What medications can be used to increase testosterone levels in patients with low testosterone?

Medications to Increase Testosterone Levels

Testosterone replacement therapy (TRT) is the primary medical intervention for increasing testosterone levels in patients with confirmed testosterone deficiency, with transdermal preparations (gels, patches) generally preferred as first-line options due to their steady pharmacokinetic profile. 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 of hypogonadism 1, 3
• Clinical symptoms warranting evaluation include:
  • Reduced energy, fatigue, depression, reduced motivation 1
  • Poor concentration, infertility, reduced sex drive 1
  • Changes in erectile function 1
• Free testosterone measurement is essential when evaluating patients with obesity or suspected binding protein abnormalities 1, 4

Available Testosterone Formulations

Transdermal Preparations

• Gels/Solutions (First-line option) 2, 5

  • Applied daily to skin of back, abdomen, upper arms, or thighs 3
  • Advantages: Easy application, good skin tolerability, steady hormone levels 3, 5
  • Disadvantages: Risk of transfer to partners/children, potentially higher cost 3
  • Examples: AndroGel 1% and 1.62%, Testim 1%, Fortesta 2%, Axiron 2% 3

• Patches 2, 5

  • Applied daily to dry, intact skin 3
  • Advantages: Easy application, no risk of transference 3
  • Disadvantages: Skin irritation at application site, poor patch adherence 3, 6
  • Example: Androderm 3

Injectable Preparations

• Short-acting injections 2, 5

  • Testosterone enanthate or cypionate administered every 1-2 weeks 3
  • Advantages: Relatively inexpensive, flexible dosing 3
  • Disadvantages: Requires injection, fluctuating testosterone levels 3, 5

• Long-acting injections 2, 5

  • Testosterone undecanoate administered every 10-12 weeks 3, 6
  • Advantages: Fewer injections, more stable hormone levels 3, 6
  • Disadvantages: Risk of pulmonary oil microembolism, restricted access in some regions 3

Other Formulations

• Subcutaneous implants (pellets) 2, 5

  • Implanted under skin, lasting 3-6 months 3, 5
  • Advantages: Long-lasting, stable testosterone levels 3, 5
  • Disadvantages: Requires incision, risk of extrusion or infection 3

• Buccal tablets 2, 5

  • Applied to gums twice daily 3
  • Advantages: No risk of skin-to-skin transfer 3
  • Disadvantages: Poor adherence, gum irritation, altered taste 3

Alternative Medications for Patients Desiring Fertility

• Human Chorionic Gonadotropin (hCG) 3

  • Promotes endogenous testosterone production without suppressing spermatogenesis 3
  • Particularly useful in secondary hypogonadism 3

• Selective Estrogen Receptor Modulators (SERMs) 3

  • Examples include clomiphene citrate
  • Increases endogenous testosterone production by blocking estrogen feedback 3

• Aromatase Inhibitors 3

  • Reduces conversion of testosterone to estradiol 3
  • May be useful in men with elevated estradiol levels 3

Monitoring and Follow-up

• Measure testosterone levels 2-3 months after initiating therapy and after any dose adjustment 1
• For injectable testosterone, measure levels midway between injections 1
• Once stable levels are achieved, monitor every 6-12 months 3, 1
• Target normal free testosterone levels rather than just total testosterone 1, 4

Contraindications and Precautions

• Do not use testosterone therapy in men with:
  • Breast cancer (active or history) 3
  • Desire for fertility (use alternative therapies instead) 3
  • Recent cardiovascular events (wait 3-6 months) 3
• Avoid alkylated oral testosterone due to risk of liver toxicity 3
• Use caution in men with severe lower urinary tract symptoms 3

Common Pitfalls to Avoid

• Initiating treatment based on a single testosterone measurement rather than confirming with two separate morning tests 1, 3
• Treating patients without confirming both low testosterone levels AND clinical symptoms 1, 3
• Relying solely on total testosterone without measuring free testosterone in patients with suspected binding protein abnormalities 1, 4
• Failing to consider lifestyle modifications (weight loss, physical activity) which can improve testosterone levels in men with obesity-related hypogonadism 3