Skip to main content
SpringerLink
Log in

High Testosterone Levels: Impact on the Heart

Implications for Testosterone Misuse

  • Living reference work entry
  • First Online:
Handbook of Substance Misuse and Addictions

Abstract

Testosterone, the main endogenous active androgen, is used to treat many clinical conditions, such as hypogonadism, infertility, erectile dysfunction, osteoporosis, anemia, and in transgender therapy (female-to-male transsexuals). Androgens are also used by athletes to enhance performance and endurance, and by nonathlete weightlifters or bodybuilders to enhance muscle development and strength. Accordingly, testosterone and other anabolic-androgenic steroids are the main class of appearance and performance enhancing drugs (APEDs), i.e., substances used to improve appearance by building muscle mass or to enhance athletic performance.

Testosterone and other androgens, mainly at supraphysiological levels, affect every single body tissue or system, including the cardiovascular system. Testosterone increases cardiovascular disease risk, causes myocardial infarction, stroke, high blood pressure, blood clots, and heart failure. Among the potential mechanisms whereby testosterone affects the cardiovascular system, both indirect and direct actions have been reported. Indirect actions of testosterone on the cardiovascular system include changes in the lipid profile, insulin sensitivity, and hemostatic mechanisms, modulation of the sympathetic nervous system and renin-angiotensin-aldosterone system. Direct actions of testosterone in the cardiovascular system involves activation of proinflammatory and redox processes, decreased nitric oxide (NO) bioavailability, and stimulation of vasoconstrictor signaling pathways.

This chapter focuses on the effects of androgens, mainly testosterone, on the vascular system. The effects of testosterone on endothelial and vascular smooth muscle cells, as well as mechanisms involved in the effects of testosterone will be reviewed. Effects of testosterone on the perivascular adipose tissue, the immune, sympathetic, and renin-angiotensin systems will also be mentioned.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

Abbreviations

AAA:

Ascending aortic aneurysms

ACh:

Acetylcholine

Ang II:

Angiotensin II

APEDs:

Appearance and performance enhancing drugs

AR:

Androgen receptor

ARKO:

AR knockout mice

AT1aR:

Angiotensin II type 1A receptor

AT2R:

Angiotensin II type 2 receptor

Bcl-2:

B cell leukemia/lymphoma-2

BKCa:

Large-conductance Ca2+-activated potassium channel

BSA:

Bovine serum albumin

Ca2+:

Calcium ion

CASMCs:

Coronary artery smooth muscle cells

Cav1.2:

L-type voltage-gated Ca2+ channel

CDP:

Collagenase-digestible protein

CDK:

Cyclin-dependent kinase

CK:

Creatine kinase

COX:

Cyclooxygenase

CSMC:

Coronary smooth muscle cell

DHEA-S:

DHEA sulfate

DHEA:

Dehydroepiandrosterone

DHT:

5α-dihydrotestosterone

ECs:

Endothelial cells

EDCFs:

Endothelium-derived contracting factors

EDHF:

Endothelium-derived hyperpolarizing factor

EDRFs:

Endothelium-derived relaxing factors

EETs:

Epoxyeicosatrienoic acids

eNOS:

Endothelial nitric oxide synthase

ERK1/2:

Extracellular signal-regulated kinase 1/2

Gas6:

Growth arrest-specific gene 6

GPRC6A:

GPCR, Class C, group 6, subtype A

H2O2:

Hydrogen peroxide

HDL:

High-density lipoprotein

HMG-CoA:

3-hydroxy 3-methylglutaryl coenzyme A reductase enzyme

HUVEC:

Human umbilical vein endothelial cell

iNOS:

Inducible nitric oxide synthase

IL-1β:

Interleukin-1beta

IP3:

Inositol trisphosphate

K+:

Potassium ion

Kcnn3:

Small conductance calcium-activated potassium channel

Kv:

Voltage-dependent potassium channel

LDL:

Low-density lipoprotein

LPS:

Lipopolysaccharide

MAPK:

Mitogen-activated protein kinase

NAR:

Normal androgen receptor

NCP:

Noncollagen protein

NF-κB:

Nuclear factor-κB

NLRP3:

NOD-, LRR-, and pyrin domain-containing protein 3 inflammasome

NO:

Nitric oxide

Nox1:

Subtype 1 NADPH oxidase

Nox4:

Subtype 4 NADPH oxidase

ORX:

