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| The predominant androgen in men, [[testosterone]], has shown to substantially decline throughout the [[aging process]].<ref name=pmid18488876>{{cite journal |last1=Stanworth |first1=Roger D |last2=Jones |first2=T Hugh |title=Testosterone for the aging male; current evidence and recommended practice |journal=Clinical Interventions in Aging |volume=3 |issue=1 |pages=25–44 |year=2008 |pmid=18488876 |pmc=2544367 |url=http://www.dovepress.com/articles.php?article_id=227 |doi=10.2147/CIA.S190 }}</ref><ref name=pmid24242682>{{cite journal |last1=Oskui |first1=P. M. |last2=French |first2=W. J. |last3=Herring |first3=M. J. |last4=Mayeda |first4=G. S. |last5=Burstein |first5=S. |last6=Kloner |first6=R. A. |title=Testosterone and the Cardiovascular System: A Comprehensive Review of the Clinical Literature |journal=Journal of the American Heart Association |volume=2 |issue=6 |pages=e000272 |year=2013 |pmid=24242682 |pmc=3886770 |doi=10.1161/JAHA.113.000272 }}</ref> The decline in both serum and total testosterone with age have been linked to several disease states in men.<ref name=pmid18488876/><ref name=pmid11158037>{{cite journal |last1=Harman |first1=S. Mitchell |last2=Metter |first2=E. Jeffrey |last3=Tobin |first3=Jordan D. |last4=Pearson |first4=Jay |last5=Blackman |first5=Marc R. |title=Longitudinal Effects of Aging on Serum Total and Free Testosterone Levels in Healthy Men |journal=The Journal of Clinical Endocrinology & Metabolism |volume=86 |issue=2 |pages=724–31 |year=2001 |pmid=11158037 |doi=10.1210/jcem.86.2.7219 }}</ref><ref name=pmid11836290>{{cite journal |last1=Feldman |first1=Henry A. |last2=Longcope |first2=Christopher |last3=Derby |first3=Carol A. |last4=Johannes |first4=Catherine B. |last5=Araujo |first5=Andre B. |last6=Coviello |first6=Andrea D. |last7=Bremner |first7=William J. |last8=McKinlay |first8=John B. |title=Age Trends in the Level of Serum Testosterone and Other Hormones in Middle-Aged Men: Longitudinal Results from the Massachusetts Male Aging Study |journal=The Journal of Clinical Endocrinology & Metabolism |volume=87 |issue=2 |pages=589–98 |year=2002 |pmid=11836290 |doi=10.1210/jcem.87.2.8201 }}</ref> In particular, [[cardiac failure]] and [[ischemic heart disease]] have been linked to this natural biochemical decline in testosterone.<ref name=pmid23475207>{{cite journal |last1=Tirabassi |first1=Giacomo |last2=Gioia |first2=Angelo |last3=Giovannini |first3=Lara |last4=Boscaro |first4=Marco |last5=Corona |first5=Giovanni |last6=Carpi |first6=Angelo |last7=Maggi |first7=Mario |last8=Balercia |first8=Giancarlo |title=Testosterone and cardiovascular risk |journal=Internal and Emergency Medicine |volume=8 |issue=Suppl 1 |pages=S65–9 |year=2013 |pmid=23475207 |doi=10.1007/s11739-013-0914-1 }}</ref><ref name=pmid12559538>{{cite journal |last1=Kontoleon |first1=Panagiotis E |last2=Anastasiou-Nana |first2=Maria I |last3=Papapetrou |first3=Petros D |last4=Alexopoulos |first4=George |last5=Ktenas |first5=Vasiliki |last6=Rapti |first6=Ageliki C |last7=Tsagalou |first7=Eleftheria P |last8=Nanas |first8=John N |title=Hormonal profile in patients with congestive heart failure |journal=International Journal of Cardiology |volume=87 |issue=2–3 |pages=179–83 |year=2003 |pmid=12559538 |doi=10.1016/S0167-5273(02)00212-7 }}</ref><ref name=pmid3409497>{{cite journal |last1=Barrett-Connor |first1=E. |last2=Khaw |first2=K. T. |title=Endogenous sex hormones and cardiovascular disease in men. A prospective population-based study |journal=Circulation |volume=78 |issue=3 |pages=539–45 |year=1988 |pmid=3409497 |doi=10.1161/01.CIR.78.3.539 }}</ref> 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.<ref name=pmid23475207/> 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.<ref name=pmid18488876/>
| | {{Short description|Overview of the effects of testosterone on the cardiovascular system}} |
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| ==Systemic effects of testosterone on the cardiovascular system== | | ==Testosterone and the Cardiovascular System== |
