Testosterone: A vascular hormone in health and disease

Journal of Endocrinology

Volumn 217, Issue 3, 2013, Pages

  Kelly, Daniel M ^a   Jones, T Hugh ^a,b  

^a UNIVERSITY OF SHEFFIELD   (United Kingdom)

^b BARNSLEY HOSPITAL NHS FOUNDATION TRUST   (United Kingdom)

Author keywords

Atherosclerosis; Inflammation; Testosterone; Vasoreactivity

Indexed keywords

CHOLESTEROL; CYTOKINE; ION CHANNEL; NITRIC OXIDE; PLACEBO; POTASSIUM CHANNEL; TESTOSTERONE; TESTOSTERONE CIPIONATE; TESTOSTERONE ESTER; TESTOSTERONE UNDECANOATE;

ADD ON THERAPY; ANDROGEN DEFICIENCY; ANTIINFLAMMATORY ACTIVITY; ARTERY; ARTERY DIAMETER; ARTICLE; ATHEROGENESIS; ATHEROSCLEROSIS; BLOOD VESSEL REACTIVITY; CARDIOVASCULAR DISEASE; CARDIOVASCULAR FUNCTION; CARDIOVASCULAR MORTALITY; CORONARY ARTERY BLOOD FLOW; CORONARY ARTERY DILATATION; CORONARY ARTERY DISEASE; CORONARY ARTERY OBSTRUCTION; DRUG MECHANISM; DRUG MEGADOSE; ELECTROCARDIOGRAM; ENDOTHELIAL DYSFUNCTION; HEART FAILURE; HEART INFARCTION; HEART MUSCLE ISCHEMIA; HORMONE ACTION; HUMAN; HYPERTENSION; HYPOGONADISM; INFLAMMATION; ISCHEMIC HEART DISEASE; NONHUMAN; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); SIGNAL TRANSDUCTION; SPECIES DIFFERENCE; ST SEGMENT DEPRESSION; STABLE ANGINA PECTORIS; TESTOSTERONE BLOOD LEVEL; VASCULAR RESISTANCE; VASCULITIS; VASOCONSTRICTION;

ATHEROSCLEROSIS; INFLAMMATION; TESTOSTERONE; VASOREACTIVITY;

ANIMALS; CARDIOVASCULAR DISEASES; HUMANS; MALE; RISK FACTORS; TESTOSTERONE; VASODILATION;

EID: 84878794252     PISSN: 00220795     EISSN: 14796805     Source Type: Journal    
DOI: 10.1530/JOE-12-0582     Document Type: Article

References (218)

