Testosterone in ADHD

• 1. Case studies: Testosterone as an effective ADHD medication in single cases
• 2. MPH and testosterone
• 3. AMP and steroids
• 4. Other about 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, regular monitoring of

• 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