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Testosterone: Not an Anti-Aging Panacea

On the car radio, I have several times happened upon “infomercial” programs touting the benefits of testosterone replacement therapy for men, broadcast by doctors who specialize in prescribing the drugs. They have lots of wonderful stories about men who feel younger, happier, and more vigorous because of their macho remedies. It’s a tribute to the power of the placebo.

I have been reviewing John Brinkley’s goat gland scam for a presentation on medical frauds. In an era before the isolation of the hormone testosterone, Brinkley transplanted goat testes into human scrotums in an attempt to treat impotence and aging. We are more sophisticated today … but not much. Longevity clinics and individual practitioners are offering testosterone to men as a general pick-me-up and anti-aging treatment. Their practice is not supported by the scientific evidence.

Men’s testosterone levels drop as they age. According to a review article in the New England Journal of Medicine

the decrease in testosterone in men occurs moderately and gradually over a period of several decades. The serum total testosterone concentration decreases from a mean of about 600 ng per deciliter (20.8 nmol per liter) at 30 years of age to a mean of about 400 ng per deciliter (13.9 nmol per liter) at 80 years, although the range is wide at all ages. In one study, approximately 20 percent of men older than 60 years of age had total serum testosterone concentrations that were below the normal range for young men.
An essential but still unanswered question is whether this decrease in the testosterone concentration is physiologic, perhaps conveying a benefit, or pathologic, causing harm.

Other things happen as men age, and a simplistic, hopeful approach is to blame many of the consequences of aging on decreased testosterone levels and to use replacement therapy to bring the levels back to those of healthy youth. That approach is not science-based. Science only supports raising testosterone levels in patients who have specific problems attributable to abnormally low levels.

A recent article in JournalWatch reviewed the subject with reference to three new studies.

A July 2010 article in the NEJM by Wu et al. found that the only symptoms that correlate to low testosterone levels are poor morning erection, low sexual desire, and erectile dysfunction. Other psychological and physical symptoms correlated poorly with low testosterone levels. Total testosterone levels were sufficient for diagnosis; free testosterone levels did not add to diagnostic accuracy.

An article in the Journal of Clinical Endocrinology and Metabolism by Krasnoff et al.  found that total testosterone was not associated with mobility limitation, subjective health, or any physical performance measures, whereas free testosterone was associated with subjective health and some (but not all) physical performance measures. Low baseline free testosterone levels were associated with subsequent decline in mobility but not in subjective health. JournalWatch editor Dr. Alan Brett comments that this study

shows correlations between free testosterone and some measures of physical performance; however, findings were mixed, and significant associations in observational studies do not necessarily indicate cause-and-effect.

 

A third study by Basaria et al. published in the New England Journal of Medicine  studied older men with limitations of mobility to see if testosterone supplementation would improve mobility by increasing muscle mass and strength. This trial was stopped early because of a higher rate of cardiovascular events in the testosterone group compared to the placebo group.

The JournalWatch editor comments:

These studies — considered alongside other recent studies in which testosterone supplementation did not yield impressive results in frail older men or in healthy older men — argue against indiscriminate use of testosterone as an “anti-aging” drug. This conclusion is supported by a new practice guideline from the Endocrine Society.

Testosterone is not harmless. The Mayo Clinic website lists several adverse effects of testosterone: sleep apnea, elevated red blood cell count, heart disease, acne, benign prostatic hypertrophy, breast enlargement, reduced sperm production, and shrinkage of testicles. Mentioning a risk of testicular shrinkage in the infomercials would put quite a dent in sales, I imagine.

Meanwhile, Suzanne Somers recommends testosterone for everyone: both men and women. On the Oprah website, readers provide testimonials:

Just ask my husband who take [sic] testosterone daily thanks to Suzanne’s books.

The unsupported opinions of celebrities and longevity opportunists versus the evidence of science-based medicine: take your pick.

Posted in: Pharmaceuticals

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17 thoughts on “Testosterone: Not an Anti-Aging Panacea

  1. Citizen Deux says:

    But we want to live as youthful gods (and goddesses) forever! And we want to do it with only “natural” potions and herbs! We want to do it easily and effortlessly! We want to believe the Cenegenics advertisements and the celebrity endorsements. We want to have out modern myths!

    Almost no one wants to lose their youth. We are beset by preachers and proseyltizers of endless vigor. No one wants to read the instructions. Everyone wants a simple answer to complex problems (take this and stay young, don’t take vaccines and avoid [fill in the blank]).

    Life is hard, get a helmet and remember – there’s one born every minute.

