Testosterone treatment raises levels of heart plaque

By Eric Barnes, AuntMinnie.com staff writer

February 22, 2017 -- A new study using coronary CT angiography (CCTA) reveals that testosterone treatments may increase the risk of heart disease by raising the volume of arterial plaque by 20% among men 65 years and older. More research is needed to assess actual risk, according to a February 21 paper in the Journal of the American Medical Association.

The multicenter trial, which followed 138 men in the U.S. National Institutes of Health (NIH)-funded Testosterone Trials (TTrials), aimed to determine if testosterone treatment could help improve a series of end points in older men, including walking ability, vitality, balance, mood, bone health, and blood counts. The results showed that men who received testosterone treatments for a year had significant increases in total coronary and noncalcified plaque volumes at CCTA -- while the increase was negligible in patients who had been given a placebo.

"It showed there was a 20% increase in plaque in those taking testosterone and just a couple percent increase in plaque in those taking a placebo," said lead author Dr. Matthew Budoff, a cardiologist and researcher from the Los Angeles Biomedical Research Institute, in an interview with AuntMinnie.com. "There was much more atherosclerosis progression in those taking testosterone therapy."

The results were the opposite of what the endocrinologists involved in the study had predicted -- that testosterone would somehow have a protective effect.

"Clearly that was incorrect," Budoff said.

Budoff's co-authors from several U.S. institutions included Susan Ellenberg, PhD; Dr. Cora Lewis; Dr. Emile Mohler III; Dr. Nanette Wenger; Dr. Shalender Bhasin; and Dr. Peter Snyder (JAMA, February 21, 2017, Vol. 317:7, pp. 708-716).

Supplement's inconclusive results

Testosterone replacement is being used with increasing frequency in aging men. Nevertheless, the cardiovascular benefits and risks of such supplementation have yielded conflicting results, the authors noted. Meta-analysis of several clinical trials showed no association between testosterone treatment and adverse events, but a clinical study of men with mobility limitations showed an excess of cardiovascular events with testosterone supplementation versus a placebo.

The Cardiovascular Trial of the TTrials aimed to test the hypothesis that testosterone treatment of older men with low testosterone actually slows progression of noncalcified coronary artery plaque volume. The 170 patients in the prospective trial were a subset of patients in the TTrials, which aimed to determine the efficacy of testosterone management of men 65 years and older with low testosterone.

While the TTrials looked at several end points for measuring the effects of testosterone supplementation, "there was no cardiovascular end point," Budoff said. "So I went to the NIH and I was able to get funding for our study that looked at about 170 men."

The participants had an average of two serum testosterone levels lower than 275 ng/dL. In all, 82 men were randomized to placebo and 88 to testosterone, applying either testosterone gel or a placebo gel for 12 months. The primary study outcome was noncalcified coronary artery plaque volume, as determined by CCTA acquired at baseline and again after the 12-month study period.

Of the 170 men enrolled, 138 (73 receiving testosterone treatment and 65 receiving placebo) actually completed the study with results analyzed. At baseline, 70 men (50.7%) had Agatston scores of 300 or higher, indicating severe atherosclerosis.

Rapid plaque growth

Testosterone treatment versus the placebo was associated with a significantly greater increase in noncalcified plaque volume from baseline to 12 months (p = 0.003), the authors concluded. In secondary outcomes, median total plaque volume again increased significantly from baseline to 12 months in the testosterone group but rose little in the placebo group (p = 0.003).

Finally, the median coronary artery calcification score changed from 255 to 244 Agatston units in the testosterone group, versus 494 to 503 in the placebo group (estimated difference, 27 Agatston units). No major adverse events occurred in either group.

Primary findings: Noncalcified plaque volume (mm3)
Outcome Placebo Testosterone Estimated difference, p-value
Baseline, median 317 204
Month 12, median 325 232
Change from baseline, unadjusted mean 4 40
Least squares mean 14 54 41, p = 0.003

Secondary findings: Total plaque volume (mm3)
Outcome Placebo Testosterone Estimated difference, p-value
Baseline, median 499 272
Month 12, median 541 318
Change from baseline, unadjusted mean 21 57
Least squares mean 28 75 47, p = 0.006

Among older men with symptomatic hypogonadism, a year of treatment with testosterone gel compared with placebo was associated with a significantly greater increase in coronary artery noncalcified plaque volume at CCTA, the authors wrote.

The testosterone and placebo groups weren't perfectly matched; in fact, the testosterone supplementation group started with less plaque but still progressed rapidly, Budoff said.

"So it remains a fairly remarkable finding but a very valid one given the results," he said, and it remained so when "we went back and did more reproducibility measures to prove that this was a real finding."

Looking at implications

Now that this study is being published, Budoff said he is hopeful that he can participate in substudies of larger testosterone supplementation trials that are currently underway, and potentially explore a number of interesting additional findings with further research. For example, there are well-known but not well-understood gender differences in heart disease.

"We have always presumed that women had less heart disease than men because of the protective effects of estrogen, but perhaps women have less heart disease than men because they have less testosterone," he said. "It's a really interesting question that might change our whole concept of heart disease in men and women when we get a better understanding of the pathophysiology of what's going on with the difference in genders."

