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Testosterone and Mortality

What is the best way to avoid death, Father Time and the Grim Reaper?

Eat your broccoli? Exercise like a wildman? Well, those are good, but one of the less obvious ways is the most important: avoid low testosterone like the plague. Yes, low testosterone can, quite literally, be the kiss of death for many men.

Think I'm exaggerating?  Well, one clear fact from the research about low testosterone is this: what you don’t know could kill you. Several studies are clear that if your T gets low enough, you are taking your chances. Let's look at some of research that demonstrates this by looking at what are called mortality, or death rates:

1.  Hypogonadal Seniors. One study found that hypogonadal senior men with total testosterone less than 250 ng/dl (8.5 nmol/l) were 33% more likely to die from all causes regardless of body weight and other traditional risk factors. [1] The reason for this? Most of the increased mortality comes from heart-related deaths. Low testosterone is a cardiovascular disaster, something that will be outlined below in more detail.

 

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2. All Middle-Aged and Senior Men. The relation of testosterone to death was  verified in yet another study where middle and senior aged men were grouped into quartiles and researchers found that mortality got worse in each quartile as testosterone was lowered. This "linearity" can be a strong verification of a theory’s veracity and researchers noted that men in the lowest quartile were a little over 40% more likely to die of all causes when compared to those in the upper quartile. Just what was the cutoff for the lowest quartile of testosterone in this study? It was 354 ng/dl (12.5 nmol/l). [2] Many of you reading this have testosterone at or below 354 ng/dl.

3.  Low Testosterone AND Low Estradiol.  It should be pointed that other research has pointed to even more dire results. One 2009 study found that when men with low testosterone also had low estradiol, they were twice as likely to die from all causes, a very steep risk factor by any standards. [3] The reason for this all-cause drop in mortality is primarily due to an increase in cardiovascular deaths. As you’ll see below, low T raises almost every major cardiovascular and arterial risk.

Now with the above studies one can't help but ask the question, "Why are so many doctors reluctant to prescribe HRT to men with low testosterone?  As you can see from #2 above, men appear to have greatly increased mortality rates at even 354 ng/dl.  How can a physician feel good about leaving a man hypogonadal when he knows it may put him at risk? 

Well, that's a big subject and one I'm not sure I still understand.  I guess the fear is that there is some inherent risk that will be discovered with testosterone therapy.  Perhaps it will affect some risk factor negatively that we have not yet noticed. Or may, for example, some of the testosterone methodologies raise estradiol levels too much.  Who knows? 

But consider the alternative:  leaving a man in a state of low testosterone makes him 2.7 times as likely to develop type II diabetes.  What be worse than this?  The elevated insulin levels and increase insulin resistance from being low testosterone are scary to say the least.

So let's ask another question:  "Why are testosterone and death so strongly associated?"  So far researchers have not found a big link between low testosterone and cancer, although it is possible something will be found in the future.  However, a big connection has been found between cardiovascular disease and researchers have little doubt as to causality.  The reason is that low testosterone has been shown to be so clearly linked with many heart disease-promoting conditions:

1.  Diabetes.  See my link on Testosterone and Diabetes.

2.  Elevated Insulin and Insulin Resistance.  See my link on Testosterone and Insulin.

 

3.  Erectile Dysfunction.  Few things are better for male health than sexual intercourse.  See my links on Testosterone and Erectile Dysfunction and Sex is Good for You.

4.  Osteoporosis. Low testosterone men surprisingly often suffer from bone-related issues, bone loss, osteopenia and osteoporosis.  See my link on Testosterone, Bone Loss and Osteoporosis.

5.  Depression.  Low testosterone men are at a greater risk for depression and anxiety.  See my link on Testosterone and Depression.

6.  Arteriosclerosis and Hardening of the Arteries.  This is just one of the many reasons that low testosterone is so hard on the cardiovascular system:  it stiffens the ol' arteries.

7.  Nitric Oxide and Blood Pressure.  Testosterone improves the activity of NOS, the very enzyme that Viagra and Cialis work on, and can exert (along with #2 and #6) a small but significant drop in blood pressure. See my link on Testosterone and Blood Pressure.

Testosterone Therapy (TRT) versus Anti-Androgen Therapy and Mortality

Some of you may be thinking that the only missing piece at this point are studies that show that testosterone therapy (TRT) decreases actual death rates.  If low testosterone is really as bad as the above indicates, then one should be able to give hypogonadal men testosterone and see their longevity increase and death rates decrease, right?  It turns out that this has been done just recently and the best study to date is quite optimistic:

8. 40+ Year Old Veterans.  Middle-aged and senior veterans on TRT were compared with those who are not and the researchers found that those on testosterone had lowered mortality rates.  Of course, the authors cautioned that larger sample sizes and followup studies were needed.  While that is always true, the results were so overwhelming that I am sure everyone took notice.  The authors wrote that "a mortality rate of 3.4 deaths per 100 person-years for testosterone-treated men" as compared with 5.7 deaths per 100 person-years in men not treated with testosterone." [4]  This is approaching double the mortality rate! [4]

9. Prostate Cancer Patients.  So, if giving low T men testosterone improves mortality rates, then wouldn't we expect the opposite to happen in men that were given anti-androgen therapy?  (Testosterone is sometimes lowered via GnRH therapy or orchiectomy, but the effect is the same.)  This is exactly what is (usually) seen in men with prostate cancer and a number of studies show an increase in cardiovascular mortality of 15-20%. [5]

 

REFERENCES:

1) [Endocrine Society 2007 Annual Meeting, Abstract 55-2, "Androgen Deficiency and All-Cause Mortality in Older Men: The Rancho Bernardo Study", http://www.medpagetoday.com/Endocrinology/GeneralEndocrinology/5861

2) Circulation. 2007; 116:2694-2701, "Endogenous Testosterone and Mortality Due to All Causes, Cardiovascular Disease, and Cancer in Men"

3) J Clin Endocrinol Metab. 2009 Jul;94(7):2482-8. Epub 2009 Apr 28, "Low Serum Testosterone and Estradiol Predict Mortality in Elderly Men"

4) J Clin Endocrinol Metab, 2012 Jun, 97(6):2050-8, "Testosterone treatment and mortality in men with low testosterone levels"

5) Circulation, 2010 Feb 16, "Androgen-Deprivation Therapy in Prostate Cancer and Cardiovascular Risk"

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