It is now well-established that elderly men with type 2 diabetes mellitus have reduced levels of testosterone (Barrett-Connor 1992; Betancourt-Albrecht and Cunningham 2003). It is known, however, that obese men and diabetic men have reduced levels of SHBG (Barrett-Connor 1990) which could account for the lower total testosterone levels found in diabetic men. Dhindsa et al (2004) studied 103 male patients who had type 2 diabetes mellitus using free testosterone (done by equilibrium dialysis) or calculated free testosterone which takes SHBG levels into account. Of the 103 patients, 57 had free testosterone by equilibrium dialysis and of these, 14 (25%) had a free T below 0.174 nmol/L and were considered hypogonadal. Using a total testosterone of 10.4 nmol/L (300ng/dl) as the lower limit of normal 45 patients (43%) were in the hypogonadal range. They also found that LH and FSH concentrations were significantly lower in the hypogonadal group. The authors thus concluded that hypogonadotropic hypogonadism was a common finding in type 2 diabetes irrespective of glycemic control, duration of disease or the presence of complications of diabetes or obesity.
A large number of side-effects have been attributed to testosterone. In our clinical experience, the incidence of significant adverse effects with treatment producing physiological testosterone levels is low, and many side effects attributed to testosterone are mainly relevant to supraphysiological replacement. Some adverse effects are specific to a given mode of delivery and have already been described. Potential adverse effects concerning the prostate have also been discussed and require appropriate monitoring of symptoms, PSA and digital rectal examination. Other tumors which may be androgen responsive include cancer of the breast and primary liver tumors, and these are both contraindications to testosterone treatment
Most Americans today are sleep deprived, which may be a contributing factor to declining testosterone levels in men. See, our body makes nearly all the testosterone it needs for the day while we’re sleeping. That increased level of T that we experience at night is one of the reasons we wake up with “Morning Wood.” (If you don’t have Morning Wood on a consistent basis, you might have low T).
Testosterone makes a contribution to nitric oxide formation. Nitric oxide, released from penile nerves stimulates guanylate cyclase which catalyzes the transformation of guanosine-5-triphosphate into 3′,5′-cyclic, guanosine monophosphate (cyclic GMP). Gyclic GMP causes vasodilatation and hence erection formation (Morelli et al 2005). The breakdown of cyclic GMP to GMP is mediated by the enzyme, phosphodiesterase type-5, the inhibitors of which (eg, sildenafil citrate) enhance erection formation and maintanence (Carson and Lue 2005).
In addition to conjugation and the 17-ketosteroid pathway, testosterone can also be hydroxylated and oxidized in the liver by cytochrome P450 enzymes, including CYP3A4, CYP3A5, CYP2C9, CYP2C19, and CYP2D6. 6β-Hydroxylation and to a lesser extent 16β-hydroxylation are the major transformations. The 6β-hydroxylation of testosterone is catalyzed mainly by CYP3A4 and to a lesser extent CYP3A5 and is responsible for 75 to 80% of cytochrome P450-mediated testosterone metabolism. In addition to 6β- and 16β-hydroxytestosterone, 1β-, 2α/β-, 11β-, and 15β-hydroxytestosterone are also formed as minor metabolites. Certain cytochrome P450 enzymes such as CYP2C9 and CYP2C19 can also oxidize testosterone at the C17 position to form androstenedione.
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