What is the mechanism of action of testosterone (T) cypionate injection?

Mechanism of Action of Testosterone Cypionate Injection

Testosterone cypionate injection works primarily by replacing or supplementing endogenous testosterone, binding to androgen receptors where it is often reduced to dihydrotestosterone (DHT) in target tissues to initiate transcription events and cellular changes related to androgen action. 1

Pharmacological Mechanism

Testosterone cypionate functions through several key mechanisms:

1. Receptor Binding and Activation:

   • After injection, testosterone is absorbed slowly from the lipid phase at the injection site
   • In plasma, 98% of testosterone binds to sex hormone-binding globulin (SHBG)
   • The remaining 2% exists as free testosterone, which is the biologically active form
   • In target tissues, testosterone is often reduced to dihydrotestosterone (DHT)
   • The steroid-receptor complex translocates to the nucleus where it initiates transcription events 1

2. Pharmacokinetic Properties:

   • Testosterone cypionate has a half-life of approximately 8 days when injected intramuscularly 1
   • Peak serum levels occur 2-5 days after injection
   • Return to baseline levels typically occurs 10-14 days after injection 2
   • The ester (cypionate) makes testosterone less polar than free testosterone, slowing absorption 1

3. Metabolism and Excretion:

   • Approximately 90% of testosterone is excreted in urine as glucuronic and sulfuric acid conjugates
   • About 6% is excreted in feces, mostly in unconjugated form
   • Primary inactivation occurs in the liver
   • Testosterone is metabolized to various 17-keto steroids through two different pathways 1

Physiological Effects

Testosterone cypionate produces the following physiological effects:

• Anabolic Effects:

  • Increases protein anabolism and decreases protein catabolism
  • Improves nitrogen balance when sufficient calories and protein are consumed
  • Enhances muscle mass and strength
  • Reduces abdominal subcutaneous adipose tissue 2, 1

• Hematological Effects:

  • Stimulates red blood cell production by enhancing erythropoietic stimulation factor
  • Can cause erythrocytosis in up to 44% of patients receiving injectable testosterone 2, 1

• Endocrine Effects:

  • Inhibits endogenous testosterone production through negative feedback on pituitary LH
  • At large doses, may suppress spermatogenesis through feedback inhibition of FSH 1
  • Can increase estradiol levels through peripheral aromatization 3

• Sexual Function:

  • Improves libido and sexual function
  • Enhances nocturnal penile tumescence 4

Clinical Considerations

When using testosterone cypionate, be aware of:

• The "roller coaster" effect characterized by fluctuating testosterone levels between injections, which may affect mood and energy levels 2
• Potential for supraphysiological peaks that can lead to increased estradiol, hematocrit, and PSA levels 3
• Need for regular monitoring of hematocrit/hemoglobin, PSA, and cardiovascular risk factors 2

Common Pitfalls

• Failing to recognize the significant fluctuations in testosterone levels that occur with cypionate injections
• Not accounting for the delayed peak (2-5 days) when evaluating treatment response
• Overlooking the need for more frequent injections in patients who experience significant symptoms at the end of the dosing interval
• Not monitoring for erythrocytosis, which occurs in up to 44% of patients receiving injectable testosterone 2