Science, Simplified

Subcutaneous Testosterone Replacement Therapy (TRT): A Promising Alternative

Testosterone Replacement Therapy (TRT) is a common treatment for individuals with hypogonadism, a condition characterized by insufficient testosterone production. Traditionally, TRT has been administered via intramuscular (IM) injections, which can be associated with discomfort, inconvenience, and fluctuations in testosterone levels. However, recent studies have explored the feasibility and benefits of subcutaneous (SC) administration of testosterone esters as a method of TRT. This blog post provides an overview of key findings and considerations regarding SC TRT.

Stable Serum Testosterone Levels

One of the primary advantages of SC TRT is its ability to maintain stable serum testosterone levels. Traditional IM injections can result in supraphysiologic testosterone levels shortly after injection, followed by a decline over the course of the injection cycle. In contrast, SC injections lead to more consistent absorption and release of testosterone into the bloodstream, reducing fluctuations.

Testosterone Enanthate and Testosterone Cypionate

Studies have demonstrated the effectiveness of SC testosterone esters, such as testosterone enanthate and testosterone cypionate, in restoring serum total testosterone concentrations to the normal range. For instance, weekly SC injections of 50 to 100 mg of testosterone enanthate successfully restored serum testosterone levels in hypogonadal men, providing a reliable TRT option.

Testosterone Undecanoate

Testosterone undecanoate, an ultralong-acting ester, has been introduced as an option to minimize peaks and troughs in serum testosterone levels. While it is traditionally administered via IM injection, SC administration of testosterone undecanoate has been explored as a potentially safer alternative for long-term TRT. Studies have shown comparable pharmacokinetics between SC and IM routes for this formulation, suggesting that SC administration could be a viable method of TRT.

Serum Concentrations of Testosterone Metabolites

Research indicates that serum concentrations of testosterone metabolites, including 5-dihydrotestosterone (DHT) and estradiol, increase similarly regardless of the administration route (SC or IM) or ester type. SC injections of testosterone enanthate have also been associated with stable DHT and estradiol concentrations, which are important considerations in TRT.

Safety and Patient Preference in TRT

Safety remains a key concern with any form of TRT. While SC administration is generally associated with fewer local reactions and less pain compared to IM injections, mild local reactions have been reported. Systemic adverse effects observed with SC TRT are consistent with those associated with other routes of administration, highlighting the importance of proper monitoring and medical supervision.

Patient preference is an important consideration in TRT. Studies have shown that patients generally prefer the SC route due to its convenience, ease of self-administration, and reduced discomfort. Improving patient engagement in treatment decisions can promote adherence to TRT, ultimately leading to better outcomes.

Guidance for SC Testosterone Replacement Therapy

Patients opting for SC TRT should receive proper training on self-injection techniques. A typical starting dose for SC testosterone esters is 75 mg/week, with adjustments based on serum testosterone levels. Monitoring should continue as recommended by clinical guidelines to ensure the effectiveness and safety of TRT.


SC administration of testosterone esters offers a promising alternative to traditional IM injections for Testosterone Replacement Therapy (TRT). It provides stable serum testosterone levels, is well-accepted by patients, and can be self-administered with ease. While more extensive, long-term studies are needed to further evaluate its safety and effectiveness in TRT, SC TRT has the potential to improve patient adherence to treatment while maintaining comparable testosterone concentrations.

Please note that before starting any form of TRT, individuals should consult with a healthcare provider to determine the most suitable treatment approach based on their specific medical needs and conditions.

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