A man began hearing voices from his body parts after receiving testosterone injections

A recent case report details the experience of a man who developed severe psychiatric symptoms, including hallucinations and delusions, after receiving injectable testosterone for a year. The authors explain how the patient’s underlying and previously undiagnosed genetic condition may have made him uniquely vulnerable to these psychiatric side effects. The report was published in The Primary Care Companion for CNS Disorders.

The report was written by psychiatrists Abhijeet Anand and Shobit Garg in India. They describe an intersection of medical and psychiatric conditions centered around Klinefelter syndrome and hormone replacement therapy.

Humans usually have 46 chromosomes, which contain a person’s DNA and determine biological sex. Females typically have two X chromosomes, and males usually have one X and one Y chromosome. Klinefelter syndrome is a genetic condition where a male is born with an extra X chromosome, resulting in an XXY pattern.

This extra chromosome tends to affect physical development and fertility. Men with Klinefelter syndrome often have smaller testes, reduced body and facial hair, and wider hips or narrower shoulders compared to typical males. Infertility is often the primary symptom that leads to a diagnosis in adulthood.

Doctors often prescribe testosterone therapy to men with this syndrome to help replace the hormones their bodies do not produce in sufficient quantities. This hormone replacement helps improve bone density, muscle strength, and overall energy levels. Medical professionals generally recognize the physical benefits of this treatment, but they are increasingly noting that introducing supplemental testosterone might carry psychiatric risks.

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Testosterone and related hormones exert their effects by binding to androgen receptors throughout the body. The physical side effects of these hormones are well documented, but their impact on the brain is less understood. Scientists note that these hormones can influence the limbic system, a brain network involved in emotion and behavior.

Fluctuations in testosterone can alter the balance of important brain chemicals. This includes dopamine, which regulates reward and pleasure, as well as glutamate and GABA, which act to excite or calm neural activity. Disruption in these systems provides a possible explanation for why some patients develop mood disturbances or even psychosis.

Historically, public attention regarding hormone use has focused almost entirely on athletes seeking to enhance their physical performance. In those contexts, people often consume highly excessive doses of testosterone without medical supervision. The psychiatric side effects of such extreme doses are well documented in scientific literature.

Studies observing non-medical users have documented a range of severe psychiatric symptoms. These can include episodes of mania, heightened aggression, severe irritability, and depressive symptoms during periods of withdrawal. These effects are generally associated with doses that far exceed what the human body naturally produces.

By contrast, doctors prescribe much smaller therapeutic doses of testosterone to treat specific medical conditions, such as delayed puberty, muscle-wasting diseases, or genetic syndromes. The medical community has generally considered these therapeutic doses to be safe for mental health. The new report highlights that even these monitored medical treatments can sometimes precipitate severe mental health crises in susceptible patients.

The case focuses on a 45-year-old married man who arrived at an emergency department experiencing a sudden onset of unusual behavior. Over the course of nine days, he had developed intense religious beliefs, became highly suspicious of his neighbors, and required very little sleep. He also reported hearing voices, including the voice of God and voices seeming to come from parts of his own body.

Neighbors had noticed his strange behavior while he was managing a farmhouse on his own and alerted his family. Before this event, the man had never experienced any mental illness. There was also no history of psychiatric conditions in his extended family.

When doctors evaluated his medical history, they found he had been dealing with infertility for fifteen years. A blood test conducted twelve years earlier showed he had a low testosterone level, but he never received treatment for it at that time. One year before his psychiatric emergency, severe body aches led doctors to diagnose him with osteoporosis, a condition where bones become weak and brittle.

To treat his weakened bones and low hormone levels, his doctors prescribed monthly intramuscular injections of testosterone alongside vitamin D supplements. He received these monthly injections for an entire year. The last dose occurred roughly one month before he arrived at the hospital in a psychiatric crisis.

During his hospital stay, doctors conducted a chromosomal analysis to better understand his overall health. The test indicated that he had Klinefelter syndrome. A physical examination aligned with this diagnosis, noting his tall stature, lack of facial and axillary body hair, and smaller testes.

The medical team initially considered a diagnosis of a primary acute and transient psychotic disorder, which is characterized by a rapid onset of fluctuating symptoms. The timing of his symptoms alongside his hormone treatments suggested a different underlying issue. The doctors diagnosed him with a substance-induced psychotic disorder triggered by the steroid therapy.

His doctors immediately stopped the testosterone injections and began treating his psychiatric symptoms with a combination of calming and antipsychotic medications. Within a few days, his irritability, grandiosity, and hallucinations improved noticeably. The doctors also started him on a different, non-hormonal medication called zoledronate to manage his osteoporosis.

After stabilizing, the patient went home with a prescription for oral antipsychotic and mood-stabilizing medications. Over the next two months of outpatient appointments, his mental health remained stable. He experienced a sustained clinical remission, meaning his sleep returned to normal and the hallucinations completely disappeared.

Eventually, his endocrinologist and psychiatrists decided to reintroduce his testosterone treatment with caution. Because his body still required hormone support, they introduced a lower dose given every three weeks. They monitored him closely for any signs of returning psychiatric symptoms and educated his family on what warning signs to observe, and he did not experience a relapse.

Case reports focus on a single patient observation and cannot establish a direct cause-and-effect relationship between a medication and a specific symptom. The timing of the psychiatric symptoms and the testosterone injections in this patient provides evidence of a link, but it does not mean that testosterone universally causes psychosis. Most people who receive hormone replacement therapy will never experience severe psychiatric side effects.

Injectable forms of testosterone tend to create peaks and valleys in hormone levels within the bloodstream. Scientists suggest that these fluctuating levels might disrupt brain chemistry in certain vulnerable individuals more intensely than steady hormone levels would. Sudden exposure to high levels of hormones might amplify underlying risks that are not yet fully understood.

People with Klinefelter syndrome may possess an inherent risk for certain psychiatric conditions. The interaction between a lifelong hormone deficiency and the sudden introduction of injectable hormones requires further study. Future research could explore exactly how fluctuating hormone levels affect neural pathways in people with varying genetic backgrounds.

Single patient observations remain highly useful in medical science despite their limitations. They highlight rare side effects that large clinical trials might miss due to strict inclusion criteria. These reports prompt doctors to screen patients more thoroughly and document unexpected outcomes.

Medical professionals prescribing hormone therapies might consider performing baseline psychiatric screenings before starting treatment. Monitoring a patient’s mental status over time provides a safeguard against adverse reactions. This allows medical teams to adjust or pause treatments if unusual behavioral changes appear.

The report, “Parenteral Testosterone–Induced Acute Psychosis in Klinefelter Syndrome,” was authored by Abhijeet Anand and Shobit Garg.