When many people think of someone with a high level of testosterone, they may picture a man loaded with strength, sexual prowess, and machismo. But while high-T has been correlated with all those things, it’s also been correlated with aggression, sexual misconduct, and violence. One of testosterone’s most common uses—as a performance-enhancing steroid—illustrates both sides of the hormone. Injecting steroids can be a quick way for athletes to dramatically improve performance, but the side effects can also be extreme, and can include excessive body hair growth, sexual dysfunction, and the hard-to-corral anger known as “roid rage.”
Testosterone is observed in most vertebrates. Testosterone and the classical nuclear androgen receptor first appeared in gnathostomes (jawed vertebrates). Agnathans (jawless vertebrates) such as lampreys do not produce testosterone but instead use androstenedione as a male sex hormone. Fish make a slightly different form called 11-ketotestosterone. Its counterpart in insects is ecdysone. The presence of these ubiquitous steroids in a wide range of animals suggest that sex hormones have an ancient evolutionary history.
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The effects of testosterone in humans and other vertebrates occur by way of multiple mechanisms: by activation of the androgen receptor (directly or as DHT), and by conversion to estradiol and activation of certain estrogen receptors. Androgens such as testosterone have also been found to bind to and activate membrane androgen receptors.
Cross-sectional studies have not shown raised testosterone levels at the time of diagnosis of prostate cancer, and in fact, low testosterone at the time of diagnosis has been linked with more locally aggressive and malignant tumors (Massengill et al 2003; Imamoto et al 2005; Isom-Batz et al 2005). This may reflect loss of hormone related control of the tumor or the effect of a more aggressive tumor in decreasing testosterone levels. One study found that 14% of hypogonadal men, with normal digital rectal examination and PSA levels, had histological prostate cancer on biopsy. It is possible that low androgen levels masked the usual evidence of prostate cancer in this population (Morgentaler et al 1996). Most longitudinal studies have not shown a correlation between testosterone levels and the future development of prostate cancer (Carter et al 1995; Heikkila et al 1999; Stattin et al 2004) but a recent study did find a positive association (Parsons et al 2005). Interpretation of such data requires care, as the presentation of prostate cancer could be altered or delayed in patients with lower testosterone levels.
Clinical trials of the effect of testosterone on glucose metabolism in men have occurred in diabetic and non-diabetic populations. Data specific to aging males is not available. A series of studies investigated the effects of testosterone or dihydrotestosterone given for 6 weeks or 3 months to middle aged, non-diabetic obese men (Marin, Holmang et al 1992; Marin, Krotkiewski et al 1992; Marin et al 1993). It was found that physiological treatment doses led to improved insulin resistance, as measured by the gold standard technique using a euglycemic clamp and/or serum glucose and insulin responses during glucose tolerance test. These improvements were associated with decreased central obesity, measured by computered tomography (CT) or waist-hip ratio, without reduced total fat mass. Insulin resistance improved more with testosterone than dihydrotestosterone treatment and beneficial effects were greater in men with lower baseline testosterone levels. Increasing testosterone levels into the supraphysiological range lead to decreased glucose tolerance.
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.
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Sharma, R., Oni, O. A., Gupta, K., Chen, G., Sharma, M., Dawn, B., … & Barua, R. S. (2015, August 6). Normalization of testosterone level is associated with reduced incidence of myocardial infarction. European Heart Journal, 36(40), 2706-2715. Retrieved from https://academic.oup.com/eurheartj/article/36/40/2706/2293361/Normalization-of-testosterone-level-is-associated