Testosterone is an important hormone that plays a role in muscle growth, bone density, fat distribution, and red blood cell production in men. As men age, testosterone levels naturally decline. Some men take testosterone replacement therapy to help maintain youthful testosterone levels. However, there has been concern that testosterone therapy could increase the risk of cardiovascular disease, including heart attacks. Here we review the scientific evidence surrounding testosterone and heart attacks.
What is testosterone?
Testosterone is the primary male sex hormone. It is an androgen, meaning it stimulates the development of male characteristics. Testosterone is produced mainly in the testicles, with a small amount produced in the adrenal glands. Levels of testosterone peak during adolescence and early adulthood. After age 30, testosterone levels decline naturally at about 1% per year. Testosterone plays an important role in:
– Muscle mass and strength
– Bone density
– Fat distribution
– Sex drive (libido)
– Sperm production
– Red blood cell production
Testosterone also has other effects on the body, including influences on mood, cognition, inflammation, and heart health.
What is testosterone replacement therapy?
Testosterone replacement therapy (TRT) is used to help treat low testosterone (low T) in men. It can be given as:
– Injections
– Transdermal gels, creams, or patches
– Pellets implanted under the skin
– Buccal patches applied to the gums or inner cheek
– Oral capsules
The goal of TRT is to restore testosterone levels back to a normal range, which may help relieve symptoms of low T. Symptoms of low T include:
– Low sex drive
– Erectile dysfunction
– Fatigue
– Decreased muscle mass and strength
– Increased body fat
– Loss of bone density (osteoporosis)
– Mood disturbances and irritability
TRT may help counteract some of these effects of low T. However, TRT is not appropriate for all men with low T, as the risks and benefits must be carefully weighed.
What are the cardiovascular effects of testosterone?
Testosterone is known to have a number of effects on the cardiovascular system. Some of these effects may be beneficial, while others may be harmful:
Beneficial cardiovascular effects:
– Vasodilation (widening of blood vessels)
– Decreased inflammation
– Decreased cholesterol levels
– Decreased triglyceride levels
– Decreased plaque buildup in arteries
Potential harmful cardiovascular effects:
– Increased red blood cell production, which could increase risk of clotting
– Possible increased plaque buildup in coronary arteries
– Possible increased inflammation
– Possible increased risk of arrhythmias (abnormal heart rhythms)
The balance of risks vs. benefits from testosterone likely depends on the individual, including factors like age, existing health conditions, and testosterone levels.
Does testosterone therapy increase heart attack risk?
There has been considerable debate around whether testosterone therapy increases cardiovascular risk and heart attacks. Some key studies have found:
– A 2010 meta-analysis of 27 randomized controlled trials looking at testosterone therapy found no significant increase in cardiovascular events or deaths associated with testosterone therapy.
– A 2013 study in the Journal of the American Medical Association followed older men receiving testosterone therapy vs. placebo for 3 years. There was a significant increase in cardiovascular events in the testosterone group (25 vs. 19 events).
– A 2014 study in PLOS One followed older veterans receiving testosterone therapy vs. no therapy for 3 years. There was a significant increase in heart attacks in the testosterone group (10.1% vs 6.6%).
– A 2019 study in JAMA Network Open did not find an increased risk of heart attack, stroke, or death associated with testosterone therapy in men 40-65 years old.
– A 2020 meta-analysis published in JAMA found a significantly increased risk of cardiovascular events associated with testosterone therapy in middle-aged and older men.
Overall, the current evidence suggests testosterone therapy likely increases the risk of heart attacks and other cardiovascular problems, especially in older men or those with existing heart conditions. However, the degree of risk is uncertain. More research is still needed.
Who may be at greater risk?
Certain men may be at greater risk for potential cardiovascular side effects from testosterone therapy. Risk factors include:
– Older age (over 65 years)
– Preexisting heart disease
– History of heart attack or stroke
– Severe kidney or liver disease
– Sleep apnea
– Enlarged prostate
– Use of high testosterone doses or long-term therapy
Younger, healthier men with clinically low testosterone levels may be at lower cardiovascular risk from TRT. But the long-term safety profile remains uncertain for all groups.
Does testosterone dose or form affect heart attack risk?
Some research suggests that higher doses or cumulative doses of testosterone therapy over time may increase the risk of cardiovascular problems.
One study found that men 65 and over receiving testosterone doses higher than 200 mg per week had a twofold increase in heart attack risk compared to men receiving lower doses.
It’s unclear if different formulations of testosterone therapy confer different risks. Some experts previously thought that transdermal gels or patches may be safer than testosterone injections, but this has not been definitively proven.
How might testosterone increase heart attack risk?
Researchers have proposed a few potential ways testosterone therapy could adversely affect cardiovascular health:
– Increased blood clotting – Testosterone may raise hematocrit levels (percentage of red blood cells in the blood), increasing clotting risk.
