Testosterone Guidelines Issued on Diagnosis and Treatment of Hypogonadism

Addressing an age-related decline in serum testosterone is not clinically advisable whereas hypogonadism necessitates appropriately diagnosed medical intervention.

With John P. Mulhall, MD, and  Shalendar Bhasin, MD 

The American Urological Association (AUA) issued its first-ever guidelines on the evaluation and management of testosterone deficiency1 with near simultaneous release of updated best practice recommendations for testosterone therapy in men with hypogonadism2 from the Endocrine Society.

The guidelines, 1,2 published at nearly the same time by two different professional organizations—the Endocrine Society and AUA—were issued, at least in part, in response to the increased media focus on the dramatic increase in men seeking treatment for low testosterone. While a decline in serum testosterone is not a disease but a natural effect of a lower production from aging cells in the testes, prescriptions for supplemental testosterone jumped 29% in just one year (2001-2002).3

In fact, there has been a tripling of men receiving testosterone (T) treatment around the US, many of who do not have a bona fide testosterone deficiency.4  This occurred without sufficient evidence to refute or correct the trend.

Hypogonadism requires best practices before treating for low testosterone.

These Best Practices and Guidelines Reflect the Recent Increase in Research 

The Endocrine Society best practices update and the AUA guidelines concur on many key points,1,2 including:

  • Risk of cardiovascular disease from low testosterone.
  • Testosterone treatments do not cause prostate cancer.
  • Diagnoses of testosterone deficiency requires more than low testosterone, must include specific symptoms and signs.

“I think that direct to consumer advertising, increased patient awareness, and a reduction in the concern among urologists of prostate cancer risk have contributed to this increase,” said John P. Mulhall, MD, director of the Male Sexual and Reproductive Medicine Program at Memorial Sloan Kettering Cancer Center and lead author of the AUA guideline.1 “It’s concerning that about 20 to 25 percent of men who go on testosterone are not receiving a testosterone double-check first, and a percentage of these men are not getting their testosterone levels checked while they are taking testosterone.”

“There are many people on testosterone who shouldn’t be getting it, and a bunch more people who should have it but don’t receive it because physicians are worried about prostate cancer and cardiovascular events. This [disconnect] was the drive behind our issuing guidelines,” Dr. Mulhall told EndocrineWeb.

As far back as 2004, attention to the lack of research on the effects of T replacement for low levels in aging men and who might benefit was cited by the Institute of Medicine.4 For the Endocrine Society, this update came about in response to sufficient, well designed research to better inform clinicians.2

“In the last two to three years, a much higher quality of evidence has been published as the result of several large randomized trials ,5-8 , so we know more about efficacy than was available before,” said Shalendar Bhasin, MD, professor of medicine at Harvard Medical School, director of the Men’s Health, Research Program at Brigham and Women’s Hospital, in Boston, Massachusetts who led effort to update the practice guidelines for the Endocrine Society, “and there has been a wider availability of high quality assays for measuring testosterone and more effort in defining the reference ranges.”

Best Practices Reflect New Evidence for Proper Diagnosis of Low T

In making a diagnosis of hypogonadism, both professional organizations recommend that clinicians order two separate testosterone tests early in the morning on nonconsecutive days, using accurate assays and reliable CDC-approved laboratories.1,2

In addition, “Every patient with low testosterone should have a luteinizing hormone test (LH) to figure out the etiology of their low testosterone,” said Dr. Mulhall.  “It is not enough to say that they have low testosterone, we should be looking to see if the patient had pituitary or other issues.”

“There was an enormous concern about the inaccuracies and imprecision of testosterone assays put out by hospital labs and commercial vendors but now we have accurate assays, which has moved us towad a hormone standardization program with labs certified by the CDC providing essentially uniform values,” Dr. Bhasin said. "Due to these more accurate measurements, the lower limit in testosterone analysis is now 263 ng/dL compared to a less precise 300 ng/dL."