Orchiectomized

ORXT:

ORX treated with testosterone

Ox-LDL:

Oxidized low-density lipoprotein

PDGF:

Platelet-derived growth factor

PGE2:

Prostaglandin E2

PGF2α:

Prostaglandin F2 alpha

PGI2:

Prostacyclin

PKC:

Protein kinase C

PTOV1:

Prostate overexpressed protein 1

PVAT:

Perivascular adipose tissue

RASMC:

Rat aortic smooth muscle cell

ROS:

Reactive oxygen species

SBP:

Systolic blood pressure

SHR:

Spontaneously hypertensive rat

siRNA:

Small interfering RNA

SK3 channel:

Small-conductance calcium-activated potassium channel-3

SMCs:

Smooth muscle cells

T-BSA:

Testosterone-3-carboxymethyl oxime conjugated to bovine serum albumin

TFM:

Testicular feminized male

THG:

Tetrahydrogestrinone

TNF-α:

Tumor necrosis factor-alpha

TP:

Thromboxane-prostanoid

TxA2:

Thromboxane A2

VCAM-1:

Vascular adhesion molecule 1

VSM:

Vascular smooth muscle

VSMCs:

Vascular smooth muscle cells

WKY:

Wistar-Kyoto rat

References

  • Ajayi AA, Mathur R, Halushka PV (1995) Testosterone increases human platelet thromboxane A2 receptor density and aggregation responses. Circulation 91:2742–2747

    Article  CAS  PubMed  Google Scholar 

  • Alves MJ, Dos Santos MR, Dias RG et al (2010) Abnormal neurovascular control in anabolic androgenic steroids users. Med Sci Sports Exerc 42:865–871

    Article  CAS  PubMed  Google Scholar 

  • Alves JV, da Costa RM, Pereira CA et al (2020) Supraphysiological levels of testosterone induce vascular dysfunction via activation of the NLRP3 inflammasome. Front Immunol 11:1647

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Baggish AL, Weiner RB, Kanayama G et al (2017) Cardiovascular toxicity of illicit anabolic-androgenic steroid use. Circulation 135:1991–2002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bahrke MS, Wright JE, Strauss RH et al (1992) Psychological moods and subjectively perceived behavioral and somatic changes accompanying anabolic-androgenic steroid use. Am J Sports Med 20:717–724

    Article  CAS  PubMed  Google Scholar 

  • Barton M, Prossnitz ER, Meyer MR (2012) Testosterone and secondary hypertension: new pieces to the puzzle. Hypertension 59:1101–1103

    Article  CAS  PubMed  Google Scholar 

  • Benedit P, Paciucci R, Thomson TM et al (2001) PTOV1, a novel protein overexpressed in prostate cancer containing a new class of protein homology blocks. Oncogene 20:1455–1464

    Article  CAS  PubMed  Google Scholar 

  • Bhasin S, Woodhouse L, Casaburi R et al (2001) Testosterone dose-response relationships in healthy young men. Am J Physiol Endocrinol Metab 281:E1172–E1181

    Article  CAS  PubMed  Google Scholar 

  • Bianchi VE (2018) Testosterone, myocardial function, and mortality. Heart Fail Rev 23:773–788

    Article  CAS  PubMed  Google Scholar 

  • Bowles DK, Maddali KK, Ganjam VK et al (2004) Endogenous testosterone increases L-type Ca2+ channel expression in porcine coronary smooth muscle. Am J Physiol Heart Circ Physiol 287:H2091–H2098

    Article  CAS  PubMed  Google Scholar 

  • Bowles DK, Maddali KK, Dhulipala VC et al (2007) PKCdelta mediates anti-proliferative, pro-apoptic effects of testosterone on coronary smooth muscle. Am J Physiol Cell Physiol 293:C805–C813

    Article  CAS  PubMed  Google Scholar 

  • Boydens C, Pauwels B, Van de Voorde J (2016) Effect of resveratrol and orchidectomy on the vasorelaxing influence of perivascular adipose tissue. Heart Vessel 31:608–615

    Article  Google Scholar 

  • Busse R, Edwards G, Félétou M et al (2002) EDHF: bringing the concepts together. Trends Pharmacol Sci 23:374–380