1. Alexandersen P, Haarbo J, Byrjalsen I, Lawaetz H & Christiansen C 1999 Natural androgens inhibit male atherosclerosis: a study in castrated, cholesterol-fed rabbits. Circulation Research 84 813-819. (doi:10.1161/ 01.RES.84.7.813)
2. Alvarez E, Cairrão E, Morgado M, Morais C & Verde I 2010 Testosterone and cholesterol vasodilation of rat aorta involves L-type calcium channel inhibition. Advances in Pharmacological Sciences. (doi:10.1155/2010/ 534184)
3. Anderson TJ, Uehata A, Gerhard MD, Meredith IT, Knab S, Delagrange D, Lieberman EH, Ganz P, Creager MA, Yeung AC et al. 1995 Close relation of endothelial function in the human coronary and peripheral circulations. Journal of the American College of Cardiology 26 1235-1241. (doi:10.1016/0735-1097(95)00327-4)
4. Araujo AB, Dixon JM, Suarez EA, Murad MH, Guey LT & Wittert GA 2011 Clinical review: endogenous testosterone and mortality in men: a systematic review and meta-analysis. Journal of Clinical Endocrinology and Metabolism 96 3007-3019. (doi:10.1210/jc.2011-1137)
5. Aversa A, Isidori AM, De Martino MU, Caprio M, Fabbrini E, Rocchietti-March M, Frajese G & Fabbri A 2000 Androgens and penile erection: evidence for a direct relationship between free testosterone and cavernous vasodilation in men with erectile dysfunction. Clinical Endocrinology 53 517-522. (doi:10.1046/j.1365-2265.2000.01118.x)
6. Aziz KE & Wakefield D 1996 Modulation of endothelial cell expression of ICAM-1, E-selectin, and VCAM-1 by b-estradiol, progesterone, and dexamethasone. Cellular Immunology 167 79-85. (doi:10.1006/ cimm.1996.0010)
7. Barrett-Connor E & Khaw KT 1988 Endogenous sex hormones and cardiovascular disease in men. A prospective population-based study. Circulation 78 539-545. (doi:10.1161/01.CIR.78.3.539)
8. Bartlett DB, Firth CM, Phillips AC, Moss P, Baylis D, Syddall H, Sayer AA, Cooper C & Lord JM 2012 The age-related increase in low-grade systemic inflammation (inflammaging) is not driven by cytomegalovirus infection. Aging Cell 11 912-915. (doi:10.1111/j.1474-9726. 2012.00849.x)
9. Basaria S, Coviello AD, Travison TG, Storer TW, Farwell WR, Jette AM, Eder R, Tennstedt S, Ulloor J, Zhang AQ et al. 2010 Adverse events associated with testosterone administration. New England Journal of Medicine 363 109-122. (doi:10.1056/NEJMoa1000485)
10. van den Beld AW, Bots ML, Janssen JA, Pols HA, Lamberts SW & Grobbee DE 2003 Endogenous hormones and carotid atherosclerosis in elderly men. American Journal of Epidemiology 157 25-31. (doi:10.1093/aje/kwf160)
11. Bettoun DJ, Scafonas A, Rutledge SJ, Hodor P, Chen O, Gambone C, Vogel R, McElwee-Witmer S, Bai C, Freedman L et al. 2005 Interaction between the androgen receptor and RNase L mediates a cross-talk between the interferon and androgen signaling pathways. Journal of Biological Chemistry 280 38898-38901. (doi:10.1074/jbc.C500324200)
12. Blacher J, Asmar R, Djane S, London GM& Safar ME 1999 Aortic pulse wave velocity as a marker of cardiovascular risk in hypertensive patients. Hypertension 33 1111-1117. (doi:10.1161/01.HYP.33.5.1111)
13. Bourghardt J, Wilhelmson AS, Alexanderson C, De Gendt K, Verhoeven G, Krettek A, Ohlsson C & Tivesten A 2010 Androgen receptor-dependent and independent atheroprotection by testosterone in male mice. Endocrinology 151 5428-5437. (doi:10.1210/en.2010-0663)
14. Browne M, Connolly C & Docherty JR 1999 Vascular actions of 17b-oestradiol in rat aorta and mesenteric artery. Journal of Autonomic Pharmacology 19 291-299. (doi:10.1046/j.1365-2680.1999.00149.x)
15. Bruck B, Brehme U, Gugel N, Hanke S, Finking G, Lutz C, Benda N, Schmahl FW, Haasis R & Hanke H 1997 Gender-specific differences in the effects of testosterone and estrogen on the development of atherosclerosis in rabbits. Arteriosclerosis, Thrombosis, and Vascular Biology 17 2192-2199. (doi:10.1161/01.ATV.17.10.2192)
16. Cairrão E, Alvarez E, Santos-Silva AJ & Verde I 2008 Potassium channels are involved in testosterone-induced vasorelaxation of human umbilical artery. Naunyn-Schmiedeberg's Archives of Pharmacology 376 375-383. (doi:10.1007/s00210-007-0213-3)
17. Caminiti G, Volterrani M, Iellamo F, Marazzi G, Massaro R, Miceli M, Mammi C, Piepoli M, Fini M & Rosano GMC 2009 Effect of long-acting testosterone treatment on functional exercise capacity, skeletal muscle performance, insulin resistance, and baroreflex sensitivity in elderly patients with chronic heart failure a double-blind, placebo-controlled, randomized study. Journal of the American College of Cardiology 54 919-927. (doi:10.1016/j.jacc.2009.04.078)
18. Campelo AE, Cutini PH & Massheimer VL 2012 Testosterone modulates platelet aggregation and endothelial cell growth through nitric oxide pathway. Journal of Endocrinology 213 77-87. (doi:10.1530/ JOE-11-0441)
19. Carson CC III & Rosano G 2011 Exogenous testosterone, cardiovascular events, and cardiovascular risk factors in elderly men: a review of trial data. Journal of Sexual Medicine 9 54-67. (doi:10.1111/j.1743- 6109.2011.02337.x)
20. Caulin-Glaser T, Watson CA, Pardi R & Bender JR 1996 Effects of 17b-estradiol on cytokine-induced endothelial cell adhesion molecule expression. Journal of Clinical Investigation 98 36-42. (doi:10.1172/ JCI118774)
21. Ceballos G, Figueroa L, Rubio I, Gallo G, Garcia A, Martinez A, Yañez R, Perez J, Morato T & Chamorro G 1999 Acute and nongenomic effects of testosterone on isolated and perfused rat heart. Journal of Cardiovascular Pharmacology 33 691-697. (doi:10.1097/00005344-199905000-00003)
22. Celermajer DS, Sorensen KE, Gooch VM, Spiegelhalter DJ, Miller OI, Sullivan ID, Lloyd JK & Deanfield JE 1992 Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet 340 1111-1115. (doi:10.1016/0140-6736(92)93147-F)
23. Channer KS & Jones TH 2003 Cardiovascular effects of testosterone: implications of the "male menopause"? Heart 89 121-122. (doi:10.1136/heart.89.2.121)
24. Chen Z, Yuhanna IS, Galcheva-Gargova Z, Karas RH, Mendelsohn ME & Shaul PW 1999 Estrogen receptor a mediates the nongenomic activation of endothelial nitric oxide synthase by estrogen. Journal of Clinical Investigation 103 401-406. (doi:10.1172/JCI5347)
25. Chester AH, Jiang C, Borland JA, Yacoub MH & Collins P 1995 Oestrogen relaxes human epicardial coronary arteries through non-endothelium-dependent mechanisms. Coronary Artery Disease 6 417-422. (doi:10.1097/00019501-199505000-00009)
26. Chou TM, Sudhir K, Hutchison SJ, Ko E, Amidon TM, Collins P & Chatterjee K 1996 Testosterone induces dilation of canine coronary conductance and resistance arteries in vivo. Circulation 94 2614-2619. (doi:10.1161/01.CIR.94.10.2614)
27. Cid MC, Kleinman HK, Grant DS, Schnaper HW, Fauci AS & Hoffman GS 1994 Estradiol enhances leukocyte binding to tumor necrosis factor (TNF)-stimulated endothelial cells via an increase in TNF-induced adhesion molecules E-selectin, intercellular adhesion molecule type 1, and vascular cell adhesion molecule type 1. Journal of Clinical Investigation 93 17-25. (doi:10.1172/JCI116941)
28. Clarke MC, Figg N, Maguire JJ, Davenport AP, Goddard M, Littlewood TD & Bennett MR 2006 Apoptosis of vascular smooth muscle cells induces features of plaque vulnerability in atherosclerosis. Nature Medicine 12 1075-1080. (doi:10.1038/nm1459)
29. Cohen JC & Hickman R 1987 Insulin resistance and diminished glucose tolerance in powerlifters ingesting anabolic steroids. Journal of Clinical Endocrinology and Metabolism 64 960-963. (doi:10.1210/jcem-64-5-960)
30. Corcoran MP, Meydani M, Lichtenstein AH, Schaefer EJ, Dillard A & Lamon-Flava S 2010 Sex hormone modulation of proinflammatory cytokine and C-reactive protein expression in macrphages from older men and postmenopausal women. Journal of Endocrinology 206 217-224. (doi:10.1677/JOE-10-0057)