Similarly, both guidelines stress that a number indicative of a low testosterone must be combined with symptoms and signs of a testosterone deficiency in order to make a formal diagnosis of hypogonadism (as opposed to a natural decline in testosterone due to aging). Common symptoms include:

  • low sex drive
  • erectile dysfunction
  • loss of energy
  • reduced muscle mass
  • decrease in bone density
  • fatigue

Signs of a testosterone deficiency may include—testicular atrophy, muscle loss, osteopenia, osteoporosis, low trauma bone fracture, and elevated HbA1c. Yet, none of the existing screening tools for hypogonadism in older men (eg, Aging Males Suorvey scales, ADAM) provide sufficient specificity to support a clinical diagnosis or reliability in monitoring treatment.9

Testosterone deficiency in men presents with very specific signs and symptoms as a result of decreased testosterone production. It is really important that low testosterone is managed with an Food and Drug Administration (FDA)-approved treatment for a diagnosable condition,” 10 Dr. Bhasin told EndocrineWeb.

Conversely, “it should not be used to treat an age-related condition or symptoms that don’t qualify as a clinally verified testosterone deficiency.” Just treating a number or a symptom is not clinically useful for these patients, he added.

Resisting Patient Pressures; Best Approach to Clinical Care

“Our first message would be that testosterone deficiency is not just low T,” said Dr. Mulhall, echoing Dr. Bhasin, “It is low T combined with select symptoms and signs.”

Key endocrinology-related takeaways distilled from the AUA guidelines:1

  • Cardiovascular risk. It remains unclear whether low testosterone as a risk factor for cardiovascular events or not. “Giving a patient supplemental testosterone cannot be said definitively either to benefit or to put the patient at risk for a cardiovascular event,” said Dr. Mulhall. “There is conflicting literature so the best we can say that low T is not necessarily beneficial.”
  • Fertility. Men who may be trying to conceive should advised against taking testosterone because it appears to impair sperm production. “Even if the testosterone is stopped, there will be a period of time needed for sperm production to recover,” said Dr. Mulhall.
  • Prostate cancer. “There is no link between testosterone therapy and prostate cancer, but we cannot qualify the benefit of testosterone therapy for a patient with prostate cancer,” said Mulhall.  “We don’t say not to use testosterone with a prostate cancer patient, because there are populations of patients with prostate cancer who may benefit from being on testosterone. These are usually low grade, low volume cancers with an undetectable PSA and a favorable pathology.”

Based on the updated Endocrine Society guidelines,2 Dr. Basin shared the following highlights with EndocrineWeb:

  • Assess cause of deficiency. It’s extremely important to distinguish classical hypogonadism or testosterone hormone deficiency from age-related decline in testosterone, according to Dr. Bhasin. “If a patient has classic hypogonadism, the risks vs. benefits of testosterone treatment is very favorable.”
  • Limits to testosterone hormone replacement. “Note that the FDA has not approved testosterone treatments for men with age-related decline,” he said. “We don’t have a good understanding of risks and benefits of testosterone for anti-aging, especially risks from long term use of testosterone supplementation in older men.

    In fact, while methyltestosterone is on the market for oral administration to manage hypogonadism, a FDA drug advisory panel failed to endorse approval for two new oral testosterone formulations to treat hypogonadism in men earlier this year.
  • Use accurate assays. Rely on CDC labs and the Endocrine Society guidelines to diagnose a testosterone deficiency including confirmation of associated signs and symptoms, and consistently test lower testosterone on more than one occasion, said Dr. Bhasin.

Dr. Bhasin offered a final word of caution. “When treating patients, monitor for both safety and efficacy. It's not sufficient to write a prescription. There is an enormous variation in the metabolism and utilization of testosterone so getting patients’ levels into the target range requires attention, particularly with regard to possible prostate issues, erythrocytosis, and other potential side effects,” he said.

 

Continue Reading:
Higher Risk for Cardiovascular Events Found With Testosterone Injections Versus Gels
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