Testosterone and mortality

A recent study that got a lot of traction in the press, Increased Risk of Non-Fatal Myocardial Infarction Following Testosterone Therapy Prescription in Men, found that men newly prescribed testosterone (T) replacement therapy had an increased risk of heart attack. The increase was substantial.

What are we to make of this in light of many other studies showing that T is inversely related to all-cause mortality, including mortality from heart disease? Consider the following: Endogenous Testosterone and Mortality Due to All Causes, Cardiovascular Disease, and Cancer in Men.

Odds ratios (95% confidence intervals) for mortality for increasing quartiles of endogenous testosterone compared with the lowest quartile were 0.75 (0.55 to 1.00), 0.62 (0.45 to 0.84), and 0.59 (0.42 to 0.85), respectively (P<0.001 for trend after adjustment for age, date of visit, body mass index, systolic blood pressure, blood cholesterol, cigarette smoking, diabetes mellitus, alcohol intake, physical activity, social class, education, dehydroepiandrosterone sulfate, androstanediol glucuronide, and sex hormone binding globulin). An increase of 6 nmol/L serum testosterone (≈1 SD) was associated with a 0.81 (95% confidence interval 0.71 to 0.92, P<0.01) multivariable-adjusted odds ratio for mortality. Inverse relationships were also observed for deaths due to cardiovascular causes and cancer and after the exclusion of deaths that occurred in the first 2 years. Conclusions— In men, endogenous testosterone concentrations are inversely related to mortality due to cardiovascular disease and all causes. Low testosterone may be a predictive marker for those at high risk of cardiovascular disease.

Reductions in mortality in this study due to T were also substantial.

One difference between the two is that the former study finding more heart attacks was in men getting exogenous T. If they were getting injections, and doubtless some of them were, they would see spikes in T levels beyond the physiological norm. Perhaps that could account for the difference. It could also be that the study was flawed in some way. For a discussion of that issue, see this from the Life extension Foundation. They conclude that the study is seriously flawed.

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3 comments
SimianOutcast says April 24, 2014

All of your (much-appreciated) linked studies seem to focus on testosterone. I’m curious as to what you think of the importance of other androgens like DHT. Do you think that 5-alpha-reductase inhibiting drugs like finasteride are dangerous to male health due to reduced DHT levels or can testosterone pick up the slack ?

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    Mangan says April 24, 2014

    I think I’ll have to plead ignorance on that one, not having looked closely at finasteride. Adverse effects seem low, if you can believe what the drug companies say.

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Sam says June 13, 2014

I have a friend who has a good theory about mortality in Men taking testosterone. He uses testosterone cream when he has small injuries or is feeling down. He says the energy rush is enormous. The problem is you feel stronger but in reality you still have an old body. He believes that people feel so much better they over exert themselves and this causes injuries or even death. I think it makes good sense.

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