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Review

Cardiovascular impact of testosterone therapy for hypogonadism

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Pages 617-625 | Received 09 Mar 2018, Accepted 24 Jul 2018, Published online: 21 Aug 2018

References

  • Ostan R, Monti D, Gueresi P, et al. Gender, aging and longevity in humans: an update of an intriguing/neglected scenario paving the way to a gender-specific medicine. Clin Sci (Lond). 2016;130:1711–1725.
  • Bliss M. The discovery of Insulin. Chicago: University of Chicago Press; 1982.
  • Guglielmi R, Frasoldati A, Zini M, et al. Italian association of clinical endocrinologists statement- eplacement therapy for primary hypothyroidism: a brief guide for clinical practice. Endocr Pract. 2016;22:1319–1326.
  • Burns CM. The history of cortisone discovery and development. Rheum Dis Clin North Am. 2016;42:1–14.
  • Nieschlag E, Nieschlag S. Testosterone deficiency: a historical perspective. Asian J Androl. 2014;16:161–168.
  • Corona G, Maggi M. Deciding which testosterone therapy to prescribe. J Sex Med. 2018;15(5):619-621.
  • Raviña E, Kubinyi H. The evolution of drug discovery: from traditional medicines to modern drugs. Weinheim: John Wiley & Sons; 2011. p. 175.
  • Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial. JAMA. 2002;288:321–333.
  • Santen RJ, Allred DC, Ardoin SP, et al. Postmenopausal hormone therapy: an Endocrine Society scientific statement. J Clin Endocrinol Metab. 2010;95:s1–s66.
  • Hernlund, Hernlund E, Svedbom A, et al. Osteoporosis in the European Union: medical management, epidemiology and economic burden. A report prepared in collaboration with the International Osteoporosis Foundation (IOF) and the European Federation of Pharmaceutical Industry Associations (EFPIA). Arch Osteoporos. 2013;8:136.
  • Corona G, Rastrelli G, Vignozzi L, et al. Emerging medication for the treatment of male hypogonadism. Expert Opin Emerg Drugs. 2012;17:239–259.
  • Khera M, Adaikan G, Buvat J, et al. Diagnosis and treatment of testosterone deficiency: recommendations from the fourth international consultation for sexual medicine (ICSM 2015). J Sex Med. 2016;13:1787–1804.
  • Corona G, Vignozzi L, Sforza A, et al. Obesity and late-onset hypogonadism. Mol Cell Endocrinol. 2015;418:120–133.
  • Corona G, Bianchini S, Sforza A, et al. Hypogonadism as a possible link between metabolic diseases and erectile dysfunction in aging men. Hormones (Athens). 2015;14:569–578.
  • Kelly DM, Jones TH. Testosterone and obesity. Obes Rev. 2015;16:581–606.
  • Cheetham TC, An J, Jacobsen SJ, et al. Association of testosterone replacement with cardiovascular outcomes among men with androgen deficiency. JAMA Intern Med. 2017;177:491–499.
  • Basaria S, Coviello AD, Travison TG, et al. Adverse events associated with testosterone administration. N Engl J Med. 2010;363:109–122.
  • Corona G, Vignozzi L, Sforza A, et al. Risks and benefits of late onset hypogonadism treatment: an expert opinion. World J Mens Health. 2013;31:103–125.
  • Morgentaler A, Feibus A, Baum N. Testosterone and cardiovascular disease–the controversy and the facts. Postgrad Med. 2015;127:159–165.
  • Vigen R, O’Donnell CI, Barón AE, et al. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA. 2013;310:1829–1836.
  • Finkle WD, Greenland S, Ridgeway GK, et al. Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. Gong Y, editor. PLoS One. 2014;9:e85805.
  • Xu L, Freeman G, Cowling BJ, et al. Testosterone therapy and cardiovascular events among men: a systematic review and meta-analysis of placebo-controlled randomized trials. BMC Med. 2013;11:108. doi: 10.1186/1741-7015-11-108.
  • FDA drug safety communication FDA cautions about using T products for low T due to aging requires labeling change to inform of possible increased risk of heart attack and stroke with use. US Food and Drug Administration. [updated 2015 Mar 3; cited 2018 Mar 4]. Available from: http://www.fda.gov/Drugs/DrugSafety/ucm436259.htmforHumanMedicalProducts/ucm402054.htm.
  • Summary safety review-testosterone replacement product- cardiovascular risk. Health Canada. [updated 2014 July 15; cited 2018 Mar 4]. Available from: http://www.hc-sc.gc.ca/dhp-mps/medeff/reviews-examens/testosterone-eng.php.Published
  • Yeap BB, Grossmann M, McLachlan RI, et al. Endocrine society of Australia position statement on male hypogonadism (part 1) assessment and indications for testosterone therapy. Med J Aust. 2016;205:173–178.