31. Corona G, Petrone L, Fisher AD, Mansani R, Bandini E, Boddi V, Lotti F, Forti G & Maggi M 2008 Six-month administration of 1% testosterone gel is able to restore erectile function in hypogonadal patients with erectile dysfunction. Archivio Italiano di Urologia, Andrologia 80 103-108.
32. Corona G, Mannucci E, Ricca V, Lotti F, Boddi V, Bandini E, Balercia G, Forti G & Maggi M 2009 The age-related decline of testosterone is associated with different specific symptoms and signs in patients with sexual dysfunction. International Journal of Andrology 32 720-728. (doi:10.1111/j.1365-2605.2009.00952.x)
33. Corona G, Rastrelli G, Monami M, Guay A, Buvat J, Sforza A, Forti G, Mannucci E & Maggi M 2011 Hypogonadism as a risk factor for cardiovascular mortality in men: a meta-analytic study. European Journal of Endocrinology 165 687-701. (doi:10.1530/EJE-11-0447)
34. Corrales JJ, Almeida M, Burgo R, Mories MT, Miralles JM & Orfao A 2006 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 of Endocrinology 189 595-604. (doi:10.1677/joe.1.06779)
35. Crews JK & Khalil RA 1999a Antagonistic effects of 17b-estradiol, progesterone, and testosterone on Ca2C entry mechanisms of coronary vasoconstriction. Arteriosclerosis, Thrombosis, and Vascular Biology 19 1034-1040. (doi:10.1161/01.ATV.19.4.1034)
36. Crews JK & Khalil RA 1999b Gender-specific inhibition of Ca2C entry mechanisms of arterial vasoconstriction by sex hormones. Clinical and Experimental Pharmacology & Physiology 26 707-715. (doi:10.1046/j. 1440-1681.1999.03110.x)
37. Death AK, McGrath KC, Sader MA, Nakhla S, Jessup W, Handelsman DJ & Celermajer DS 2004 Dihydrotestosterone promotes vascular cell adhesion molecule-1 expression in male human endothelial cells via a nuclear factor-kB-dependent pathway. Endocrinology 145 1889-1897. (doi:10.1210/en.2003-0789)
38. Deenadayalu VP, White RE, Stallone JN, Gao X & Garcia AJ 2001 Testosterone relaxes coronary arteries by opening the largeconductance, calcium-activated potassium channel. American Journal of Physiology. Heart and Circulatory Physiology 281 H1720-H1727.
39. Demirbag R, Yilmaz R, Ulucay A & Unlu D 2005 The inverse relationship between thoracic aortic intima media thickness and testosterone level. Endocrine Research 31 335-344. (doi:10.1080/07435800500449494)
40. Denmeade SR & Isaacs JT 2002 A history of prostate cancer treatment. Nature Reviews. Cancer 2 389-396. (doi:10.1038/nrc801)
41. Ding AQ & Stallone JN 2001 Testosterone-induced relaxation of rat aorta is androgen structure specific and involves KC channel activation. Journal of Applied Physiology 91 2742-2750.
42. Dockery F, Bulpitt CJ, Donaldson M, Fernandez S & Rajkumar C 2003a The relationship between androgens and arterial stiffness in older men. Journal of the American Geriatrics Society 51 1627-1632. (doi:10.1046/ j.1532-5415.2003.51515.x)
43. Dockery F, Bulpitt CJ, Agarwal S, Donaldson M & Rajkumar C 2003b Testosterone suppression in men with prostate cancer leads to an increase in arterial stiffness and hyperinsulinaemia. Clinical Science 104 195-201. (doi:10.1042/CS20020209)
44. Edwards E, Hamilton J & Duntley S 1939 Testosterone proponate as a therapeutic agent in patients with organic disease of the peripheral vessels. New England Journal of Medicine 220 865. (doi:10.1056/ NEJM193905252202103)
45. English KM, Jones RD, Jones TH, Morice AH & Channer KS 2000a Aging reduces the responsiveness of coronary arteries from male Wistar rats to the vasodilatory action of testosterone. Clinical Science 99 77-82. (doi:10.1042/CS19990345)
46. English KM, Steeds RP, Jones TH, Diver MJ & Channer KS 2000b Low-dose transdermal testosterone therapy improves angina threshold in men with chronic stable angina: A randomized, double-blind, placebo-controlled study. Circulation 102 1906-1911. (doi:10.1161/01.CIR.102. 16.1906)
47. English KM, Mandour O, Steeds RP, Diver MJ, Jones TH & Channer KS 2000c Men with coronary artery disease have lower levels of androgens than men with normal coronary angiograms. European Heart Journal 21 890-894. (doi:10.1053/euhj.1999.1873)
48. English KM, Jones RD, Jones TH, Morice AH & Channer KS 2001 Gender differences in the vasomotor effects of different steroid hormones in rat pulmonary and coronary arteries. Hormone and Metabolic Research 33 645-652. (doi:10.1055/s-2001-18689)
49. English KM, Jones RD, Jones TH, Morice AH & Channer KS 2002 Testosterone acts as a coronary vasodilator by a calcium antagonistic action. Journal of Endocrinological Investigation 25 455-458.
50. Farhat MY, Wolfe R, Vargas R, Foegh ML & Ramwell PW 1995 Effect of testosterone treatment on vasoconstrictor response of left anterior descending coronary artery in male and female pigs. Journal of Cardiovascular Pharmacology 25 495-500. (doi:10.1097/00005344- 199503000-00023)
51. Fernández-Balsells MM, Murad MH, Lane M, Lampropulos JF, Albuquerque F, Mullan RJ, Agrwal N, Elamin MB, Gallegos-Orozco JF, Wang AT et al. 2010 Clinical review 1: adverse effects of testosterone therapy in adult men: a systematic review and meta-analysis. Journal of Clinical Endocrinology and Metabolism 95 2560-2575. (doi:10.1210/jc. 2009-2575)
52. Franklin SS, GustinWIV, Wong ND, Larson MG, Weber MA, Kannel WB & Levy D 1997 Hemodynamic patterns of age-related changes in blood pressure. The Framingham Heart Study. Circulation 96 308-315. (doi:10.1161/01.CIR.96.1.308)
53. Fukui M, Kitagawa Y, Nakamura N, KadonoM,Mogami S, Hirata C, Ichio N, Wada K, Hasegawa G & Yoshikawa T 2003 Association between serum testosterone concentration and carotid atherosclerosis in men with type 2 diabetes. Diabetes Care 26 1869-1873. (doi:10.2337/diacare.26. 6.1869)
54. Gerdes D, Christ M, Haseroth K, Notzon A, Falkenstein E & Wehling M 2000 Nongenomic actions of steroids - from the laboratory to clinical implications. Journal of Pediatric Endocrinology & Metabolism 13 853-878.
55. Goglia L, Tosi V, Sanchez AM, Flamini MI, Fu XD, Zullino S, Genazzani AR & Simoncini T 2010 Endothelial regulation of eNOS, PAI-1 and t-PA by testosterone and dihydrotestosterone in vitro and in vivo. Molecular Human Reproduction 16 761-769. (doi:10.1093/molehr/gaq049)
56. Goncharov N, Katsya G, Gaivoronskaya L, Zoloedov V, Uskov V & Gooren L 2012 Effects of short-term testosterone administration on variables of the metabolic syndrome, in particular aldosterone. Hormone Molecular Biology and Clinical Investigation 12 401-406. (doi:10.1515/hmbci- 2012-0023)
57. Greenstein A, Mabjeesh NJ, Sofer M, Kaver I, Matzkin H &Chen J 2005 Does sildenafil combined with testosterone gel improve erectile dysfunction in hypogonadal men in whom testosterone therapy alone failed. Journal of Urology 173 530-532.
58. Guay AT, Perez JB, Jacobson J & Newton RA 2001 Efficacy and safety of sildenafil citrate for treatment of erectile dysfunction in a population with associated organic risk factors. Journal of Andrology 22 793-797.
59. Haddad RM, Kennedy CC, Caples SM, Tracz MJ, Boloña ER, Sideras K, Uraga MV, Erwin PJ & Montori VM 2007 Testosterone and cardiovascular risk in men: a systematic review and meta-analysis of randomized placebo-controlled trials. Mayo Clinic Proceedings 82 29-39.
60. Haider A, Gooren LJ, Padungtod P & Saad F 2009 Improvement of the metabolic syndrome and of non-alcoholic liver steatosis upon treatment of hypogonadal elderly men with parenteral testosterone undecanoate. Experimental and Clinical Endocrinology & Diabetes 118 167-171. (doi:10.1055/s-0029-1202774)
