Men and testosterone therapy have been a hot topic in the news recently.
Stories are filled with cautions about the use of testosterone therapy in men causing heart attacks and leading many doctors to question testosterone supplementation.A closer look at the study may provide more insight. The study released is referenced at the end of this post. (1)
This study looked at 55,593 men who started testosterone therapy. Some were over the age of 65 and a smaller number were under 65.
There are two important subgroups - those with cardiovascular disease and those without.
The study also looked at those not using testosterone and using phosphodiesterase type 5 inhibitors (e.g. sildenafil / tadalafil / Viagra). Essentially, the study was an analysis of insurance data.
This is what the study found:
Group 1 - Men > 65 years old with heart disease had 2 times increased risk of MI
Group 2 - Men > 65 years old without known cardiovascular disease (2,047) had 2 times increased risk of MI (8 cases)
Group 3 - Men < 65 years old with cardiovascular disease (n=4,006) had 2-3 times increased risk of MI (21 cases)
Group 4 - Men < 65 years old without known cardiovascular disease had no increased risk of MI
Group 5 - Men taking PT5I meds had no increase in MIs
What does this study tell us? What questions does it stimulate us to ask?
It tells us:
- A man's age may be more of an indicator of cardiovascular health than a patient's previous diagnoses
- Sexual activity alone is not the trigger for the increase in MI rates since there was no increase in MIs in men using circulation-increasing sexual performance drugs
- Men without known diagnoses of cardiovascular disease under the age of 65 are not likely to have an MI once starting testosterone therapy. This is important since this is the highest growing population of men starting to use testosterone
It makes us ask:
- What is it about starting testosterone that increases MI risk? Is it the increase in estrogen, produced when testosterone is metabolized by aromatase? Is it the change in cardiovascular tone? The increase in libido that stimulates more sexual activity than commonly seen with just PT5I medications?
- What happens to men after the initial 90 days if they continue on testosterone therapy?
- Does changing the way (mode of delivery - topical / injection / pellet / sublingual) we supplement testosterone change a patient's cardiovascular outcomes?
- Does dosage make a difference?
One of our clinical consultants on staff, Dr. Alison McAllister, has a few main takeaways from the study:
Cardiovascular disease is extremely common, and the fact that age was a better predictor in recognizing sub-optimal cardiovascular patterns is not surprising. I was surprised that men didn't have an increase in non-fatal MIs with PT5I medications; however, in my clinical experience these medications don't enhance libido, but rather facilitate erections. Therefore, men using testosterone who may or may not also use PT5I medications seem much more likely to want to have sex and therefore may be having more sexual encounters. I also think that men using testosterone are likely to increase physical activity in multiple ways - weight lifting, running, a faster pace of moving, etc. None of these studies looked at this information. However, years ago, there was a study (2) showing that men who used L-arginine after an MI had a higher rate of recurrent MIs. In that study, one finding was that men using MIs were much more active because they felt better and basically did too much.
I do think the role of estrogen and dosage is an important consideration. Giving testosterone in ways that does not increase clotting risks, coagulation, and causing changes in RBC counts, hemoglobin or hematocrit would very likely not increase the risk of MI. To this extent, I think one could make an argument for lower dose topical testosterone therapies combined with aromatase inhibitors. If physicians are continuing to dose testosterone topically at levels that change serum values, they are more likely to see changes in estrogen and blood indices before they see changes in serum testosterone levels. That is a much larger topic, but I've seen many men using testosterone topical gel at doses of 100 mg with low serum values and yet, estrogen levels are > 50, LH is suppressed, and RBC / hemoglobin / hematocrit are elevated, suggesting that low serum values are underestimating actual serum assimilation. Because this is not an uncommon prescription, I think it is likely that a large number of the men in the study were using this dosing protocol. In fact, this article did not break down the incidence of MI by dosage or route of delivery at all.
Where do I think we stand now? The way I interpret this information is to be extremely careful in giving testosterone to men over the age of 65. Discuss easing into more activities as they start to feel better rather than jumping into the life of an 18 year old. Dose at physiological doses, watch estrogen levels, and discuss what we don't know with patients. I don't see anything in this study that suggests testosterone is too risky for men to use or try, but I do think we need to be smart in having these discussions with men. I think it's very important to re-iterate that men under the age of 65 with no reported cardiovascular disease had no increase in MI. Perhaps, because they were more likely to be exercising and having sex regularly and less likely to aromatize their testosterone, there was less strain on their heart health. In this group, I think we can feel very comfortable talking to them about testosterone support.
These are all very important questions to ask in clinical trials. This is not the first study to suggest this information, but hopefully will stimulate more studies to try and determine the answers.
- Webinar: Practitioner's Guide to Physiologic Hormone Balance
- Blog: How to Convert Patients to BHRT from Conventional Therapies
- Blog: Testosterone Replacement Therapy - Assuring an Accurate Dose
(1) W. D. Finkle, S. Greenland, G. K. Ridgeway, J. L. Adams, M. A. Frasco, M. B. Cook, J. F. Fraumeni, Jr., and R. N. Hoover. Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PLoS ONE 9 (1):1-7, 2014.
(2) Schulman SP, Becker LC, Kass DA, Champion HC, Terrin ML, Forman S, Ernst KV, Kelemen MD, Townsend SN, Capriotti A, Hare JM, Gerstenblith G. L-arginine therapy in acute myocardial infarction: the Vascular Interaction With Age in Myocardial Infarction (VINTAGE MI) randomized clinical trial. JAMA. 2006;295(1):58-64.