of AAS could represent self-medication, which could subsequently lead to addiction,

Prenatal testosterone exposure correlated significantly with inattention and hyperactivity/impulsivity in the offspring.14
Prenatal testosterone exposure is (indirectly) indexed by a low index finger to ring finger length ratio (Longer index finger divided by length of ring finger, 2D:4D), whereas a high 2D:4D indicates high prenatal estrogen exposure.15. One study found a significant correlation between a low 2D:4D ratio and ADHD in German men, but not in German women or Chinese men or women.16 Another study found an association of high prenatal testosterone (i.e., lower right 2D:4D) with high hyperactive-impulsive ADHD symptoms in girls but not in preschool-aged boys.17
Another study found no association between 2D:4D and ADHD symptoms or ADHD subtypes in children with ADHD.18
The association between a more masculine right 2D:4D (i.e., increased prenatal testosterone exposure) and increased ADHD inattention symptomatology could be mediated by decreased conscientiousness.19

One study found in both boys and girls with ADHD20

  • DHEA-S reduced
    • low DHEA-S correlated with higher impulsivity
  • SHBG unchanged
    • low SHGB correlated with increased ADHD symptoms
  • free testosterone unchanged
    • no correlation of free testosterone to ADHD symptoms

In SHR (Spontaneously hypertensive rats), serum level comparison to WKR (Wistar-Kyoto rats) found:21

  • Testosterone and free estriol increased in 10-week-old SHR and WKR compared with 5-week-old SHR and WKR
  • Progesterone, corticosterone, and cortisol elevated in 10-week-old SHR compared with 5-week-old SHR and 5 or 10-week-old WKR

According to one hypothesis, the preponderance of males affected by behavioral disorders in childhood may be influenced by excess testosterone and the preponderance in females affected by emotional disorders in adolescence and adulthood may be influenced by excess estrogen.22

  1. Rogne A, Hassel B (2022): Improvement of attention deficit/hyperactivity disorder (ADHD) in three adult men during testosterone treatment: a case series. J Med Case Rep. 2022 Nov 18;16(1):425. doi: 10.1186/s13256-022-03651-w. PMID: 36397172; PMCID: PMC9673294.

  2. Wang LJ, Chou MC, Chou WJ, Lee MJ, Lin PY, Lee SY, Lee YH (2017): Does Methylphenidate Reduce Testosterone Levels in Humans? A Prospective Study in Children with Attention-Deficit/Hyperactivity Disorder. Int J Neuropsychopharmacol. 2017 Mar 1;20(3):219-227. doi: 10.1093/ijnp/pyw101. PMID: 27816940; PMCID: PMC5408967. n = 203

  3. Wang LJ, Huang YH, Chou WJ, Lee SY, Tsai CS, Lee MJ, Chou MC (2020): Potential disturbance of methylphenidate of gonadal hormones or pubescent development in patients with attention-deficit/hyperactivity disorder: A twelve-month follow-up study. Prog Neuropsychopharmacol Biol Psychiatry. 2021 Jun 8;108:110181. doi: 10.1016/j.pnpbp.2020.110181. PMID: 33227299. n = 216

  4. Ergür AT, Gül H, Gül A (2019): Methylphenidate and Central Precocious Puberty: A Probable Side Effect among Seven Children with the Attention Deficit Hyperactivity Disorder. Clin Psychopharmacol Neurosci. 2019 Aug 31;17(3):446-449. doi: 10.9758/cpn.2019.17.3.446. PMID: 31352713; PMCID: PMC6705097.

  5. Wang LJ, Lee SY, Chou WJ, Lee MJ, Tsai CS, Lee TL, Yang CJ, Yang KC, Chen CK, Shyu YC. Testicular Function After Long-Term Methylphenidate Treatment in Boys with Attention-Deficit/Hyperactivity Disorder. J Child Adolesc Psychopharmacol. 2019 Aug;29(6):433-438. doi: 10.1089/cap.2018.0126. Epub 2018 Dec 21. PMID: 30575416. N > 110.000

  6. Mattison DR, Plant TM, Lin HM, Chen HC, Chen JJ, Twaddle NC, Doerge D, Slikker W Jr, Patton RE, Hotchkiss CE, Callicott RJ, Schrader SM, Turner TW, Kesner JS, Vitiello B, Petibone DM, Morris SM (2011): Pubertal delay in male nonhuman primates (Macaca mulatta) treated with methylphenidate. Proc Natl Acad Sci U S A. 2011 Sep 27;108(39):16301-6. doi: 10.1073/pnas.1102187108. PMID: 21930929; PMCID: PMC3182701.

  7. Ramasamy R, Dadhich P, Dhingra A, Lipshultz L (2014): Case Report: Testicular failure possibly associated with chronic use of methylphenidate. F1000Res. 2014 Sep 2;3:207. doi: 10.12688/f1000research.5163.1. PMID: 25383187; PMCID: PMC4215747.

  8. Akaltun İ (2016): Report of a 14-Year-Old Boy Whose Testosterone Level Decreased After Starting on Methylphenidate. J Child Adolesc Psychopharmacol. 2016 Mar;26(2):181. doi: 10.1089/cap.2015.0209. PMID: 26863036.