61. Hak AE, Witteman JC, de Jong FH, Geerlings MI, Hofman A & Pols HA 2002 Low levels of endogenous androgens increase the risk of atherosclerosis in elderly men: the Rotterdam study. Journal of Clinical Endocrinology and Metabolism 87 3632-3639. (doi:10.1210/jc.87.8.3632)
62. Hall J, Jones RD, Jones TH, Channer KS & Peers C 2006 Selective inhibition of L-type Ca2C channels in A7r5 cells by physiological levels of testosterone. Endocrinology 147 2675-2680. (doi:10.1210/ en.2005-1243)
63. Hamm L 1942 Testosterone propionate in the treatment of angina pectoris. Journal of Clinical Endocrinology and Metabolism 2 325-328. (doi:10.1210/jcem-2-5-325)
64. Harada N, Sasano H, Murakami H, Ohkuma T, Nagura H & Takagi Y 1999 Localized expression of aromatase in human vascular tissues. Circulation Research 84 1285-1291. (doi:10.1161/01.RES.84.11.1285)
65. Hatakeyama H, Nishizawa M, Nakagawa A, Nakano S, Kigoshi T & Uchida K 2002 Testosterone inhibits tumor necrosis factor-a-induced vascular cell adhesion molecule-1 expression in human aortic endothelial cells. FEBS Letters 530 129-132. (doi:10.1016/S0014-5793(02)03440-3)
66. Heinlein CA & Chang C 2002 The roles of androgen receptors and androgen-binding proteins in nongenomic androgen actions. Molecular Endocrinology 16 2181-2187. (doi:10.1210/me.2002-0070)
67. Herman SM, Robinson JT, McCredie RJ, Adams MR, Boyer MJ & Celermajer DS 1997 Androgen deprivation is associated with enhanced endothelium-dependent dilatation in adult men. Arteriosclerosis, Thrombosis, and Vascular Biology 17 2004-2009. (doi:10.1161/01.ATV. 17.10.2004)
68. Honda H, Unemoto T & Kogo H 1999 Different mechanisms for testosterone-induced relaxation of aorta between normotensive and spontaneously hypertensive rats. Hypertension 34 1232-1236. (doi:10.1161/01.HYP.34.6.1232)
69. Hou J, Baichwal V & Cao Z 1994 Regulatory elements and transcription factors controlling basal and cytokine-induced expression of the gene encoding intercellular adhesion molecule 1. PNAS 91 11641-11645. (doi:10.1073/pnas.91.24.11641)
70. Hougaku H, Fleg JL, Najjar SS, Lakatta EG, Harman SM, Blackman MR & Metter EJ 2006 Relationship between androgenic hormones and arterial stiffness, based on longitudinal hormone measurements. American Journal of Physiology. Endocrinology and Metabolism 290 E234-E242. (doi:10.1152/ajpendo.00059.2005)
71. Hughes GS, Mathur RS & Margolius HS 1989 Sex steroid hormones are altered in essential hypertension. Journal of Hypertension 7 181-187. (doi:10.1097/00004872-198903000-00003)
72. Ikeda Y, Aihara K, Yoshida S, Sato T, Yagi S, Iwase T, Sumitomo Y, Ise T, Ishikawa K, Azuma H et al. 2009 Androgen-androgen receptor system protects against angiotensin II-induced vascular remodeling. Endocrinology 150 2857-2864. (doi:10.1210/en.2008-1254)
73. Jackson G 2012 Erectile dysfunction and coronary disease: evaluating the link. Maturitas 72 263-264. (doi:10.1016/j.maturitas.2012.03.012)
74. Jaffe MD 1977 Effect of testosterone cypionate on postexercise ST segment depression. British Heart Journal 39 1217-1222. (doi:10.1136/ hrt.39.11.1217)
75. Jiang P, Xu J, Zheng S, Huang J, Xiang Q, Fu X & Wang T 2010 17b-Estradiol down-regulates lipopolysaccharide-induced MCP-1 production and cell migration in vascular smooth muscle cells. Journal of Molecular Endocrinology 45 87-97. (doi:10.1677/JME-09-0166)
76. Johannsson G, Gibney J, Wolthers T, Leung KC & Ho KK 2005 Independent and combined effects of testosterone and growth hormone on extracellular water in hypopituitary men. Journal of Clinical Endocrinology and Metabolism 90 3989-3994. (doi:10.1210/jc.2005-0553)
77. Johnson JL 2007 Matrix metalloproteinases: influence on smooth muscle cells and atherosclerotic plaque stability. Expert Review of Cardiovascular Therapy 5 265-282. (doi:10.1586/14779072.5.2.265)
78. Jones RD, English KM, Pugh PJ, Morice AH, Jones TH & Channer KS 2002 Pulmonary vasodilatory action of testosterone: evidence of a calcium antagonistic action. Journal of Cardiovascular Pharmacology 39 814-823. (doi:10.1097/00005344-200206000-00006)
79. Jones RD, Pugh PJ, Hall J, Channer KS & Jones TH 2003a Altered circulating hormone levels, endothelial function and vascular reactivity in the testicular feminised mouse. European Journal of Endocrinology 148 111-120. (doi:10.1530/eje.0.1480111)
80. Jones RD, Pugh PJ, Jones TH & Channer KS 2003b The vasodilatory action of testosterone: a potassium-channel opening or a calciumantagonistic action? British Journal of Pharmacology 138 733-744. (doi:10.1038/sj. bjp.0705141)
81. Jones RD, Ruban LN, Morton IE, Roberts SA, English KM, Channer KS & Jones TH 2003c Testosterone inhibits the prostaglandin F2a-mediated increase in intracellular calcium in A7r5 aortic smooth muscle cells: evidence of an antagonistic action upon store-operated calcium channels. Journal of Endocrinology 178 381-393. (doi:10.1677/joe.0. 1780381)
82. Jones RD, English KM, Jones TH& Channer KS 2004a Testosterone-induced coronary vasodilatation occurs via a non-genomic mechanism: evidence of a direct calcium antagonism action. Clinical Science 107 149-158. (doi:10.1042/CS20030386)
83. Jones RD, Jones TH & Channer KS 2004b The influence of testosterone upon vascular reactivity. European Journal of Endocrinology 151 29-37. (doi:10.1530/eje.0.1510029)
84. Jones RD, Rowell KO, Pugh PJ, Shorthouse AJ, Adam IA, Vaughan R, Rocco G, Hopkinson DN, Channer KS & Jones TH 2004c Testosteroneinduced vasodilatation of isolated human mesenteric and pulmonary resistance arteries is independent of the vascular endothelium. Endocrine Abstracts 7 P66.
85. Jones TH 2010a Testosterone deficiency: a risk factor for cardiovascular disease? Trends in Endocrinology and Metabolism 21 496-503. (doi:10.1016/j.tem.2010.03.002)
86. Jones TH 2010b Effects of testosterone on type 2 diabetes and components of the metabolic syndrome. Journal of Diabetes 2 146-156. (doi:10.1111/ j.1753-0407.2010.00085.x)
87. Jones TH & Saad F 2009 The effects of testosterone on risk factors for, and the mediators of, the atherosclerotic process. Atherosclerosis 207 318-327. (doi:10.1016/j.atherosclerosis.2009.04.016)
88. Jones TH 2011 Cardiovascular risk during androgen deprivation therapy for prostate cancer. British Medical Journal 342 d3105.
89. Kalaitzidis D & Gilmore TD 2005 Transcription factor cross-talk: the estrogen receptor and NF-kB. Trends in Endocrinology and Metabolism 16 46-52. (doi:10.1016/j.tem.2005.01.004)
90. Kalinchenko SY, Kozlov GI, Gontcharov NP & Katsiya GV 2003 Oral testosterone undecanoate reverses erectile dysfunction associated with diabetes mellitus in patients failing on sildenafil citrate therapy alone. Aging Male 6 94-99.
91. Kalinchenko SY, Tishova YA, Mskhalaya GJ, Gooren LJ, Giltay EJ & Saad F 2010 Effects of testosterone supplementation on markers of the metabolic syndrome and inflammation in hypogonadal men with the metabolic syndrome: the double-blinded placebo-controlled Moscow study. Clinical Endocrinology 73 602-612. (doi:10.1111/j.1365-2265. 2010.03845.x)
92. Kanda N, Tsuchida T & Tamaki K 1996 Testosterone inhibits immunoglobulin production by human peripheral blood mononuclear cells. Clinical and Experimental Immunology 106 410-415. (doi:10.1046/ j.1365-2249.1996.d01-842.x)
93. Kang SM, Jang Y, Kim JY, Chung N, Cho SY, Chae JS & Lee JH 2002 Effect of oral administration of testosterone on brachial arterial vasoreactivity in men with coronary artery disease. American Journal of Cardiology 89 862-864. (doi:10.1016/S0002-9149(02)02202-6)
