Issue: October 2018
October 18, 2018
3 min read

Should men with symptoms of low testosterone — but without hypogonadism — be prescribed testosterone therapy?

Issue: October 2018
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Healthy men who complain of symptoms of low testosterone — but without hypogonadism — should not be routinely prescribed testosterone therapy.

Kevin M. Pantalone

The definition of male hypogonadism varies, with different experts/societies/labs having different reference ranges for total testosterone. Generally, most experts would agree that a total testosterone level less than 250 ng/dL is considered low, whereas some experts endorse a higher level of around 350 ng/dL as the lower limit of normal. There are also additional ways of assessing for testosterone status beyond measuring total testosterone: free testosterone or bioavailable testosterone can also be measured. Each test has its own set of positives and negatives; ultimately, clinicians need to order the testing which they feel is most appropriate for a particular patient.

The symptoms of low testosterone are rather vague and non-specific and can be related to many other health conditions, such as obstructive sleep apnea, overweight or obesity, or a sedentary lifestyle. Evaluation of symptoms such as fatigue may note borderline-low testosterone values, and in a minority of cases, a trial of testosterone therapy may be considered, depending on the results of the overall evaluation. However, this should generally be an exception to the rule, rather than the rule.

Often, men who present with symptoms of hypogonadism are physically inactive, overweight or obese, have chronic medical conditions like type 2 diabetes and/or undiagnosed/untreated obstructive sleep apnea. In these men who are found to have normal testosterone levels, treatment should be directed at lifestyle modification. This may not only help them lose weight and become healthier, but also feel better. In addition, the symptoms of male hypogonadism can also be related to numerous other medical conditions, and a thorough evaluation needs to occur, not just an assessment of testosterone levels.

Testosterone therapy in hypogonadal men has benefits, but it also has risks. It can increase the risk for blood clots, and increase hematocrit levels, particularly if patients are treated to supratherapeutic levels (either intentionally or unintentionally). The CV safety of testosterone therapy also remains unclear. Thus, exposing many men to testosterone therapy, particularly those with established CV disease, who have normal testosterone levels, would not appear to be good practice.

Kevin M. Pantalone, DO, ECNU, FACE, is a staff endocrinologist and director of clinical research in the department of endocrinology at Cleveland Clinic. Disclosure: Pantalone reports he has received speakers’ fees from Astra Zeneca, Merck and Novo Nordisk; consulting fees from Eli Lilly, Merck, Novo Nordisk and Sanofi; and researcher funding from Merck and Novo Nordisk.



It is frequently said that the symptoms of low testosterone are nonspecific and, maybe, are not so critical. I disagree completely.

Abraham Morgentaler

Testosterone therapy has been considered controversial. Many physicians, led by endocrinologists, have taken an extremely cautious, conservative approach, believing testosterone therapy should be reserved only for those with severely low levels of total testosterone, and usually with identified causes. Personally, I believe that is a misguided approach.

The question in medicine always comes down to balancing benefits vs. harms. For many years, what held us back in prescribing testosterone therapy was that we could somehow precipitate the development of new prostate cancer, or, if there was a hidden cancer, we might cause it to grow more rapidly. Today, we know that neither of those is true, based on extensive studies. The risk seems very low.

We now have level 1 evidence that testosterone therapy has a number of benefits, including improving symptoms of low sexual desire and sexual activity, and improvement in mood. Just by itself, that is remarkable. What other medication, aside from antidepressants, helps with mood? Additionally, yes, many of my patents will also report a resolution of what they call “brain fog,” or an improved sense of wellbeing. The problem is there often is a bias against treating these men.

When a patient says, “I am not feeling right,” to simply dismiss those symptoms as “nonspecific” is a disservice. If you can identify a medical cause, it is treatable. As many as a quarter to a third of the patients I see who have low testosterone and have responded well to therapy have previously been seen by other doctors, often primary care or endocrinologists, and were told that their levels may be low, but they don’t merit treatment.

Who is a good candidate? The evidence now is really quite strong that it is free testosterone levels, not total testosterone levels, that matter. Additionally, the variability of sex hormone-binding globulin among men varies widely, and this influences total testosterone — but not free testosterone levels — greatly.

Total testosterone has become the gold standard measurement, even though it’s not terribly accurate. The recommendation is to treat or not treat based on sometimes very small differences in a test that doesn’t reflect what we’re dealing with at all.

Our more recent evidence explains why the blood test we’ve been using may not be the best indicator of a man’s androgen status. The way forward is by going back and considering the man as a whole and to recognize the variety of symptoms that are associated with low testosterone and the benefits of treatment. We need to stop being dismissive of symptoms that are incredibly important to our patients.

Abraham Morgentaler, MD, FACS, is the director of Men’s Health Boston and associate clinical professor of surgery at Beth Israel Deaconess Medical Center and Harvard Medical School.

Disclosure: Morgentaler reports he has received payments from Aceres and Aytu Bioscience.