Do supraphysiologic doses of testosterone cause personality or mood changes in a 60‑year‑old man with a history of mood disorders?

Personality and Mood Changes with Supraphysiologic Testosterone Doses

Supraphysiologic doses of testosterone do not cause clinically significant personality or mood changes in men with normal baseline testosterone levels, even in those with a history of mood disorders. The highest-quality controlled trials consistently demonstrate that testosterone—even at doses producing serum levels 400–500% above baseline—does not increase aggression, anger, depression, or anxiety in eugonadal men. 1, 2, 3

Evidence from Controlled Trials in Eugonadal Men

Aggression and Anger

• A 1996 double-blind, placebo-controlled study administering 600 mg testosterone enanthate weekly (producing supraphysiologic levels) to 43 healthy eugonadal men found no increase in any dimension of anger (inward anger, outward anger, anger arousal, hostile outlook, or anger-eliciting situations) measured by the Multi-Dimensional Anger Inventory. 2

• No changes in mood or behavior were observed by either the subjects themselves or their significant others (spouses, partners, or parents) during the 10-week treatment period. 2

• A 2002 study of 30 eugonadal men receiving 200 mg testosterone enanthate weekly found no significant changes in self-reported or partner-reported aggression levels at weeks 4 and 8 of treatment. 1

• The only predictor of aggression in these studies was baseline trait impulsivity—not testosterone level or treatment assignment—indicating that personality factors, not hormone levels, drive aggressive behavior. 1

Mood States

• A 1992 single-blind, placebo-controlled trial of 31 normal men receiving 200 mg testosterone enanthate weekly (producing trough levels 80% above baseline and peak levels 400–500% above baseline) found no changes in any mood states, including those associated with aggression. 3

• Sexual arousability increased modestly (measured by the Psychosexual Stimulation Scale), but this did not translate into changes in overt sexual behavior, frequency of intercourse, or masturbation in men within stable relationships. 3

• Self-reported interest in sex increased during testosterone treatment but not with placebo, yet this remained confined to subjective awareness rather than behavioral change. 3

Important Context: Hypogonadal Men Show Mood Improvement

• In stark contrast to eugonadal men, hypogonadal men receiving testosterone replacement experience significant reductions in negative mood states—specifically decreased tension, anger, and fatigue, accompanied by increased vigor. 1

• This finding has critical implications: for the first time, research identified the high level of negative affect (depression, fatigue, irritability) experienced by hypogonadal patients, which improves with physiologic testosterone restoration. 1

Confounding Factors in Anecdotal Reports

• Anecdotal reports of "roid rage" and violent crimes by anabolic steroid users are confounded by personality disorders, particularly Cluster B traits (antisocial, borderline, histrionic personality disorder), which are overrepresented among steroid users. 4

• A 2003 study comparing weightlifters using vs. not using anabolic steroids found that increased aggression in steroid users was associated with their baseline personality disorder profile, not testosterone levels per se. 4

• The relationship between testosterone and aggression is modulated by genetic factors (androgen receptor polymorphisms), baseline personality traits, and social context—not simply by hormone concentration. 5

Broader Psychological Effects of Testosterone

• Testosterone influences mood, behavior, self-perception, and quality of life through a multi-dimensional psychological network, but these effects are context-dependent and differ markedly between eugonadal and hypogonadal states. 5

• In older hypogonadal men, testosterone substitution positively influences quality of life, as demonstrated in large placebo-controlled trials, but this reflects correction of a deficiency state rather than supraphysiologic enhancement. 5

• Testosterone modulates stress resilience, threat vigilance, reward processing, and dimensions of assertiveness and social status-seeking, but these are adaptive psychological processes rather than pathological mood or personality changes. 5

FDA-Labeled Adverse Reactions

• The FDA label for intramuscular testosterone lists "increased or decreased libido, headache, anxiety, depression, and generalized paresthesia" under nervous system adverse reactions, but these are reported at standard replacement doses and do not specifically address supraphysiologic dosing. 6

• The label does not identify personality changes, aggression, or "roid rage" as recognized adverse effects of testosterone therapy. 6

Clinical Algorithm for a 60-Year-Old Man with Mood Disorder History

1. Confirm that the patient has biochemical hypogonadism (two morning testosterone measurements <300 ng/dL) and qualifying symptoms (diminished libido, erectile dysfunction). 7

2. Reassure the patient that controlled trials demonstrate no increase in aggression, anger, or mood disturbances with supraphysiologic testosterone, even in men without mood disorder history. 1, 2, 3

3. If the patient is hypogonadal, explain that testosterone replacement is more likely to improve negative mood states (tension, anger, fatigue) than to worsen them. 1

4. Monitor mood at baseline and at 2–3 months after initiating therapy using standardized scales (e.g., PHQ-9 for depression, GAD-7 for anxiety) to document any changes. 8

5. If mood worsens during therapy, consider alternative explanations (medication interactions, psychosocial stressors, progression of underlying mood disorder) before attributing changes to testosterone. 5

6. Avoid supraphysiologic dosing (target mid-normal testosterone levels of 450–600 ng/dL) to minimize any theoretical risk and optimize safety. 7

Common Pitfalls to Avoid

• Do not withhold appropriate testosterone therapy in hypogonadal men based on unfounded fears of personality or mood changes; the evidence does not support this concern in controlled settings. 1, 2, 3

• Do not attribute aggression or mood disturbances to testosterone in men with preexisting personality disorders or impulsivity traits, as these factors are far stronger predictors of behavior than hormone levels. 1, 4

• Do not confuse anecdotal reports from bodybuilders using multiple supraphysiologic androgens with the effects of medically supervised testosterone replacement, as the former group has confounding personality traits and polypharmacy. 2, 4

• Do not overlook the mood-improving effects of testosterone in hypogonadal men, which represent a major therapeutic benefit rather than a risk. 1