What are the recent FDA label changes for testosterone replacement products, including gels, patches, and injectable formulations?

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Last updated: October 3, 2026 • View editorial policy

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2015 FDA Labeling Change for Testosterone Products: Cardiovascular Risk Warning

In 2015, the FDA mandated a labeling change for all testosterone products to include a warning about possible increased cardiovascular risk (heart attack and stroke), particularly when used to treat age-related low testosterone, though subsequent high-quality evidence from the 2023 TRAVERSE trial has not supported this concern 1.

The Specific FDA Label Update

The FDA required manufacturers to add warnings to all testosterone product labels based on conflicting observational data available through 2014-2015. The key changes included:

  • Cardiovascular warning: Possible increased risk of heart attack and stroke with testosterone use
  • Indication restriction: Labels were modified to clarify that testosterone products are approved only for men with hypogonadism due to specific medical conditions (disorders of the testes, pituitary, or hypothalamus), not for age-related low testosterone alone 1

Context: Why This Change Occurred

The FDA action followed highly publicized concerns from observational studies suggesting cardiovascular risks, particularly in older men using testosterone for age-related decline 2. This created significant impact on clinical practice and public perception of testosterone therapy.

Critical Update: Post-2015 Evidence Contradicts the Warning

The cardiovascular safety concerns that prompted the 2015 label change have not been substantiated by subsequent rigorous research:

The TRAVERSE Trial (2023) - Highest Quality Evidence

The most definitive study addressing this question enrolled 5,246 men aged 45-80 years with confirmed hypogonadism (testosterone <300 ng/dL with symptoms) who either had preexisting cardiovascular disease or high cardiovascular risk. After mean follow-up of 21.7 months using transdermal 1.62% testosterone gel:

  • No increased risk of nonfatal stroke compared to placebo
  • No increase in major adverse cardiac events 3

Additional Supporting Evidence

Multiple subsequent studies have failed to demonstrate increased cardiovascular risk:

  • 23 studies published through June 2017 (12 clinical trials, 11 observational studies) showed no increased cardiovascular events with testosterone therapy 2
  • The Testosterone Trials (790 men ≥65 years) showed 9 major adverse cardiovascular events in the testosterone arm versus 16 in placebo 2
  • Large observational studies actually reported reduced cardiovascular events and mortality with testosterone therapy, with progressive risk reduction correlating with longer treatment duration 2

Formulation-Specific Considerations

The evidence suggests potential differences between delivery methods:

Transdermal preparations (gels, patches) may have better cardiovascular safety profiles than injections, possibly because:

  • They maintain more stable testosterone levels without supraphysiological peaks
  • Injectable formulations create fluctuations with time spent in both supraphysiological and subtherapeutic ranges between injections 1

Common pitfall: Some evidence suggested injectable testosterone carried higher cardiovascular risk than gels, but this may reflect patient selection bias rather than true formulation differences 1.

Current Clinical Implications

Despite the 2015 FDA warning remaining on labels, the weight of evidence—particularly the 2023 TRAVERSE trial—supports that:

  • Testosterone therapy does not increase stroke risk in appropriately selected men with confirmed hypogonadism 3
  • The American Heart Association/American Stroke Association 2024 guidelines state that "initiation or continuation of testosterone replacement therapy is reasonable and does not increase the risk of stroke" in men 45-80 years with confirmed hypogonadism 3
  • Multiple professional societies support testosterone use in appropriately selected patients despite the FDA label warning 1

Monitoring Requirements That Remain Important

Regardless of the cardiovascular controversy, all testosterone products require monitoring for:

  • Hematocrit: Check at baseline, 3-6 months, then annually; stop if >54% 4, 5, 4
  • PSA and prostate examination: Before treatment, at 3-6 months, then per age-appropriate screening guidelines 4, 5, 4
  • Testosterone levels: At 2-3 months after initiation to ensure mid-normal range (timing varies by formulation) 1, 4, 1, 5, 4

Formulation-Specific Safety Warnings on Current Labels

Beyond cardiovascular concerns, labels include warnings about:

  • Gels: Risk of transfer to women and children through skin contact; patients must cover application sites and wash before contact 4, 5, 4
  • Injectable testosterone undecanoate: Risk of pulmonary oil microembolism; restricted access in the United States 1
  • Patches: Skin irritation at application site 1, 4, 1, 5, 4

The 2015 FDA labeling change added cardiovascular warnings that have not been validated by the highest quality subsequent evidence, particularly the 2023 TRAVERSE trial, though the warnings remain on product labels.

References

1
Guideline

practical use of pharmacotherapy for obesity.

Gastroenterology, 2017

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