Also, could the rapid rise in plaque among the men supplementing with testosterone have something to do with taking a group of 70-year-olds and supplementing heavily enough to restore them to the levels of much younger men?

"That might be overreplacing some of the necessary testosterone," Budoff said. "I'm not saying testosterone in all forms of replacement is bad, I'm just suggesting that making a 70-year-old into a 45-year-old again may not be the healthiest thing for the coronary arteries. And that's what our study suggests. There are some large-scale studies underway that will look at overall effect of testosterone supplementation on heart attack and stroke, and I think this study supports earlier data from the [Testosterone in Older Men (TOM)] trial showing some harm from taking testosterone."

Men may benefit from testosterone replacement
Male cancer survivors who develop testosterone deficiency after receiving radiation therapy and/or chemotherapy may benefit from testosterone replacement...
SPECT shows testosterone's path in grumpy old men
Andropause, a term used to describe the effects of sagging hormone levels in aging men, is of fairly recent coinage. Yet the effects of age-related hypogonadism...

Copyright © 2017 AuntMinnie.com

Last Updated np 2/22/2017 10:13:33 AM

21 comments so far ...
2/28/2017 5:59:49 AM
jeffrey dach md
Testosterone treatment raises levels of heart plaque. Surely You Must be Joking?

Problems with the JAMA Budoff Testosterone Plaque Study JAMA Feb 2017

Problem Number one:  if this was a truly randomized study, the starting calcium scores for treatment group and placebo group should be similar.  As you can see, they were very different (255 vs. 454) , suggesting some problem with randomization.

Second Problem: It is well known that heavily calcified arteries with high calcium score  cause streak artifact and technical difficulties obtaining accurate readings for non-calcified plaque.  This casts doubt on the results for soft non-calcified plaque.

Third problem:   The clinical relevance of coronary artery calcium score is well established, and it is in routine use. The clinical relevance of non-calcified plaque is controversial and it is not in routine clinical use.

Results Are Discordant: Calcium score and total plaque measurements should be trending in the same direction. They are trending in the opposite direction. Therefore, the results of the Budoff study are discordant and suspect.

Fourth Problem with Budoff Study:

Another red warning flag:  Dr Budoff is concluding from his study that testosterone increases plaque formation in men with coronary artery disease.  However, Dr Budoff reports in his study,  over 12 months of testosterone use, there were no cardiovascular events.

If Dr Budoff’s study was true, then this implies that Testosterone worsens coronary artery disease in males by causing more plaque formation,  more myocardial ischemia, more arterial occlusion, more myocardial infarction and increased mortality from heart disease.  As we can clearly see from a real life experience at two  Urology clinics over 8 years treating 77 males with known coronary artery disease, none of this actually happens as reported by Dr.Haider.(8)

In reviewing registries for 20,000 males receiving testosterone therapy, average age of 46, Dr. Robert Tan had this to say:”There was no evidence of worsening preexisting MI or stroke in patients treated with testosterone.”(9) Numerous studies show testosterone improves ischemic threshold in men with angina and improves quality of life (14-15)

In conclusion:

The Budoff study reports discordant results which are suspect for technical error. The study contradicts forty years of published data on Testosterone and Cardiovascular disease.  

For references see: http://jeffreydachmd.com/...-plaque-calcium-score/
jeffrey dach md

2/28/2017 6:50:49 AM
Dr. Joseph Mama
First thought:  "Guy must run a 'rejuvenation' clinic."    
Good gig?


2/28/2017 8:04:33 AM
Quote from Dr. Joseph Mama

First thought:  "Guy must run a 'rejuvenation' clinic."    


Good gig?

The 'manopause' racket.
- are you a bit fluffy
- hard time getting up from the couch
- wife isn't much fun anymore
--> You may have manopause
And for only a pile of money out of pocket we are going to turn you into a 22 year old college stud.

2/28/2017 8:35:53 AM
jeffrey dach md
Hi Dr. Joseph Mama, 

I am also a board certified diagnostic and interventional radiologist, so I suggest you address my comments above instead of engaging in ad hominem personal attacks.  Perhaps you can explain why you are defending Dr Budoff's flawed study which contradicts 40 years of published medical literature.
Number two, my clinic is not a "rejuvenation clinic".  We do not offer rejuvenation as a treatment program.  What we offer is no different from any other outpatient medical practice.  What we typically see in our office is a parade of difficult out-patient medical problems which have been ignored or missed by conventional medicine. The only rejuvenation we have in my office is the rejuvenation provided by a cup of coffee or a glass of water, both provided for free.
If prescribing testosterone to aging males is a defining feature of  running a "rejuvenation clinic", then your real target is the thousands of urologists doing just that in between laser TURPS. I apologize for any "insensitivity " here, as there is no disrespect to aging men in need of a TURP, as I may need one day as well.
from jeffrey dach md

2/28/2017 9:05:21 AM
Longevity or anti-aging medicine is a rapidly growing field which has made huge strides in the last few years.  Check out Calico Labs which is a lab funded by Google with a 1.5 billion backing for this purpose.  So there is nothing wrong with running a "rejuvenation" clinic if it is backed by scientific evidence.  It's also very insensitive to poke fun at older peoples problems as you may have them yourself one day and may not find it that funny at that time.  Note that I am too young to have these issues so speak from a position of sensitivity not experience.