Testosterone therapy may offer modest benefits for mood and select cognitive outcomes in adult men, though the effects appeared to be inconsistent and population dependent, according to a systematic review.
In the review, investigators examined 11 randomized controlled trials involving more than 600 male participants aged 18 to 85 years. Study populations included healthy eugonadal men, older adults with hypogonadism, men with treatment-resistant depression (TRD), and patients with mild Alzheimer's disease. Across the studies, testosterone therapy was evaluated using a range of formulations and doses, with psychiatric and cognitive outcomes assessed alongside safety.
Depressive symptoms showed the clearest signal of benefit. In men with TRD and low or borderline testosterone levels, adjunctive testosterone therapy was associated with significant reductions in depressive symptom scores in several trials compared with placebo. By contrast, the results were more variable when testosterone was used as monotherapy in hypogonadal men with major depressive disorder, with some studies showing no significant advantages compared with placebo.
The cognitive effects were domain specific rather than global. Moderate testosterone supplementation was linked to improvements in verbal memory and visuospatial processing in older or hypogonadal men, while effects on overall cognition were inconsistent. In trials involving participants with mild Alzheimer's disease, testosterone therapy produced modest improvements in some cognitive measures—but these didn't consistently translate into sustained or broad cognitive benefit.
Quality of life and sexual function improved more consistently across the studies, regardless of baseline psychiatric status. Conversely, anxiety outcomes were mixed, and supraphysiologic testosterone dosing in younger eugonadal men was linked to small increases in aggression without clear mood benefit.
Across the trials, the investigators noted that testosterone therapy was generally well tolerated. Reported adverse events were mostly mild and transient, including acne, edema, and injection-site reactions. No major cardiovascular, hepatic, or thromboembolic complications were reported. However, some studies noted hematocrit increases requiring monitoring or discontinuation.
The investigators emphasized that heterogeneity in study design, populations, dosing regimens, and outcome measures may have limited firm conclusions. They argued that testosterone therapy should be viewed as a complementary strategy rather than a primary treatment for psychiatric or cognitive symptoms. They advised that the treatment be reserved among male patients with documented androgen deficiency and implemented under endocrinologic supervision.
He investigators concluded that larger, longer-term randomized trials are needed to clarify which patient subgroups may derive meaningful neuropsychiatric benefit and to better define long-term cognitive and safety outcomes of testosterone therapy in routine clinical practice.
"When prescribed under endocrinologic supervision, with appropriate clinical and biochemical monitoring, [testosterone therapy] may represent a valuable component of personalized, neuroendocrine-informed care for depressive and cognitive symptoms in men with confirmed androgen deficiency," concluded lead study author Luis M. Canal de Velasco, MD, of Panamerican University, and colleagues.
The study authors reported no conflicts of interest.
Source: Cureus