  • [cited 2018 Mar 4]. Available from: http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/referrals/Testosterone-containing_medicines/human_referral_prac_000037.jsp&mid=WC0b01ac05805c516f
  • Aversa A, Bruzziches R, Francomano D, et al. Effects of testosterone undecanoate on cardiovascular risk factors and atherosclerosis in middle-aged men with late-onset hypogonadism and metabolic syndrome results from a 24-month, randomized, double-blind, placebo-controlled study. J Sex Med. 2010;7:3495–3503.
  • Aversa A, Bruzziches R, Francomano D, et al. Efficacy and safety of two different testosterone undecanoate formulations in hypogonadal men with metabolic syndrome. J Endocrinol Invest. 2010;33:776–783.
  • Cornoldi A, Caminiti G, Marazzi G, et al. Effects of chronic testosterone administration on myocardial ischemia, lipid metabolism and insulin resistance in elderly male diabetic patients with coronary artery disease. Int J Cardiol. 2010;142:50–55.
  • Gopal RA, Bothra N, Acharya SV, et al. Treatment of hypogonadism with testosterone in patients with type 2 diabetes mellitus. Endocr Pract. 2010;16:570–576.
  • Kalinchenko SY, Tishova YA, Mskhalaya GJ, et al. 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. Clin Endocrinol (Oxf). 2010;73:602–612.
  • Srinivas-Shankar U, Roberts SA, Connolly MJ, et al. 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. J Clin Endocrinol Metab. 2010;95:639–650.
  • Amiaz R, Pope HG Jr, Mahne T, et al. Testosterone gel replacement improves sexual function in depressed men taking serotonergic antidepressants a randomized, placebo-controlled clinical trial. J Sex Marital Ther. 2011;37:243–254.
  • Ho CC, Tong SF, Low WY, et al. A randomized, double-blind, placebo-controlled trial on the effect of long-acting testosterone treatment as assessed by the Aging Male Symptoms scale. BJU Int. 2012;110:260–265.
  • Jones TH, Arver S, Behre HM, et al. Testosterone replacement in hypogonadalmen with type 2 diabetes and/or metabolic syndrome (the TIMES2 study). Diabetes Care. 2011;34:828–837.
  • Kaufman JM, Miller MG, Garwin JL, et al. Efficacy and safety study of 1.62% testosterone gel for the treatment of hypogonadal men. J Sex Med. 2011;8:2079–2089.
  • Hoyos CM, Yee BJ, Phillips CL, et al. Body compositional and cardiometabolic effects of testosterone therapy in obese men with severe obstructive sleep apnoea arandomised placebo-controlled trial. Eur J Endocrinol. 2012;167:531–541.
  • Behre HM, Tammela TL, Arver S, et al. A randomized, double-blind, placebo-controlled trial of testosterone gel on body composition and health-related quality-of-life in men with hypogonadal to low-normal levels of serum testosterone and symptoms of androgen deficiency over 6 months with 12 months open-label follow-up. Aging Male. 2012;15:198–207.
  • Hackett G, Cole N, Bhartia M, et al. Testosterone replacement therapy with long-acting testosterone undecanoate improves sexual function and quality-of-life parameters vs. placebo in a population of men with type 2 diabetes. J Sex Med. 2013;10:1612–1627.
  • Hildreth KL, Barry DW, Moreau KL, et al. Effects of testosterone and progressive resistance exercise in healthy, highly functioning older men with low-normal testosterone levels. J Clin Endocrinol Metab. 2013;98:1891–1900.
  • Maggio M, Snyder PJ, Ceda GP, et al. Is the haematopoietic effect of testosterone mediated by erythropoietin? The results of a clinical trial in older men. Andrology. 2013;1:24–28.
  • Borst SE, Yarrow JF, Conover CF, et al. Musculoskeletal and prostate effects of combined testosterone and finasteride administration in older hypogonadal men a randomized, controlled trial. Am J Physiol Endocrinol Metab. 2014;306:E433–42.
  • Gianatti EJ, Dupuis P, Hoermann R, et al. Effect of testosterone treatment on glucose metabolism in men with type 2 diabetes a randomized controlled trial. Diabetes Care. 2014;37:2098–2107.
  • Janjgava S, Zerekidze T, Uchava L, et al. Influence of testosterone replacement therapy on metabolic disorders in male patients with type 2 diabetes mellitus and androgen deficiency. Eur J Med Res. 2014;23:19 56.