    Article  CAS  PubMed  Google Scholar 

  • Bustamante D, Lara H, Belmar J (1989) Changes of norepinephrine levels, tyrosine hydroxylase and dopamine-beta-hydroxylase activities after castration and testosterone treatment in vas deferens of adult rats. Biol Reprod 40:541–548

    Article  CAS  PubMed  Google Scholar 

  • Campbell WB, Falck JR (2007) Arachidonic acid metabolites as endothelium-derived hyperpolarizing factors. Hypertension 49:590–596

    Article  CAS  PubMed  Google Scholar 

  • Campelo AE, Cutini PH, Massheimer VL (2012) Cellular actions of testosterone in vascular cells: mechanism independent of aromatization to estradiol. Steroids 77:1033–1040

    Article  CAS  PubMed  Google Scholar 

  • Carbajal-García A, Reyes-García J, Montaño LM (2020) Androgen effects on the adrenergic system of the vascular, airway, and cardiac myocytes and their relevance in pathological processes. Int J Endocrinol 2020:8849641

    Article  PubMed  PubMed Central  Google Scholar 

  • Casscells W (1992) Migration of smooth muscle and endothelial cells. Critical events in restenosis. Circulation 86:723–729

    Article  CAS  PubMed  Google Scholar 

  • Chaytor AT, Martin PE, Edwards DH et al (2001) Gap junctional communication underpins EDHF-type relaxations evoked by ACh in the rat hepatic artery. Am J Physiol Heart Circ Physiol 280:H2441–H2450

    Article  CAS  PubMed  Google Scholar 

  • Chignalia AZ, Schuldt EZ, Camargo LL et al (2012) Testosterone induces vascular smooth muscle cell migration by NADPH oxidase and c-Src-dependent pathways. Hypertension 59:1263–1271

    Article  CAS  PubMed  Google Scholar 

  • Chignalia AZ, Oliveira MA, Debbas V et al (2015) Testosterone induces leucocyte migration by NADPH oxidase-driven ROS- and COX2-dependent mechanisms. Clin Sci (Lond) 129:39–48

    Article  CAS  Google Scholar 

  • Chinnathambi V, Balakrishnan M, Ramadoss J et al (2013a) Testosterone alters maternal vascular adaptations: role of the endothelial NO system. Hypertension 61:647–654

    Article  CAS  PubMed  Google Scholar 

  • Chinnathambi V, Yallampalli C, Sathishkumar K (2013b) Prenatal testosterone induces sex-specific dysfunction in endothelium-dependent relaxation pathways in adult male and female rats. Biol Reprod 89:97

    Article  PubMed  PubMed Central  Google Scholar 

  • Chinnathambi V, Blesson CS, Vincent KL et al (2014a) Elevated testosterone levels during rat pregnancy cause hypersensitivity to angiotensin II and attenuation of endothelium-dependent vasodilation in uterine arteries. Hypertension 64:405–414

    Article  CAS  PubMed  Google Scholar 

  • Chinnathambi V, More AS, Hankins GD et al (2014b) Gestational exposure to elevated testosterone levels induces hypertension via heightened vascular angiotensin II type 1 receptor signaling in rats. Biol Reprod 91:6

    Article  PubMed  PubMed Central  Google Scholar 

  • Crews JK, Khalil RA (1999) Antagonistic effects of 17 beta-estradiol, progesterone, and testosterone on Ca2+ entry mechanisms of coronary vasoconstriction. Arterioscler Thromb Vasc Biol 19:1034–1040

    Article  CAS  PubMed  Google Scholar 

  • Cruz-Topete D, Dominic P, Stokes KY (2020) Uncovering sex-specific mechanisms of action of testosterone and redox balance. Redox Biol 31:101490

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • De Smet MA, Lapauw B, De Backer T (2017) Sex steroids in relation to cardiac structure and function in men. Andrologia 49(2). https://doi.org/10.1111/and.12610

  • Death AK, McGrath KC, Sader MA et al (2004) Dihydrotestosterone promotes vascular cell adhesion molecule-1 expression in male human endothelial cells via a nuclear factor-kappaB-dependent pathway. Endocrinology 145:1889–1897

    Article  CAS  PubMed  Google Scholar 

  • dos Santos MR, Dias RG, Laterza MC et al (2013) Impaired post exercise heart rate recovery in anabolic steroid users. Int J Sports Med 34:931–935

    Article  PubMed  Google Scholar 

  • El Scheich T, Weber A-A, Klee D et al (2013) Adolescent ischemic stroke associated with anabolic steroid and cannabis abuse. J Pediatr Endocrinol Metab 26:161–165

