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Sex hormones,
including testosterone, have important extragonadal effects and experimental and clinical data point to important effects
of sex hormones on the cardiovascular system (Reckelhoff, 2005)…. low levels are associated with the progression of atherosclerosis, production of pro-inflammatory
cytokines, increased arterial thickness, increased levels of glucose, total cholesterol, and low-density lipoprotein, all
important in cardiovascular disease.
Commonly, testosterone
replacement improves cardiovascular and metabolic functions (Ruige et al., 2011; Hyde et al., 2012). In addition, a prospective observational study with men aged 70–96 years demonstrated
that low testosterone in men, independent of pre-existing health conditions, and other risk factors, is associated with increased
mortality risk (Fukai et al., 2011).
Experimental
data demonstrate that testosterone induces relaxation of many vascular beds, including coronary, mesenteric, iliac, renal,
and femoral arteries in several animal species such as rabbit, dog, rat, pig, both in
vivo and in vitro conditions [lowers blood pressure]. In general, most studies indicate that the relaxation
induced by testosterone involves endothelium-independent mechanisms, potassium channel-opening actions and calcium antagonistic
effects (Yue et al., 1995; Chou et al., 1996; Crews and Khalil, 1999; Murphy and Khalil, 1999; English et al., 2000, 2002; Deenadayalu et al., 2001)…. Using endothelial cell cultures these authors demonstrated that testosterone enhances
NO production by directly acting in the endothelial cells via PKC- and MAPK-dependent pathways. Testosterone also significantly
increased DNA synthesis indicating that androgens may also modulate vascular endothelial cell growth (Campelo et al., 2012). In addition, testosterone, at physiological concentrations and via androgen receptor activation,
induces proliferation, migration, and colony formation activity of EPCs (Foresta et al., 2008), indicating that the release of EPCs by bone marrow may be an additional mechanism by which
testosterone modulates endothelial function (Foresta et al., 2006)…. Testosterone also stimulates thromboxane synthase as well as COX-1 and COX-2, which
are key enzymes in the synthesis of prostaglandins (Cheuk et al., 2000; Song et al., 2004). Accordingly, the aging-associated decrease in testosterone levels may interfere with vascular
function via changes in the thromboxane/COX pathway (Figure 1).
Hypogonadism is a condition
associated with endothelial dysfunction (Akishita et al., 2007; Foresta et al., 2008). A study where male patients were submitted to examination of vasomotor function of the brachial
artery and intima-media thickness (IMT) of the carotid artery, showed that low levels of testosterone are associated with
endothelial dysfunction, independent of age, body mass index, hypertension, hyperlipidemia, diabetes mellitus, or current
smoking, suggesting a protective effect of testosterone on endothelial function (Akishita et al., 2007). Likewise, testosterone has been shown to improve
hemodynamic parameters in patients and animal models of heart failure, especially via a reduction in peripheral vascular resistance
and increased coronary blood flow through vasodilation and via direct effects in the cardiac tissue (e.g., by inhibition of
cardiac cAMP-phosphodiesterases; Bordallo et al., 2011; Nguyen et al., 2011)…. Transdermal testosterone replacement therapy increased androgen bioavailability and
decreased pulse wave velocity, indicating that testosterone replacement can diminish arterial stiffness associated with male
hypogonadism (Yaron et al., 2009). [The use of transdermal or other prepackaged testosterone products are designed to only increase
the level from low to normal for the elderly. Far greater benefits are obtained
by increasing the dose by two to 3 fold so as to obtain a high youthful level. Two
positives examples are Jk and Dr. Paul Thompson of Cenegenics who is seen on television and in magazines. They are two examples. The higher level is necessary
to counter the reduce bioactivity that occurs with aging. Remember that pharma
is in the business of treating illness, thus they oppose the use of effective dose of testosterone—their normal business
practice.]
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