The predominant androgen in men,

testosterone Testosterone is the primary sex hormone and anabolic steroid in males. In humans, testosterone plays a key role in the development of male reproductive tissues such as testes and prostate, as well as promoting secondary sexual characteristi ...

, has shown to substantially decline throughout the

aging process Ageing ( BE) or aging ( AE) is the process of becoming older. The term refers mainly to humans, many other animals, and fungi, whereas for example, bacteria, perennial plants and some simple animals are potentially biologically immortal. In ...

. The decline in both serum and total testosterone with age have been linked to several disease states in men. In particular,

cardiac failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...

and ischemic heart disease have been linked to this natural biochemical decline in testosterone. Previously, the higher cardiovascular risk in men has been attributed in part to the negative effects of systemic testosterone, however, more recent research has highlighted the protective nature of testosterone against cardiovascular disease. The magnitude and mechanism of action by which low testosterone in men is influential in the pathogenesis of cardiovascular risk and the potential benefits of testosterone therapy has yet to be fully determined. __TOC__

Systemic effects of testosterone on the cardiovascular system

Low testosterone is associated with an increased risk for coronary artery disease through the promotion of a pro-atherosclerotic environment.https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ReproductiveHealthDrugsAdvisoryCommittee/UCM413736.pdf Some research has identified testosterone as a vasodilator and an

endothelium The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vesse ...

-repairing hormone within many regions in the body, including the coronary arteries. Recent research depicts testosterone as important in decreasing the production of inflammatory cytokines such as

tumor necrosis factor alpha Tumor necrosis factor (TNF, cachexin, or cachectin; formerly known as tumor necrosis factor alpha or TNF-α) is an adipokine and a cytokine. TNF is a member of the TNF superfamily, which consists of various transmembrane proteins with a homolo ...

, interleukin-1beta and

interleukin-6 Interleukin 6 (IL-6) is an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine. In humans, it is encoded by the ''IL6'' gene. In addition, osteoblasts secrete IL-6 to stimulate osteoclast formation. Smoo ...

, which are influential in atherosclerotic profiles. Although it is believed that the reduction in inflammatory cytokines is related to a decreased atherosclerotic profile, the full explanation of this mechanism requires further research. Testosterone has also shown to be effective as an anti-atherosclerotic through preventing aortic

cholesterol Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell mem ...

deposition in both rabbits fed high cholesterol diets and mice with low-density lipoprotein gene knockout. Fatty deposition within the aorta associated with low endogenous testosterone has been determined to be independent of the androgen receptor. Although the mechanism has yet to be fully determined, aromatase activity and the activation of estrogen receptor alpha is partially responsible for the atherosclerotic profile characteristic of low testosterone. Decreased systemic testosterone in men has also been reported in men with heart failure, whereby the severity of the disease is proportional to the reduction in systemic testosterone levels. Although a direct mechanism of action is not fully understood, some research attribute low testosterone to advancing side effects of heart failure, such as decreased exercise ability, decreased muscle mass, fatigue/

dyspnea Shortness of breath (SOB), also medically known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing di ...

and

cachexia Cachexia () is a complex syndrome associated with an underlying illness, causing ongoing muscle loss that is not entirely reversed with nutritional supplementation. A range of diseases can cause cachexia, most commonly cancer, congestive heart ...

Testosterone replacement therapy

Physiological testosterone is crucial for normal functionality in men. Long-term administration of physiological testosterone in mouse models has shown to be atheroprotective by increasing the HDL portion of cholesterol (the anti-atherosclerotic cholesterol). The beneficial action of testosterone in elevating the HDL fraction can be attributed to its conversion via aromatase activity in adipose tissue into 17-beta estradiol and its subsequent activation of estrogen alpha-receptors; thus, more testosterone leads to greater conversion into estrogen and thus a healthier lipid profile. This understanding has been determined in several studies, although results of these studies are contradictory.

Testosterone replacement therapy Androgen replacement therapy (ART), often referred to as testosterone replacement therapy (TRT) or hormone replacement therapy (HRT), is a form of hormone therapy in which androgens, often testosterone, are supplemented or replaced exogenously ...

in men diagnosed with pre-existing heart disease has been related to an increased risk of myocardial infarction. Furthermore, recent research has linked testosterone replacement therapy to an increase in deaths and other cardiovascular occurrences in men whom document a history of coronary artery disease. Further research is required to determine the full extent to which testosterone replacement therapy in aging men plays a role in the risk and/or advantage of cardiovascular occurrences.

References

{{Reflist, 2 Cardiology Cardiovascular system Testosterone