Diagnosing Testosterone Deficiency in Men

Testosterone is the main male hormone and plays a significant role in a man’s health and wellbeing. Sometimes, men develop testosterone deficiency (TD) (or male hypogonadism), which can be caused by advancing age, medications (opioids), genetic disorders, obesity, and comorbid conditions like metabolic syndrome which can affect the hypothalamic-pituitary-testicular axis resulting in decreased testosterone production. TD often results in reduced libido, fatigue, depression, sexual dysfunction, body composition changes like increased body fat and/or muscle mass loss, and bone density changes, but symptomology varies from person to person.

Diagnosing TD is not always a straightforward process. Some health care professionals may feel uncomfortable diagnosing TD, especially due to concerns about prostate and cardiovascular health, steroid (synthetic testosterone) abuse, and the belief that declining testosterone levels are a natural part of the aging process. A 2013 nationwide Canadian study revealed that over 25% of the Canadian health care providers surveyed were not comfortable diagnosing and treating TD because of significant knowledge gaps related to the topic.

Several medical associations have created resources and guidelines for diagnosing and treating TD to support providers and address these knowledge gaps. According to the most recent TD guidelines from the American Urological Association (AUA), the Canadian Urological Association (CUA), and the Endocrine Society, there are several considerations a health care provider should evaluate when diagnosing TD, some of which have been compiled into the following list.

Essential Considerations for TD Diagnosis

• The above-mentioned medical societies recommend only diagnosing TD in men with low total testosterone levels and symptoms consistent with the common clinical manifestations of the condition. Possible TD symptoms include:
  • Decreased sex drive
  • Sexual dysfunction (including erectile dysfunction, delayed ejaculation, reduced ejaculate volume, decreased intensity of orgasm, and infertility)
  • Decreased energy or endurance
  • Changes in mood
  • Depression
  • Poor concentration or memory
  • Irritability
  • Loss of facial or body hair
  • Decreased muscle mass and strength
  • Decreased bone density
  • Increased body fat
  • Increased breast tissue development
• The current guidelines for establishing a TD diagnosis recommend combining the findings of a thorough patient history, a physical examination, and two serum total testosterone measurements.
• Experts agree that the best initial TD screening test is a morning fasting total testosterone draw; however, the cut-off point for diagnosis is variable. The AUA recommends using a total testosterone level of 300 ng/dL or below (on two separate occasions) as the cut-off for a TD diagnosis. The CUA suggests using 10 nmol/L (288 ng/dL) as the cut-off.
• When conducting a physical examination, the recommendation is for providers to focus on the parts of the body that may be affected by TD, including:
  • Testicles
  • Penis
  • Prostate (digital rectal examination to check for enlargement or abnormalities)
  • Facial and body hair
  • Breast tissues
  • Weight and fat distribution
  • Muscle mass
• Several validated screening questionnaires may help support a TD diagnosis, but they should not be used to replace a comprehensive patient history, physical exam, and serum testosterone testing. Providers may consider using the Androgen Deficiency in the Aging Male (ADAM), Aging Males’ Symptoms Scale, or the Massachusetts Male Aging Study Questionnaire to aid in the possible diagnosis of TD.
• For patients with a confirmed TD diagnosis, best practice guidelines suggest providers obtain a serum luteinizing hormone (LH) level to determine primary or secondary hypogonadism and consider a prolactin level to rule out prolactinoma if both LH and testosterone are low, particularly if testosterone is below 150 ng/dL. LH is a hormone that stimulates Leydig cells to produce testosterone. In primary TD, the testicles fail to produce testosterone, and in secondary TD cases, a hormonal problem with the pituitary or hypothalamus is causing the condition. Therefore, in TD patients:
  • An elevated LH level with a low to normal testosterone level points to primary TD (hypergonadotropic hypogonadism)
  • A low or normal LH level points to secondary TD, or central hypothalamic-pituitary defect (hypogonadotropic hypogonadism)

Resources:

Bhasin, S., Brito, J.P., Cunningham, G.R., Hayes, F.J., Hodis, H.N., Matsumoto, A.M., Snyder, P.J., Swerdloff, R.S., Wu, F.C., & Yialamas, M.A. (2018). Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline. The Journal of Clinical Endocrinology & Metabolism, 103(5), 1715–1744. https://www.endocrine.org/clinical-practice-guidelines/testosterone-therapy.

Grober, E.D., Krakowsky, Y., Khera, M., Holmes, D.T., Lee, J.C., Grantmyre, J.E., Patel, P., Bebb, R.A., Fitzpatrick, R., Campbell, J.D., Carrier, S., & Morgentaler, A. (2021). Canadian Urological Association guideline on testosterone deficiency in men: Evidence-based Q&A. Canadian Urological Association Journal, 15(5), E234-E243. https://cuaj.ca/index.php/journal/article/view/7252.

Mulhall, J.P., Trost, L.W., Brannigan, R.E., et al. (2018). Evaluation and management of testosterone deficiency: AUA guideline. J Urol, 200: 423. https://www.auanet.org/guidelines/guidelines/testosterone-deficiency-guideline.