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15 December 2017

Low Testosterone is Associated with Elevated Cardiovascular Disease Biomarkers

Low Testosterone is Associated with Elevated Cardiovascular Disease Biomarkers

Pastuszak AW, Kohn TP, Estis J, Lipshultz LI. Low Plasma Testosterone Is Associated With Elevated Cardiovascular Disease Biomarkers. The journal of sexual medicine. 2017;14(9):1095-1103.

The fear of increased risk of heart attack and stroke with testosterone therapy was mainly caused by two high profile but flawed studies. Even though many new studies have refuted these alleged cardiovascular risks and even demonstrated that testosterone therapy is associated with a reduced cardiovascular risk, concern still remains.

Other lines of research have also countered the alleged cardiovascular risks. For example it has been shown that declining testosterone levels in men can be a signal of deteriorating health, and men with testosterone deficiency hypogonadism) who remain untreated have an increased risk of heart attack and stroke. This is contrary to what the few flawed studies concluded. Furthermore, testosterone deficiency discovered during hospitalization (regardless of cause) is associated with in-hospital and long-term mortality in elderly male patients. Specifically, testosterone deficiency in hospitalized men has been significantly associated with a 3.3-fold increased risk of all-cause mortality and a 2.1-fold increased risk of cardiovascular mortality.

To get a better understanding of the relation between testosterone and cardiovascular health and disease, it is useful to look at studies that have investigated mechanisms underlying heart attack and stroke. Here we summarize the results of a study published in the Journal of Sexual Medicine. It examined the relation between testosterone levels and cardiovascular risk using a large panel of 10 objective biomarkers that have been linked to cardiovascular health.

Key Points

  • Cardiovascular biomarkers can be used as surrogate endpoints to evaluate treatment more efficiently and quickly than to wait for clinical events (hard endpoints) such as heart attacks and strokes to happen.
  • Low testosterone levels are associated with harmful elevations in 9 of 10 cardiovascular biomarkers: cardiac troponin I (cTnI), endothelin-1 (ET-1), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), N-terminal proB-type natriuretic peptide (NTproBNP), high-density lipoprotein (HDL) cholesterol, high-sensitivity C-reactive protein (hs-CRP), hemoglobin A1c (HbA1c), and leptin.
  • Previous studies have shown that testosterone treatment improves several cardiovascular biomarkers; CRP, interleukin-1beta, TNF-α, interleukin-1beta, and leptin.
  • The ability of testosterone treatment to improve leptin sensitivity is especially notable considering that leptin resistance may play a causative role in the metabolic decline seen with aging.

15 September 2015

Normalization of testosterone level is associated with reduced risk of heart attack, stroke and mortality in men

Normalization of testosterone level is associated with reduced risk of heart attack, stroke and mortality in men

The effects of testosterone replacement therapy on cardiovascular outcomes such as heart attack and stroke are controversial and have been generating heated discussions among clinicians as well as researchers. This, coupled with biased media sensationalism blowing up the supposed “dangers” of testosterone therapy has created great confusion among suffering men, who could gain tremendous health benefits from testosterone therapy.

In this editorial we report the results of a new study that examined the relationship between normalization of total testosterone levels with testosterone therapy and cardiovascular events as well as all-cause mortality, in patients without a previous history of heart attack and stroke. This notable study was published in the European Heart Journal on August 6th, 2015.

1 May 2015

Testosterone, Cardiovascular Risk, Mortality and Longevity

Testosterone, Cardiovascular Risk, Mortality and Longevity

Testosterone Therapy and Cardiovascular Risk: Advances and Controversies. Morgentaler A, Miner MM, Caliber M, Guay AT, Khera M, Traish AM. Mayo Clin. Proc. 2015;90(2):224-251.

Testosterone and mortality. Muraleedharan V, Jones TH. Clin. Endocrinol. (Oxf). 2014;81(4):477-487.

One of the most debated issues related to testosterone replacement therapy is its effects on cardiovascular risk and clinical events, like for example heart attack. A few flawed studies over the past years made it appear that testosterone replacement therapy increases cardiovascular risk and incidence of heart attacks. However, less known is the vast and rapidly accumulating body of evidence showing the contrary; that higher testosterone levels and testosterone replacement therapy actually may reduce mortality and increase longevity.

This editorial summarises key conclusions from a special medical review article on testosterone and cardiovascular risk, written by the Androgen Study Group, as provides answers to the following two questions:

  1. Is testosterone deficiency directly involved in the pathogenesis of these conditions or is it merely a biomarker of ill health and the severity of underlying disease processes?
  2. Does testosterone replacement therapy retard disease progression and ultimately enhance the clinical prognosis and survival?

1 January 2015

Testosterone-boosting Medications and Cardiovascular Risk

Testosterone-boosting Medications and Cardiovascular Risk

- a systematic review and meta-analysis

Cardiovascular risk associated with testosterone-boosting medications: a systematic review and meta-analysis. Corona G, Maseroli E, Rastrelli G, et al. Expert opinion on drug safety. Oct 2014;13(10):1327-1351.

Accumulating evidence shows beneficial effects of testosterone therapy on a wide range of health outcomes, including inflammation, insulin sensitivity, muscle mass, body fat mass, lipid profiles, endothelial (blood vessel) function, bone mineral density, energy and vitality, mood, sexual function and overall quality of life. Despite this, concerns have been raised that testosterone therapy could have detrimental effects on cardiovascular disease.

This editorial summarizes results from a comprehensive systematic review and meta-analysis, the largest to date, of all placebo-controlled randomized clinical trials (RCTs) on the effect of testosterone therapy on cardiovascular-related problems.

19 August 2014

Testosterone Treatment and Heart Attack Risk

Testosterone Treatment and Heart Attack Risk

- New study shows testosterone treatment can even be beneficial

Risk of Myocardial Infarction in Older Men Receiving Testosterone Therapy. Baillargeon, J., et al., Ann Pharmacother 1060028014539918, first published on July 2, 2014 as doi:10.1177/1060028014539918, 2014

Testosterone therapy has been in use for more than 70 years for the treatment of hypogonadism, also called testosterone deficiency. In the past 30 years there has been a growing body of scientific research demonstrating that testosterone deficiency is associated with increased body weight/adiposity/waist circumference, insulin resistance, type 2 diabetes, hypertension, inflammation, atherosclerosis and cardiovascular disease, erectile dysfunction (ED) and increased risk of mortality. In line with the detrimental health outcomes seen with testosterone deficiency, testosterone therapy has been shown to confer beneficial effects on multiple risk factors and risk biomarkers related to these clinical conditions.

Despite these well-documented health benefits, testosterone therapy is still controversial, in large part due to a few flawed studies about potential elevated heart attack risk with testosterone therapy. On July 2, 2014, a study was published which demonstrated that testosterone therapy is not associated with an increased risk of heart attack, and may actually confer protection against heart attack.


Last updated: 2019
G.MKT.GM.MH.02.2018.0506