94. Kapoor D, Clarke S, Channer KS & Jones TH 2007 The effect of testosterone replacement therapy on adipocytokines and C-reactive protein in hypogonadal men with type 2 diabetes. European Journal of Endocrinology 156 595-602. (doi:10.1530/EJE-06-0737)
95. Kaszubska W, Hooft van Huijsduijnen R, Ghersa P, DeRaemy-Schenk AM, Chen BP, Hai T, DeLamarter JF & Whelan J 1993 Cyclic AMPindependent ATF family members interact with NF-kB and function in the activation of the E-selectin promoter in response to cytokines. Molecular and Cellular Biology 13 7180-7190.
96. Keating NL, O'Malley AJ & Smith MR 2006 Diabetes and cardiovascular disease during androgen deprivation therapy for prostate cancer. Journal of Clinical Oncology 24 4448-4456. (doi:10.1200/JCO. 2006.06.2497)
97. Kelly DM & Jones TH 2013 Testosterone: a metabolic hormone in health and disease. Journal of Endocrinology 217 R25-R45. (doi:10.1530/ JOE-12-0455)
98. Kelly DM, Sellers DJ, Woodroofe MN, Jones TH & Channer KS 2012 Effect of testosterone on inflammatory markers in the development of early atherogenesis in the testicular-feminized mouse model. Endocrine Research. In press. (doi:10.3109/07435800.2012.735307)
99. Kenny AM, Bellantonio S, Gruman CA, Acosta RD & Prestwood KM 2002 Effects of transdermal testosterone on cognitive function and health perception in older men with low bioavailable testosterone levels. Journals of Gerontology. Series A, Biological Sciences and Medical Sciences 57 M321-M325. (doi:10.1093/gerona/57.5.M321)
100. Khaw KT & Barrett-Connor E 1988 Blood pressure and endogenous testosterone in men: an inverse relationship. Journal of Hypertension 6 329-332. (doi:10.1097/00004872-198804000-00010)
101. Khaw KT, Dowsett M, Folkerd E, Bingham S, Wareham N, Luben R, Welch A & Day N 2007 Endogenous testosterone and mortality due to all causes, cardiovascular disease, and cancer in men: European prospective investigation into cancer in Norfolk (EPIC-Norfolk) Prospective Population Study. Circulation 116 2694-2701. (doi:10.1161/CIRCULATIONAHA. 107.719005)
102. Khosla S, Atkinson EJ, Dunstan CR & O'Fallon WM 2002 Effect of estrogen versus testosterone on circulating osteoprotegerin and other cytokine levels in normal elderly men. Journal of Clinical Endocrinology and Metabolism 87 1550-1554. (doi:10.1210/jc.87.4.1550)
103. Kuvin JT, Patel AR, Sliney KA, Pandian NG, Rand WM, Udelson JE & Karas RH 2001 Peripheral vascular endothelial function testing as a noninvasive indicator of coronary artery disease. Journal of the American College of Cardiology 38 1843-1849. (doi:10.1016/S0735- 1097(01)01657-6)
104. Lanfranco F, Zitzmann M, Simoni M & Nieschlag E 2004 Serum adiponectin levels in hypogonadal males: influence of testosterone replacement therapy. Clinical Endocrinology 60 500-507. (doi:10.1111/ j.1365-2265.2004.02007.x)
105. Laughlin GA, Barrett-Connor E & Bergstrom J 2008 Low serum testosterone and mortality in older men. Journal of Clinical Endocrinology and Metabolism 93 68-75. (doi:10.1210/jc.2007-1792)
106. Lee M 2011 Focus on phosphodiesterase inhibitors for the treatment of erectile dysfunction in older men. Clinical Therapeutics 33 1590-1608. (doi:10.1016/j.clinthera.2011.09.029)
107. Lesser MA 1942 The treatment of angina pectoris with testosterone propionate; preliminary report. New England Journal of Medicine 226 51-54. (doi:10.1056/NEJM194201082260203)
108. Levine GN, D'Amico AV, Berger P, Clark PE, Eckel RH, Keating NL, Milani RV, Sagalowsky AI, Smith MR & Zakai N 2010 Androgen deprivation therapy in prostate cancer and cardiovascular risk: a science advisory from the American Heart Association, American Cancer Society and American Urological Association: endorsed by the American Society for Radiation Oncology. Circulation 121 833-840. (doi:10.1161/CIRCULATIONAHA.109.192695)
109. Lu Y, Fu Y, Ge Y, Juncos LA, Reckelhoff JF & Liu R 2012 The vasodilatory effect of testosterone on renal afferent arterioles. Gender Medicine 9 103-111. (doi:10.1016/j.genm.2012.02.003)
110. Lugg JA, Rajfer J & González-Cadavid NF 1995 Dihydrotestosterone is the active androgen in the maintenance of nitric oxide-mediated penile erection in the rat. Endocrinology 136 1495-1501. (doi:10.1210/ en.136.4.1495)
111. Ly LP, Jimenez M, Zhuang TN, Celermajer DS, Conway AJ & Handelsman DJ 2001 A double-blind, placebo-controlled, randomized clinical trial of transdermal dihydrotestosterone gel on muscular strength, mobility, and quality of life in older men with partial androgen deficiency. Journal of Clinical Endocrinology and Metabolism 86 4078-4088. (doi:10.1210/jc.86.9.4078)
112. Maggio M, Basaria S, Ble A, Lauretani F, Bandinelli S, Ceda GP, Valenti G, Ling SM & Ferrucci L 2006 Correlation between testosterone and the inflammatory marker soluble interleukin-6 receptor in older men. Journal of Clinical Endocrinology and Metabolism 91 345-347. (doi:10.1210/jc.2005-1097)
113. Mäkinen J, Järvisalo MJ, Pöllänen P, Perheentupa A, Irjala K, Koskenvuo M, Mäkinen J, Huhtaniemi I & Raitakari OT 2005 Increased carotid atherosclerosis in andropausal middle-aged men. Journal of the American College of Cardiology 45 1603-1608. (doi:10.1016/ j.jacc.2005.01.052)
114. Malkin CJ, Pugh PJ, Jones RD, Kapoor D, Channer KS & Jones TH 2004a The effect of testosterone replacement on endogenous inflammatory cytokines and lipid profiles in hypogonadal men. Journal of Clinical Endocrinology and Metabolism 89 3313-3318. (doi:10.1210/jc.2003- 031069)
115. Malkin CJ, Pugh PJ, Morris PD, Kerry KE, Jones RD, Jones TH & Channer KS 2004b Testosterone replacement in hypogonadal men with angina improves ischaemic threshold and quality of life. Heart 90 871-876. (doi:10.1136/hrt.2003.021121)
116. Malkin CJ, Jones RD, Jones TH & Channer KS 2006a Effect of testosterone on ex vivo vascular reactivity in man. Clinical Science 111 265-274. (doi:10.1042/CS20050354)
117. Malkin CJ, Pugh PJ, West JN, van Beek EJ, Jones TH & Channer KS 2006b Testosterone therapy in men with moderate severity heart failure: a double-blind randomized placebo controlled trial. European Heart Journal 27 57-64. (doi:10.1093/eurheartj/ehi443)
118. Malkin CJ, Pugh PJ, Morris PD, Asif S, Jones TH & Channer KS 2010 Low serum testosterone and increased mortality in men with coronary heart disease. Heart 96 1821-1825. (doi:10.1136/hrt.2010.195412)
119. Mancini A, Leone E, Festa R, Grande G, Silvestrini A, de Marinis L, Pontecorvi A, Maira G, Littarru GP & Meucci E 2008 Effects of testosterone on antioxidant systems inmale secondary hypogonadism. Journal of Andrology 29 622-629. (doi:10.2164/jandrol.107.004838)
120. Manolakou P, Angelopoulou R, Bakoyiannis C & Bastounis E 2009 The effects of endogenous and exogenous androgens on cardiovascular disease risk factors and progression. Reproductive Biology and Endocrinology 7 44. (doi:10.1186/1477-7827-7-44)
121. Mathur A, Malkin C, Saeed B, Muthusamy R, Jones TH & Channer K 2009 Long-term benefits of testosterone replacement therapy on angina threshold and atheroma in men. European Journal of Endocrinology 161 443-449. (doi:10.1530/EJE-09-0092)
122. McCrohon JA, Jessup W, Handelsman DJ & Celermajer DS 1999 Androgen exposure increases human monocyte adhesion to vascular endothelium and endothelial cell expression of vascular cell adhesion molecule-1. Circulation 99 2317-2322. (doi:10.1161/01.CIR.99.17. 2317)
123. McKay LI & Cidlowski JA 1998 Cross-talk between nuclear factor-kB and the steroid hormone receptors: mechanisms of mutual antagonism. Molecular Endocrinology 12 45-56. (doi:10.1210/me.12.1.45)
124. Miller MR & Megson IL 2007 Recent developments in nitric oxide donor drugs. British Journal of Pharmacology 151 305-321. (doi:10.1038/sj.bjp. 0707224)
