Low and High Testosterone Associated With PTSD Symptoms in Males and Females

In both males and females, low levels of testosterone may be a risk factor for future posttraumatic stress disorder (PTSD) symptoms, according to a study published yesterday in Translational Psychiatry. Elevated testosterone was also associated with PTSD symptom risk, while individuals in the middle had the lowest risk.

“Our findings are consistent with previous work that has shown testosterone to have anxiolytic and antidepressant effects in men,” wrote Hanyang Shen, M.P.H., M.Sc., of Stanford University, and colleagues. “In women, there is also some evidence that testosterone can have anxiolytic and antidepressant effects, but high levels may also lead to new onset mood episodes.”

The researchers made use of the vast UK Biobank repository, which contains medical, genetic, social, lifestyle, and environmental data on more than 500,000 middle-aged adults. Their sample included 62,565 males (average age 57) and 67,906 females (average age 55) who completed a mental health questionnaire mailed out in 2016 and had previously provided blood samples; the researchers excluded individuals whose baseline testosterone was at the extreme low or high end of normal human range. The mental health questionnaire included six questions on PTSD symptoms derived from the PTSD Checklist for DSM-5.

Male and female participants were then divided into 10 groups (deciles) based on total testosterone (TT) levels, with group one (lowest levels) serving as the reference. Shen and colleagues found that relative to group one, all other groups had lower PTSD symptom scores, after adjusting for other variables. The scores exhibited a U-shaped pattern, with decile seven associated with the fewest PTSD symptoms in both males (TT range of 12.54 to 13.50 nmol/L) and females (TT range of 1.11 to 1.25 nmol/L).

Among both males and females, stronger associations between testosterone levels and future PTSD symptoms were seen in adults with a BMI of 30 or higher.

“Analyzing data from 130,471 participants, this study is over 60 times larger than the largest previous investigation of the relationship between testosterone and future PTSD symptoms, affording the testing of more nuanced models than previously investigated,” the researchers wrote. “[M]ore studies exploring how BMI, and other body composition measures that more directly distinguish body fat from muscle, modify the impact of testosterone on psychiatric disorders need to be conducted to further unveil this mechanism.”

For related information, see the Psychiatric News article “Can Hormonal Treatments Help Your Patients?”

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Psychiatrists Should Be Alert to Testosterone Abuse

The Food and Drug Administration on Tuesday announced that a new warning of the serious adverse outcomes associated with testosterone and other anabolic androgenic steroids (AAS), including those related to heart and mental health, will now appear on all prescription testosterone products.

The use of prescription testosterone products as hormone replacement therapy is FDA approved for men who have low testosterone due to certain medical conditions. Additionally, there is evidence to suggest that men with depression who use testosterone gel may experience improvements in mood. However, it is well known that testosterone and other AAS are abused by adults and adolescents, including athletes and body builders.

“Abuse of testosterone, usually at doses higher than those typically prescribed and usually in conjunction with other AAS, is associated with serious safety risks affecting the heart, brain, liver, mental health, and endocrine system,” according to an FDA statement. “Reported serious adverse outcomes include heart attack, heart failure, stroke, depression, hostility, aggression, liver toxicity, and male infertility. Individuals abusing high doses of testosterone have also reported withdrawal symptoms, such as depression, fatigue, irritability, loss of appetite, decreased libido, and insomnia.”

According to the FDA, the classwide labeling changes will include additional information about other adverse outcomes associated with abuse and dependence of testosterone/AAS as well as advice to prescribers on the importance of measuring serum testosterone concentration if abuse is suspected.

For related information, see “Large Trial Suggests Testosterone Offers Moderate Benefits.”

Testosterone Replacement Shows Modest Benefits for Depression and Mood

In addition to improving sexual and physical function, testosterone-replacement therapy may decrease depressive symptoms and improve mood in older men with low testosterone levels, according to a study in the New England Journal of Medicine.

A total of 790 men 65 years and older with a serum testosterone concentration of less than 275 ng per deciliter were randomly assigned to receive testosterone gel or placebo gel for 1 year. Each man participated in one or more of three trials—the Sexual Function Trial, the Physical Function Trial, and the Vitality Trial; the latter trial included assessments of fatigue, positive and negative mood symptoms (as measured by the Positive and Negative Affect Scale, or PANAS), and depression level (measured by Patient Health Questionnaire 9, or PHQ-9) after 3, 6, 9, and 12 months of treatment.

Testosterone treatment increased serum testosterone levels to the mid-normal range for men 19 to 40 years of age during the treatment period. Among participants in the Vitality Trial, there were significant differences between the testosterone and placebo group in the PANAS positive affect score (mean difference, 0.47 points), the PANAS negative affect score (mean difference, −0.49 points), and the PHQ-9 depression score (mean difference, −0.72 points). The men who received testosterone were more likely than men who received placebo to report that their energy was better at the end of the trial.

These results, combined with the findings from the other trials, “should inform decisions about testosterone treatment for men 65 years of age or older whose levels are low for no apparent reason other than age. Such decisions will also require knowing the risks of testosterone treatment, which will necessitate larger and longer trials,” the authors concluded.

For related information, see the Psychiatric News article “Discontinuing Hormone Therapy May Increase Risk of Depression in Some Women.”

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Sex Hormones Linked With Risk of Committing Sexual Crimes, Study Finds

Elevated levels of the two sex hormones—luteinizing hormone (LH) and follicle-stimulating hormone (FSH)—predict recidivism among male sex offenders better than do elevated levels of the sex hormone testosterone, report John Bradford, M.D., one of Canada's leading sex-offender experts, and colleagues in the latest issue of the Journal of the American Academy of Psychiatry and the Law. LH and FSH, which are also referred to as gonadotrophic hormones, are made by the pituitary gland. LH stimulates the testes to produce testosterone. FSH stimulates the testes to make sperm.

"This study is an important one, with a surprising finding that gonadotrophic hormones were better predictors of recidivism for sexual crimes than testosterone," Richard Krueger, M.D., an associate clinicial professor of psychiatry at Columbia University College of Physicians and Surgeons who has studied sexual offenders, said in an interview with Psychiatric News. 

However, it is doubtful that elevated levels of LH and FSH are alone responsible for sexual crimes, Bradford and colleagues pointed out in their report. So what other factors might contribute to such behavior? Perhaps hostility, the researchers suggested, since they found that hostility was associated with the impact of LH and FSH on recidivism.

For information about research on sexual offenses including pedophilia, see Psychiatric News. Psychological insights into sex offenders can be found in the American Psychiatric Publishing book Bad Men Do What Good Men Dream: A Forensic Psychiatrist Illuminates the Darker Side of Human Behavior and Dangerous Sex Offenders: A Task Force Report of the American Psychiatric Association.

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