  • Asih PR, Wahjoepramono EJ, Aniwiyanti V, et al. Testosterone replacement therapy in older male subjective memory complainers double-blind randomized crossover placebo-controlled clinical trial of physiological assessment and safety. CNS Neurol Disord Drug Targets. 2015;14:576–586.
  • Basaria S, Harman SM, Travison TG, et al. Effects of testosterone administration for 3 years on subclinical atherosclerosis progression in older men with low or low-normal testosterone levels a randomized clinical trial. JAMA. 2015;314:570–581.
  • Basaria S, Travison TG, Alford D, et al. Effects of testosterone replacement in men with opioid-induced androgen deficiency a randomized controlled trial. Pain. 2015;156:280–288.
  • Cherrier MM, Anderson K, Shofer J, et al. Testosterone treatment of men with mild cognitive impairment and low testosterone levels. Am J Alzheimers Dis Other Demen. 2015;30:421–430.
  • Glintborg D, Christensen LL, Kvorning T, et al. Differential effects of strength training and testosterone treatment on soluble CD36 in aging men Possible relation to changes in body composition. Scand J Clin Lab Invest. 2015;75:659–666.
  • Paduch DA, Polzer PK, Ni X, et al. Testosterone replacement in androgen-deficient men with Ejaculatory Dysfunction a randomized controlled trial. J Clin Endocrinol Metab. 2015;100:2956–2962.
  • Brock G, Heiselman D, Maggi M, et al. Effect of testosterone solution 2% on testosterone concentration, sex drive and energy in hypogonadal men results of a placebo controlled study. J Urol. 2016;195:699–705.
  • Chillarón JJ, Fernández-Miró M, Albareda M, et al. Testosterone undecanoate improves lipid profile in patients with type 1 diabetes and hypogonadotrophic hypogonadism. Endocr J. 2016;63:849–855.
  • Dhindsa S, Ghanim H, Batra M, et al. Insulin resistance and inflammation in hypogonadotropic hypogonadism and their reduction after testosterone replacement in men with type 2 diabetes. Diabetes Care. 2016;39:82–91.
  • Magnussen LV, Glintborg D, Hermann P, et al. Effect of testosterone on insulin sensitivity, oxidative metabolism and body composition in aging men with type 2 diabetes on metformin monotherapy. Diabetes Obes Metab. 2016;18:980–989.
  • Snyder PJ, Bhasin S, Cunningham GR, et al. Testosterone trials investigators. Effects of testosterone treatment in older men. N Engl J Med. 2016;374:611–624.
  • Corona G, Maseroli E, Rastrelli G, et al. Cardiovascular risk associated with testosterone boosting medications a systematic review and meta-analysis. Expert Opin Drug Saf. 2014;13:1327–1351.
  • Hedges LV, Vevea JL. Fixed - and random-effects models in meta-analysis. Psychol Methods. 1998;3:486–504.
  • Calof OM, Singh AB, Lee ML, et al. Adverse events associated with testosterone replacement in middle-aged and older men: a meta-analysis of randomized, placebo-controlled trials. J Gerontol A BiolSci Med Sci. 2005;60:1451–1457.
  • Haddad RM, Kennedy CC, Caples SM, et al. Testosterone and cardiovascular risk in men: a systematic review and meta-analysis of randomized placebo-controlled trials. Mayo Clin Proc. 2007;82:29–39.
  • Fernández-Balsells MM, Murad MH, Lane M, et al. Clinical review 1: adverse effects of testosterone therapy in adult men: a systematic review and meta-analysis. J ClinEndocrinolMetab. 2010;95:2560–2575.
  • Borst SE, Shuster JJ, Zou B, et al. Cardiovascular risks and elevation of serum DHT vary by route of testosterone administration: a systematic review and meta-analysis. BMC Med. 2014;12:211.
  • Albert SG, Morley JE. Testosterone therapy, association with age, initiation and mode of therapy with cardiovascular events: a systematic review. Clin Endocrinol (Oxf). 2016;85:436–443.
  • Alexander GC, Iyer G, Lucas E, et al. Cardiovascular risks of exogenous testosterone use among men: a systematic review and meta-analysis. Am J Med. 2017;130:293–305.
  • Corona G, Rastrelli G, Reisman Y, et al. The safety of available treatments of male hypogonadism in organic and functional hypogonadism. Expert Opin Drug Saf. 2018;17:277–292.
  • Corona G, Sforza A, Maggi M. Testosterone replacement therapy: long-term safety and efficacy. World J Mens Health. 2017;35:65–76.
  • Corona G, Dicuio M, Rastrelli G, et al. Testosterone treatment and cardiovascular and venous thromboembolism risk: what is ‘new’? J Investig Med. 2017;65:964–973.
