What is the release profile and effects of intramuscular (IM) testosterone cypionate?

Release Profile and Effects of Intramuscular Testosterone Cypionate

Intramuscular testosterone cypionate (IM-TC) creates significant fluctuations in serum testosterone levels, with peaks occurring 2-5 days post-injection and returning to baseline by days 13-14, necessitating dosing every 1-2 weeks to maintain therapeutic levels. 1

Pharmacokinetics

• Testosterone cypionate is a less polar testosterone ester that is slowly absorbed from the lipid phase when injected intramuscularly, allowing for administration at intervals of two to four weeks 2
• The half-life of testosterone cypionate when injected intramuscularly is approximately eight days 2
• After a standard 200 mg IM injection, serum testosterone levels show a threefold rise with peak values occurring between days 2 to 5 post-injection 1
• Testosterone levels decline to basal levels by days 13-14 after injection, creating a "peak and valley" pattern 1, 3
• This pharmacokinetic profile results in periods of both supratherapeutic and subtherapeutic testosterone levels between injections 3

Dosing Regimens

• Standard dosing is 100-200 mg every 2 weeks or 50 mg weekly 3
• Weekly administration (vs. biweekly) provides more stable serum testosterone levels 3
• For monitoring purposes, testosterone levels should be measured midway between injections, targeting a mid-normal value (500-600 ng/dL) 3

Physiological Effects

Beneficial Effects

• Increases protein anabolism and decreases protein catabolism 2
• Improves nitrogen balance when sufficient calories and protein are consumed 2
• Stimulates production of red blood cells by enhancing production of erythropoietic stimulation factor 2
• Provides improvements in sexual function:
  • Small but significant improvement in global sexual function (SMD, 0.35 [95% CI, 0.23 to 0.46]) 3
  • Small improvement in erectile function (SMD, 0.27 [95% CI, 0.09 to 0.44]) 3
• May provide small improvements in objective physical function as measured by gait speed (SMD, 0.14 [95% CI, 0.02 to 0.27]) 3
• Associated with weight loss, improvements in fasting plasma glucose, insulin resistance, triglyceride levels, HDL cholesterol, lean body mass, and waist circumference in men with obesity and hypogonadism 3

Adverse Effects

• Hematological effects: Significant increase in hematocrit (from 42.7% to 46.6% after 4 months of treatment) 4
• Cardiovascular concerns: Some evidence suggests testosterone injections may be associated with greater risk of cardiovascular events compared to gels, possibly related to fluctuating testosterone levels 3
• Lipid profile changes: 21% depression of HDL cholesterol levels, with elevated total cholesterol/HDL-C ratios that persist for several weeks after discontinuation 5
• Hormonal effects:
  • Increases in estradiol (threefold rise between days 2-7 post-injection) 1
  • Suppression of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) 2
  • Decreased spermatogenesis through feedback inhibition 2
• Local injection site reactions: pain, soreness, bruising, erythema, swelling, nodules, or furuncles 3
• Other effects:
  • Testicular size and consistency often diminish 3
  • Fertility is greatly compromised during therapy 3
  • Fluid retention (uncommon and generally mild) 3

Monitoring Recommendations

• Initial follow-up at 1-2 months to assess efficacy 3
• Subsequent monitoring every 3-6 months for the first year, then yearly 3
• Measure testosterone levels midway between injections 3
• Monitor hematocrit/hemoglobin and PSA levels 3
• Assess for symptoms of sleep apnea, which can be exacerbated by testosterone therapy 3

Clinical Considerations

• IM testosterone cypionate is relatively inexpensive compared to other formulations 3
• Subcutaneous administration of testosterone may provide more stable serum levels compared to IM injections 6
• When comparing IM testosterone cypionate to subcutaneous testosterone enanthate, both provide significant increases in total testosterone, but subcutaneous administration is associated with lower post-therapy hematocrit and estradiol levels 7
• Intranasal testosterone gel does not significantly affect hematocrit levels compared to IM testosterone cypionate, which may benefit patients wishing to avoid polycythemia 4

Pitfalls and Caveats

• The fluctuating testosterone levels with IM injections may contribute to adverse effects 3
• Safety concerns regarding cardiovascular risk may be related to high-risk patient populations rather than the testosterone itself 3
• Monitoring should occur at appropriate intervals between injections to accurately assess testosterone levels 3
• FDA required a labeling change in 2015 to inform about possible increased risk of heart attack and stroke with testosterone preparations used for age-related hypogonadism 3