A review of testosterone supplementation and cardiovascular risk

Nikita Jhawar; Razvan Chirila

doi:10.2478/rjim-2022-0022

.blurhash-client-img { display: none !important; }

A review of testosterone supplementation and cardiovascular risk

Romanian Journal of Internal Medicine

Volume 61 (2023): Issue 1 (March 2023)

By: Nikita Jhawar and Razvan Chirila

Open Access

|Mar 2023

Abstract

Testosterone therapy is commonly utilized to treat hypogonadism. After diagnosis with morning serum testosterone level in patients with symptoms of hypogonadism, therapy has been shown to improve symptoms. Research focusing on cardiovascular risks associated with testosterone therapy has produced contradictory statements. We review trials that have investigated the impact of testosterone supplementation on heart failure, coronary artery disease, and myocardial ischemia.

References

1. GOODALE T, SADHU A, PETAK S, ROBBINS R. Testosterone and the Heart. Methodist Debakey Cardiovasc J. 2017;13(2):68–72.10.14797/mdcj-13-2-68551268228740585
Search in Google Scholar Back to article
2. HU JR, DUNCAN MS, MORGANS AK, BROWN JD, MEIJERS WC, FREIBEG MS, et al. Cardiovascular effects of androgen deprivation therapy in prostate cancer. Arterioscler Thromb Vasc Biol. 2020;40:e55–e64.10.1161/ATVBAHA.119.313046704754931969015
Search in Google Scholar Back to article
3. KAUR H, GH WERSTUCK. The effect of testosterone on cardiovascular disease and cardiovascular risk factors in men: A review of clinical and preclinical data. CJC Open. 2021:1238–1248.10.1016/j.cjco.2021.05.007863624434888506
Search in Google Scholar Back to article
4. ELAGIZI A, KOHLER TS, LAVIE CJ. Testosterone and Cardiovascular Health. Mayo Clinic Proceedings. 2018;93(1):83–100.10.1016/j.mayocp.2017.11.00629275030
Search in Google Scholar Back to article
5. DANDONA P, DHINDSA S, GHANIM H, SAAD F. Mechanisms underlying the metabolic actions of testosterone in humans: A narrative review. Diabetes Obes Metab. 2021;23(1):18–28.10.1111/dom.1420632991053
Search in Google Scholar Back to article
6. Testosterone replacement therapy benefits outweigh risks, say researchers. American Association of Clinical Endocrinologists website, http://media.aace.com/press-release/aaceannualmeeting-press-releases/testosterone-replacement-therapy-benefitsoutweigh -.Accessed October 27, 2017.
Search in Google Scholar Back to article
7. SHORES MM, MATSUMOTO AM. Testosterone, aging and survival: biomarker or deficiency. Curr Opin Endocrinol Diabetes Obes. 2014;21(3):209–216.10.1097/MED.0000000000000057431376524722173
Search in Google Scholar Back to article
8. OHLSSON C, BARRETT-CONNOR E, BHASIN S, et al. High serum testosterone is associated with reduced risk of cardiovascular events in elderly men. J Am Coll Cardiol. 2011;58(16):1674–1681.10.1016/j.jacc.2011.07.01921982312
Search in Google Scholar Back to article
9. KLONER RA, CARSON C, DOBS A, KOPECKY S, MOHLER ER. Testosterone and cardiovascular disease. J Am Coll Cardiol. 2016;67(5):545–557.10.1016/j.jacc.2015.12.00526846952
Search in Google Scholar Back to article
10. UKKOLA O, HUTTUNEN T, PUURUNEN VP, PIIRA O, NIVA J, LEPOJARVI S, et al. Total testosterone levels, metabolic parameters, cardiac remodeling and exercise capacity in coronary artery disease patients with different stages of glucose tolerance. Ann Med. 2013;45(3):206–212.10.3109/07853890.2012.71195123548167
Search in Google Scholar Back to article
11. MALKIN CJ, PUGH PJ, MORRIS PD, ASIF S, JONES TH, CHANNER KS. Low serum testosterone and increased mortality in men with coronary heart disease. Heart. 2010;96(22):1821–1825.10.1136/hrt.2010.19541220959649
