Most men lose some physical strength and sexual ability as they age. Many men attempt to prevent these changes with diet, exercise and by taking testosterone. Approximately 2.3 million men ages 40 to 60 years filled testosterone prescriptions in 2013.
The Food and Drug Administration (FDA) has approved testosterone for men with low blood levels of testosterone [hypo-testicular function]. Testosterone supplements increase muscle mass, decrease body-fat, strengthen bones, and correct erectile dysfunction. There is evidence that exercise increases the beneficial effects of testosterone [JL Vingren et al; Sports Med 40 (12);2010; 1037-1063].There is also evidence that testosterone therapy might also cause cardiovascular problems, including heart attacks and strokes, especially in men with a history of coronary artery disease. This evidence is controversial since other studies have shown a decrease risk of cardiovascular disease.
The 2013 Veterans Administration study [R.Vigen et al; JAMA 310 (17); 2013; 1829-1836] was a retrospective analysis of 8709 men with low testosterone levels (<300 ng/dL) who underwent coronary angiography in the Veterans Affairs (VA) system between 2005 and 2011. The use of testosterone therapy of any type was associated with increased risk of mortality, MI, and ischemic stroke. The total of all adverse outcomes were 19.9% in the no testosterone therapy group vs 25.7% in the testosterone therapy group. This was an absolute risk difference of 5.8% with the use of any form of testosterone. A more recent 2015 retrospective VA study examined 83 010 male veterans with documented low testosterone levels [R Sharma et al; Eur Heart J (2015) 36 (40): 2706-2715]. In this large study normalization of testosterone levels was associated with a significant reduction in all-cause mortality, MI, and stroke.
It is important to note that in the 2013 VA study repeat measurements to document normalization of testosterone levels and to evaluate abnormally high testosterone levels after testosterone supplementation were frequently not done.
Multiple prior studies have shown that testosterone therapy may protect against heart disease and decrease mortality. In a study published in June 2012 in the Journal of Clinical Endocrinology and Metabolism [MM Shores et al; J Clin Endocrinol Metab. 2012 Jun; 97(6):2050-8] that also examined veterans, the authors concluded that testosterone treatment resulted in a 39 percent decreased mortality risk vs. men not treated with testosterone. Importantly, many studies have shown that men with lower testosterone levels are at a higher risk of mortality.
A 2007 study also in the Journal of Clinical Endocrinology and Metabolism [G A Laughlin et al; J Clinical Endocrinol Metab 2007; 93(1); 1797]studied 794 men aged 50-91 years old for over 11 years and showed that men with testosterone levels in the lowest quartile were 40 percent more likely to die than those with higher levels. In this study, low testosterone also predicted increased risk of cardiovascular disease.
An important recent study appears to clarify some of the above conflicting data [Unpublished study presented Endocrine Society’s 2016 97th annual meeting San Diego] Men have higher testosterone and lower estrogen levels than premenopausal women. Therefore, doctors have suspected that testosterone may promote cardiovascular disease or that estrogen may protect against it, or both, according to Elaine Yu, MD, MSc, the study’s lead investigator and an assistant professor at Harvard Medical School, Boston.
This study, conducted in 400 healthy men ages 20 to 50, found that higher levels of testosterone led to lower levels of HDL cholesterol, or “good” cholesterol-possibly increasing cardiovascular risk. Estrogen had no effect on HDL cholesterol but low levels of estrogen led to higher fasting blood glucose (sugar) levels, worsening insulin resistance and increased risk of cardiovascular disease.
In summary, higher testosterone levels and lower estrogen levels in men worsen cardiovascular risk factors that may help to explain gender differences in heart disease.
In summary if testosterone therapy is given it is important to obtain frequent post treatment blood tests including testosterone [free and total] and estrogen levels. Until multiple large randomized prospective studies are done testosterone will remain a potentially beneficial yet controversial therapy. CAVEAT EMPTOR.