    Article  PubMed  Google Scholar 

  • Elagizi A, Köhler TS, Lavie CJ (2018) Testosterone and cardiovascular health. Mayo Clin Proc 93:83–100

    Article  CAS  PubMed  Google Scholar 

  • Farhat MY, Wolfe R, Vargas R et al (1995) Effect of testosterone treatment on vasoconstrictor response of left anterior descending coronary artery in male and female pigs. J Cardiovasc Pharmacol 25:495–500

    Article  CAS  PubMed  Google Scholar 

  • Félétou M, Vanhoutte PM (2006) Endothelium-derived hyperpolarizing factor: where are we now? Arterioscler Thromb Vasc Biol 26:1215–1225

    Article  PubMed  Google Scholar 

  • Félétou M, Vanhoutte PM (2009) EDHF: an update. Clin Sci (Lond) 117:139–155

    Article  Google Scholar 

  • Félétou M, Huang Y, Vanhoutte PM (2011) Endothelium-mediated control of vascular tone: COX-1 and COX-2 products. Br J Pharmacol 164:894–912

    Article  PubMed  PubMed Central  Google Scholar 

  • Fujimoto R, Morimoto I, Morita E et al (1994) Androgen receptors, 5 alpha-reductase activity and androgen-dependent proliferation of vascular smooth muscle cells. J Steroid Biochem Mol Biol 50:169–174

    Article  CAS  PubMed  Google Scholar 

  • Gonzales RJ, Krause DN, Duckles SP (2004) Testosterone suppresses endothelium-dependent dilation of rat middle cerebral arteries. Am J Physiol Heart Circ Physiol 286:H552–H560

    Article  CAS  PubMed  Google Scholar 

  • Gonzales RJ, Ghaffari AA, Duckles SP et al (2005) Testosterone treatment increases thromboxane function in rat cerebral arteries. Am J Physiol Heart Circ Physiol 289:H578–H585

    Article  CAS  PubMed  Google Scholar 

  • Griffith TM (2004) Endothelium-dependent smooth muscle hyperpolarization: do gap junctions provide a unifying hypothesis? Br J Pharmacol 141:881–903

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hashimura K, Sudhir K, Nigro J et al (2005) Androgens stimulate human vascular smooth muscle cell proteoglycan biosynthesis and increase lipoprotein binding. Endocrinology 146:2085–2090

    Article  CAS  PubMed  Google Scholar 

  • Herman SM, Robinson JT, McCredie RJ et al (1997) Androgen deprivation is associated with enhanced endothelium-dependent dilatation in adult men. Arterioscler Thromb Vasc Biol 17:2004–2009

    Article  CAS  PubMed  Google Scholar 

  • Herring MJ, Oskui PM, Hale SL et al (2013) Testosterone and the cardiovascular system: a comprehensive review of the basic science literature. J Am Heart Assoc 2:e000271

    Article  PubMed  PubMed Central  Google Scholar 

  • Higashiura K, Blaney B, Morgan E et al (1996) Inhibition of testosterone 5 alpha-reductase: evidence for tissue-specific regulation of thromboxane A2 receptors. J Pharmacol Exp Ther 279:1386–1391

    CAS  PubMed  Google Scholar 

  • Higashiura K, Mathur RS, Halushka PV (1997) Gender-related differences in androgen regulation of thromboxane A2 receptors in rat aortic smooth-muscle cells. J Cardiovasc Pharmacol 29:311–315

    Article  CAS  PubMed  Google Scholar 

  • Hutchison SJ, Sudhir K, Chou TM et al (1997) Testosterone worsens endothelial dysfunction associated with hypercholesterolemia and environmental tobacco smoke exposure in male rabbit aorta. J Am Coll Cardiol 29:800–807

    Article  CAS  PubMed  Google Scholar 

  • Imig JD (2020) Eicosanoid blood vessel regulation in physiological and pathological states. Clin Sci (Lond) 134:2707–2727

    Article  CAS  Google Scholar 

  • Jones RD, English KM, Jones TH et al (2004) Testosterone-induced coronary vasodilatation occurs via a non-genomic mechanism: evidence of a direct calcium antagonism action. Clin Sci (Lond) 107:149–158

