Sub Optimal Testosterone Study from VA Hospital Exposes Veterans to Higher Risks

[Marco N Cognito]

Association of Testosterone Therapy With Mortality, Myocardial Infarction, and Stroke in Men With Low Testosterone Levels

http://jama.jamanetwork.com/article.aspx?articleid=1764051

"The absolute rate of events were 19.9% in the no testosterone therapy group vs 25.7% in the testosterone therapy group, with an absolute risk difference of 5.8% (95% CI, −1.4% to 13.1%) at 3 years after coronary angiography."

 

[Marco N Cognito]

guess this trumps the studies saying low t is bad for hearts

Low T IS a detriment to CV health. Low T (and E2) may be why my Lp(a) (a marker for atherogenesis) has risen lately.

The problem with these studies I posted are that they are one-sided and don't always take into account many other epigenetic factors that influence gene expression, etc. I think T is a modulator of pretty much all functions. In other words, you take too much, your risk of adverse events increases, you have too little, same thing. Dose dependent.

Hopefully Nelson will chime in here.

 

[Jerry Brainum]

The results of this study at first seem troubling, because they seemed to have taken into account variables, such as CVD risk factors that may have confounded the results of the study. On the other hand, if you look at the suspected causes of how testosterone therapy may cause CVD, you get a better picture of the effects. The authors note that testosterone therapy boosts levels of thromboxane-A, which promotes platelet adhesion and thus leads to increased vascular clotting effects. But what isn't mentioned is that prostacylin opposes the actions of thromboxane-A. Just using prophylactic aspirin at a dose of 80 milligrams favors an increase in prostacyclin over thromboxane-A. So this tells me that men on TRT should possibly consider using the 80 mg aspirin dose as a preventive, or some other method that favors prostacyclin over thromboxane. As for the DHT effect, that is more troubling. I've seen studies implicating DHT as a cause of future congestive heart failure, and it does stimulate smooth muscle proliferation in arteries, which is associated with atherosclerosis. The obvious cure for this would be to use a 5-alpha reductase inhibitor to control DHT production. But I'm aware that most of those who participate in this forum think that finesteride is a bad drug linked to impotence. I've known at least 40 men over the years who've used finesteride with no effect on sexual function, so I'm inclined to believe that any such effect is more idiosyncratic in nature. I'm not saying it doesn't happen, but it just doesn't happen to every man who uses the drug. I've seen posts on the TRT forum on ******** where men ask about how to actually boost DHT levels. I think this would be a mistake for those on TRT, as excess DHT I think may be the real culprit behind the relation of TRT to CVD.Also, there is no discussion of estrogen levels in the subjects. Elevated estrogen is a risk factor for CVD in men, and this may have confounded the results, as it did in the previous study that showed a connection between TRT and CVD. Finally, it's also important to note that the majority of studies that have examined the relationship between TRT and CVD has found only beneficial effects. However, most of them also show that low T is a definite risk factor for CVD onset.

 

[Nelson Vergel]

This study did not manage estradiol levels, hematocrit or optimized total and free testosterone levels.

Did you guys read this??? 40 percent of men did not have their testosterone levels checked after they started TRT. Most did not even reach 500 ng/dl. Pure malpractice!!

"Of the patients prescribed testosterone therapy, 734 patients (60.0%) had another testosterone value checked after starting treatment. These patients had a mean of 3.3 measurements. Among these patients, the baseline testosterone level was 175.5 ng/dL and increased to 332.2 ng/dL for the first repeat testosterone measurement."

 

[Jerry Brainum]

This study did not manage estradiol levels or optimized total and free testosterone levels.

Did you guys read this??? 40 percent of men did not have their testosterone levels checked after they started TRT. Most did not even reach 500 ng/dl. Pure malpractice!!

"Of the patients prescribed testosterone therapy, 734 patients (60.0%) had another testosterone value checked after starting treatment. These patients had a mean of 3.3 measurements. Among these patients, the baseline testosterone level was 175.5 ng/dL and increased to 332.2 ng/dL for the first repeat testosterone measurement."

If this is the case, then the increased CVD effects noted in the study once again prove that it's LOW testosterone that is the problem with CVD onset, rather than the converse.

