Testosterone dependence: How real is the risk?

Men are being too easily enticed lately into ill-advised use of testosterone supplementation. Even men with only minimal, vague complaints are promised a hormonal fountain of youth and ageless virility. Many potential candidates seem to be under the misconception that “T” replacement will boost or energize their natural testicular production. In fact, exogenous testosterone suppresses testicular function.

Related - Men too often receive T for ‘soft’ indications

Before embarking on a trial of testosterone rejuvenation, men need to be made fully aware that, if and when they ever decide to discontinue testosterone supplements, their recovery from drug-induced “low T” may be highly symptomatic and prolonged. In some cases, testicular function may never return, even to its pretreatment baseline.

It is important to recognize that several authoritative sources dismiss the risk of profound withdrawal symptoms or long-term unwanted dependency. Prescribing information for each of the testosterone gel supplements reassures, “Drug dependence is not documented in individuals using therapeutic doses of anabolic steroids for approved indications” (see prescribing information, paragraph 9.3, on respective commercial websites). As yet, however, there have been no well-designed studies that assess the risk of long-term dependency on testosterone replacement therapy (TRT). As the adage has it, “Absence of proof does not constitute proof of absence.”

While little has been published in the medical literature regarding this risk, one recent multicenter review of the impact of testosterone therapy on subsequent fertility cautions, “Cessation of testosterone therapy may result in the restoration of baseline serum testosterone levels. However, these hypogonadal men may feel markedly symptomatic and desire higher serum testosterone levels” (Fertil Steril 2013; 99:718-24).

Meanwhile, online communications in the public sector are replete with warnings. Harry Fisch, MD, former director of the Male Reproductive Center of New York Presbyterian Hospital, warns nationwide viewers of "The Dr. Oz Show," “Many men are unaware that TRT shuts down a man's natural production of the hormone, often causing the testosterone-producing cells to stop working and his testicles to soften and shrink. If a guy suddenly stops taking testosterone after using it for more than a month or so, he's very likely to feel terrible-he could have low energy, low sex drive, be irritable, and even feel depressed. These withdrawal symptoms powerfully motivate guys to keep refilling their ‘T’ prescriptions!”

Francois Eid, MD, former director of the Sexual Function Center at New York Presbyterian Hospital, warns on his practice website, “Men often mistake the increased energy and improved mood they experience while using testosterone replacement as proof of its effectiveness. In reality, the steroidal nature of testosterone is what causes these changes. Once the treatment is stopped, men can experience withdrawal and severe depression, as well as the permanent inability to naturally produce testosterone."

An article in the Harvard Men’s Health Watch explains to subscribers, “Men get started on testosterone replacement and they feel better, but then it’s hard to come off of it… Men often feel a big difference when they stop therapy, because their body’s testosterone production has not yet recovered” (Harv Mens Health Watch 2014; 12:1,7).

In a New York Times Op-Ed column, “Don’t Ask Your Doctor About ‘Low T’,” John LaPuma, MD, warns readers, “Too many doctors are now writing testosterone prescriptions without even measuring the patient’s hormone levels, much less re-testing for confirmation and adjusting the dose after prescription. Up to a quarter of these prescriptions are dispensed without a blood test. From a psychological perspective, this isn’t helping men. From a medical perspective, it’s devastating. In addition to cardiac risks, prescription T can mean a permanent shut-off in men’s own, albeit diminished, testosterone production. In other words, once you start, you may well be hooked for life."

Next: How long is the slump?

More on Testosterone

Data fail to support concerns over T therapy, CV risk

Long-term data show no link between TRT, prostate Ca

Decision to use testosterone must be individualized

How long is the slump?

How profound and how long lasting is this slump? If a man no longer desires to be dependent on androgen supplementation, what price should he anticipate paying in terms of overall loss of vigor, as well as in loss of libido and sexual performance? For how long? What is the risk that a man, once he has initiated TRT (sometimes based only on a single, marginally low serum testosterone level) will then find that his endogenous testosterone production has been deeply and perhaps permanently impaired?

For men with clear, clinical indications of significant testicular hypofunction, TRT can be a life-changing intervention. Hormonal “dependency” for these men, like insulin treatment for diabetics, is therapeutic, not addictive.

Less certain, however, is the value, beyond placebo effect, of prescribing this treatment for men with marginal decreases in their serum testosterone levels. Even if recovery after cessation of TRT is eventually achieved, how many men would ever agree to begin a trial in the first place if made aware that they might have to suffer through 6 to 18 months or more of significantly worse symptoms, before endogenous testicular function returns? And that return would be not to an improved level, but merely to their marginal, pretreatment level, at best.

Dr. Eid offers these words of caution: “Unfortunately, extensive marketing from the pharmaceutical industry encourages the widespread use of testosterone replacement. The aggressive pressure they place on physicians to prescribe testosterone borders on medical irresponsibility. The long-term dangers of inappropriate testosterone use could be far more severe than we know today."

For the sake of a marginally low testosterone count, it may be that we are placing men who initiate TRT at risk of long-term, even lifetime suppression of their testicular function. Millions of men are receiving new TRT prescriptions each year. Even if only a small percentage prove to be susceptible to long-term dependency, the men so affected could represent a very large population, in terms of their absolute number.

Could it be that we are committing a large number of men, needlessly and unaware, to a lifetime of dependency on TRT? Hopefully not, but hoping is not good enough. We owe it to our patients to assess this risk objectively now.UT

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