    Article  CAS  Google Scholar 

  • Karanian JW, Ramwell PW (1996) Effect of gender and sex steroids on the contractile response of canine coronary and renal blood vessels. J Cardiovasc Pharmacol 27:312–319

    Article  CAS  PubMed  Google Scholar 

  • Kumai T, Tanaka M, Watanabe M et al (1994) Possible involvement of androgen in increased norepinephrine synthesis in blood vessels of spontaneously hypertensive rats. Jpn J Pharmacol 66:439–444

    Article  CAS  PubMed  Google Scholar 

  • Kumar S, Gordon GH, Abbott DH et al (2018) Androgens in maternal vascular and placental function: implications for preeclampsia pathogenesis. Reproduction 156:R155–R167

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lanfranco F, Zitzmann M, Simoni M et al (2004) Serum adiponectin levels in hypogonadal males: influence of testosterone replacement therapy. Clin Endocrinol 60:500–507

    Article  CAS  Google Scholar 

  • Leitman DC, Benson SC, Johnson LK (1984) Glucocorticoids stimulate collagen and noncollagen protein synthesis in cultured vascular smooth muscle cells. J Cell Biol 98:541–549

    Article  CAS  PubMed  Google Scholar 

  • Ligi I, Grandvuillemin I, Andres V et al (2010) Low birth weight infants and the developmental programming of hypertension: a focus on vascular factors. Semin Perinatol 34:188–192

    Article  PubMed  Google Scholar 

  • Ling S, Dai A, Williams MR et al (2002) Testosterone (T) enhances apoptosis-related damage in human vascular endothelial cells. Endocrinology 143:1119–1125

    Article  CAS  PubMed  Google Scholar 

  • Liu PY, Death AK, Handelsman DJ (2003) Androgens and cardiovascular disease. Endocr Rev 24:313–340

    Article  CAS  PubMed  Google Scholar 

  • Lopes RA, Neves KB, Pestana CR et al (2014) Testosterone induces apoptosis in vascular smooth muscle cells via extrinsic apoptotic pathway with mitochondria-generated reactive oxygen species involvement. Am J Physiol Heart Circ Physiol 306:H1485–H1494

    Article  PubMed  Google Scholar 

  • Maenhaut N, Van de Voorde J (2011) Regulation of vascular tone by adipocytes. BMC Med 9:25

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mäkinen JI, Perheentupa A, Irjala K et al (2011) Endogenous testosterone and brachial artery endothelial function in middle-aged men with symptoms of late-onset hypogonadism. Aging Male 14:237–242

    Article  PubMed  Google Scholar 

  • Masuda A, Mathur R, Halushka PV (1991) Testosterone increases thromboxane A2 receptors in cultured rat aortic smooth muscle cells. Circ Res 69:638–643

    Article  CAS  PubMed  Google Scholar 

  • Matsuda K, Ruff A, Morinelli TA et al (1994) Testosterone increases thromboxane A2 receptor density and responsiveness in rat aortas and platelets. Am J Phys 267:H887–H893

    CAS  Google Scholar 

  • Matsuda K, Mathur RS, Ullian ME et al (1995) Sex steroid regulation of thromboxane A2 receptors in cultured rat aortic smooth muscle cells. Prostaglandins 49:183–196

    Article  CAS  PubMed  Google Scholar 

  • Matsumoto T, Goulopoulou S, Taguchi K et al (2015) Constrictor prostanoids and uridine adenosine tetraphosphate: vascular mediators and therapeutic targets in hypertension and diabetes. Br J Pharmacol 172:3980–4001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McCredie RJ, McCrohon JA, Turner L et al (1998) Vascular reactivity is impaired in genetic females taking high-dose androgens. J Am Coll Cardiol 32:1331–1335

    Article  CAS  PubMed  Google Scholar 

  • McCrohon JA, Jessup W, Handelsman DJ et al (1999) Androgen exposure increases human monocyte adhesion to vascular endothelium and endothelial cell expression of vascular cell adhesion molecule-1. Circulation 99:2317–2322

    Article  CAS  PubMed  Google Scholar 

  • Mishra JS, Hankins GD, Kumar S (2016) Testosterone downregulates angiotensin II type-2 receptor via androgen receptor-mediated ERK1/2 MAP kinase pathway in rat aorta. J Renin-Angiotensin-Aldosterone Syst 17:1470320316674875