 

[Nelson Vergel]

They should call the study

"Poorly Designed Study Exposes Men to Unnecessary Risks"

 

[Buddy Scott]

just wondering if this is the same article

http://news.msn.com/science-technology/testosterone-medications-linked-with-heart-attacks

I read it, and of course it is causing a lot of discussion at home

 

[Nelson Vergel]

You can make your own conclusions:

Of the 1710 outcome events, 748 men died, 443 had MIs, and 519 had strokes.

Of 7486 patients not receiving testosterone therapy, 681 died, 420 had MIs, and 486 had strokes. So, 21 percent of men not using testosterone had a cardiovascular event.

Among 1223 patients receiving testosterone therapy, 67 died, 23 had MIs, and 33 had strokes. So, 10 percent of men using testosterone had a cardiovascular event.

Most men used testosterone patches (which is no longer accepted as standard therapy due to suboptimal testosterone increases)

40 % were not retested for testosterone,so no one knows if they were taking testosterone and what their levels were after they started therapy. The treatment of these men did not follow recommended guidelines. Reference: How should doctors monitor men receiving testosterone replacement therapy?

Most men's testosterone only went up to 332 mg/dL (we consider this low in 2013 since we aim at total testosterone blood levels above 500 ng/dL). These men are considered to still be hypogonadal. Hypogonadism has been reported to increase cardiovascular events. Reference: Total testosterone over 550 ng/dL reduced the risk of cardiovascular events

Also, the study showed no estradiol and hematocrit monitoring or reporting. High estradiol and hematocrit can increase cardiovascular risks. Both parameters can be easily managed if monitored. Reference: Estradiol of < 21.80 pg/ml and > 30.11 pg/ml resulted in greater mortality in men

Under treating men with prior history of heart disease may be worse than not treating them at all. Most of these men with history of heart disease remained hypogonadal even on testosterone treatment (testosterone patches are no longer used since they are sub-optimal therapy). We have several references that link hypogonadism to increased cardiovascular problems.

This type of retrospective studies only sets back the field with poorly gathered data from suboptimal therapies that we no longer use due to their poor absorption. Luckily, the VA hospital system is probably now not mandating the use of patches as the main option for testosterone replacement in their medication formularies.
From the VA study:

"In the cohort of 8709 veterans with a total testosterone level less than 300 ng/dL who underwent coronary angiography, there was a high burden of comorbidities. Approximately 20% had a prior history of MI, 50% had diabetes, and more than 80% had CAD. Of the 8709 patients, 1223 (14.0%) initiated testosterone therapy after a median of 531 days (interquartile range [IQR], 229-894 days) following angiography. "

"Of the patients prescribed testosterone therapy, 734 patients (60.0%) had another testosterone value checked after starting treatment. So 40% were not retested. These patients had a mean of 3.3 measurements. Among these patients, the baseline testosterone level was 175.5 ng/dL and increased to 332.2 ng/dL for the first repeat testosterone measurement."

"Of the patients receiving testosterone therapy, 13 (1.1%) were prescribed testosterone gel; 436 (35.7%), injections; and 774 (63.3%), patches. The most common gel dispensed was testosterone 1% 5-g packets; injections, testosterone 200-mg/mL injections; and patch testosterone, 2.5-mg/24-hour patch. We did not detect a significant difference in the risk of adverse outcomes across the 3 testosterone formulations"

"The association between testosterone therapy use and adverse outcomes observed in this study differs from the association observed in a prior retrospective VA study. These discrepant results may be due to differences in the patient populations and methods used to control for confounding. In the study by Shores et al,28 investigators noted a 39% reduction in mortality risk among patients treated with testosterone therapy. The patients in that cohort had a lower incidence of heart disease (&#8201;~&#8201;20%) defined by angina, MI, CAD, coronary artery bypass graft surgery, percutaneous transluminal coronary angioplasty, or heart failure. This contrasts with our cohort in which more than 20% had a prior history of MI and heart failure, and more than 50% had confirmed obstructive CAD on angiography. "

"Once initiated, a patient was assumed to have continued treatment until an outcome event occurred or the end of follow-up. " But 40 percent of patients were not tested for testosterone after they started treatment.