  9. Adriani W, Leo D, Guarino M, Natoli A, Di Consiglio E, De Angelis G, Traina E, Testai E, Perrone-Capano C, Laviola G (2006): Short-term effects of adolescent methylphenidate exposure on brain striatal gene expression and sexual/endocrine parameters in male rats. Ann N Y Acad Sci. 2006 Aug;1074:52-73. doi: 10.1196/annals.1369.005. PMID: 17105903.

  10. Strajhar P, Vizeli P, Patt M, Dolder PC, Kratschmar DV, Liechti ME, Odermatt A (2019): Effects of lisdexamfetamine on plasma steroid concentrations compared with d-amphetamine in healthy subjects: A randomized, double-blind, placebo-controlled study. J Steroid Biochem Mol Biol. 2019 Feb;186:212-225. doi: 10.1016/j.jsbmb.2018.10.016. PMID: 30381248. n = 24

  11. Artık A, Çengel Kültür SE, Portakal O, Karaboncuk AY (2022): The association between autistic traits and serum testosterone, oxytocin, and androstenedione levels in prepubertal male drug naive children with attention-deficit/hyperactivity disorder. Int J Dev Neurosci. 2022 Nov 18. doi: 10.1002/jdn.10241. PMID: 36398591. n = 86

  12. Kildal E, Hassel B, Bjørnebekk A (2022): ADHD symptoms and use of anabolic androgenic steroids among male weightlifters. Sci Rep. 2022 Jun 8;12(1):9479. doi: 10.1038/s41598-022-12977-w. PMID: 35676515; PMCID: PMC9178025. n = 140

  13. Hauger LE, Westlye LT, Bjørnebekk A (2020): Anabolic androgenic steroid dependence is associated with executive dysfunction. Drug Alcohol Depend. 2020 Mar 1;208:107874. doi: 10.1016/j.drugalcdep.2020.107874. PMID: 31972519. n = 174

  14. Bitsko RH, Holbrook JR, O’Masta B, Maher B, Cerles A, Saadeh K, Mahmooth Z, MacMillan LM, Rush M, Kaminski JW (2022): A Systematic Review and Meta-analysis of Prenatal, Birth, and Postnatal Factors Associated with Attention-Deficit/Hyperactivity Disorder in Children. Prev Sci. 2022 Mar 18:10.1007/s11121-022-01359-3. doi: 10.1007/s11121-022-01359-3. PMID: 35303250; PMCID: PMC9482663. REVIEW und METASTUDY

  15. Williams JH, Greenhalgh KD, Manning JT (2003): Second to fourth finger ratio and possible precursors of developmental psychopathology in preschool children. Early Hum Dev. 2003 May;72(1):57-65. doi: 10.1016/s0378-3782(03)00012-4. PMID: 12706312.

  16. Wernicke J, Zabel JT, Zhang Y, Becker B, Montag C (2020): Association between tendencies for attention-deficit/hyperactivity disorder (ADHD) and the 2D:4D digit ratio: a cross-cultural replication in Germany and China. Early Hum Dev. 2020 Apr;143:104943. doi: 10.1016/j.earlhumdev.2019.104943. PMID: 32126477. REVIEW, n = 192

  17. Roberts BA, Martel MM (2013):. Prenatal Testosterone and Preschool Disruptive Behavior Disorders. Pers Individ Dif. 2013 Nov;55(8):962-966. doi: 10.1016/j.paid.2013.08.002. PMID: 25598567; PMCID: PMC4295489. n = 109

  18. Lemiere J, Boets B (2010): Danckaerts M. No association between the 2D:4D fetal testosterone marker and multidimensional attentional abilities in children with ADHD. Dev Med Child Neurol. 2010 Sep;52(9):e202-8. doi: 10.1111/j.1469-8749.2010.03684.x. PMID: 20491856. N = 110

  19. Martel MM (2009): Conscientiousness as a mediator of the association between masculinized finger-length ratios and attention-deficit/hyperactivity disorder (ADHD). J Child Psychol Psychiatry. 2009 Jul;50(7):790-8. doi: 10.1111/j.1469-7610.2009.02065.x. PMID: 19298468; PMCID: PMC4311552. n = 312

  20. Wang LJ, Lee SY, Chou MC, Lee MJ, Chou WJ (2019): Dehydroepiandrosterone sulfate, free testosterone, and sex hormone-binding globulin on susceptibility to attention-deficit/hyperactivity disorder. Psychoneuroendocrinology. 2019 May;103:212-218. doi: 10.1016/j.psyneuen.2019.01.025. PMID: 30711898. n = 220

  21. Kozłowska A, Wojtacha P, Równiak M, Kolenkiewicz M, Tsai ML (2019): Differences in serum steroid hormones concentrations in Spontaneously Hypertensive Rats (SHR) - an animal model of Attention-Deficit/Hyperactivity Disorder (ADHD). Physiol Res. 2019 Mar 6;68(1):25-36. doi: 10.33549/physiolres.933907. PMID: 30433797.

  22. Martel MM, Klump K, Nigg JT, Breedlove SM, Sisk CL (2009): Potential hormonal mechanisms of attention-deficit/hyperactivity disorder and major depressive disorder: a new perspective. Horm Behav. 2009 Apr;55(4):465-79. doi: 10.1016/j.yhbeh.2009.02.004. PMID: 19265696; PMCID: PMC3616481.

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