Man Takes Testosterone, Starts Hearing Voices

One 45-year-old man’s decision to start taking synthetic testosterone seems to have led to a rare, peculiar side effect: psychosis.

Doctors in India detailed the strange turn of events in a recent case report. The man began to hear voices and developed paranoid delusions a year into being placed on testosterone replacement therapy. Thankfully, doctors successfully treated his symptoms and he was taken off testosterone without no further relapse of his psychosis.

“While somatic adverse effects [of testosterone replacement therapy] are well recognized, psychiatric complications such as mood disturbances, mania, and psychosis remain underappreciated, particularly with therapeutic dosing,” the authors wrote in their paper, published late last month in The Primary Care Companion for CNS Disorders.

According to the case study, neighbors were the first to spot something off about the man while he was working alone managing a farmhouse, and they alerted his family. He began to express a paranoid suspicion of his neighbors, manic behavior, and reported hearing second-person auditory hallucinations, such as the voice of God and voices emanating from his body parts. Nine days into these symptoms, he finally ended up in an emergency department.

Doctors placed him on anti-psychotics and tried to figure out what had triggered these symptoms. The man had no personal nor family history of mental illness. Over a decade ago, however, tests showed that he was infertile and had low testosterone levels, and a year before his psychotic episode, he had been prescribed monthly testosterone along with vitamin D supplementation to manage his severe osteoporosis (in men with low testosterone, the treatment can help restore bone density).

The doctors’ workup soon confirmed the man had unknowingly been living with a condition known as Klinefelter syndrome . People with Klinefelter have an extra X chromosome (XXY), which results in low testosterone, smaller testes, infertility, and taller height. Testosterone replacement therapy is often used to manage the condition, but in this case, it seems to have triggered the man’s psychosis.

According to the doctors, people with Klinefelter are already known to have an inherently heightened risk of psychiatric illness, which can include psychosis. The man’s injections created very high peaks and very low valleys of testosterone in his system, which likely disrupted the pathways in the brain that govern dopamine, an important neurotransmitter that plays a role in psychiatric disorders like schizophrenia.

The man responded well to treatment, and his symptoms markedly improved within days of being taken off testosterone, further bolstering the doctors’ theory. By the 10-day mark, he was discharged from the hospital.

“The temporal association between 1 year of parenteral testosterone and psychosis onset, absent prior psychiatric illness, polymorphic presentation, low testosterone at presentation (trough level), and rapid resolution upon discontinuation strongly support substance-induced psychotic disorder,” the doctors wrote.

Obviously, most people who take testosterone do not develop psychosis.