  2. cervantes says:

    This is of course reminiscent of female hormone replacement therapy, which was originally touted as a fountain of youth and in particular youthful sexuality. Peter Conrad’s The Medicalization of Society tells a few such stories, would be worthy of a review here perhaps.

  3. Calli Arcale says:

    Reading the story of “Dr” Brinkley was what got me into quackery. Well, that and visiting places like the Bakken Library as a child. (They’ve got a number of vintage quackery items in their collection, which revolves around electricity and particularly early uses of electricity.) It’s a fascinating story of a man willing to push the limits of what he could get away with as far as he possibly could. That was, of course, ultimately his undoing — if he’d been more modest, he probably could’ve pursued his quackery for much longer, but his flamboyance and constant push to increase business eventually drew attention from regulatory bodies. He’s a large part of the reason why we have an FCC, which wouldn’t seem to have anything to do with quackery, but it does. Colorful character, colorful story. The real tragedy, of course, is that so many had to die before he could be stopped. (Forgiving the lunacy of transplanting goat glands and expecting them to do something useful in the absence of any sort of antirejection drugs, he paid no attention whatsoever to infection control, leading to a lot of deaths.)

    cervantes — it is indeed analogous to female hormone replacement, and it’s amazing how long the idea has been around.

    Dr Hall — another quack surgeon you may want to look at for your talk (unless you are running out of time) would be Serge Voronoff. He started off transplanting testicles and thyroid tissue of young animals into old animals (and monkey thyroid tissue into humans), but eventually had a good business in Paris transplanting monkey testicular tissue into men and monkey ovarian tissue into women. He was about the same timeframe as Brinkley.

  4. TsuDhoNimh says:

    The serum total testosterone concentration decreases from a mean of about 600 ng per deciliter (20.8 nmol per liter) at 30 years of age to a mean of about 400 ng per deciliter (13.9 nmol per liter) at 80 years, although the range is wide at all ages.

    How wide is the range? How many old geezers have levels above the 30-year olds’ mean level?

  5. impaktdevices says:

    Whenever I hear celebrities peddling some new miracle cure, I am reminded of all of the celebrities who used to peddle cigarettes…

  6. Prometheus says:

    This is reminiscent of the Human Growth Hormone (HGH) fad. Both HGH and testosterone levels decline with age, leading to the simplistic hypothesis that if the decline is prevented (or corrected), that aging will stop.

    This is analogous to the hypothesis that since your car’s paintwork fades with age, repainting the car will prevent the motor or transmission from aging.

    Here is another thing to consider. Humans live much longer than other primates of a similar size, even those primates that are most closely related to us (evolutionarily). Chimpanzees live an average of 35 years in captivity (with regular food and good medical care), with the oldest I could find living into its early 50′s. Gorillas have about the same lifespan.

    Although the research is not exhaustive, it appears that – in chimpanzees at least – there is not an age-associated decline in HGH and testosterone. This is often cited as an indication that the human experience of declining HGH and testosterone is abnormal.

    Another explanation might be that the reason humans live so long (average of 70+ years) is that their HGH and testosterone levels do decline with age.

    That is something that should be explored before giving HGH and/or testosterone to prevent (or reverse) aging. In fact, the data for testosterone “supplementation” suggest – as Dr. Hall mentions above – that it will reduce lifespan.

    Of course, one way to prevent aging is to die younger. But I don’t think that is what most people had in mind.

    Prometheus

  7. antipodean says:

    TsuDho Nihm

    I can’t remember the exact proportion from having analysed FT levels in a large study but there is a very large inter-individual variability in FT levels. Some men will have low levels of FT naturally with no ill effects and vise versa

  8. Jeff says:

    I haven’t researched this subject, but there are some doctors, like Harvard urologist Abraham Morgentaler who use testosterone replacement therapy in their practices.

    I haven’t read his book, only this profile and interview, in which he talks about TRT.

  9. qetzal says:

    There was an entertaining series of blog posts over at White Coat Underground a few months ago, discussing one Dr. John Crisler, who’s apparently very big on TRT. The good doctor himself shows up in the comments to defend his treatment regimen, but there’s a very bright aura of woo there. Lots of different special tests that are needed, lots of individually tailoring multiple aspects of the therapy, and grandiose claims of how much better it is than ‘conventional’ treatments. Predictably, Dr. Crisler’s claims are “supported” by lots of testimonials, articles in the lay press, videos, and presentations, but no peer-reviewed publications.

    Interested readers can check out Dr. Crisler, I fear for your medical soul and Dr. Crisler responds.