| Low testosterone is associated with an increased risk for [[coronary artery disease]] through the promotion of a pro-atherosclerotic environment.<ref name=pmid23475207/><ref name=pmid17984376>{{cite journal |last1=Nettleship |first1=J. E. |last2=Jones |first2=T. H. |last3=Channer |first3=K. S. |last4=Jones |first4=R. D. |title=Physiological Testosterone Replacement Therapy Attenuates Fatty Streak Formation and Improves High-Density Lipoprotein Cholesterol in the Tfm Mouse: An Effect That Is Independent of the Classic Androgen Receptor |journal=Circulation |volume=116 |issue=21 |pages=2427–34 |year=2007 |pmid=17984376 |doi=10.1161/CIRCULATIONAHA.107.708768 }}</ref><ref>http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/ReproductiveHealthDrugsAdvisoryCommittee/UCM413736.pdf{{full citation needed|date=February 2017}}</ref> Some research has identified testosterone as a [[vasodilator]] and an [[endothelium]]-repairing hormone within many regions in the body, including the coronary arteries.<ref name=pmid20807333>{{cite journal |last1=Corona |first1=Giovanni |last2=Monami |first2=Matteo |last3=Rastrelli |first3=Giulia |last4=Aversa |first4=Antonio |last5=Tishova |first5=Yuliya |last6=Saad |first6=Farid |last7=Lenzi |first7=Andrea |last8=Forti |first8=Gianni |last9=Mannucci |first9=Edoardo |last10=Maggi |first10=Mario |title=Testosterone and Metabolic Syndrome: A Meta‐Analysis Study |journal=The Journal of Sexual Medicine |volume=8 |issue=1 |pages=272–83 |year=2011 |pmid=20807333 |doi=10.1111/j.1743-6109.2010.01991.x }}</ref><ref name="(9)">{{cite journal |last1=Webb |first1=Carolyn M. |last2=McNeill |first2=John G. |last3=Hayward |first3=Christopher S. |last4=de Zeigler |first4=Dominique |last5=Collins |first5=Peter |title=Effects of testosterone on coronary vasomotor regulation in men with coronary heart disease |journal=Circulation |volume=100 |issue=16 |pages=1690–6 |year=1999 |pmid=10525487 |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=10525487 |doi=10.1161/01.cir.100.16.1690}}</ref> Recent research depicts testosterone as important in decreasing the production of inflammatory cytokines such as [[tumor necrosis factor alpha]], [[IL1B|interleukin-1beta]] and [[interleukin-6]], which are influential in atherosclerotic profiles.<ref name=pmid20807333/><ref name=pmid16731790>{{cite journal |last1=Corrales |first1=JJ |last2=Almeida |first2=M |last3=Burgo |first3=R |last4=Mories |first4=MT |last5=Miralles |first5=JM |last6=Orfao |first6=A |title=Androgen-replacement therapy depresses the ex vivo production of inflammatory cytokines by circulating antigen-presenting cells in aging type-2 diabetic men with partial androgen deficiency |journal=The Journal of Endocrinology |volume=189 |issue=3 |pages=595–604 |year=2006 |pmid=16731790 |doi=10.1677/joe.1.06779 }}</ref> 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.<ref name=pmid16731790/><ref name=pmid12967330>{{cite journal |last1=Malkin |first1=CJ |last2=Pugh |first2=PJ |last3=Jones |first3=RD |last4=Jones |first4=TH |last5=Channer |first5=KS |title=Testosterone as a protective factor against atherosclerosis--immunomodulation and influence upon plaque development and stability |journal=The Journal of Endocrinology |volume=178 |issue=3 |pages=373–80 |year=2003 |pmid=12967330 |doi=10.1677/joe.0.1780373 }}</ref>
| | [[Testosterone]] is a [[steroid hormone]] primarily produced in the [[testes]] in males and in smaller amounts in the [[ovaries]] and [[adrenal glands]] in females. It plays a crucial role in the development of male [[reproductive tissues]] and secondary sexual characteristics. Beyond its reproductive functions, testosterone has significant effects on the [[cardiovascular system]]. |
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| Testosterone has also shown to be effective as an anti-atherosclerotic through preventing aortic [[cholesterol]] deposition in both rabbits fed high cholesterol diets and mice with low-density lipoprotein gene knockout.<ref name=pmid20807333/><ref name=pmid11248122>{{cite journal |last1=Nathan |first1=Lauren |last2=Shi |first2=Weibin |last3=Dinh |first3=Hillary |last4=Mukherjee |first4=Tapan K. |last5=Wang |first5=Xuping |last6=Lusis |first6=Aldons J. |last7=Chaudhuri |first7=Gautam |title=Testosterone inhibits early atherogenesis by conversion to estradiol: Critical role of aromatase |journal=Proceedings of the National Academy of Sciences |volume=98 |issue=6 |pages=3589–93 |year=2001 |jstor=3055279 |bibcode=2001PNAS...98.3589N |pmid=11248122 |pmc=30697 |doi=10.1073/pnas.051003698 }}</ref> Fatty deposition within the aorta associated with low endogenous testosterone has been determined to be independent of the androgen receptor.<ref name=pmid20807333/> 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.<ref name=pmid20807333/>
| | ===Physiological Role of Testosterone=== |
| | Testosterone influences the cardiovascular system through various mechanisms. It affects the [[endothelium]], the inner lining of [[blood vessels]], and modulates [[vascular tone]] and [[blood pressure]]. Testosterone also impacts [[lipid metabolism]], [[inflammation]], and [[coagulation]], all of which are critical factors in cardiovascular health. |
