Table 2.
Formulations of exogenous testosterone replacement therapy
| Names | Strengths | Limitations | Comparative Efficacy |
References |
|---|---|---|---|---|
| Testosterone undecanoate | - Bypasses first-pass liver metabolism due to aliphatic side chain and is absorbed directly by the lymphatic system and then by blood | - Requires large and frequent dosing to mimic physiologic testosterone levels - Serum concentration difficult to predict due to high intra- and inter-individual variability - Risk of increased blood pressure and cardiac events |
A small but significant increase in systolic BP versus topical testosterone (gel or patch), A greater number of gastrointestinal-associated side effects compared to topical testosterone. (17) | Nieschlag 2015 (19), Nieschlag et al. 1975 (21), Swerdloff et al. 2020 (16) |
| Striant® | - Requires only 2x/day dosing to result in stable serum testosterone concentrations and mimics physiologic circadian rhythm release - Medication effects can easily be reversed due to easy access of tablets in the oral cavity |
- Side effects of local irritation, inflammation, or gingivitis in some patients | Superior to Androderm (74) Equal to AndroGel (81) | Tsametis & Isidori 2018 (20), Korbonits et al. 2004 (24), Dinsmore & Wyllie 2012 (25) |
| Long acting: Testosterone enanthate, Testosterone cypionate Extra-long acting: Testosterone undecanoate | - More lipophilic than other formulations allowing for extended storage, gradual release, and prolonged presence of testosterone in the blood - Requires fewer administrations – 2-4x/month (long acting) or 1-2x/2 months (extra-long acting) - Easy access - Cost effective |
- Pain associated with deep intramuscular administration - Fluctuations in energy, mood, and libido in many patients - Risk of pulmonary oil microembolism and anaphylaxis with extra-long acting formulation |
Equal to AndroGel (82) | Nieschlag 2015 (19), Tsametis & Isidori 2018 (20), Behre et al. 1999 (26), Fujioka et al. 1986 (27), Middleton et al. 2015 (28), Mackey et al. 1995 (29) |
| Gel: AndroGel®, Testim®, and Fortesta® Solution: Axiron® Patch: Androderm® | - Mimics physiologic diurnal release - Short duration of action, allowing for quick discontinuation - User friendly |
- Requires daily administration - High cost - Side effects of skin irritation and potential contact transfer to another person - Less effective in obese individuals |
AndroGel equal to Androderm (83) AndroGel equal to Depo Testosterone (82) AndroGel equal to Deletestryl (82) AndroGel Equal to Striant (81) Testim superior to Androderm (84) Testim superior to AndroGel (85) |
Tsametis & Isidori 2018 (20), de Ronde 2009 (30), |
| Testopel® | - Only requires implantation of pellets every 4-6 months - No risk of contact transference |
- Necessity for surgical procedure to implant sub dermally - Risk of pellet extrusion, infection, and fibrosis |
Tsametis & Isidori 2018 (20), Seftel 2007 (31), Kelleher et al. 1999 (32), Fennell et al. 2010 (33) | |
| Natesto® | - Decreased risk of transference due to inconspicuous site of application - Non-invasive and user-friendly - Increases testosterone, while maintaining FSH, LH, and semen parameters |
- Side effects of rhinorrhea, epistaxis, nasopharyngitis, sinusitis, and nasal scabbing | Maintenance of spermatogenesis in >95% of men, in contrast to injections or gels, Short duration of action, frequency of administration and clinical pharmacokinetic profile compared to long-acting testosterone injections, gels and pellets.(32) | Tsametis & Isidori 2018 (20), Gronski et al. 2019 (34), Masterson et al. 2018 (35), Kim et al. 2016 (32), MALE et al. 1990 (33), Rogol et al. 2016 (34), Rogol et al. 2018 (35) |