What is the most cost-effective form of testosterone replacement therapy (TRT)?

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Last updated: March 10, 2025View editorial policy

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From the Guidelines

The most cost-effective form of testosterone replacement therapy (TRT) is intramuscular testosterone injections, such as generic testosterone cypionate or enanthate, due to their lower cost and similar clinical effectiveness compared to transdermal formulations. According to the American College of Physicians guideline 1, intramuscular formulations are considerably lower in cost, with an annual cost of $156.24 per beneficiary, compared to $2135.32 for transdermal formulations. A standard regimen involves injecting 100-200mg every 1-2 weeks intramuscularly, usually in the thigh or gluteal muscle. Some patients find splitting the dose to twice weekly helps maintain more stable hormone levels.

  • Key considerations for TRT include:
    • Proper medical evaluation and ongoing monitoring of hormone levels, hematocrit, and prostate health
    • Patient preferences, with some studies showing that patients prefer injectable testosterone over gel-based regimens due to lower cost 1
    • Insurance coverage, which can vary significantly but may make any form of testosterone therapy more affordable
  • The injections are cost-effective because they bypass first-pass liver metabolism, allowing for less frequent dosing and better bioavailability compared to oral formulations.
  • It is essential to note that while cost is an important factor, it should not be the only consideration when choosing a TRT option, and individual patient needs and preferences should be taken into account.

From the Research

Cost-Effectiveness of Testosterone Replacement Therapy (TRT)

The cost-effectiveness of TRT can be evaluated based on the available forms of treatment and their respective administration frequencies.

  • Intramuscular injections of testosterone esters, such as testosterone enanthate, are commonly prescribed and have been shown to be efficacious in improving bone and muscle mass 2.
  • However, these esters have unfavorable pharmacokinetics, resulting in fluctuations in mood, energy, and sexual function, and require frequent injections every 2-4 weeks 2.
  • Long-acting injectable testosterone undecanoate (Nebido) has been developed to address these issues, with a more favorable pharmacokinetic profile and less frequent administration (every 3 months) 2, 3.
  • Hydroalcoholic gel containing 1% testosterone has also been shown to be effective and has a higher grade of patient satisfaction, with daily application delivering sufficient amounts of testosterone to restore normal hormonal values 3.
  • Subcutaneous administration of testosterone esters has gained popularity due to its ease of self-administration and potential for improved patient adherence 4.
  • A study comparing the safety of subcutaneous vs intramuscular administration of testosterone esters is desirable, but available evidence suggests that subcutaneous testosterone therapy results in comparable pharmacokinetics and mean serum testosterone levels 4.

Comparison of TRT Forms

The following forms of TRT have been compared in terms of their cost-effectiveness:

  • Intramuscular injections of testosterone esters (e.g., testosterone enanthate)
  • Long-acting injectable testosterone undecanoate (Nebido)
  • Hydroalcoholic gel containing 1% testosterone
  • Subcutaneous administration of testosterone esters
  • Oral testosterone formulations (e.g., oral undecanoate T) have been shown to have variable absorption and poor bioavailability due to the first-pass effect of the liver 3, 5.

Most Cost-Effective Form of TRT

Based on the available evidence, intramuscular injections with testosterone esters are the most inexpensive modality, but they are difficult to self-administer and associated with some discomfort 4.

  • Subcutaneous administration of testosterone esters may be a more practical and reasonable option, with easier self-administration and less discomfort compared to the intramuscular route 4.
  • Long-acting injectable testosterone undecanoate (Nebido) has a favorable pharmacokinetic profile and less frequent administration, which may improve patient compliance 2, 3.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Testosterone therapy--what, when and to whom?

The aging male : the official journal of the International Society for the Study of the Aging Male, 2004

Research

Testosterone Therapy With Subcutaneous Injections: A Safe, Practical, and Reasonable Option.

The Journal of clinical endocrinology and metabolism, 2022

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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