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| 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.<ref name=pmid23475207/> 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]] and [[cachexia]].<ref name=pmid23475207/>
| | ===Effects on Vascular Function=== |
| | Testosterone has been shown to induce [[vasodilation]] by increasing the production of [[nitric oxide]] in endothelial cells. This process helps in reducing [[vascular resistance]] and improving [[blood flow]]. Testosterone's vasodilatory effects are thought to contribute to its potential protective role against [[hypertension]] and other cardiovascular diseases. |
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| ==Testosterone replacement therapy== | | ===Impact on Lipid Profile=== |
| 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).<ref name=pmid20807333/><ref name=pmid16760629>{{cite journal |last1=Vigna |first1=GB |last2=Bergami |first2=E |title=Testosterone replacement, cardiovascular system and risk factors in the aging male |journal=[[Journal of Endocrinological Investigation]] |volume=28 |issue=11 Suppl Proceedings |pages=69–74 |year=2005 |pmid=16760629 }}</ref> 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.<ref name=pmid20807333/> This understanding has been determined in several studies, although results of these studies are contradictory.<ref name=pmid20807333/><ref name=pmid9225239>{{cite journal |last1=Shono |first1=N |last2=Kumagai |first2=S |last3=Higaki |first3=Y |last4=Nishizumi |first4=M |last5=Sasaki |first5=H |title=The relationships of testosterone, estradiol, dehydroepiandrosterone-sulfate and sex hormone-binding globulin to lipid and glucose metabolism in healthy men |journal=Journal of Atherosclerosis and Thrombosis |volume=3 |issue=1 |pages=45–51 |year=1996 |pmid=9225239 |doi=10.5551/jat1994.3.45}}</ref><ref name=pmid6711424>{{cite journal |last1=Dai |first1=WS |last2=Gutai |first2=JP |last3=Kuller |first3=LH |last4=Laporte |first4=RE |last5=Falvo-Gerard |first5=L |last6=Caggiula |first6=A |title=Relation between plasma high-density lipoprotein cholesterol and sex hormone concentrations in men |journal=The American Journal of Cardiology |volume=53 |issue=9 |pages=1259–63 |year=1984 |pmid=6711424 |doi=10.1016/0002-9149(84)90075-4}}</ref>
| | Testosterone influences the [[lipid profile]] by affecting levels of [[cholesterol]] and [[triglycerides]]. It has been observed to lower [[high-density lipoprotein]] (HDL) cholesterol and may increase [[low-density lipoprotein]] (LDL) cholesterol, although the clinical significance of these changes is still under investigation. The overall impact of testosterone on lipid metabolism is complex and may vary depending on individual factors such as age and baseline hormone levels. |
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| [[Testosterone replacement therapy]] in men diagnosed with pre-existing heart disease has been related to an increased risk of myocardial infarction.<ref name=pmid24489673>{{cite journal |last1=Gong |first1=Yan |last2=Finkle |first2=William D. |last3=Greenland |first3=Sander |last4=Ridgeway |first4=Gregory K. |last5=Adams |first5=John L. |last6=Frasco |first6=Melissa A. |last7=Cook |first7=Michael B. |last8=Fraumeni |first8=Joseph F. |last9=Hoover |first9=Robert N. |title=Increased Risk of Non-Fatal Myocardial Infarction Following Testosterone Therapy Prescription in Men |journal=PLoS ONE |volume=9 |issue=1 |pages=e85805 |year=2014 |pmid=24489673 |pmc=3905977 |doi=10.1371/journal.pone.0085805 |bibcode=2014PLoSO...985805F }}</ref> 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.<ref name=pmid24193080>{{cite journal |last1=Vigen |first1=Rebecca |last2=O'Donnell |first2=Colin I. |last3=Barón |first3=Anna E. |last4=Grunwald |first4=Gary K. |last5=Maddox |first5=Thomas M. |last6=Bradley |first6=Steven M. |last7=Barqawi |first7=Al |last8=Woning |first8=Glenn |last9=Wierman |first9=Margaret E. |last10=Plomondon |first10=Mary E. |last11=Rumsfeld |first11=John S. |last12=Ho |first12=P. Michael |title=Association of Testosterone Therapy With Mortality, Myocardial Infarction, and Stroke in Men With Low Testosterone Levels |journal=JAMA |volume=310 |issue=17 |pages=1829–36 |year=2013 |pmid=24193080 |doi=10.1001/jama.2013.280386 }}</ref> 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.<ref name="(17)">{{cite web |publisher=Endocrine Society |title=The risk of Cardiovascular Events in Men Receiving Testosterone Therapy: An Endocrine Society Statement |url=https://www.endocrine.org/~/media/endosociety/Files/Advocacy%20and%20Outreach/Position%20Statements/Other%20Statements/The%20Risk%20of%20Cardiovascular%20Events%20in%20Men%20Receiving%20Testosterone%20Therapy.pdf |date=February 7, 2014 }}</ref>
