Meta-Analyses of the Risks, Benefits, Complications, Adverse events, and Outcomes Associated with Testosterone Replacement

Meta-Analyses of the Risks, Benefits, Complications, Adverse events, and Outcomes Associated with Testosterone Replacement

One would think that the cardiovascular and endocrine worlds would embrace this as a gamechanger for preventing both diabetes and CVD.

Not so.

Not only is this not the case but testosterone continues to be denigrated, chastised, ignored, and feared without any other reason than ignorance and confirmation bias.

Journal Club Findings

At the last journal club, Dr. Kadambi reviewed the most recent paper demonstrating the most recent long-term study demonstrating the benefit of testosterone. Over 8 years of study, in the placebo group there were 40% of men with prediabetes that went on to develop diabetes. Average weight gain was 9 kg in the placebo group. In the 200 men in the testosterone treatment group, no one went on to develop diabetes and 90% of men had a HgBA1C of less than 5.7 which put them in the normal blood sugar range and not requiring any diabetes meds. Average weight loss was 9 kg. The authors state that there were improvements in lipids, carbohydrate markers, waist circumference, and QOL. Finally, Sounds pretty darn good to me.

However, the author states: “This is not about treating the general population.” “We don’t want to run around giving people testosterone. Lord knows the world has enough testosterone.” “For anybody contemplating this kind of therapy, one has to balance the good with the bad, and testosterone we know can increase prostate size.” He added: “There’s a small fear that testosterone replacement could, say, enhance prostate cancer.” You have got to be kidding me??? They lost all credibility when they opened their mouths. Therefore webinar #8 is designed to dispel these myths.

In the above study, there was a 0.4% risk of MI, and a 5.7% risk of MI in the untreated group. The mortality in the testosterone group was 7% whereas the mortality in the placebo group for CVD was 16%. The authors emphasize that only men with true hypogonadism should be treat. But they note that long-term weight loss with diet and exercise is impossible to achieve, yet they don’t recommend testosterone for men unless they have TT levels of < 300. And what about all those studies that I  possess (over 30 papers) proving that testosterone given to non-hypogonadal men results in the same identical outcomes. All of these authors’ claims that testosterone should not be used unless men are hypogonadal are purely personal opinions and not evidenced based as so eloquently stated by Morgentaler.

Several of the papers’ authors made claim to the precautionary principle whereby benefits must be balanced with the risks.  The risks mentioned were, of course, the increase risk of blood clots secondary to polycythemia as well as the purported risk of testosterone enhancing the growth or incidence of prostate cancer. No RCT demonstrates or proves this. One would think that such authors would have read the literature and understand the plethora of data and studies (RCTs) demonstrating no increased risk of blood clots (except in worthless Grade D retrospective reviews of insurance data bases) and no increase risk of prostate cancer. However, authors always seem to throw in these caveats as if there was some real reproducible RCTs consistently demonstrating these harms. This a perfect example of seeing what one wants to see and ignoring all the data demonstrating the opposite.

The Final Part

It has been my endeavor to present all the data, studies, most influential, and most peer-reviewed prestigious articles that have been published on testosterone. Of the hundreds of papers that have been published and that I have stashed in my office, garage, car, bedroom, and kitchen table, I spent tremendous time sifting through those papers which I thought would be the most beneficial for attendees to have access to and have in their library. My commentary for each paper reviewed in the webinars was to enable attendees to become aware of the science behind the use of testosterone as well as become familiar with the controversies in order to defend the use of testosterone as well as be fluent and well versed in being able to discuss HRT topics with colleagues and patients. Nevertheless, our colleagues, peers, patients, zealots, and naysayers will continue to have a confirmation bias against the use of testosterone. I see it and experience this prejudice on a daily basis. It is fascinating/disheartening/outrageous/unbelievable that the medical community does not grasp the tremendous benefits, safety, and efficacy of testosterone. And thus, there will be one last webinar on testosterone in order to educate and prepare you to understand the negative bias against testosterone despite the tremendous safety and efficacy.

Recently one author suggested that testosterone should not be utilized due to the risks and harms. He went on to say that he can lower HgBA1C just as well with diabetes meds without the concerns and complications of testosterone.

What You Need to Know Before Prescribing Testosterone: Part 8 is devoted to this idiot.

I have chosen the top 5 papers from the last 10 years to review all the risks, complications, etc. It is my goal to review what’s on the other side of the coin. Rather, what is the (supposed) risk of testosterone in contrast to all the benefits. My intent is to teach everyone to become the experts in discussing pros and cons of testosterone. Any clinician that prescribes testosterone should/must be aware of these papers as well as be able to discuss/defend the use of testosterone. As usual, all these articles will be provided to add to your library. What you will not be able to place in your library is my critical, biased, and sarcastic dialogue as I review these papers which are meta-analyses of multiple studies. Reality is not consensus of negative opinions, rather it is EBM that should guide our therapy and allow us to prescribe testosterone with confidence and purpose, and without fear of harm or reprisal. This will be the last and best of the testosterone webinars with my original intent to teach you everything that you should know and master before prescribing testosterone.

Looking for more meta-analyses on testosterone, like if TR increases the risk for blood clots? Learn about BHRT Part II: Expand Treatment Options