Search in Google Scholar Back to article
12. OSKUI PM, FRENCH WJ, HERRING MJ, MAYEDA GS, BURSTEIN S, KLONER R. Testosterone and the cardiovascular system: a comprehensive review of the clinical literature. J Am Heart Assoc. 2013;2(6):e000272.10.1161/JAHA.113.000272388677024242682
Search in Google Scholar Back to article
13. ORY J, NACKEERAN S, BALAJI NC, HARE JM, RAMASAMY AR. Secondary Polycythemia in Men Receiving Testosterone Therapy Increases Risk of Major Adverse Cardiovascular Events and Venous Thromboembolism in the First Year of Therapy. J Urol. 2022;207(6):1295–1301.10.1097/JU.000000000000243735050717
Search in Google Scholar Back to article
14. FALLARA G, POZZI E, BELLADELLI F, CORSINI C, BOERI L, CAPOGROSSO P, et al. Cardiovascular Morbidity and Mortality in Men - Findings From a Meta-analysis on the Time-related Measure of Risk of Exogenous Testosterone. J Sex Med. 2022;19(8):1243–1254.10.1016/j.jsxm.2022.05.14535753891
Search in Google Scholar Back to article
15. GAGLIONI-JUCA T, BASARIA S. Testosterone replacement therapy and cardiovascular risk. Nature /Reviews. 2019;16:555–574.
Search in Google Scholar Back to article
16. AUKRUST P, UELAND T, GULLESTAD L, YNDESTAD A. Testosterone: a novel therapeutic approach in chronic heart failure? J Am Coll Cardiol. 2009 Sep 1;54(10):928–9.10.1016/j.jacc.2009.05.03919712803
Search in Google Scholar Back to article
17. JANKOWSKA EA, TKACZYSZYN M, KALICIŃSKA E, BANASIAK W, PONIKOWSKI P. Testosterone deficiency in men with heart failure: pathophysiology and its clinical, prognostic and therapeutic implications. Kardiol Pol. 2014;72(5):403–9.10.5603/KP.a2014.002524526551
Search in Google Scholar Back to article
18. PUGH PJ, JONES RD, WEST JN, JONES TH, CHANNER KS. Testosterone treatment for men with chronic heart failure. Heart. 2004;90(4):446–447.10.1136/hrt.2003.014639176816115020527
Search in Google Scholar Back to article
19. TOMA M, MCALISTER FA, COGLIANESE EE, VIDI V, VAISAWALA S, BAKAL JA, et al. Testosterone supplementation in heart failure: a meta-analysis. Circ Heart Fail. 2012;5(3):315–321.10.1161/CIRCHEARTFAILURE.111.96563222511747
Search in Google Scholar Back to article
20. CAMINITI G, VOLTERRANI M, IELLAMO F, MARAZZI G, MASSARO R, MICELLI M, et al. 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. J Am Coll Cardiol.2009;54(10):919–927.10.1016/j.jacc.2009.04.07819712802
Search in Google Scholar Back to article
21. NJOROGE JN, TRESSEL W, BIGGS ML, MATSUMOTO AM, SMITH NL, ROSENBERG E, et al. Circulating Androgen Concentrations and Risk of Incident Heart Failure in Older Men: The Cardiovascular Health Study. J Am Heart Assoc. 2022 Nov;11(21):e026953.10.1161/JAHA.122.026953967363636285783
Search in Google Scholar Back to article
22. OSKUI PM, FRENCH WJ, HERRING MJ, MAYEDA GS, BURSTEIN S, KLONER R. Testosterone and the cardiovascular system: a comprehensive review of the clinical literature. J Am Heart Assoc. 2013;2(6):e000272.10.1161/JAHA.113.000272
Search in Google Scholar Back to article
23. LAI J, GE Y, SHAO Y, XUAN T, XIA S, LI M. Low serum testosterone level was associated with extensive coronary artery calcification in elderly male patients with stable coronary artery disease. Coron Artery Dis. 2015;26(5):437–441.10.1097/MCA.000000000000026025968306
Search in Google Scholar Back to article
24. PARK BJ, SHIM JY, LEE YJ, LEE JH, LEE HR. Inverse relationship between bioavailable testosterone and subclinical coronary artery calcification in non-obese Korean men. Asian J Androl. 2012;14(4):612–615.10.1038/aja.2012.19372006722522505
Search in Google Scholar Back to article