125. Miller VM & Mulvagh SL 2007 Sex steroids and endothelial function: translating basic science to clinical practice. Trends in Pharmacological Sciences 28 263-270. (doi:10.1016/j.tips.2007.04.004)
126. Mills TM & Lewis RW 1999 The role of andorgens in the erectile response: a 1999 perspective. Molecular Urology 3 75-86.
127. Mills TM, Dai Y, Stopper VS & Lewis RW 1999a Androgenic maintenance of the erectile response in the rat. Steroids 64 605-609. (doi:10.1016/ S0039-128X(99)00040-9)
128. Mills TM, Lewis RW & Stopper VS 1999b Androgenic maintenance of inflow and veno-occlusion during erection in the rat. Biology of Reproduction 59 1413-1418. (doi:10.1095/biolreprod59.6.1413)
129. Montaño LM, Calixto E, Figueroa A, Flores-Soto E, Carbajal V & Perusquía M 2008 Relaxation of androgens on rat thoracic aorta: testosterone concentration dependent agonist/antagonist L-type Ca2C channel activity, and 5b-dihydrotestosterone restricted to L-type Ca2C channel blockade. Endocrinology 149 2517-2526. (doi:10.1210/en. 2007-1288)
130. Morelli A, Filippi S, Mancina R, Luconi M, Vignozzi L,MariniM, Orlando C, Vannelli GB, Aversa A, Natali A et al. 2004 Androgens regulate phosphodiesterase type 5 expression and functional activity in corpora cavernosa. Endocrinology 145 2253-2263. (doi:10.1210/en.2003-1699)
131. Morgentaler A & Schulman C 2009 Testosterone and prostate safety. Frontiers of Hormone Research 37 197-203.
132. Mukherjee TK, Dinh H, Chaudhuri G & Nathan L 2002 Testosterone attenuates expression of vascular cell adhesion molecule-1 by conversion to estradiol by aromatase in endothelial cells: implications in atherosclerosis. PNAS 99 4055-4060. (doi:10.1073/pnas.052703199)
133. Muller M, van den Beld AW, Bots ML, Grobbee DE, Lamberts SW & van der Schouw YT 2004 Endogenous sex hormones and progression of carotid atherosclerosis in elderly men. Circulation 109 2074-2079. (doi:10.1161/01.CIR.0000125854.51637.06)
134. Murphy JG & Khalil RA 1999 Decreased (Ca(2C))(i) during inhibition of coronary smooth muscle contraction by 17b-estradiol, progesterone, and testosterone. Journal of Pharmacology and Experimental Therapeutics 291 44-52.
135. Nakagami F, Nakagami H, Osako MK, Iwabayashi M, Taniyama Y, Doi T, Shimizu H, Shimamura M, Rakugi H & Morishita R 2010 Estrogen attenuates vascular remodeling in Lp(a) transgenic mice. Atherosclerosis 211 41-47. (doi:10.1016/j.atherosclerosis.2010.01.016)
136. Nakamura Y, Suzuki T, Igarashi K, Kanno J, Furukawa T, Tazawa C, Fujishima F, Miura I, Ando T, Moriyama N et al. 2006 PTOV1: a novel testosterone-induced atherogenic gene in human aorta. Journal of Pathology 209 522-531. (doi:10.1002/path.1993)
137. Nathan L, ShiW, Dinh H, Mukherjee TK, Wang X, Lusis AJ & Chaudhuri G 2001 Testosterone inhibits early atherogenesis by conversion to estradiol: critical role of aromatase. PNAS 98 3589-3593. (doi:10.1073/ pnas.051003698)
138. Navarro-Dorado J, Orensanz LM, Recio P, Bustamante S, Benedito S, Martínez AC, García-Sacristán A, Prieto D & Hernández M 2008 Mechanisms involved in testosterone-induced vasodilatation in pig prostatic small arteries. Life Sciences 83 569-573. (doi:10.1016/j.lfs. 2008.08.009)
139. Neish AS,Williams AJ, Palmer HJ, Whitley MZ & Collins T 1992 Functional analysis of the human vascular cell adhesion molecule 1 promoter. Journal of Experimental Medicine 176 1583-1593. (doi:10.1084/jem.176. 6.1583)
140. Nettleship JE, Jones TH, Channer KS & Jones RD 2007a 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. Circulation 116 2427-2434. (doi:10.1161/CIRCULATIONAHA.107.708768)
141. Nettleship JE, Pugh PJ, Channer KS, Jones T & Jones RD 2007b Inverse relationship between serum levels of interleukin-1b and testosterone in men with stable coronary artery disease. Hormone and Metabolic Research 39 366-371. (doi:10.1055/s-2007-976543)
142. Ng MK, Liu PY, Williams AJ, Nakhla S, Ly LP, Handelsman DJ & Celermajer DS 2002 Prospective study of effect of androgens on serum inflammatory markers in men. Arteriosclerosis, Thrombosis, and Vascular Biology 22 1136-1141. (doi:10.1161/01.ATV.0000022167.80130.A6)
143. Nguyen PL, Je Y, Schutz FA, Hoffman KE, Hu JC, Parekh A, Beckman JA & Choueiri TK 2011 Association of androgen deprivation therapy with cardiovascular death in patients with prostate cancer: a meta-analysis of randomized trials. Journal of the American Medical Association 306 2359-2366. (doi:10.1001/jama.2011.1745)
144. Norata GD, Tibolla G, Seccomandi PM, Poletti A & Catapano AL 2006 Dihydrotestosterone decreases tumor necrosis factor-a and lipopolysaccharide- induced inflammatory response in human endothelial cells. Journal of Clinical Endocrinology and Metabolism 91 546-554. (doi:10.1210/jc.2005-1664)
145. Norata GD, Cattaneo P, Poletti A & Catapano AL 2010 The androgen derivative 5a-androstane-3b,17b-diol inhibits tumor necrosis factor a and lipopolysaccharide induced inflammatory response in human endothelial cells and in mice aorta. Atherosclerosis 212 100-106. (doi:10.1016/j.atherosclerosis.2010.05.015)
146. Ohlsson C, Barrett-Connor E, Bhasin S, Orwoll E, Labrie F, Karlsson MK, Ljunggren O, Vandenput L, MellströmD & Tivesten A 2011 High serum testosterone is associated with reduced risk of cardiovascular events in elderly men. The MrOS (Osteoporotic Fractures in Men) study in Sweden. Journal of the American College of Cardiology 58 1674-1681. (doi:10.1016/j.jacc.2011.07.019)
147. Ong PJ, Patrizi G, Chong WC, Webb CM, Hayward CS & Collins P 2000 Testosterone enhances flow-mediated brachial artery reactivity in men with coronary artery disease. American Journal of Cardiology 85 269-272. (doi:10.1016/S0002-9149(99)00630-X)
148. Osterlund KL, Handa RJ & Gonzales RJ 2010 Dihydrotestosterone alters cyclooxygenase-2 levels in human coronary artery smooth muscle cells. American Journal of Physiology. Endocrinology and Metabolism 298 E838-E845. (doi:10.1152/ajpendo.00693.2009)
149. Ota H, Akishita M, Akiyoshi T, Kahyo T, Setou M, Ogawa S, Iijima K, Eto M & Ouchi Y 2012 Testosterone deficiency accelerates neuronal and vascular aging of SAMP8 mice: protective role of eNOS and SIRT1. PLoS ONE 7 e29598. (doi:10.1371/journal.pone.0029598)
150. Page ST, Herbst KL, Amory JK, Coviello AD, Anawalt BD, Matsumoto AM & Bremner WJ 2005 Testosterone administration suppresses adiponectin levels in men. Journal of Andrology 26 85-92.
151. Penson DF, Ng C, Cai L, Rajfer J & González-Cadavid NF 1996 Androgen and pituitary control of penile nitric oxide synthase and erectile function in the rat. Biology of Reproduction 55 567-574. (doi:10.1095/ biolreprod55.3.567)
152. Perusquía M & Villalón CM 1999 Possible role of Ca2C channels in the vasodilating effect of 5b-dihydrotestosterone in rat aorta. European Journal of Pharmacology 371 169-178. (doi:10.1016/S0014- 2999(99)00161-2)
153. Perusquía M, Hernández R, Morales MA, Campos MG & Villalón CM 1996 Role of endothelium in the vasodilating effect of progestins and androgens on the rat thoracic aorta. General Pharmacology 27 181-185. (doi:10.1016/0306-3623(95)00091-7)
154. Perusquía M, Navarrete E, González L & Villalón CM 2007 The modulatory role of androgens and progestins in the induction of vasorelaxation in human umbilical artery. Life Sciences 81 993-1002. (doi:10.1016/j.lfs. 2007.07.024)
155. Phillips GB, Jing TY, Resnick LM, Barbagallo M, Laragh JH & Sealey JE 1993 Sex hormones and hemostatic risk factors for coronary heart disease in men with hypertension. Journal of Hypertension 11 699-702. (doi:10.1097/00004872-199307000-00003)
