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As with the improper use of antidepressants, over-administration of testosterone can also lead to adverse effects. These findings indicate that TRT can be beneficial in certain contexts but is not broadly recommended for depression treatment. However, randomised placebo-controlled trials examining TRT's impact on depressive symptoms have produced inconsistent results.13 SSRIs can cause sexual dysfunction in 40% to 65% of individuals, potentially worsening depression and hindering medication adherence.12 Despite their higher risk, men are less likely to seek help, with only 15 percent receiving psychotropic medications or therapy in 2020 compared to 26 percent of women.3
In any respect, the causal role of testosterone deficiency and behavioral disorders including effect on cognitive abilities is still debated. A higher incidence of mood disorders that occurs with aging is then related to decreased testosterone and/or other androgens. Indeed, the exact mechanisms and reasons of sex differences in brain structures that mediate some of these functional dissimilarities are unknown.
While many people focus on the physical benefits of testosterone replacement, its impact on mental health is just as important. Some people adjust well to this change, while others may experience mood swings, anxiety, or depression as their body adapts. This can affect the body's natural hormone balance, leading to potential mental side effects. Additionally, lifestyle factors like diet, exercise, stress levels, and sleep habits can also impact how TT affects mental health. Testosterone therapy can also affect sleep, which is directly linked to mental health.
Regarding serum lipoprotein levels and routes of AAS administration, one study concluded that oral AAS produce marked reductions in serum concentrations of high-density lipoprotein (HDL) cholesterol and apolipoprotein A-I level with an increase in low-density lipoprotein cholesterol concentration and hepatic triglyceride lipase activity compared to intramuscular (IM) route. Testosterone is known to increase the 5-HT (serotonin) transporter mRNA expression and binding in rats and humans.153,154 Testosterone has also been shown to increase the firing rate of serotonin-secreting neurons in the dorsal raphe nucleus in rats.155 A serotonin deficit results in long term decreases in hippocampal cells proliferation.156,157 Raphe grafts that are enriched with serotonin producing neurons restored the proliferation of hippocampal cells.158 This testosterone mediated increase in serotonin results in preservation of hippocampal volume, thereby exerting antidepressant effects. They conclude that testosterones efficacy as an antidepressant is not well supported, even in these hypogonadal men.16 Investigating further, Pope et al. agreed that testosterone is generally not an effective treatment option for depressed men.
While within 30 min after administration, non-genomic effects are important, later genomic effects are expected to be the major mediator. But beyond cyclic variations, testosterone undergoes chaotic temporary changes that are usually described as noise. Implants that slowly release testosterone totally ignore daily variations that occur physiologically. In some studies, even the best-known circadian rhythm is not taken into account.