Dr. Kumar’s Take
This review is important because it shows that how testosterone is given makes a difference. Injections increased lean mass and strength 3 to 5 times more than gels and patches did, and gels and patches did not improve leg strength at all. That means therapy decisions are not just about convenience, but about effectiveness. For men who need TRT primarily for muscle and strength, injectable routes may deliver the best outcomes.
Key Takeaways
✔ Testosterone injections raised fat-free mass by 5.7% versus placebo. Gels and patches raised it by 1.7%.
✔ Injections improved total body strength by 11.2%. Gels and patches improved it by 2.1%.
✔ Gels and patches did not improve leg strength. Injections improved it by 10.4%.
✔ Route of administration should be tailored to patient goals, tolerance, and safety.
Actionable Tip
If muscle mass and strength are a priority in testosterone therapy, ask your doctor whether injectable testosterone is right for you. Gels and patches may be easier to use but, in this analysis, gave a much smaller muscular benefit.
Brief Summary
This systematic review and meta-analysis pooled double-blind, placebo-controlled trials of testosterone in middle-aged and older men. The authors compared how much injections and skin-applied forms (gels and patches) each improved fat-free mass and muscle strength versus placebo. Injections produced gains 3 to 5 times larger than gels and patches on every outcome. These differences highlight the clinical importance of administration route selection.
Study Design
Researchers searched PubMed and the Cochrane register through March 2017 for double-blind trials that compared intramuscular or transdermal (gel or patch) testosterone with placebo for at least 8 weeks in men with an average age of 45 or older. Oral testosterone and dihydrotestosterone trials were excluded. Men did not need low testosterone to be included, though 13 of the trials enrolled men in the low range. Fat-free mass came from 31 trials (1,213 men on testosterone, 1,168 on placebo). Upper and lower body strength came from 17 trials. No trial compared the routes head to head. Each route was compared with its own placebo.
Results
- All routes combined: testosterone raised fat-free mass by 3.4% and total body strength by 6.1% versus placebo.
- Injections: fat-free mass up 5.7%, total body strength up 11.2%, leg strength up 10.4%, arm strength up 12.9%.
- Gels and patches: fat-free mass up 1.7%, total body strength up 2.1%, arm strength up 4.5%. Leg strength did not change versus placebo.
- In practical terms, the authors estimate a 90 kg man would gain about 5.1 kg of fat-free mass on injections versus about 1.5 kg on gels or patches.
- Men 60 and older showed the same pattern: fat-free mass up 7.3% with injections and 1.7% with gels and patches.
- One caution: most trials measured fat-free mass by DEXA, which also counts body water, and testosterone can add about 2 kg of fluid.
Why Route of Administration Matters for Muscle
The route of testosterone delivery affects blood hormone levels. Injections create higher peaks, which may stimulate muscle protein synthesis more effectively. Gels and patches provide steadier levels that stay in the normal range. The authors think these higher testosterone levels at least partly explain the larger muscle response to injections.
Related Studies and Research
Podcast: Testosterone Replacement Therapy Explained: Anchor episode on routes, dosing, and monitoring.
Subcutaneous vs Intramuscular Testosterone: Patient-preferred alternative with stable levels.
TRT and Sexual Function in Hypogonadism: Clinical data on sexual health and symptom relief.
Frequently Asked Questions
Why do injections work better than gels or oral testosterone?
Injections produce higher peaks in blood testosterone, which may better stimulate muscle protein synthesis. Gels provide steadier but lower levels. This review did not include oral testosterone, so it cannot rank oral forms.
Are injections the only option?
No. Gels and patches still raised fat-free mass and arm strength in this review, just by less. They can suit men for whom muscle is not the main goal. They may be more convenient and better tolerated.
Are injections riskier?
Injections may increase hematocrit more than other routes, which requires careful monitoring. The choice should balance goals, risks, and lifestyle.
How quickly do muscles respond?
The trials in this review lasted from 2.5 months to 3 years. The authors chose an 8-week minimum because gains in fat-free mass and strength are usually measurable within that time.
Conclusion
Not all testosterone replacement therapies are equal when it comes to muscle. In this review, injections increased lean mass and strength 3 to 5 times more than gels and patches, which did not improve leg strength. Oral testosterone was not studied. For men prioritizing physical performance and muscle health, the administration route should be a key part of the treatment decision.