156. Ponikowska B, Jankowska EA, Maj J, Wegrzynowska-Teodorczyk K, Biel B, Reczuch K, Borodulin-Nadzieja L, Banasiak W & Ponikowski P 2010 Gonadal and adrenal androgen deficiencies as independent predictors of increased cardiovascular mortality in men with type II diabetes mellitus and stable coronary artery disease. International Journal of Cardiology 143 343-348. (doi:10.1016/j.ijcard. 2009.03.072)
157. Pugh PJ, Jones RD, Jones TH & Channer KS 2002 Intrinsic responses of rat coronary arteries in vitro: influence of testosterone, calcium, and effective transmural pressure. Endocrine 19 155-161. (doi:10.1385/ ENDO:19:2:155)
158. Pugh PJ, Jones TH & Channer KS 2003 Acute haemodynamic effects of testosterone in men with chronic heart failure. European Heart Journal 24 909-915. (doi:10.1016/S0195-668X(03)00083-6)
159. Pugh PJ, Jones RD, Malkin CJ, Hall J, Nettleship JE, Kerry KE, Jones TH & Channer KS 2005 Physiologic testosterone therapy has no effect on serum levels of tumour necrosis factor-a in men with chronic heart failure. Endocrine Research 31 271-283. (doi:10.1080/ 07435800500406205)
160. Quan A, Teoh H & Man RY 1999 Acute exposure to a low level of testosterone impairs relaxation in porcine coronary arteries. Clinical and Experimental Pharmacology & Physiology 26 830-832. (doi:10.1046/j. 1440-1681.1999.03138.x)
161. Read MA, Whitley MZ, Williams AJ & Collins T 1994 NF-kB and IkBa: an inducible regulatory system in endothelial activation. Journal of Experimental Medicine 179 503-512. (doi:10.1084/jem.179.2.503)
162. Reckelhoff JF, Zhang H & Granger JP 1998 Testosterone exacerbates hypertension and reduces pressure-natriuresis in male spontaneously hypertensive rats. Hypertension 31 435-439. (doi:10.1161/01.HYP.31. 1.435)
163. Reckelhoff JF, Yanes LL, Iliescu R, Fortepiani LA & Granger JP 2005 Testosterone supplementation in aging men and women: possible impact on cardiovascular-renal disease. American Journal of Physiology. Renal Physiology 289 F941-F948. (doi:10.1152/ajprenal. 00034.2005)
164. Rivard A & Andrés V 2000 Vascular smooth muscle cell proliferation in the pathogenesis of atherosclerotic cardiovascular diseases. Histology and Histopathology 15 557-571.
165. Rosano GM, Leonardo F, Pagnotta P, Pelliccia F, Panina G, Cerquetani E, della Monica PL, Bonfigli B, Volpe M & Chierchia SL 1999 Acute anti-ischemic effect of testosterone in men with coronary artery disease. Circulation 99 1666-1670. (doi:10.1161/01.CIR.99.13.1666)
166. RosnerW, Hryb DJ, Khan MS, Nakhla AM & Romas NA 1999 Sex hormonebinding globulin mediates steroid hormone signal transduction at the plasma membrane. Journal of Steroid Biochemistry and Molecular Biology 69 481-485. (doi:10.1016/S0960-0760(99)00070-9)
167. Rowell KO, Hall J, Pugh PJ, Jones TH, Channer KS & Jones RD 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. Journal of Endocrinological Investigation 32 718-723.
168. Sader MA, Griffiths KA, Skilton MR, Wishart SM, Handelsman DJ & Celermajer DS 2003 Physiological testosterone replacement and arterial endothelial function in men. Clinical Endocrinology 59 62-67. (doi:10.1046/j.1365-2265.2003.01796.x)
169. Salom JB, Burguete MC, Pérez-Asensio FJ, Torregrosa G & Alborch E 2001 Relaxant effects of 17-b-estradiol in cerebral arteries through Ca(2C) entry inhibition. Journal of Cerebral Blood Flow and Metabolism 21 422-429.
170. Schrör K, Morinelli TA, Masuda A, Matsuda K, Mathur RS & Halushka PV 1994 Testosterone treatment enhances thromboxane A2 mimetic induced coronary artery vasoconstriction in guinea pigs. European Journal of Clinical Investigation 24 50-52. (doi:10.1111/j.1365-2362. 1994.tb02059.x)
171. Scragg JL, Jones RD, Channer KS, Jones TH & Peers C 2004 Testosterone is a potent inhibitor of L-type Ca2C channels. Biochemical and Biophysical Research Communications 318 503-506. (doi:10.1016/ j.bbrc.2004.04.054)
172. Scragg JL, Dallas ML & Peers C 2007 Molecular requirements for L-type Ca2C channel blockade by testosterone. Cell Calcium 42 11-15. (doi:10.1016/j.ceca.2006.11.003)
173. Seyrek M, Yildiz O, Ulusoy HB & Yildirim V 2007 Testosterone relaxes isolated human radial artery by potassium channel opening action. Journal of Pharmacological Sciences 103 309-316. (doi:10.1254/ jphs.FP0060883)
174. Shabsigh R, Kaufman J, Steidle J & Padma-Nathan H 2004 Randomized study of testosterone gel as adjunctive therapy to sildenafil in hypogonadal men with erectile dysfunction who do not respond to sildenafil alone. Journal of Urology 172 658-663.
175. Simon D, Charles MA, Nahoul K, Orssaud G, Kremski J, Hully V, Joubert E, Papoz L & Eschwege E 1997 Association between plasma total testosterone and cardiovascular risk factors in healthy adult men: the Telecom Study. Journal of Clinical Endocrinology and Metabolism 82 682-685. (doi:10.1210/jc.82.2.682)
176. Simoncini T, Hafezi-Moghadam A, Brazil DP, Ley K, Chin WW & Liao JK 2000a Interaction of oestrogen receptor with the regulatory subunit of phosphatidylinositol-3-OH kinase. Nature 407 538-541. (doi:10.1038/ 35035131)
177. Simoncini T, Maffei S, Basta G, Barsacchi G, Genazzani AR, Liao JK & De Caterina R 2000b Estrogens and glucocorticoids inhibit endothelial vascular cell adhesion molecule-1 expression by different transcriptional mechanisms. Circulation Research 87 19-25. (doi:10.1161/ 01.RES.87.1.19)
178. Smith JC, Bennett S, Evans LM, Kynaston HG, Parmar M, Mason MD, Cockcroft JR, Scanlon MF & Davies JS 2001 The effects of induced hypogonadism on arterial stiffness, body composition, and metabolic parameters in males with prostate cancer. Journal of Clinical Endocrinology and Metabolism 86 4261-4267. (doi:10.1210/jc.86.9.4261)
179. Smith AM, Bennett RT, Jones TH, Cowen ME, Channer KS & Jones RD 2008 Characterization of the vasodilatory action of testosterone in the human pulmonary circulation. Vascular Health and Risk Management 4 1459-1466.
180. Sorensen KE, Celermajer DS, Spiegelhalter DJ, Georgakopoulos D, Robinson J, Thomas O & Deanfield JE 1995 Non-invasive measurement of human endothelium dependent arterial responses: accuracy and reproducibility. British Heart Journal 74 247-253. (doi:10.1136/hrt.74.3.247)
181. Srinivas-Shankar U, Roberts SA, Connolly MJ, Connell MDLO, Adams JE, Oldham JA & Wu FCW 2010 Effects of testosterone on muscle strength, physical function, body composition, and quality of life in intermediate-Frail and Frail elderly men: a randomized, double-blind, placebo-controlled study. Journal of Clinical Endocrinology and Metabolism 95 639-650. (doi:10.1210/jc.2009-1251)
182. Stein B & Yang MX 1995 Repression of the interleukin-6 promoter by estrogen receptor is mediated by NF-kB and C/EBPb. Molecular and Cellular Biology 15 4971-4979.
183. Stigher LH & Tulgan J 1943 Treatment of angina pectoris by testosterone propionate. New York State Journal of Medicine 43 1424-1428.
184. Sullivan ML, Martinez CM, Gennis P & Gallagher EJ 1998 The cardiac toxicity of anabolic steroids. Progress in Cardiovascular Diseases 41 1-15. (doi:10.1016/S0033-0620(98)80019-4)
185. Supakar PC, Jung MH, Song CS, Chatterjee B & Roy AK 1995 Nuclear factor kB functions as a negative regulator for the rat androgen receptor gene and NF-kB activity increases during the age-dependent desensitization of the liver. Journal of Biological Chemistry 270 837-842. (doi:10.1074/ jbc.270.2.837)
186. Svartberg J, von Mühlen D, Schirmer H, Barrett-Connor E, Sundfjord J & Jorde R 2004 Association of endogenous testosterone with blood pressure and left ventricular mass in men. The Tromsø Study. European Journal of Endocrinology 150 65-71. (doi:10.1530/eje.0.1500065)
