What are the treatment options for low free testosterone?

Treatment Options for Low Free Testosterone

Testosterone replacement therapy (TRT) is the primary treatment for confirmed low free testosterone, with transdermal preparations (gels, patches) generally preferred as first-line options due to their steady-state pharmacokinetics. 1, 2

Diagnostic Confirmation Before Treatment

• Diagnosis requires both consistently low testosterone measurements (<300 ng/dL) on at least two separate morning tests AND the presence of symptoms/signs 1
• Free testosterone measurement is essential when evaluating patients with obesity or suspected binding protein abnormalities 1, 2
• Clinical symptoms warranting evaluation include:
  • Reduced energy, endurance, and motivation 1
  • Fatigue and depression 1
  • Poor concentration 1
  • Reduced sex drive and changes in erectile function 1
  • Infertility 1

Treatment Options

1. Testosterone Replacement Therapy

• Transdermal Testosterone Preparations

  • Gels and patches provide steady testosterone levels day-to-day 3, 1
  • Advantages: Non-invasive, avoid discomfort of injections 3
  • Disadvantages: Potential skin irritation, variable absorption, higher cost, risk of transfer to others 3

• Intramuscular Injections

  • FDA-approved for replacement therapy in males with symptoms of testosterone deficiency 4
  • Can be given at intervals of two to four weeks 4
  • Advantages: Avoid daily administration, lower cost 3
  • Disadvantages: Fluctuating testosterone levels, discomfort of injections 3

• Implantable Testosterone Pellets

  • Offer longer-term treatment option 3
  • Disadvantages: Require procedure for implantation 3

2. Non-Testosterone Options

• Selective Estrogen Receptor Modulators (SERMs)

  • Clomiphene citrate has shown promise for raising testosterone levels 5, 6
  • Best suited for functional central hypogonadism 6
  • Note: Use is off-label and data supporting efficacy on symptoms are insufficient 6

• Human Chorionic Gonadotropin (hCG)

  • FDA-approved non-testosterone treatment option 5
  • Disadvantages: Expensive and requires patient-administered injections 5

• Lifestyle Modifications

  • Weight loss and exercise can raise endogenous testosterone production 5
  • Consider in men with obesity-related hypogonadism 3

Monitoring Therapy

• After initiating treatment, monitor testosterone levels at 2-3 months and after any dose change 1, 2
• For patients receiving testosterone injections, measure levels midway between injections 1
• Once stable levels are confirmed, monitoring every 6-12 months is typically sufficient 1
• Target normal free testosterone levels rather than just total testosterone 1, 2

Special Considerations

• Before initiating treatment, measure luteinizing hormone (LH) levels to determine if hypogonadism is primary or secondary 1, 2
• Consider measuring serum prolactin to rule out hyperprolactinemia 1, 2
• In patients with obesity, low total testosterone may be due to low sex hormone-binding globulin (SHBG) 3, 1
• Testosterone therapy should be avoided in patients with prostate or breast cancer, erythrocytosis, untreated obstructive sleep apnea, or severe heart failure 7

Common Pitfalls to Avoid

• Relying solely on total testosterone without measuring free testosterone in patients with suspected binding protein abnormalities 1
• Initiating treatment based on a single testosterone measurement rather than confirming with two separate morning tests 1, 8
• Treating patients with testosterone without confirming both low testosterone levels and clinical symptoms 1, 7
• Failing to monitor testosterone levels after initiating therapy 1