Journal Article 1 – Testosterone replacement in Late Onset Hypogonadism and Cardiovascular risk

TITLE Normalization of testosterone level is associated

with reduced incidence of myocardial infarction

and mortality in men

AUTHORS Rishi Sharma1, Olurinde A. Oni1, Kamal Gupta2, Guoqing Chen3, Mukut Sharma1,

Buddhadeb Dawn2, Ram Sharma1, Deepak Parashara2,4, Virginia J. Savin5,

John A. Ambrose6, and Rajat S. Barua


Article Url – 

Q Which studies have shown increase risk of Myocardial infarction with Testosterone use in men with late onset hypogonadism ?

Vigen et al and Finkle et al showed increased risk of Myocardial infarction with testosterone use in elderly men with late onset hypogonadism.

Q What is the current status of Testosterone use in Late onset hypogonadism ?

It is ambiguous, however FDA has issued a warning against its use.

Q What kind of study is this ?

It is a retrospective cohort study.

Q What cut off of testosterone value did they take in this study ?

Since different labs have different normative ranges, the authors defined low testosterone as that which was below the laboratory cut off value instead of using a single arbitrary lab value.

Q What were the outcomes that were measured ?

  1. Incidence of Myocardial infarction
  2. Incidence of stroke
  3. Incidence of All cause mortality

Q Which were the three groups in which the patients were divided ?

  1. Grp 1 –Those who received testosterone therapy with normalization of testosterone level
  2. Grp 2- those who received testosterone but did not have normalization of testosterone level
  3. Grp 3- those who had low testosterone but did not receive testosterone therapy

Q Which statistically test was used to compare the difference between the groups ?

Univariate and multivariate Cox proportional hazard regression model

Q What was the effect on all cause mortality ?

Those in than normalized testosterone had lower all cause mortality those untreated and those in whom testosterone was not normalized. Infact those in whom teststerone was not normalized too had a lower all-cause mortality than those who were not treated.

Q What about Myocardial infarction and stroke ?

Those with normalized testosterone had greater MI free survival and lesser incidence of stroke than the other two groups.

Q What was the limitation of Vigen et al study ?
Vigen included patients who came for coronary angiography and restrospectively checked if they took testosterone or not. There is a strong element of bias in the patient selection. Those who came for coronary angiography obviously had a strong CV risk to begin with.

Q What is the limitation of Finkle et al study ?

Finkle compared the risk of having a non fatal MI within 90 days of prescription of testosterone and compared it to the risk before they tool the testosterone. 3 month may have been too short a period to judge the effectiveness of therapy of testosterone and capture the outcome of interest.


Results from our present study suggest that in men without a history of previous MI or stroke who have low TT levels, TRT might be associated with decreased risks of MI, ischaemic stroke, and all-cause mortality in long-term follow-up.

Our study also highlights that TRT should aim for doses resulting in normalization of TT level as this was shown to be associated with reduction in adverse CV events.


The study tries to answer an important question – ‘Is testosterone replacement in elderly men safe ?’ We still donot have an answer to this and unlikely to have one till be have a robust randomized placebo control trial. However compared to other retrospective studies like Vigen and Finkle, this study is has more patient data with longer follow up. Also the point of normalization of Testosterone level is interesting. However this very point is controversial as well. There is now enough evidence for and against testosterone use in elderly, however we are far from having any conclusion.


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