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Testosterone was administered in an unsafe manner

Posted by edfriedman on 09 May 2014 at 18:57 GMT

In the January 29, 2014 PLoS One article, “Increased Risk of Non-Fatal Myocardial Infarction Following Testosterone Therapy Prescription in Men,” the authors conclude that "In older men, and in younger men with pre-existing diagnosed heart disease, the risk of MI following initiation of TT prescription is substantially increased.[1]"

It is known that for men with systolic chronic heart failure, serum estradiol levels higher or lower than the optimal amount increase the rate of mortality, both in the short term and in the long term[2]. Exogenous testosterone not only raises the level of serum testosterone but also the level of serum estradiol. The failure of the authors to monitor and control estradiol levels is a serious defect in their research.

Higher endogenous levels of estradiol, but not testosterone, are associated with an increased incidence of coronary heart disease in men.[3] Also, for elderly men receiving exogenous testosterone, those who experienced adverse cardiovascular events had serum estradiol levels which were on average more than 1.9 times higher than for those who did not.[4]

Testosterone is known to increase the risk of polycythemia. When hematocrit levels were monitored and kept at a safe level, no increase in adverse cardiovascular events were observed[5]. It is possible that testosterone therapy does in fact increase the risk of adverse cardiovascular events in men, but until researchers monitor both estradiol and hematocrit levels and keep them both at the safest levels possible, it is impossible to come to such a conclusion.


1. Finkle WD, Greenland S, Ridgeway GK, et al. Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PLoS ONE. 2014;9(1): e85805. doi: 10.1371/journal.pone.0085805
2. Jankowska EA, Rozentryt P, Ponikowska B, et al. Circulating estradiol and mortality in men with systolic heart failure. JAMA. 2009;301(18):1892-1901.
3. Phillips GB, Castelli WP, Abbott RD, McNamara PM. Association of hyperestrogenemia and coronary heart disease in men in the Framingham cohort. Am J Med. 1983;74(5):863-869.
4. Basaria S, Davda MN, Travison TJ, Ulloor J, Singh R, Bhasin S. Risk factors associated with cardiovascular events during testosterone administration in older men with mobility limitation. J Gerontol A Biol Sci Med Sci. 2013;68(2):153-160.
5. Hajjar RR, Kaiser FE, Morley JE. Outcome of long-term testosterone replacement in older hypogonadal males: A retrospective analysis. JCEM. 1997;82(11):3793-3796.

No competing interests declared.