    Article  PubMed  PubMed Central  Google Scholar 

  • Mishra JS, More AS, Hankins GDV et al (2017) Hyperandrogenemia reduces endothelium-derived hyperpolarizing factor-mediated relaxation in mesenteric artery of female rats. Biol Reprod 96:1221–1230

    Article  PubMed  PubMed Central  Google Scholar 

  • Montezano AC, Touyz RM (2012) Molecular mechanisms of hypertension – reactive oxygen species and antioxidants: a basic science update for the clinician. Can J Cardiol 28:288–295

    Article  CAS  PubMed  Google Scholar 

  • More AS, Mishra JS, Hankins GD et al (2015) Enalapril normalizes endothelium-derived hyperpolarizing factor-mediated relaxation in mesenteric artery of adult hypertensive rats prenatally exposed to testosterone. Biol Reprod 92:155

    Article  PubMed  PubMed Central  Google Scholar 

  • Mukherjee TK, Dinh H, Chaudhuri G et al (2002) Testosterone attenuates expression of vascular cell adhesion molecule-1 by conversion to estradiol by aromatase in endothelial cells: implications in atherosclerosis. Proc Natl Acad Sci U S A 99:4055–4060

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Müntzing J (1971) Effects of sexual hormones on the adrenergic innervation and the monoamine oxidase activity in the rat ventral prostate. Acta Pharmacol Toxicol (Copenh) 30:208–214

    Article  Google Scholar 

  • Nakamura Y, Suzuki T, Igarashi K et al (2006) PTOV1: a novel testosterone-induced atherogenic gene in human aorta. J Pathol 209:522–531

    Article  CAS  PubMed  Google Scholar 

  • Nakao J, Change WC, Murota SI et al (1981) Testosterone inhibits prostacyclin production by rat aortic smooth muscle cells in culture. Atherosclerosis 39:203–209

    Article  CAS  PubMed  Google Scholar 

  • Naseem SM, Heald FP (1987) Sex mediated lipid metabolism in human aortic smooth muscle cells. Biochem Biophys Res Commun 144:284–291

    Article  CAS  PubMed  Google Scholar 

  • National Institute on Drug Abuse. http://www.drugabuse.gov

  • Nheu L, Nazareth L, Xu GY et al (2011) Physiological effects of androgens on human vascular endothelial and smooth muscle cells in culture. Steroids 76:1590–1596

    Article  CAS  PubMed  Google Scholar 

  • Nishizawa H, Shimomura I, Kishida K et al (2002) Androgens decrease plasma adiponectin, an insulin-sensitizing adipocyte-derived protein. Diabetes 51:2734–2741

    Article  CAS  PubMed  Google Scholar 

  • Ojeda NB, Royals TP, Black JT et al (2010) Enhanced sensitivity to acute angiotensin II is testosterone dependent in adult male growth-restricted offspring. Am J Physiol Regul Integr Comp Physiol 298:R1421–R1427

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Palatini P, Giada F, Garavelli G et al (1996) Cardiovascular effects of anabolic steroids in weight-trained subjects. J Clin Pharmacol 36:1132–1140

    Article  CAS  PubMed  Google Scholar 

  • Pi M, Parrill AL, Quarles LD (2010) GPRC6A mediates the non-genomic effects of steroids. J Biol Chem 285:39953–39964

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pirompol P, Teekabut V, Weerachatyanukul W et al (2016) Supra-physiological dose of testosterone induces pathological cardiac hypertrophy. J Endocrinol 229:13–23

    Article  CAS  PubMed  Google Scholar 

  • Pope HG, Kanayama G, Athey A et al (2014) The lifetime prevalence of anabolic-androgenic steroid use and dependence in Americans: current best estimates. Am J Addict Am Acad Psychiatr Alcohol Addict 23:371–377

    Google Scholar 

  • Porello RA, Dos Santos MR, De Souza FR et al (2018) Neurovascular response during exercise and mental stress in anabolic steroid users. Med Sci Sports Exerc 50:596–602

    Article  PubMed  Google Scholar 

  • Quan A, Teoh H, Man RY (1999) Acute exposure to a low level of testosterone impairs relaxation in porcine coronary arteries. Clin Exp Pharmacol Physiol 26:830–832

    Article  CAS  PubMed  Google Scholar 

  • Rastogi RB, Agarwal RA, Bhargava KP et al (1977) Effect of castration and testosterone treatment on catecholamine metabolism in ventral prostates of normal and chemically sympathectomized rats. Can J Physiol Pharmacol 55:1015–1022