  • Budoff MJ, Ellenberg SS, Lewis CE, et al. Testosterone treatment and coronary artery plaque volume in older men with low testosterone. JAMA. 2017;317:708–716.
  • Abd Alamir M, Ellenberg SS, Swerdloff RS, et al. The Cardiovascular Trial of the Testosterone Trials: rationale, design, and baseline data of a clinical trial using computed tomographic imaging to assess the progression of coronary atherosclerosis. Coron Artery Dis. 2016;27:95–103.
  • No Authors listed. Testosterone treatment of men with alcoholic cirrhosis a double-blind study. The copenhagen study group for liver diseases. Hepatology. 1986;6:807–813.
  • Corona G, Maseroli E, Maggi M. Injectable testosterone undecanoate for the treatment of hypogonadism. Expert Opin Pharmacother. 2014;15:1903–1926.
  • Corona G, Rastrelli G, Maseroli E, et al. Testosterone replacement therapy and cardiovascular risk: a review. World J Mens Health. 2015;33:130–142.
  • Ohlander SJ, Varghese B, Pastuszak AW, et al. Erythrocytosis Following Testosterone Therapy. Sex Med Rev. 2018;6:77–85.
  • Corona G, Rastrelli G, Maggi M. The pharmacotherapy of male hypogonadism besides androgens. Expert Opin Pharmacother. 2015;16:369–387.
  • Corona G, Giagulli VA, Maseroli E, et al. Testosterone supplementation and body composition: results from a meta-analysis of observational studies. J Endocrinol Invest. 2016;39:967–981.
  • Corona G, Giagulli VA, Maseroli E, et al. THERAPY OF ENDOCRINE DISEASE: testosterone supplementation and body composition: results from a meta-analysis study. Eur J Endocrinol. 2016;174:R99–116.
  • Isidori AM, Balercia G, Calogero AE, et al. Outcomes of androgen replacement therapy in adult male hypogonadism: recommendations from the Italian society of endocrinology. J Endocrinol Invest. 2015;38:103–112.
  • Corona G, Maseroli E, Rastrelli G, et al. Is late-onset hypogonadotropic hypogonadism a specific age-dependent disease, or merely an epiphenomenon caused by accumulating disease-burden? Minerva Endocrinol. 2016;41:196–210.
  • Corona G, Rastrelli G, Di Pasquale G, et al. Cardiovascular risk: meta-analysis of interventional studies. J Sex Med. 2018;15:820–838.
  • Hackett G, Kirby M, Edwards D, et al. UK policy statements on testosterone deficiency. Int J Clin Pract. 2017 Mar 20 [Epub ahead of print]. DOI:10.1111/ijcp.12901.
  • Shores MM, Smith NL, Forsberg CW, et al. Testosterone treatment and mortality in men with low testosterone levels. J Clin Endocrinol Metab. 2012;97:2050–2058.
  • Muraleedharan V, Marsh H, Kapoor D, et al. Testosterone deficiency is associated with increased risk of mortality and testosterone replacement improves survival in men with type 2 diabetes. Eur J Endocrinol. 2013;169:725–733.
  • Sharma R, Oni OA, Gupta K, et al. Normalization of testosterone level is associated with reduced incidence of myocardial infarction and mortality in men. Eur Heart J. 2015;36:2706–2715.
  • Traish AM, Haider A, Haider KS, et al. Long-term testosterone therapy improves cardiometabolic function and reduces risk of cardiovascular disease in men with hypogonadism: a real-life observational registry study setting comparing treated and untreated (Control) Groups.J. Cardiovasc Pharmacol Ther. 2017 Sep;22(5):414–433.
  • Hacket GI. Testosterone Replacement therapy and mortality in older men. Drug Saf. 2016;39:117–130.
  • Baillargeon J, Urban RJ, Kuo YF, et al. Risk of myocardial infarction in older men receiving testosterone therapy. Ann Pharmacother. 2014;48:1138–1144.
  • Anderson JL, May HT, Lappé DL, et al. Impact of testosterone replacement therapy on myocardial infarction, stroke, and death in men with low testosterone concentrations in an integrated health care system. Am J Cardiol. 2016;117(1):794–799.
  • Wallis CJ, Lo K, Lee Y, et al. Survival and cardiovascular events in men treated with testosterone replacement therapy: an intention-to-treat observational cohort study. Lancet Diabetes Endocrinol. 2016;4:498–506.
  • Cheetham CT, An JJ, Jacobsen SJ. Association of testosterone replacement with cardiovascular outcomes among men with androgen deficiency. JAMA Intern Med. 2017;177:491–499.

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