Testosterone Treatment and Hormonophobia – Cardiovascular risk, the Media, and the Authorities

 

One of the most controversial and debated issue related to testosterone replacement therapy is its effects on cardiovascular risk and related clinical outcomes.

 

In this video presentation, Dr. Morgentaler clarifies misperceptions of testosterone replacement therapy and cardiovascular disease risk, which have created unwarranted concerns and distorted public discussion of testosterone replacement therapy as a medical treatment.

 

Dr. Morgentaler starts by introducing the two methodologically studies by Vigen [1] (published Nov 2013) and Finkle [2] (published Jan 2014), which implicated increased cardiovascular risk (MI, stroke and mortality) with testosterone replacement therapy. Dr. Morgentaler then exposes the multiple methodological flaws of those studies, which invalidate their conclusions. Despite the serious flaws in both of these studies, they horrified both physicians and the general public, and had a remarkable negative impact on medical practice. 

 

Dr. Morgentaler attributes this aftermath to “hormonophobia”, i.e. a persistent, irrational fear of sex hormones (testosterone and estrogen) despite evidence to the contrary. He also underscores that testosterone is unlike any other scientific topic in that it creates opinions that are not based on the totality of evidence from all available research data. One example is the association between testosterone and prostate cancer. Now, we are facing a tsunami of worry about testosterone and cardiovascular risk, says Dr. Morgentaler.

 

He ends his presentation by highlighting notable studies with completely contradictory results to those that created the media craze:

 

*2012 Shores et al - Testosterone treatment and mortality in men with low testosterone levels: [3] 

 

The mortality in testosterone-treated men was 10.3% compared with 20.7% in untreated men.

 

* 2013 Muraleedharan et al - Testosterone deficiency is associated with increased risk of mortality and testosterone replacement improves survival in men with type 2 diabetes: [4]

 

Mortality was increased in the low testosterone group (17.2%) compared with the normal testosterone group (9%) when controlled for covariates. testosterone replacement therapy was associated with a reduced mortality of 8.4%, compared with 19.2% in the untreated group.

 

* 2015 Corona et al - Cardiovascular risk associated with testosterone-boosting medications: a systematic review and meta-analysis: [5]

 

"Our analyses, performed on the largest number of studies collected so far, indicate that TS is not related to any increase in cardiovascular risk, even when composite or single adverse events were considered. In randomized controlled trials performed in subjects with metabolic derangements a protective effect of testosterone replacement therapy on cardiovascular risk was observed. The present systematic review and meta-analysis does not support a causal role between testosterone replacement therapy and adverse cardiovascular events. Our results are in agreement with a large body of literature from the last 20 years supporting testosterone replacement therapy of hypogonadal men as a valuable strategy in improving a patient's metabolic profile, reducing body fat and increasing lean muscle mass, which would ultimately reduce the risk of heart disease."

 

Dr. Morgentaler also points out the many studies showing that low testosterone levels are associated with increased cardiovascular and all-cause mortality. He says, “testosterone deficiency is bad, yet no study shows that high testosterone is also bad – but it is the high testosterone that is being accused of being bad.” The milestone review paper published in Mayo Clinic Proceedings - written by Dr. Morgentaler and his Associates of the Androgen Study Group – concludes: [6]

 

“In summary, we find no scientific basis for the suggestion that testosterone replacement therapy increases cardiovascular risk. In fact, as of this date, we are unaware of any compelling evidence that testosterone replacement therapy is associated with increased cardiovascular risk. On the contrary, the weight of evidence accumulated by researchers around the world over several decades clearly indicates that higher levels of testosterone are associated with amelioration of cardiovascular risk factors and reduced risk of mortality.”

 

Note: For more information about the study "Cardiovascular risk associated with testosterone-boosting medications: a systematic review and meta-analysis", see my previous article.

 

References:

1.            Vigen, R., et al., Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA, 2013. 310(17): p. 1829-36.

2.            Finkle, W.D., et al., Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PLoS One, 2014. 9(1): p. e85805.

3.            Shores, M.M., et al., Testosterone treatment and mortality in men with low testosterone levels. J Clin Endocrinol Metab, 2012. 97(6): p. 2050-8.

4.            Muraleedharan, V., 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(6): p. 725-33.

5.            Corona, G., et al., Cardiovascular risk associated with testosterone-boosting medications: a systematic review and meta-analysis. Expert Opin Drug Saf, 2014. 13(10): p. 1327-51.

6.            Morgentaler, A., et al., Testosterone therapy and cardiovascular risk: advances and controversies. Mayo Clin Proc, 2015. 90(2): p. 224-51.