187. Svartberg J, von Mühlen D, Mathiesen E, Joakimsen O, Bønaa KH & Stensland-Bugge E 2006 Low testosterone levels are associated with carotid atherosclerosis in men. Journal of Internal Medicine 259 576-582. (doi:10.1111/j.1365-2796.2006.01637.x)
188. Takase B, Uehata A, Akima T, Nagai T, Nishioka T, Hamabe A, Satomura K, Ohsuzu F & Kurita A 1998 Endothelium-dependent flow-mediated vasodilation in coronary and brachial arteries in suspected coronary artery disease. American Journal of Cardiology 82 1535-1539. (doi:10.1016/S0002-9149(98)00702-4)
189. Teoh H, Quan A & Man RY 2000a Acute impairment of relaxation by low levels of testosterone in porcine coronary arteries. Cardiovascular Research 45 1010-1018. (doi:10.1016/S0008-6363(99)00398-3)
190. Teoh H, Quan A, Leung SW & Man RY 2000b Differential effects of 17b-estradiol and testosterone on the contractile responses of porcine coronary arteries. British Journal of Pharmacology 129 1301-1308. (doi:10.1038/sj.bjp.0703164)
191. Tep-areenan P, Kendall DA & Randall MD 2002 Testosterone-induced vasorelaxation in the rat mesenteric arterial bed is mediated predominantly via potassium channels. British Journal of Pharmacology 135 735-740. (doi:10.1038/sj.bjp.0704522)
192. Thompson PD, Cullinane EM, Sady SP, Chenevert C, Saritelli AL, Sady MA & Herbert PN 1989 Contrasting effects of testosterone and stanozolol on serum lipoprotein levels. JAMA 261 65-71.
193. Toot JD, Reho JJ, Ramirez RJ, Novak J & Ely DL 2012 Alterations in vasomotor systems and mechanics of resistance-sized mesenteric arteries from SHR and WKY male rats following in vivo testosterone manipulation. Biology of Sex Differences 3 1. (doi:10.1186/2042- 6410-3-1)
194. TraishAM, ParkK,DhirV,KimNN,Moreland RB&Goldstein I 1999 Effects of castration and androgen replacement on erectile function in a rabbit model. Endocrinology 140 1861-1868. (doi:10.1210/en.140.4.1861)
195. Unemoto T, Matsushita M, Tamura K, Tanaka Y, Koike K & Kogo H 2007 Role of BK channels in testosterone-induced relaxation of the aorta in spontaneously hypertensive rats. Biological & Pharmaceutical Bulletin 30 1477-1480. (doi:10.1248/bpb.30.1477)
196. Vignozzi L, Cellai I, Santi R, Lombardelli L, Morelli A, Comeglio P, Filippi S, Logiodice F, Carini M, Nesi G et al. 2012 Antiinflammatory effect of androgen receptor activation in human benign prostatic hyperplasia cells. Journal of Endocrinology 214 31-43. (doi:10.1530/ JOE-12-0142)
197. Vikan T, Schirmer H, Njølstad I & Svartberg J 2009 Endogenous sex hormones and the prospective association with cardiovascular disease and mortality in men: the Tromsø Study. European Journal of Endocrinology 161 435-442. (doi:10.1530/EJE-09-0284)
198. Walker TC 1942 Use of testosterone propionate and estrogenic substance in treatment of essential hypertension, angina pectoris, and peripheral vascular disease. Journal of Clinical Endocrinology and Metabolism 2 560-568. (doi:10.1210/jcem-2-9-560)
199. Wang C, Cunningham G, Dobs A, Iranmanesh A, Matsumoto AM, Snyder PJ, Weber T, Berman N, Hull L, Swerdloff RS 2004 Long-term testosterone gel (AndroGel) treatment maintains beneficial effects on sexual function and mood, lean and fat mass, and bone mineral density in hypogonadalmen. Journal of Clinical Endocrinology andMetabolism 89 2085-2098. (doi:10.1210/jc.2003-032006)
200. Webb CM, Adamson DL, de Zeigler D & Collins P 1999a Effect of acute testosterone on myocardial ischemia in men with coronary artery disease. American Journal of Cardiology 83 437-439. (doi:10.1016/S0002- 9149(98)00880-7)
201. Webb CM, McNeill JG, Hayward CS, de Zeigler D & Collins P 1999b Effects of testosterone on coronary vasomotor regulation in men with coronary heart disease. Circulation 100 1690-1696. (doi:10.1161/01. CIR.100.16.1690)
202. White RE, Owen MP & Stallone JN 2007 Testosterone-induced vasorelaxation of rat mesenteric microvasculature is KC channel- and nitric oxide-dependent but estrogen-independent (abstract). FASEB Journal 972 10.
203. Williams MR, Ling S, Dawood T, Hashimura K, Dai A, Li H, Liu JP, Funder JW, Sudhir K & Komesaroff PA 2002 Dehydroepiandrosterone inhibits human vascular smooth muscle cell proliferation independent of ARs and ERs. Journal of Clinical Endocrinology and Metabolism 87 176-181. (doi:10.1210/jc.87.1.176)
204. Wu FC & von Eckardstein A 2003 Androgens and coronary artery disease. Endocrine Reviews 24 183-217. (doi:10.1210/er.2001-0025)
205. Wu SZ & Weng XZ 1993 Therapeutic effects of an androgenic preparation on myocardial ischemia and cardiac function in 62 elderly male coronary heart disease patients. Chinese Medical Journal 106 415-418.
206. Xing D, Feng W, Miller AP, Weathington NM, Chen YF, Novak L, Blalock JE & Oparil S 2007 Estrogen modulates TNF-a-induced inflammatory responses in rat aortic smooth muscle cells through estrogen receptor-b activation. American Journal of Physiology. Heart and Circulatory Physiology 292 H2607-H2612. (doi:10.1152/ajpheart. 01107.2006)
207. Yamada K, Hayashi T, Kuzuya M, Naito M, Asai K & Iguchi A 1996 Physiological concentration of 17b-estradiol inhibits chemotaxis of human monocytes in response to monocyte chemotactic protein 1. Artery 22 24-35.
208. Yang YM, Lv XY, Huang WD, Xu ZR & Wu LJ 2005 Study of androgen and atherosclerosis in old-age male. Journal of Zhejiang University. Science. B 6 931-935. (doi:10.1631/jzus.2005.B1206)
209. Yassin AA & Saad F 2008 Testosterone and erectile dysfunction. Journal of Andrology 29 593-604. (doi:10.2164/jandrol.107.004630)
210. Yildirim E & Erol K 2011 The effects of testosterone on isolated sheep coronary artery. Anadolu Kardiyoloji Dergisi 11 343-350.
211. Yildiz O, Seyrek M, Gul H, Un I, Yildirim V, Ozal E, Uzun M & Bolu E 2005 Testosterone relaxes human internal mammary artery in vitro. Journal of Cardiovascular Pharmacology 45 580-585. (doi:10.1097/01.fjc. 0000161400.06704.1e)
212. Yu J, Akishita M, Eto M, Ogawa S, Son BK, Kato S, Ouchi Y & Okabe T 2010 Androgen receptor-dependent activation of endothelial nitric oxide synthase in vascular endothelial cells: role of phosphatidylinositol 3-kinase/akt pathway. Endocrinology 151 1822-1828. (doi:10.1210/en. 2009-1048)
213. Yue P, Chatterjee K, Beale C, Poole-Wilson PA & Collins P 1995 Testosterone relaxes rabbit coronary arteries and aorta. Circulation 91 1154-1160. (doi:10.1161/01.CIR.91.4.1154)
214. Zhang X, Wang L, Jiang T, Zhang H, Dou Y, Zhao J, Zhao H, Qiao Z & Qiao J 2002 Effects of testosterone and 17-b-estradiol on TNF-a-induced E-selectin and VCAM-1 expression in endothelial cells: Analysis of the underlying receptor pathways. Life Sciences 71 15-29. (doi:10.1016/ S0024-3205(02)01567-9)
215. Zitzmann M, Brune M, Kornmann B, Gromoll J, von Eckardstein S, von Eckardstein A & Nieschlag E 2001 The CAG repeat polymorphism in the AR gene affects high density lipoprotein cholesterol and arterial vasoreactivity. Journal of Clinical Endocrinology and Metabolism 86 4867-4873. (doi:10.1210/jc.86.10.4867)
216. Zitzmann M, Brune M & Nieschlag E 2002 Vascular reactivity in hypogonadal men is reduced by androgen substitution. Journal of Clinical Endocrinology and Metabolism 87 5030-5037. (doi:10.1210/ jc.2002-020504)
217. Zitzmann M, Vorona E, Wenk M, Saad F & Nieschlag E 2009 Testosterone administration decreases carotid artery intima media thickness as a marker of impaired vascular integrity in middle-aged overweight men. Journal of Men's Health 6 243.
218. Zuloaga KL & Gonzales RJ 2011 Dihydrotestosterone attenuates hypoxia inducible factor-1a and cyclooxygenase-2 in cerebral arteries during hypoxia or hypoxia with glucose deprivation. American Journal of Physiology. Heart and Circulatory Physiology 301 H1882-H1890. (doi:10.1152/ajpheart.00446.2011)