By Liam O'Neill, PhD
The September issue of Medical Care features two articles on the surge in testosterone (also called “T”) prescribing among middle-aged men and its possible implications for public health. Jasuja and colleagues examined the electronic health records (EHRs) of 111,631 males who were prescribed Testosterone Replacement Therapy (TRT) from a Veterans Administration (VA) outpatient clinic from 2009 to 2012 . Amazingly, the study found that only three percent of men who received TRT for the first time actually met the urological guidelines for hypogonadism. These results illustrate the complete disconnect between clinical practice and urological guidelines. In his editorial, Handelsman describes the TRT phenomenon as a "bubble" that is driven by direct-to-consumer advertising, offshore pharmacies, and the quest for corporate profits. What may be missing from the scientific debate on TRT is the "patient's perspective" -- or at least this patient's perspective -- which is at odds with the dire conundrum described in these articles.
The crux of the issue is this: what is the appropriate diagnostic threshold that would indicate an underlying pathology rather than an age-related functional deficit? In other words, how can we distinguish among patients who are "genuinely sick" versus those who may just be having a bad decade? The most commonly used diagnostic threshold is total T (tT) of less than 300 ng/dL. Consider that total T tends to decline as we age and that the average tT for an 85-year old male is 376. Thus, a 32-year old male with a tT of 325, would have lower T-levels than an 85-year old and would feel about as energetic. Yet his levels would still not be "low enough" to qualify for treatment with the only medicine that actually works for this condition. Even this scenario does not really convey the essence of what is at stake. To paraphrase Bob Dylan, “How does it feel?”
How does it feel?
One does not just wake up one morning with a T-level of 300, anymore than one goes broke on his 45th birthday. For such things take time. They are years in the making -- and the un-making. Programmed by evolution, the body will do whatever it takes to hold T-levels within a narrow range. If Plan “A” fails, there is always Plan “B”, Plan “C” and so on. This also can make diagnosis difficult. To reach a T-level that low means that every levy has been breached and every defense has been overwhelmed. It means the body has simply given up on trying to feel “normal.” And no amount of vitamins, over-priced "T-boosters," or herbal supplements will be enough to turn the ship around. Left untreated, this hypogonadal state increases the risk of every major comorbid condition, and according to some experts, the overall mortality rate from all causes is almost double that of healthy controls.
Just as a $400 check is not enough to lift one out of poverty, neither is a tT of 400 or even 500 enough to lift one out of the “gray zone” of androgen deficiency. For it leaves no margin for error and one's ability to cope with stressors is severely compromised. Simply put, nothing good ever happens to someone with T-levels that low.
Suppose that the Food and Drug Administration (FDA) were to implement a Draconian policy that limited TRT to only those patients who met the “ideal” criteria for androgen deficiency, which according to the VA study, included only three percent of all veterans who were prescribed TRT. This policy would ensure that thousands of patients with borderline T-levels and multiple chronic comorbidities would be denied access to a treatment that could greatly improve their quality of life. Neither would it prevent “false positives.” That is because long-term use of T will cause one’s endogenous production to shut down and drop below the diagnostic threshold. Moreover, such a policy would signify a return to the dark ages -- when one’s only source of T was some guy from the gym named Gunther.
If T-therapy were harming patients, there is no health care system that is better positioned to document those harms than the VA. If T-therapy caused prostate cancer or heart attacks, the VA would be all over it. Just as they were in the early 2000’s, when they first raised the alarm about Vioxx and heart attacks, well before the drug was finally pulled from the market in 2004. That TRT is so widely prescribed throughout the VA should speak volumes about both its safety and efficacy. A future study using the same dataset should measure the long-term impact of TRT on fasting blood sugar, cholesterol, PSA, and so forth. Such a study would go a long way toward resolving the current controversy.
Liam O'Neill is Associate Professor of Health Management at the University of North Texas School of Public Health in Fort Worth, Texas.