A recent case of a 51 year old male with an interest in testosterone replacement illustrates the benefits of the multi-parametric prostate MRI scan. Noting a PSA value of only ng/ml; the digital rectal exam (DRE) identified an area of interest on the left side, albeit, it was not definitive for prostate cancer. Neither the gray scale ultrasound nor Color Flow Doppler ultrasound evaluation suggested any specific abnormality consistent with the area of interest previously identified on DRE. An MRI scan was suggested as the next best step in the evaluation. The scan isolated a region of interest on the left side at the Apex to Middle portion of the prostate gland concordant with the findings on the DRE. Based upon the findings of the MRI scan, a targeted biopsy with 6 needle cores was recommended and implemented. An Antiandrogen was initiated pre-biopsy to mitigate against “needle tracking”. Specifically, an Antiandrogen selectively blocks the receptor on the prostate cell from attracting testosterone as it exits the capsule, thereby, disabling the cells in preparation for cell death or apoptosis. The Pathology evaluation revealed a grade of cancer that was amenable to being treated conservatively or focally. In this case, the failure to use a MRI scan would have exposed this patient to the possibility of missing the cancer altogether; associated with sampling bias, a very real possibility for needle tracking (assuming cancer was found), or worse yet, the go ahead to supplement with testosterone, when in fact, the cancer was missed. Using testosterone in this scenario would have stimulated cancer cells to grow wildly, while causing the PSA to spike abnormally, thereby, making the diagnosis of prostate cancer – a potentially uncontrollable clinical event, albeit, avoidable. Given the expertise of a Urolologic consultation, this case turned out well. The patient is now contemplating a focal treatment with high intensity focused ultrasound with a plan to supplement with testosterone once his cancer has been cured. An inability to document the resolution of prostate cancer by a repeat MRI scan and/or a stable PSA post-operatively will preclude this patient from using testosterone replacement therapy.
In general, Bhasin says, doctors should give more information to patients considering the treatments. For example, he says, "doctors don’t tell you that testosterone supplements may end up a long-term proposition." When men begin using a supplement, he explains, they typically lose the ability to create testosterone on their own. So if a health problem should arise that forces them to stop taking the supplements, it may take months or years to recover the ability to create adequate levels of testosterone naturally, during which time they may experience withdrawal symptoms like poor mood and low vitality.
“I find it very distressing that testosterone is used in middle-aged men — when we don’t know whether it’s even safe — for something that may be a normal physiologic adaptive mechanism to aging," he says.
Both experts agree that men with a history of heart attack or stroke should steer clear of testosterone supplements. They also agree that there are scenarios in which the benefits of testosterone therapy nearly always outweigh the risks, like hypogonadism, a disease in which the body produces little or no hormone due to poorly functioning testes or pituitary or hypothalamus glands.
The second theory is similar and is known as "evolutionary neuroandrogenic (ENA) theory of male aggression".   Testosterone and other androgens have evolved to masculinize a brain in order to be competitive even to the point of risking harm to the person and others. By doing so, individuals with masculinized brains as a result of pre-natal and adult life testosterone and androgens enhance their resource acquiring abilities in order to survive, attract and copulate with mates as much as possible.  The masculinization of the brain is not just mediated by testosterone levels at the adult stage, but also testosterone exposure in the womb as a fetus. Higher pre-natal testosterone indicated by a low digit ratio as well as adult testosterone levels increased risk of fouls or aggression among male players in a soccer game.  Studies have also found higher pre-natal testosterone or lower digit ratio to be correlated with higher aggression in males.