    Article  CAS  PubMed  Google Scholar 

  • Razmara A, Krause DN, Duckles SP (2005) Testosterone augments endotoxin-mediated cerebrovascular inflammation in male rats. Am J Physiol Heart Circ Physiol 289:H1843–H1850

    Article  CAS  PubMed  Google Scholar 

  • Ribeiro Júnior RF, Ronconi KS, Jesus ICG et al (2018) Testosterone deficiency prevents left ventricular contractility dysfunction after myocardial infarction. Mol Cell Endocrinol 460:14–23

    Article  PubMed  Google Scholar 

  • Ross R (1999) Atherosclerosis – an inflammatory disease. N Engl J Med 340:115–126

    Article  CAS  PubMed  Google Scholar 

  • Roved J, Westerdahl H, Hasselquist D (2017) Sex differences in immune responses: hormonal effects, antagonistic selection, and evolutionary consequences. Horm Behav 88:95–105

    Article  CAS  PubMed  Google Scholar 

  • Rowell KO, Hall J, Pugh PJ et al (2009) Testosterone acts as an efficacious vasodilator in isolated human pulmonary arteries and veins: evidence for a biphasic effect at physiological and supra-physiological concentrations. J Endocrinol Investig 32:718–723

    Article  CAS  Google Scholar 

  • Saldanha PA, Cairrão E, Maia CJ et al (2013) Long- and short-term effects of androgens in human umbilical artery smooth muscle. Clin Exp Pharmacol Physiol 40:181–189

    Article  CAS  PubMed  Google Scholar 

  • Santamarina RD, Besocke AG, Romano LM et al (2008) Ischemic stroke related to anabolic abuse. Clin Neuropharmacol 31:80–85

    Article  PubMed  Google Scholar 

  • Schrör K, Morinelli TA, Masuda A et al (1994) Testosterone treatment enhances thromboxane A2 mimetic induced coronary artery vasoconstriction in guinea pigs. Eur J Clin Investig 24(Suppl 1):50–52

    Article  Google Scholar 

  • Scragg JL, Jones RD, Channer KS et al (2004) Testosterone is a potent inhibitor of L-type Ca(2+) channels. Biochem Biophys Res Commun 318:503–506

    Article  CAS  PubMed  Google Scholar 

  • Shepherd R, Cheung AS, Pang K et al (2021) Sexual dimorphism in innate immunity: the role of sex hormones and epigenetics. Front Immunol 11:604000

    Article  PubMed  PubMed Central  Google Scholar 

  • Somjen D, Kohen F, Gayer B et al (2004) Role of putative membrane receptors in the effect of androgens on human vascular cell growth. J Endocrinol 180:97–106

    Article  CAS  PubMed  Google Scholar 

  • Son BK, Akishita M, Iijima K et al (2010) Androgen receptor-dependent transactivation of growth arrest-specific gene 6 mediates inhibitory effects of testosterone on vascular calcification. J Biol Chem 285:7537–7544

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Steroids and Other Appearance and Performance Enhancing Drugs (APEDs) Research Report https://www.drugabuse.gov/publications/research-reports/steroids-other-appearance-performance-enhancing-drugs-apeds/what-are-side-effects-anabolic-steroid-misuse

  • Tharp DL, Masseau I, Ivey J et al (2009) Endogenous testosterone attenuates neointima formation after moderate coronary balloon injury in male swine. Cardiovasc Res 82:152–160

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Toot JD, Reho JJ, Novak J et al (2011) Testosterone increases myogenic reactivity of second-order mesenteric arteries in both defective and normal androgen receptor adult male rats. Gend Med 8:40–52

    Article  PubMed  Google Scholar 

  • Tostes RC, Carneiro FS, Carvalho MHC et al (2016) Reactive oxygen species: players in the cardiovascular effects of testosterone. Am J Physiol Regul Integr Comp Physiol 310:R1–R14

    Article  PubMed  Google Scholar 

  • Touyz RM, Alves-Lopes R, Rios FJ et al (2018) Vascular smooth muscle contraction in hypertension. Cardiovasc Res 114:529–539

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Urhausen A, Albers T, Kindermann W (2004) Are the cardiac effects of anabolic steroid abuse in strength athletes reversible? Heart Br Card Soc 90:496–501

