Testosterone Replacement | November 2022 | Clinical Corner

November 1, 2022





Age related low testosterone is associated with aging as testosterone levels naturally decrease after the age of 30. The American Urology Association (AUA) has reported that two out of every 100 men deal with low testosterone levels. Testosterone therapy might seem like the ultimate anti-aging formula, yet the health benefits of testosterone therapy for age-related decline in testosterone aren't clear.



Evidence shows that men with age-related low testosterone may show small improvements in sexual functioning, however, evidence shows little to no improvement in physical function, depressive symptoms, energy and vitality, or cognition.1 This is contrary to what some urologists believe to be benefits of testosterone replacement therapy (TRT).


TRT has many risks including worsening sleep apnea, acne or other skin reactions, stimulating cancerous and noncancerous growth of the prostate (which is more of a theoretical potential due to lack of evidence),2 gynecomastia, testicular atrophy, and polycythemia. Thus, routine monitoring and cessation of treatment if no improvement in sexual function after 12 months is recommended.



  1. Monitoring for non-injectable preparations
    1. History and exam
      1. Follow-up at 3-6 months after initiation of therapy, and then annually if stable
  2. Monitoring for Establishing Injection Dose
  1. Total Serum Testosterone
    1. Obtain 3-6 months after starting therapy, then annually if stable
    2. Goal total Serum Testosterone level 400 to 700 ng/dl
  2. Complete Blood Count
    1. Obtain 3-6 months after starting therapy, then annually if stable
    2. Stop Androgen Replacement if Hematocrit >54%
  3. Prostate Specific Antigen (PSA) and Digital Rectal Exam (DRE)
    1. Indicated if older than age 40 years and baseline PSA >0.6 ng/ml
    2. Obtain PSA, DRE baseline and 3-6 months after initiation of therapy
      1. Refer to urology if >1.4 ng/ml increase within 12 months or prostate nodularity
  4. Bone Mineral Density
    1. Indicated in men with Osteoporosis or low mechanism fracture
    2. Obtain at 1-2 years after initiation of therapy
  5. Liver Function Tests
    1. If using oral Testosterone (which is not recommended)
  1. Serum Testosterone at one week post injection
    1. Level above normal: decrease subsequent doses
  2. Serum Testosterone at two weeks post injection
    1. Level below normal: increase injection frequency3



  • Testosterone therapy for age-related low testosterone is controversial and is considered off-label by the U.S. Food and Drug Administration.4
  • Testosterone therapy leads to small improvements in erectile and global sexual function in patients with age-related low testosterone levels but offers no other benefits.
  • Testosterone therapy is not recommended in men with age-related low testosterone to improve energy, vitality, physical function, or cognition.
  • Consider discontinuing therapy for age-related low testosterone levels unless sexual function improves.
  • Consider prescribing intramuscular over transdermal testosterone therapy because of identical benefit and much lower cost.


  1. J Clin Endocrinol Metab. 2018;103:1715-1744. [PMID: 29562364] doi:10.1210/jc.2018-00229
  2. https://www.acpjournals.org/doi/10.7326/M19-0882
  3. https://fpnotebook.com/Uro/Pharm/TststrnSplmntn.htm
  4. https://www.aafp.org/pubs/afp/issues/2021/0101/p60.html