Testosterone for ADHD

• 1. Case studies: Testosterone as an effective ADHD medication in individual cases
• 2. MPH and testosterone
• 3. AMP and steroids
• 4. Other information on testosterone for ADHD

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

In three male Caucasian persons with ADHD-C aged 24, 37 and 43, ADHD symptoms improved within one week of testosterone monotherapy and remained so permanently (10 - 60 mg testosterone/day as a skin gel).¹
Winter depression and sleep problems also improved.
Before testosterone treatment, the 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 the reference values.
Only the youngest of the three test subjects had a loss of libido under MPH.
The testosterone treatment did not result in any severe side effects for the test subjects, in particular no increase in aggressiveness.
With testosterone therapy, regular monitoring of

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

A moderately decreased serum level of free testosterone appears 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 us to generalize that testosterone is an effective medication for ADHD in general. ADHD has hundreds, if not thousands, of different causes. The fact that a treatment is effective for individual persons with ADHD does not allow any conclusions to be drawn about how often this would also be the case for other people with ADHD.

2. MPH and testosterone¶

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

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

The duration, formulation and dosage of MPH did not affect the development of gonadal hormones or the Tanner stage.³
A group of 7 case studies reported a correlation between MPH intake and premature puberty. Basal hormone levels (luteinizing hormone [LH], follicle-stimulating hormone and estrogen/testosterone) were in 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 a decrease 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-Deoxycortisol
• Androgens
  • Dehydroepiandrosterone
  • Dehydroepiandrosterone sulfate
  • Δ4-Androstene-3,17-dione [Androstenedione]
• Progesterone (only for men)

The plasma levels of

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

4. Other information on testosterone for ADHD¶

In prepubertal people with ADHD, serum testosterone levels and serum androstenedione levels correlated with measures of autistic traits, while 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 AAS have a risk potential for ADHD symptoms. Against the background described above, it is also conceivable that the use of AAS could constitute self-medication, which could lead to addiction as a consequence,

Prenatal testosterone exposure was significantly correlated with inattention and hyperactivity/impulsivity in the offspring.¹⁴
Prenatal testosterone exposure is (indirectly) indicated by a low ratio of index finger to ring finger length (index finger length divided by ring finger length, 2D:4D), while 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
A large study found no robust correlation between bioavailable testosterone levels and ADHD in adults.²⁰

One study found in both boys and girls with ADHD²¹

• 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 levels were compared to WKR (Wistar-Kyoto rats):²²

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

According to one hypothesis, the predominance of males with behavioral disorders in childhood could be influenced by an excess of testosterone and the predominance of female people with ADHD with emotional disorders in adolescence and adulthood by an excess of estrogen.²³

One study reported a doubled rate of testosterone deficiency in adult persons with ADHD after 5 years of stimulant use (1.2%) compared to persons with ADHD without stimulant use (0.67%) or non-stimulant use (0.68%).²⁴