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

Mechanism of Action of Testosterone Cypionate

Testosterone cypionate acts by binding to androgen receptors in target tissues, where it is often reduced to dihydrotestosterone, which then initiates transcription events and cellular changes related to androgen action. 1

Pharmacokinetics

Testosterone cypionate is a testosterone ester formulation with specific pharmacokinetic properties:

• It is less polar than free testosterone and is administered as an oil-based intramuscular injection 1
• After intramuscular injection, it is absorbed slowly from the lipid phase 1
• Peak serum levels occur 2-5 days after injection 2, 3
• Return to baseline levels occurs approximately 10-14 days after injection 2, 3
• The half-life is approximately 8 days 1
• It is typically dissolved in cottonseed oil (whereas testosterone enanthate is typically in sesame oil) 3

Metabolism and Distribution

Once in circulation, testosterone:

• Is 98% bound to sex hormone-binding globulin (SHBG) in plasma, with only about 2% in free form 1
• Is inactivated primarily in the liver 1
• Is metabolized to various 17-keto steroids through two different pathways 1
• About 90% is excreted in urine as glucuronic and sulfuric acid conjugates 1
• Approximately 6% is excreted in feces, mostly in unconjugated form 1

Cellular Mechanism

At the cellular level, testosterone's activity involves:

1. Binding to cytosol receptor proteins, often after reduction to dihydrotestosterone in many tissues 1
2. Formation of a steroid-receptor complex that is transported to the nucleus 1
3. Initiation of transcription events and cellular changes related to androgen action 1

Physiological Effects

Testosterone cypionate produces the following physiological effects:

• Growth and maturation of male sex organs (prostate, seminal vesicles, penis, scrotum) 1
• Development of male hair distribution patterns 1
• Laryngeal enlargement and vocal cord thickening 1
• Alterations in body musculature and fat distribution 1
• Retention of nitrogen, sodium, potassium, and phosphorus 1
• Decreased urinary excretion of calcium 1
• Increased protein anabolism and decreased protein catabolism 1
• Stimulation of red blood cell production by enhancing erythropoietic stimulation factor 1

Feedback Mechanisms

Important regulatory mechanisms include:

• Inhibition of endogenous testosterone release through feedback inhibition of pituitary luteinizing hormone (LH) 1, 4
• At large doses, possible suppression of spermatogenesis through feedback inhibition of pituitary follicle stimulating hormone (FSH) 1, 4

Clinical Considerations

When using testosterone cypionate, clinicians should be aware of:

• The "roller coaster" effect characterized by fluctuating serum testosterone levels between injections 2, 3
• Risk of erythrocytosis, which occurs in up to 44% of patients receiving injectable testosterone 3
• Potential for supraphysiologic testosterone levels shortly after injection, with levels declining to baseline by days 13-14 5

This pharmacological profile explains why testosterone cypionate is typically administered at intervals of 2-4 weeks, though more frequent administration may provide more stable serum levels 3.