| | ===Testosterone and Cardiovascular Risk=== |
| | The relationship between testosterone levels and cardiovascular risk is a subject of ongoing research. Some studies suggest that low testosterone levels are associated with an increased risk of [[cardiovascular disease]] (CVD), while others indicate that high levels may also pose risks. The balance of testosterone's effects on the cardiovascular system is influenced by factors such as age, existing health conditions, and lifestyle. |
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| ==References== | | ===Therapeutic Use of Testosterone=== |
| {{Reflist|2}}
| | [[Testosterone replacement therapy]] (TRT) is used to treat [[hypogonadism]] and other conditions associated with low testosterone levels. While TRT can improve symptoms such as [[fatigue]], [[depression]], and [[sexual dysfunction]], its impact on cardiovascular health remains controversial. Some studies suggest that TRT may increase the risk of cardiovascular events, while others report neutral or even beneficial effects. |
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| [[Category:Cardiology]] | | ==Related Pages== |
| [[Category:Cardiovascular system]] | | * [[Cardiovascular disease]] |
| | * [[Endocrinology]] |
| | * [[Hormone replacement therapy]] |
| | * [[Lipid metabolism]] |
| | * [[Vasodilation]] |
| | |
| | [[Category:Cardiovascular physiology]] |
| | [[Category:Endocrinology]] |
| [[Category:Testosterone]] | | [[Category:Testosterone]] |
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Overview of the effects of testosterone on the cardiovascular system
Testosterone and the Cardiovascular System[edit]
Testosterone is a steroid hormone primarily produced in the testes in males and in smaller amounts in the ovaries and adrenal glands in females. It plays a crucial role in the development of male reproductive tissues and secondary sexual characteristics. Beyond its reproductive functions, testosterone has significant effects on the cardiovascular system.
Physiological Role of Testosterone[edit]
Testosterone influences the cardiovascular system through various mechanisms. It affects the endothelium, the inner lining of blood vessels, and modulates vascular tone and blood pressure. Testosterone also impacts lipid metabolism, inflammation, and coagulation, all of which are critical factors in cardiovascular health.
Effects on Vascular Function[edit]
Testosterone has been shown to induce vasodilation by increasing the production of nitric oxide in endothelial cells. This process helps in reducing vascular resistance and improving blood flow. Testosterone's vasodilatory effects are thought to contribute to its potential protective role against hypertension and other cardiovascular diseases.
Impact on Lipid Profile[edit]
Testosterone influences the lipid profile by affecting levels of cholesterol and triglycerides. It has been observed to lower high-density lipoprotein (HDL) cholesterol and may increase low-density lipoprotein (LDL) cholesterol, although the clinical significance of these changes is still under investigation. The overall impact of testosterone on lipid metabolism is complex and may vary depending on individual factors such as age and baseline hormone levels.
Testosterone and Cardiovascular Risk[edit]
The relationship between testosterone levels and cardiovascular risk is a subject of ongoing research. Some studies suggest that low testosterone levels are associated with an increased risk of cardiovascular disease (CVD), while others indicate that high levels may also pose risks. The balance of testosterone's effects on the cardiovascular system is influenced by factors such as age, existing health conditions, and lifestyle.
Therapeutic Use of Testosterone[edit]
Testosterone replacement therapy (TRT) is used to treat hypogonadism and other conditions associated with low testosterone levels. While TRT can improve symptoms such as fatigue, depression, and sexual dysfunction, its impact on cardiovascular health remains controversial. Some studies suggest that TRT may increase the risk of cardiovascular events, while others report neutral or even beneficial effects.
Related Pages[edit]
