In 2009, the manufacturer of Androgel began its “Is it Low T?” campaign, asking older American males to “man up” and consider testosterone therapy.
By 2012, the campaign’s TV ads were encouraging men to “step out of the shadows” and visit the company’s Low T website, where visitors could take a quiz and visually commiserate with images of other aging males who weren’t performing like they used to on the golf course, basketball court or bedroom.
And men responded to that call.
According to the Food and Drug Administration (FDA), 2.2 million men stepped out of the shadows in 2013 and asked for a testosterone prescription, up from 850,000 in 2010. (Aging being what it is, a significant number of those men suffered a minor but nagging orthopedic injury just by stepping out of the shadows. Careful now.)
Most of those men were between age 40 and 64, but 300,000 on both sides of that bracket gave it a try, too. Most stuck with the supplements for a few months and then quit.
As an English major and a physician, I found immense liberal-artsy pleasure in a testosterone therapy campaign that asked men to step out of the shadows, seeing that shadowy is exactly what defines the body of scientific literature investigating testosterone therapy in the aging male.
Let’s start with the black and white.
- As the name suggests, testicles make most of a man’s testosterone; a very small portion comes from the adrenal glands.
- On a daily basis, testosterone levels vary widely in every individual. There’s a large predictable peak in the morning, and then it bounces around at lower levels for the rest of the day, so much so that 15 percent of young healthy men will have a low testosterone level at some point during a 24-hour period. But it’s the peak that has been deemed the most important measure.
- Testosterone levels decline steadily as men age, although it’s not the base-jumping fall that women experience in menopause. Testosterone levels decrease about 1 to 2 percent each year after age 40.
- There are some areas where testosterone therapy is not at all controversial: in men with overt testicular failure due to trauma, cancer, mumps orchitis, or a genetic condition called Klinefelter syndrome. Or in men with an injury to “Gonad Central” — the pituitary gland — which sits at the base of the brain and sends hormonal signals that directly regulate testicular function. These men clearly require testosterone therapy, but they make up less than 1 percent of those on therapy.
That’s it for the black and white. The rest of it is kind of hazy, as I discovered when I began to read through the transcript from an FDA Advisory Committee meeting held in September 2014.
The committee was convened to investigate the appropriateness of the current prescribing patterns for testosterone therapy and to take a closer look at the potential for the drug to increase the risk of cardiovascular disease, such as heart attacks and strokes.
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The panel was populated with FDA officials and national-caliber experts from high-ranking academic institutions. A few gave expert testimony on behalf of the science, a few as paid consultants to the Low T industry. Others asked questions of presenters.
Whoever was speaking, the shadowy descriptives prevailed.
There were words like equivocal, unclear, inconclusive (treatment benefit is “tantalizing, but it’s inconclusive;” treatment risk is “concerning but inconclusive”), controversial, multi-factorial, inconsistent. And there were phrases like “we don’t know,” “not sure,” “may be considered” or “potentially deleterious.”
Recurrent sentiments like, “While these data have limitations and are not conclusive, they suggest a potential benefit,” put me face down in my laptop out of exasperation. And I stayed there: you can still see the outline of the command key on my forehead.
No Easy Answers
Here’s a list of what still lies in the shadows:
- What is a normal testosterone level supposed to be? Somewhere between 300 to 1,000 nanograms per deciliter (ng/dL). The width of the range tells you something about our understanding of this elusive hormone. And the level is not adjusted for age, even though it’s clear that levels fall over the years. Which raises the issue, is the decline a natural part of the aging process or a part of the problem?
- The symptoms of low testosterone (defined as under 280-300 ng/dL) — decreased energy, libido, mood, fitness, etc. — are non-specific and overlap greatly with the experience of aging. To that point, only 14 percent of the men who show up to enroll in testosterone therapy trials (presumably because they felt they had low T symptoms and could therefore benefit from being in the trial) are actually found to have low testosterone levels.
- The two most serious concerns with using testosterone therapy — potentially stimulating prostate cancer and heart disease — just happen to be very common problems in the aging male. There’s some solid science to suggest that testosterone therapy could trigger or worsen either, and the concern has led researchers to exclude participants with heart disease or prostate cancer from clinical trials for testosterone therapy. We worry about giving these men testosterone, and so we leave them out of the studies, but then how will we ever know how safe it is?
New Warning Label
The FDA Advisory Committee ultimately did decide to issue a label warning that testosterone therapy could increase the risk of having problems with heart disease and strokes. The T Trial, a large randomized controlled study sponsored by the National Institutes of Health, is now comparing testosterone to placebo in men 65 and older with low testosterone. It’s supposed to publish findings sometime this year; hopefully they will provide some clarity.
In the meantime, as a male doctor smack in the middle of that 40-64 age range, I’d recommend that if you’re considering testosterone therapy, you find a doctor who will make sure something else isn’t going on and who’ll check a couple of morning testosterone levels and a PSA (prostate test).
‘A Grand Experiment’
Shockingly, the FDA reported during the hearing that 28 percent of patients started on testosterone had not had a level checked; hopefully this is coming from strip-mall “Manly Man” clinics, and not from mainline physicians.
If you turn out to be low on the “T” and decide to start on therapy, understand that this is still a bit of a grand experiment and that you are now one of its subjects.
A little extra T could help you, and it might not. It could hurt you, and it might not.
How’s that for shadowy advice?
Dr. Craig Bowron is a physician and writer in St. Paul, Minn., whose articles have appeared in Slate, the Washington Post, Huffington Post, Minnesota Monthly and other publications.