Comparison of Outcomes for Hypogonadal Men Treated with Intramuscular Testosterone Cypionate versus Subcutaneous Testosterone Enanthate

J Urol. 2022 Mar;207(3):677-683. doi: 10.1097/JU.0000000000002301. Epub 2021 Oct 25.


Purpose: Intramuscular testosterone cypionate (IM-TC) is known to cause significant rises in estradiol (E2), hematocrit (HCT), and prostate specific antigen (PSA) due to its supraphysiological testosterone peaks, whereas a novel subcutaneous testosterone enanthate autoinjector (SCTE-AI) was designed with a lower testosterone peak-to-trough ratio to mitigate these reactions. We compare the total testosterone (TT), E2, HCT and PSA response to treatment with IM-TC versus SCTE-AI.

Materials and methods: A total of 234 hypogonadal men were treated with testosterone replacement therapy (TRT) via IM-TC 100 mg weekly or SCTE-AI 100 mg weekly. TT, E2, HCT and PSA levels were obtained at baseline and 12 weeks post-treatment. Significant differences in baseline and post-treatment levels were identified by univariate analysis. Linear regression models determined whether treatment modality was independently associated with post-TRT levels of TT, E2, HCT and PSA.

Results: Post-TRT, both cohorts had significant increases in trough TT compared to their baseline levels (IM-TC: 313.6 ng/dL to 536.4 ng/dL, p <0.001; SCTE-AI: 246.6 ng/dL to 552.8 ng/dL, p <0.001). After linear regression, type of TRT modality was not found to be associated with TT levels (p=0.057). SCTE-AI was independently associated with lower post-therapy E2 (p <0.001) and HCT (p <0.001). Neither TRT modality was associated with significant post-therapy elevation of PSA (p=0.965).

Conclusions: While IM-TC and SCTE-AI provide a significant increase in TT levels, SCTE-AI is associated with lower levels of post-therapy HCT and E2 compared to IM-TC after adjusting for significant covariates. SCTE-AI is an effective testosterone delivery system with a potentially preferable safety profile over IM-TC.

Keywords: drug delivery systems; hypogonadism; injections; intramuscular; subcutaneous; testosterone.

Publication types

  • Comparative Study

MeSH terms

  • Biomarkers / blood
  • Hormone Replacement Therapy / methods*
  • Humans
  • Hypogonadism / drug therapy*
  • Injections, Intramuscular
  • Injections, Subcutaneous
  • Male
  • Middle Aged
  • Prostate-Specific Antigen / blood
  • Testosterone / administration & dosage
  • Testosterone / analogs & derivatives*


  • Biomarkers
  • Testosterone
  • testosterone enanthate
  • Prostate-Specific Antigen
  • testosterone 17 beta-cypionate