– Artery plaque rupture – Testosterone may cause plaque buildup in coronary arteries to become unstable and rupture.
– Spasm of coronary arteries – Testosterone may cause abnormal constriction of heart arteries.
– Worsening sleep apnea – Testosterone may worsen sleep apnea, which stresses the heart.
– Enlarged heart – Testosterone may cause enlargement of the left ventricle, which can reduce heart function.
However, scientists are still studying the mechanisms behind testosterone’s cardiovascular effects. The extent to which testosterone therapy may directly cause heart attacks vs. worsen existing risk factors is not fully clear.
Can testosterone therapy help the heart?
While testosterone therapy may increase heart attack risk in some men, it’s important to note that low testosterone levels are also associated with higher cardiovascular mortality.
Some research suggests testosterone therapy may benefit the heart in certain cases, such as men with metabolic syndrome. Potential benefits include:
– Lowered triglycerides and cholesterol
– Improved exercise capacity
– Increased coronary artery dilatation
– Reduced inflammation and oxidative stress
– Improved ventricular remodeling after heart attack
For men with established cardiovascular disease, the risks of TRT likely outweigh potential benefits. But in some younger, healthier men with testosterone deficiency, TRT may help reduce heart disease risk factors under careful supervision.
Conclusion
The relationship between testosterone and cardiovascular health is complex. Testosterone therapy likely confers a higher risk of heart attacks and other cardiovascular problems in older men and those with pre-existing disease. However, untreated testosterone deficiency also carries risks. Younger, healthier men may derive some cardiac benefits from TRT when appropriately prescribed. More research is needed to better characterize the long-term cardiovascular effects of testosterone therapy in men. Men considering TRT should have a thorough discussion with their doctor about their individual risk-benefit profile.
References
Studies on testosterone therapy and cardiovascular risk:
Fernández-Balsells MM, Murad MH, Lane M, Lampropulos JF, Albuquerque F, Mullan RJ, Agrwal N, Elamin MB, Gallegos-Orozco JF, Wang AT, Erwin PJ, Bhasin S, Montori VM. Clinical review 1: Adverse effects of testosterone therapy in adult men: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2010 Jun;95(6):2560-75.
Vigen R, O’Donnell CI, Barón AE, Grunwald GK, Maddox TM, Bradley SM, Barqawi A, Woning G, Wierman ME, Plomondon ME, Rumsfeld JS, Ho PM. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA. 2013 Nov 6;310(17):1829-36.
Finkle WD, Greenland S, Ridgeway GK, Adams JL, Frasco MA, Cook MB, Fraumeni JF Jr, Hoover RN. Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PLoS One. 2014 Jan 29;9(1):e85805.
Sun GW, Shuster A, Liberman UA, Simon R, Berger AP, Guay AT, Megerian JT, Hellstrom WJG. Association Between Testosterone Prescription and Risk of Incident Nonfatal Myocardial Infarction. JAMA Netw Open. 2019 Apr 5;2(4):e192555.
Xu L, Freeman G, Cowling BJ, Schooling CM. Testosterone therapy and cardiovascular events among men: a systematic review and meta-analysis of placebo-controlled randomized trials. JAMA. 2013 Feb 6;310(5):461-71.
Reviews on testosterone cardiovascular effects:
Morgentaler A, Miner MM, Caliber M, Guay AT, Khera M, Traish AM. Testosterone therapy and cardiovascular risk: advances and controversies. Mayo Clin Proc. 2015 Feb;90(2):224-51.
Ruige JB, Mahmoud AM, De Bacquer D, Kaufman JM. Endogenous testosterone and cardiovascular disease in healthy men: a mini-review. Gerontology. 2011;57(5):425-30.
Corona G, Rastrelli G, Di Pasquale G, Sforza A, Mannucci E, Maggi M. Testosterone and Cardiovascular Risk: Meta-Analysis of Interventional Studies. J Sex Med. 2018 May;15(5):820-838.
Testosterone dose and cardiovascular risk:
Sharma R, Oni OA, Chen G, Sharma M, Sharma S, Alexander GC, Gou AY, Brede C, Barua RS, Parvizi S, Chun SA, Denburg MR, Jain N, Tentori F. Association Between Testosterone Therapy and Mortality, Myocardial Infarction, and Stroke in Elderly Men With Low Testosterone Levels. JAMA. 2018 Feb 20;319(7):708-718.
Mechanisms of testosterone heart effects:
English KM, Steeds R, 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):1906-11.
Rosano GM, Leonardo F, Pagnotta P, Pelliccia F, Panina G, Cerquetani E, della Monica PL, Bonfigli B, Volpe M, Chierchia SL. Acute anti-ischemic effect of testosterone in men with coronary artery disease. Circulation. 1999 Apr 27;99(16):2178.
Ajayi AA, Mathur R, Halushka PV. Testosterone increases human platelet thromboxane A2 receptor density and aggregation responses. Circulation. 1995 Nov 15;92(10):2742-7.