  10. rork says:

    Supplementary Fig 1 of the Wu paper does a good job of showing the range of total and free T in their population. Mean total was 16.5 nmol/liter, and maybe (eyeball measurements) 10-15% are below 10, and 20-25% above 20. They explicitly say that 2.5% are below 7.3 and 2.5% above 30.6.
    It appears one cannot obtain the damn data to be able to plot even the simplest things like Age vs. T – why does it have to be this way? This is in an area where the models used can be rather touchy, and those folks use some pretty fancy methods, so it seems like coughing up the data would be required. As it is, it is impossible for anyone else to demonstrate or even try to demonstrate anything different than whatever the authors chose to do.

  11. Werdna says:

    …and what’s with all this emphasis on youth anyway. When I was young I was an idiot I don’t miss those days. My wife even tells me that I look better at 40 than I did at twenty – but her opinion could be biased :)

  12. Dr. Joe says:

    Pretty amusing that a number of the references come from NEJM

  13. LMA says:

    Is this what they’re talking about in the new ads (not infomercials but ads like all the other prescription drug ads) with the tagline “ask your doctor about ‘Low Tee’”?

  14. GinaPera says:

    Nice job, Harriet.

    If you haven’t read Pope Brock’s book Charlatan, about he goat gland huckster, it is a rip-roaring read, documenting not only Briinkley’s fraudulent medical practice but also the “groundbreaking work” he did in radio evangelism, political demagoguery, and so much more. A sweeping panorama of American psychopathology in the 20th Century.

    Of course I’ll take science-based medicine over Suzanne Somers, but trouble is, sometimes science-based medicine wears blinders and that’s a problem.

    Supplementing testosterone without good reasons is dangerous indeed, for all the reasons you mention.

    But what about men whose testosterone is abnormally low? How many endocrinologists know that testosterone levels are affected by brain chemicals, and if the signals to manufacture testosterone aren’t sent, well, know which questions to askt? I’ve met a few well-regarded endocrinologists who haven’t gotten the memo that the brain is connected to the body — and vice-versa.

    Yes, a high-level neuroendocrinologist might know this — and might even be able to recommend a psychoactive medication or some type of supplement that could correct the low testosterone upstream rather than down, increasing endogenous androgens. Because somehow I doubt that low testosterone is the only problem. It might be just a symptom of other brain issues.

    For some individuals, the aging process means that dopamine receptors have kicked the bucket in larger numbers. Some are low on the dopamine side to begin with, and this die-off sends them over the edge.

    We know that many women with ADHD, for example, experience a profound heightening of cognitive deficits around perimenopause and menopause. Hormones. Neurotransmitters. It’s all connected.

    What’s tragic is when these women are given estrogen, creating unnecessary health risks, without ever considering dopamine-reuptake inhibitors (i.e. neurostimulants). Sometimes women might still benefit from estrogen’s cognitive enhancements, but if they also have ADHD, estrogen can be effective at a much lower, and thus safer, dose if combined with stimulants.

    One has to wonder if the same might be true for some men.

    Gina Pera, author
    Is It You, Me, or Adult A.D.D.?

  15. Chris says:

    Gina, read the second paragraph of this article. It starts off with “I have been reviewing John Brinkley’s goat gland scam for a presentation on medical frauds.”… and includes a link to her review of that book.

  16. GinaPera says:

    Thanks Chris, but I didn’t miss that sentence.

    “Reviewing John Brinkley’s goat gland scam” didn’t at all indicate a link to a book or a review. (There are other discussions of Brinkley.) So perhaps others missed the obscure reference, too.

    It’s just as well I mentioned the book, I think. The review mentions only one facet of Brinkley’s “career,” and the book covers so much more than that.

  17. Harriet Hall says:

    Gina Pera tells Chris she didn’t miss that sentence, and that it “didn’t at all indicate a link.” Whaaat?! It certainly DID indicate a link, in fact it WAS a link. The phrase “John Brinkley’s goat gland scam” was a hyperlink to my book review, and I can only suspect she recognized that and read the review, since she used the phrase “a rip-roaring read” which was the same wording I used in my book review. Also interesting that she criticizes my review for failing to mention other nonmedical facets of Brinkley’s career, since I specifically said “Apart from his medical adventures, he practically invented modern political campaigning techniques, revolutionized advertising, and was almost single-handedly responsible for popularizing country music and the blues with his radio station.”

    I don’t know if this represents an inability to read, a faulty memory, or some less innocent purpose. At any rate, I am not impressed.

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