25. TURHAN S, TULUNAY C, GÜLEC S, OZDOL C, KILICKAP M, ALTIN T, et al. The association between androgen levels and premature coronary artery disease in men. Coron Artery Dis. 2007;18(3):159–162.10.1097/MCA.0b013e328012a92817429287
Search in Google Scholar Back to article
26. MATHUR A, MALKIN C, SAEED B, MUTHUSAMY R, JONES TH, CHANNER K. Long-term benefits of testosterone replacement therapy on angina threshold and atheroma in men. Eur J Endocrinol. 2009;161(3):443–449.10.1530/EJE-09-009219542238
Search in Google Scholar Back to article
27. BUDOFF MJ, ELLENBERG SS, LEWIS CE, MOHLER ER, WENGER NK, BHASIN S, et al. Testosterone treatment and coronary artery plaque volume in older men with low testosterone. JAMA. 2017;317(7):708–716.10.1001/jama.2016.21043546543028241355
Search in Google Scholar Back to article
28. ALEXANDER GC, IYER G, LUCAS E, LIN D, SINGH S. Cardiovascular risks of exogenous testosterone use among men: a systematic review and meta-analysis. Am J Med. 2017;130(3):293–305.10.1016/j.amjmed.2016.09.01727751897
Search in Google Scholar Back to article
29. ENGLISH KM, STEEDS RP, JONES TH, DIVER MJ, CHANNER KS. Low-dose transdermal testosterone therapy improves angina threshold in men with chronic stable angina: A randomized, double-blind, placebo-controlled study. Circulation. 2000 Oct 17;102(16):190610.1161/01.CIR.102.16.1906
Search in Google Scholar Back to article
30. ROSANO GM, LEONARDO F, PAGNOTTA P, PELLICCIA F, PANINA G, CARQUETANI E, et al. Acute anti-ischemic effect of testosterone in men with coronary artery disease. Circulation. 1999 Apr 6;99(13):1666–70.10.1161/01.CIR.99.13.1666
Search in Google Scholar Back to article
31. WEBB CM, ADAMSON DL, DE ZEIGLER D, COLLINS P. Effect of acute testosterone on myocardial ischemia in men with coronary artery disease. Am J Cardiol. 1999 Feb 1;83(3):437–9, A9.
Search in Google Scholar Back to article
32. MORLEY JE, PERRY HM III. Androgens and women at the menopause and beyond. J Gerontol A Biol Sci Med Sci. 2003;58(5):M409–M416.10.1093/gerona/58.5.M409
Search in Google Scholar Back to article
33. BRAND JS, VAN DER SCHOUW YT. Testosterone, SHBG and cardiovascular health in postmenopausal women. Int J Impot Res. 2010;22(2):91–104.10.1038/ijir.2009.6420090761
Search in Google Scholar Back to article
34. ELRAIYAH T, SONBOL MB, WANG Z, KHAIRALSEED T, ASI N, UNDAVALLI C, et al. Clinical review: The benefits and harms of systemic testosterone therapy in postmenopausal women with normal adrenal function: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2014 Oct;99(10):3543–50.10.1210/jc.2014-2262539349525279572
Search in Google Scholar Back to article
35. SPOLETINI I, VITALE C, PELLICCIA F, FOSSATI C, ROSANO GM. Androgens and cardiovascular disease in postmenopausal women: a systematic review. Climacteric. 2014; 17(6):625-34. doi: 10.3109/13697137.2014.887669.24559253
Open DOI Search in Google Scholar Back to article
36. SHUFELT CL, BRAUNSTEIN GD. Safety of testosterone use in women. Maturitas. 2009;63(1):63–6.10.1016/j.maturitas.2009.01.01219250779
Search in Google Scholar Back to article
37. LEE JH, SHAH PH, UMA D, SALVI DJ, RABBANI R, HAMID P. Testosterone Replacement Therapy in Hypogonadal Men and Myocardial Infarction Risk: Systematic Review & Meta-Analysis. Cureus. 2021;13(8):e17475.10.7759/cureus.17475840517434513525
Search in Google Scholar Back to article
38. NGUYEN CP, HIRSCH MS, MOENY D, KAUL S, MOHAMOUD M, JOFFE HV. Testosterone and “Age-Related Hypogonadism”--FDA Concerns. N Engl J Med. 2015 Aug 20;373(8):689–91.10.1056/NEJMp1506632890539926287846
Search in Google Scholar Back to article