Testosterone Therapy and Adverse Outcomes

November 11, 2013
Testosterone Therapy and Adverse Outcomes Reference:  JAMA Nov 2013 Headlines on the morning news, “Men taking testosterone have up to 30% increased risk of adverse events from taking the testosterone”.   8700 men in the VA system with testosterone levels below 300 were treated with topical testosterone therapy.  They were then followed for an average of 531 days (not very long).  The rate of heart attacks and strokes were tabulated and the report published because the statistical findings were so remarkable.   Sounds like Testosterone therapy is  a dangerous thing, right?  30% increased risk in just 1 year and a half can’t be ignored. What’s going on?   I’m delighted to see this report.  I think it highlights some very important issues.  Here is my read.  If you Google low testosterone and mortality, it’s easy to find hundreds of references indicating trouble with “low T”. That’s what got the whole thing started.   The problem comes with method and measurement.  When you give a hormone topically, it goes into your lymph system.  Hormones, (testosterone, estrogen, progesterone, cortisol, Vitamin D) are all based on the fat molecule, cholesterol.  Fat doesn’t dissolve in water.  When those hormones are secreted, they last in the blood somewhere between 5-20 seconds.  Most of them are bound by a transport molecule called SHBG or Sex Hormone Binding Globulin.  This study was based on blood levels.  Prior to treatment most folks have an equilibrium between their blood and their lymph, because their bodies are doing what comes naturally and are in homeostasis.  The hormone is coming from the right place at the right time.  When you treat topically, you aren’t putting it into the blood, you are putting it into the lymph system which is outside the blood stream.  To get to blood levels that are high enough to keep people happy, you have to give very large doses. The normal human male makes about 6-12 mg of testosterone a day.  Giving  topical doses of 50-100 mg a day, which is common with the standard treatment regimens (not mentioned in this study), results in better blood levels, but unfortunately, you have bathed your body in very high total intracellular levels.  We should be measuring our hormones by salivary levels when we give topical doses.  An alternative route is to get 24 hour urine measurements of all the hormones your body makes to make sure you are getting the right dose and mix, because we find all the breakdown products, and what is happening to them. Do we get adverse effects from too much testosterone?  This is a very important insight, though not unexpected.  I suspect if we have you gobs of cortisol, we could show bad things happening.  (Anyone who has taken Prednisone for a while will concur.)  Imagine flippantly giving you way too much thyroid? WWW. What will work for me.   I’m changing my practice with this study.  I’ve been leaning to using a fixed dose of testosterone by shot because with a needle you ensure penetration of the skin, and you give an average of just 13 mg a day, roughly the right dose.  But should I use blood levels to check the dose.  I don’t think so.  This is just one study, but we should always react quickly when remarkable findings emerge when it makes sense, and a sensible alternative method exists. Pop Quiz
1.  If I search on Google for health outcomes and low testosterone, I find lots and lots of scary studies that show low T to be bad for men.  T or F
Very true. 2.   Testosterone and estrogen are easily measured in the blood because that's where we secrete the hormones to.  T or F False. They are fat based hormones and disappear in free form from the serum within 15-20 seconds, leaving tiny amounts behind.  Measuring those tiny amounts may be fraught with error. 3.   Measuring hormones in the serum and using that as a basis for replacement might result in overtreatment.  T or F Bingo 4.   Hormones do their work in the tissue, not in the blood.  Saliva levels reflect what's in the tissue much more accurately than blood levels.  T or F That's it in a nutshell.
5. The average man makes about 3-5 mg of Testosterone a day.  T or F
Want answers:  Dr Whitcomb can help you sort out this confusion at www.LiveLongMD.com

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