What are the treatment options for low free testosterone levels?

Treatment Options for Low Free Testosterone Levels

Testosterone replacement therapy is indicated for men with consistently low free testosterone levels (<300 ng/dL on at least two separate morning tests) who also exhibit symptoms of hypogonadism such as reduced energy, fatigue, depression, reduced sex drive, or changes in erectile function. 1, 2

Diagnostic Confirmation

• Diagnosis requires both:

  • Consistently low testosterone measurements (<300 ng/dL) on at least two separate morning tests 1
  • Presence of clinical symptoms (reduced energy, fatigue, depression, reduced motivation, poor concentration, reduced sex drive) 1

• Free testosterone measurement is essential when evaluating patients with:

  • Obesity 3, 1
  • Suspected binding protein abnormalities 1, 4
  • Conditions that affect sex hormone-binding globulin (SHBG) 5, 4

Treatment Options

First-Line Options

• Transdermal testosterone preparations (gels, patches):
  • Preferred due to steady-state pharmacokinetics 1, 2
  • Apply to clean, dry, intact skin of upper arms and shoulders 2
  • Starting dose: 40.5 mg of testosterone daily (2 pump actuations or single 40.5 mg packet) 2
  • Dose can be adjusted between 20.25 mg and 81 mg based on response 2
  • Advantages: stable day-to-day testosterone levels, avoid discomfort of injections 3
  • Disadvantages: potential for transfer to others (especially children), skin irritation, variable absorption 3, 2

Alternative Options

• Injectable testosterone (e.g., testosterone enanthate):

  • Administered intramuscularly every 2-4 weeks 5
  • Advantages: less frequent administration, potentially lower cost than gels 3, 5
  • Disadvantages: fluctuating testosterone levels, discomfort from injections 3

• Implantable testosterone pellets:

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

Monitoring Therapy

• After initiating treatment:

  • Check testosterone levels at 2-3 months and after any dose adjustment 1, 2
  • For patients on injections, measure levels midway between injections 1
  • Once stable levels are confirmed, monitor every 6-12 months 1

• Dose adjustment criteria:

  • If pre-dose morning testosterone >750 ng/dL: Decrease daily dose by 20.25 mg 2
  • If pre-dose morning testosterone 350-750 ng/dL: No change 2
  • If pre-dose morning testosterone <350 ng/dL: Increase daily dose by 20.25 mg 2

Pre-Treatment Evaluation

• Measure luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to determine if hypogonadism is primary (testicular) or secondary (pituitary-hypothalamic) 3, 1
• Consider measuring serum prolactin to rule out hyperprolactinemia 1
• In obese patients, consider that:
  • Low total testosterone may be due to low SHBG 3, 1
  • Increased aromatization of testosterone to estradiol in adipose tissue can suppress LH secretion 1

Special Considerations

• FDA-approved indications for testosterone therapy include:

  • Primary hypogonadism: testicular failure due to conditions like cryptorchidism, orchitis, Klinefelter's syndrome 2
  • Hypogonadotropic hypogonadism: gonadotropin or LHRH deficiency or pituitary-hypothalamic injury 2

• Testosterone therapy has not been FDA-approved for "age-related hypogonadism" 2, 6

• Potential benefits of testosterone replacement in symptomatic men include:

  • Improved sexual function and libido 3
  • Increased well-being and energy 3
  • Increased muscle mass and strength 3
  • Improved bone density 3

Common Pitfalls to Avoid

• Relying solely on total testosterone without measuring free testosterone in patients with suspected binding protein abnormalities 1, 4
• Initiating treatment based on a single testosterone measurement rather than confirming with two separate morning tests 1
• Treating patients without confirming both low testosterone levels and clinical symptoms 1
• Failing to monitor testosterone levels after initiating therapy 1
• Not considering fertility implications in younger men - testosterone replacement can decrease spermatogenesis 7