    Article  CAS  Google Scholar 

  • Vanberg P, Atar D (2010) Androgenic anabolic steroid abuse and the cardiovascular system. Handb Exp Pharmacol 195:411–457

    Article  CAS  Google Scholar 

  • Vanhoutte PM, Shimokawa H, Feletou M et al (2017) Endothelial dysfunction and vascular disease – a 30th anniversary update. Acta Physiol (Oxf) 219:22–96

    Article  CAS  Google Scholar 

  • Verdonk K, Danser AH, van Esch JH (2012) Angiotensin II type 2 receptor agonists: where should they be applied? Expert Opin Investig Drugs 21:501–513

    Article  CAS  PubMed  Google Scholar 

  • Wells KE, Miguel R, Alexander JJ (1996) Sex hormones affect the calcium signaling response of human arterial cells to LDL. J Surg Res 63:64–72

    Article  CAS  PubMed  Google Scholar 

  • Wilhelmson AS, Fagman JB, Johansson I et al (2016) Increased intimal hyperplasia after vascular injury in male androgen receptor-deficient mice. Endocrinology 157:3915–3923

    Article  CAS  PubMed  Google Scholar 

  • Williams MR, Ling S, Dawood T et al (2002) Dehydroepiandrosterone inhibits human vascular smooth muscle cell proliferation independent of ARs and ERs. J Clin Endocrinol Metab 87:176–181

    Article  CAS  PubMed  Google Scholar 

  • Yoo JK, Fu Q (2020) Impact of sex and age on metabolism, sympathetic activity, and hypertension. FASEB J 34:11337–11346

    Article  CAS  PubMed  Google Scholar 

  • Yue P, Chatterjee K, Beale C et al (1995) Testosterone relaxes rabbit coronary arteries and aorta. Circulation 91:1154–1160

    Article  CAS  PubMed  Google Scholar 

  • Zhang X, Wang LY, Jiang TY et al (2002) Effects of testosterone and 17-beta-estradiol on TNF-alpha-induced E-selectin and VCAM-1 expression in endothelial cells. Analysis of the underlying receptor pathways. Life Sci 71:15–29

    Article  CAS  PubMed  Google Scholar 

  • Zhang X, Thatcher SE, Rateri DL et al (2012) Transient exposure of neonatal female mice to testosterone abrogates the sexual dimorphism of abdominal aortic aneurysms. Circ Res 110:e73–e85

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang X, Thatcher S, Wu C et al (2015) Castration of male mice prevents the progression of established angiotensin II-induced abdominal aortic aneurysms. J Vasc Surg 61:767–776

    Article  PubMed  Google Scholar 

  • Zhou P, Fu L, Pan Z et al (2008) Testosterone deprivation by castration impairs expression of voltage-dependent potassium channels in rat aorta. Eur J Pharmacol 593:87–91

    Article  CAS  PubMed  Google Scholar 

  • Zhu D, Hadoke PW, Wu J et al (2016) Ablation of the androgen receptor from vascular smooth muscle cells demonstrates a role for testosterone in vascular calcification. Sci Rep 6:24807

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Shinagawa-ku, Tokyo, Japan

    Takayuki Matsumoto

  2. Department of Pharmacology, Ribeirao Preto Medical School University of Sao Paulo, Ribeirao Preto, Brazil

    Josiane F. Silva & Rita C. Tostes

Authors
  1. Takayuki Matsumoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Josiane F. Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rita C. Tostes
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rita C. Tostes .

Editor information

Editors and Affiliations

  1. Department of Biomedical Sciences, University of Westminster, London, UK

    Vinood B. Patel

  2. Dept of Nutrition & Dietetics, King's College London, London, UK

    Victor R. Preedy

Rights and permissions

Reprints and permissions

Copyright information

© 2022 Springer Nature Switzerland AG

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Matsumoto, T., Silva, J.F., Tostes, R.C. (2022). High Testosterone Levels: Impact on the Heart. In: Patel, V.B., Preedy, V.R. (eds) Handbook of Substance Misuse and Addictions. Springer, Cham. https://doi.org/10.1007/978-3-030-67928-6_135-1

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-67928-6_135-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-67928-6

  • Online ISBN: 978-3-030-67928-6

  • eBook Packages: Springer Reference MedicineReference Module Medicine

Publish with us

Policies and ethics

Search

Navigation