Testosterone and vascular functions in aging
Human Aging, Position Paper
Longevity of adults has changed little
Senior runners postponed disability 8.7 years
Estrogen with progesterone lengthens women lives
Testosterone and vascular functions in aging
estrogen and longevity
Free radicals part of aging process
FAD AGING CURES EXPOSED, by leading scientists
genes that slow aging
Genes and aging
Insulin's effect upon the SKN-1 gene and aging
Telemores, sexual size dimorphism and gender gap in life expectancy
SKIN AGING: causes & treatments
Carbohydrates and aging and age related diseases
Arthritis reduced with vigorous physical activity
Why Women Live Longer than Men

An excellent review of the literature

Estradiol and testosterone differ from each other by one functional group, thus their bio-activities often overlap.  (Dihydrotestosterone form is responsible for most of the sex related changes.)  Very possible following menopause the 2 other estrogens (since estradiol is declines with menopause) maintain the vascular benefits into old age, while with men there is no similar process following andropause.  There are no longer-term studies of testosterone replacement in men to confirm or contradict this theory.  A search of scholar.google entering “testosterone replacement + rats” is tentatively confirmative.  

For the full article go to  http://journal.frontiersin.org/article/10.3389/fphys.2012.00089/full

REVIEW ARTICLE  Front. Physiol., 10 April 2012 | http://dx.doi.org/10.3389/fphys.2012.00089

Testosterone and vascular function in aging

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.]


Of course similar, though greater benefits are true for natural hormone replacement therapy for women, see HRT.  And of course pharma has used the worse formulation Prempro and the NIH’s WHI study (2002) to limit HRT usage.  Note A century ago men lived longer than women, mainly because of the risks of delivering children and the drain of going through over a half-dozen pregnancies.  Men are still subjected to greater environmental hazards in the work place, a factor contributing to the difference in death rate.  I would also include the earlier decline in testosterone which is about 50 percent when compared to a study done in 1916 and 6 subsequent studies confirming the progressive decline in testosterone levels through to 2004, at http://healthfully.org/malehormones/id26.html bottom of page for graphs.  I suspect that estrogen mimic, possible from the increase in soya bean products whose usage by food manufacturers has steadily increased and more recent sources such as BPA (bisphenol A).      

http://sageke.sciencemag.org/cgi/content/abstract/2005/23/pe17  Sci. Aging Knowl. Environ., 8 June 2005
Vol. 2005, Issue 23, p. pe17

Why Females Live Longer Than Males: Control of Longevity by Sex Hormones

Abstract:  Females live longer than males in many species, including humans. We have traced a possible explanation for this phenomenon to the beneficial action of estrogens, which bind to estrogen receptors and increase the expression of longevity-associated genes, including those encoding the antioxidant enzymes superoxide dismutase and glutathione peroxidase. As a result, mitochondria from females produce fewer reactive oxygen species than those from males.


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