Q&A: Proper testosterone deficiency therapy starts with correct diagnosis

Testosterone deficiency — defined by the American Urological Association as a testosterone level of 300 ng/dL or fewer — occurs in as many as 39% of middle-aged and older U.S. men, data in Translational Andrology and Urology show.

Although an interest in the condition is growing among health care professionals, an understanding of it is not, experts said.

“Testosterone testing and prescriptions have nearly tripled in recent years,” the authors of the American Urological Association’s 2018 guidelines on testosterone deficiency wrote. “However, it is clear from clinical practice that there are many men using testosterone without a clear indication.”

Shivaraj Nagalli, MD, FACP, an internist at Shelby Baptist Medical Center in Alabaster, Alabama, said in an interview that testosterone deficiency is one of the most “misunderstood topics” among primary care physicians and internists.

In conjunction with Men’s Health Month, we asked Nagalli to discuss frequent misunderstandings regarding testosterone deficiency, risk factors for the condition, treatments and more.

Healio Primary Care: What are some common misperceptions about testosterone deficiency among internists, family physicians and primary care physicians?

Nagalli: The first misperception is that random one-time screening is indicated for men aged 65 years and older. However, the ACP and the European Society of Endocrinology recommend against routine screening for hypogonadism in asymptomatic men.

A second misperception is that all men who have low testosterone need testosterone therapy. It is important to remember that as men grow older, testosterone levels gradually decline 1% to 2% every year. This is why routine screening is not recommended and why not all patients who are found to have low testosterone levels need to be treated.

Testosterone deficiency can be due to a problem in the testes (primary hypogonadism) or somewhere else secondary hypogonadism.

Regardless of the type, hypogonadism’s symptoms such as fatigue, low energy levels and insomnia are not exclusive to testosterone deficiency. Therefore, the more common causes of these symptoms need to be ruled out before moving on to testosterone replacement. It is also important to note that testosterone levels fluctuate throughout the day and peak at around 8 a.m. As a result, it is best to measure these levels between 8 a.m. and 10 a.m. In addition, because oral glucose can alter the levels of testosterone, patients should fast before these levels are checked.

Healio Primary Care: What are some of the risk factors for testosterone deficiency?

Nagalli: Obesity, chronic alcoholism, as well as chronic use of opioids, anabolic steroids and gonadotropin-releasing hormone analogs are some of the risk factors for low testosterone levels. Testicular torsion, testicular trauma and history of radiation therapy to the pelvis can also lead to testosterone deficiency.

Healio Primary Care: Are there certain foods that contribute to testosterone deficiency? Which ones? How strong is the association?

Nagalli: There is limited evidence to suggest that foods such as tofu and other soy-based products, processed foods, licorice and those containing polyunsaturated fats decrease the levels of testosterone, as is chronic alcohol and opioid use. In addition, fried foods were associated with low testosterone levels in a study of patients with chronic kidney disease.

Healio Primary Care: What medical condition(s) are men with testosterone deficiency at higher risk for developing?

Nagalli: Low testosterone levels can result in low energy levels, decreases in libido and muscle mass, fractures with low impact trauma, gynecomastia and loss of axillary and pubic hair. Poor concentration and memory as well as insomnia are also possible. When the testosterone deficiency is due to primary hypogonadism, infertility may also be present.

Healio Primary Care: How should physicians treat testosterone deficiency in the primary care setting? What are the risks associated with treatment?

Nagalli: Management starts with confirming the diagnosis and evaluating its cause.

First, primary care physicians need to assess the clinical significance of the low testosterone levels. Are patients symptomatic? Does the patient have a constellation of symptoms, such as a decrease in libido and muscle mass, fractures with low impact trauma, gynecomastia, loss of axillary and pubic hair? Once the testosterone deficiency is confirmed, the next step is to check for LH, FSH levels and prolactin levels and to refer the patients to an endocrinologist. These patients will also need an MRI of the brain to check for prolactinoma.

Lifestyle modifications are recommended to help treat testosterone deficiency. In addition, testosterone can be replaced via transdermal routes (eg, testosterone gels) and parenteral routes (eg, testosterone enanthate or testosterone cypionate). The choice of therapy depends on patient preferences, costs and insurance coverage.

Once a pharmaceutical approach has been chosen, an assessment of the continued need for this medication should occur frequently. Testosterone levels should be checked every 2 to 3 months until the levels stabilize, with the goal of reaching about halfway between 300 ng/dL and 900 ng/dL for all men except those who are older. In older patients, a bit lower than halfway is more appropriate because of the risks associated with testosterone replacement.

The use of testosterone replacements is associated with risks for hypercoagulability, thromboembolism, CVD (myocardial infarction/ exacerbation of heart failure) and prostate cancer. The risk for suppression of spermatogenesis also exists.

Healio Primary Care: What is the ACP’s stance on testosterone therapy? In what ways do other medical societies’ guidelines differ? How can physicians reconcile these differences?

Nagalli: ACP suggests that men with age-related low testosterone may experience slight improvements in sexual and erectile function with testosterone replacement and, hence, this treatment can be considered. However, it does not recommend prescribing testosterone for men with less specific symptoms such as energy, vitality, physical function or cognition.

The Endocrine Society suggests offering testosterone on an individualized basis to older men who have symptoms and signs suggestive of testosterone deficiency and who have consistently and unequivocally low serum testosterone levels after explicit discussion of the potential risks and benefits.

The selection of candidates for testosterone therapy should be individualized to each patient by assessing the risks for testosterone replacement via a thorough discussion between prescribing physicians and their patients.

References:

Anaissie J, et al. Transl Androl Urol. 2017;doi: 10.21037/tau.2016.11.16.

Mulhall JP, et al. J Urol. 2018;doi:10.1016/j.juro.2018.03.115.

Unity Healthcare. June is men’s health month. https://www.unicityhealthcare.com/mens-health-month-bringing-awareness-mens-health-issues-month-june/. Accessed June 18, 2021.

Urology Care Foundation. Men’s health month. https://www.urologyhealth.org/media-center/mens-health-month. Accessed June 18, 2021.