From the Guidelines
Injection testosterone is generally preferred over topical forms due to its superior reliability in achieving consistent hormone levels and lower costs, as suggested by the American College of Physicians guideline 1. When considering testosterone replacement therapy, several factors influence the choice between injection and topical formulations.
- Injectable testosterone, such as testosterone cypionate or enanthate (typically 50-200mg every 1-2 weeks), delivers medication directly into muscle tissue, providing stable blood levels and more predictable results.
- Topical testosterone (gels, creams, patches) must be applied daily and can have variable absorption rates depending on skin condition, application technique, and environmental factors.
- Injections also eliminate the risk of transferring testosterone to others through skin contact, which is a significant concern with topical forms. However, injections require proper technique, may cause injection site pain, and involve regular needle use.
- Topical options might be better for patients who fear needles or prefer daily administration over periodic injections. The choice ultimately depends on patient preference, lifestyle considerations, and how well the individual responds to treatment, though injections typically provide more reliable testosterone levels for treating hypogonadism, as supported by a study comparing patient preferences and outcomes 2. Additionally, the annual cost of intramuscular formulation is significantly lower than that of transdermal formulations, according to the 2016 Medicare Part D Drug Claims data 3.
- The American College of Physicians suggests considering intramuscular rather than transdermal formulations when initiating testosterone treatment to improve sexual function in men with age-related low testosterone, due to the lower costs and similar clinical effectiveness and harms 1.
From the FDA Drug Label
Testosterone esters in oil injected intramuscularly are absorbed slowly from the lipid phase; thus testosterone enanthate can be given at intervals of two to four weeks. The main reason to use injection versus topical testosterone is the sustained release of the hormone, allowing for less frequent administration, in this case, every two to four weeks 4.
- The pharmacokinetics of testosterone esters, such as testosterone enanthate, enable slow absorption from the injection site, providing a prolonged effect.
- This prolonged effect is not typically achievable with topical formulations, which may require more frequent application.
From the Research
Comparison of Injection and Topical Testosterone
- The choice between injection and topical testosterone depends on various factors, including patient preference, lifestyle, and medical history 5.
- Topical testosterone gel formulations have been shown to restore testosterone levels to mid-normal physiological levels and alleviate symptoms of testosterone deficiency 6.
- Studies have compared the efficacy and safety of topical testosterone gel with intramuscular testosterone injections, with some showing that topical gel produces stable testosterone concentrations and improves quality of life 5.
Advantages of Topical Testosterone
- Topical testosterone gel formulations provide sustained physiologic concentrations of serum testosterone, reducing extraphysiologic variations in serum testosterone concentrations 5.
- Topical gel application can be more convenient and less invasive than intramuscular injections, with some studies showing improved patient-reported outcomes 6, 5.
- Topical testosterone gel can be applied to various anatomical sites, with some studies showing that application to the arms/shoulders results in higher testosterone levels 7.
Disadvantages of Topical Testosterone
- Topical testosterone gel formulations can pose a risk of secondary exposure, particularly to women and children 6.
- Some studies have shown that topical testosterone gel may not be as effective as intramuscular injections in achieving optimal testosterone levels, particularly in patients with more severe hypogonadism 8.
Injection Testosterone
- Injection testosterone, such as testosterone undecanoate, can provide a longer-acting formulation with fewer injections required per year 8.
- Studies have shown that injection testosterone can be safe and efficacious for the treatment of hypogonadal men, with a substantially lower frequency of administration compared to topical gel 8.
- However, injection testosterone can cause extraphysiologic variations in serum testosterone concentrations, which can lead to fluctuations in symptoms and side effects 5.