Can an adult male receiving pembrolizumab (Keytruda) safely take testosterone replacement therapy?

Can You Take Testosterone with Keytruda?

Yes, testosterone replacement therapy (TRT) can generally be taken concurrently with pembrolizumab (Keytruda), as there are no documented drug interactions between these medications and the FDA label for Keytruda does not list testosterone as a contraindication. 1

Key Considerations

No Direct Drug Interaction

The Keytruda FDA label does not identify testosterone as an interacting medication or contraindication 1. These drugs work through entirely different mechanisms—pembrolizumab blocks the PD-1 immune checkpoint pathway 1, while testosterone acts as hormone replacement. There is no pharmacological basis for a direct interaction.

Clinical Context Matters

For men with documented hypogonadism (testosterone <300 ng/dL with symptoms):

• TRT is appropriate if clinically indicated, regardless of concurrent Keytruda therapy
• The 2020 American College of Physicians guideline recommends TRT specifically for improving sexual function in men with age-related low testosterone 2
• Recent cardiovascular safety data from the TRAVERSE trial (2023) demonstrated that TRT does not increase risk of myocardial infarction or stroke, even in high-risk patients 3

Prostate cancer considerations are critical:

• If the patient is receiving Keytruda for prostate cancer, TRT requires careful evaluation
• Recent systematic reviews (2026) show TRT does not increase biochemical recurrence in men with low-to-intermediate risk localized prostate cancer after definitive treatment 4
• However, TRT remains contraindicated in recurrent or metastatic prostate cancer outside clinical trials 4, 5

Monitoring Requirements

When combining these therapies, standard TRT monitoring applies 6, 2:

• Baseline and annual testosterone levels
• Baseline and annual hematocrit (TRT increases red blood cell production; Keytruda can cause anemia) 1
• Baseline and annual PSA in men ≥40 years 7
• Monitor for TRT-specific adverse effects: polycythemia, sleep apnea exacerbation, fluid retention 6
• Monitor for Keytruda-specific immune-related adverse events independently 1

Important Caveats

Hematologic overlap: Both medications affect blood counts but in opposite directions. Keytruda can cause anemia and lymphopenia 1, while TRT increases hemoglobin and hematocrit 6, 8. This may require more frequent CBC monitoring initially.

Immune considerations: There is no evidence that testosterone affects the efficacy or toxicity profile of immune checkpoint inhibitors. The one animal study examining pembrolizumab's effect on reproductive hormones 9 is not relevant to this clinical question, as it examined pembrolizumab's effect on ovarian function in female mice, not testosterone therapy in males receiving immunotherapy.

Cancer type specificity: If Keytruda is being used for melanoma, lung cancer, head and neck cancer, or other non-prostate malignancies, there are no oncologic concerns with concurrent TRT. The historical concern about testosterone "fueling" cancer growth is specific to prostate tissue 6, 5.

Practical Algorithm

1. Confirm hypogonadism diagnosis: Two morning testosterone levels <300 ng/dL plus symptoms 2, 7
2. Identify cancer type being treated with Keytruda:
   • If prostate cancer: TRT only if low-intermediate risk, post-definitive treatment, and shared decision-making completed 4, 5
   • If other cancer types: Proceed with standard TRT evaluation
3. Baseline labs: Testosterone, CBC with differential, PSA (if ≥40 years), liver function 6, 7
4. Initiate TRT using patient-preferred formulation (intramuscular is most cost-effective) 2
5. Monitor at 3-6 months, then annually: Testosterone level, hematocrit, PSA, symptom response 6, 7

The bottom line: There is no pharmacological or clinical reason to avoid TRT in men receiving Keytruda, provided standard TRT prescribing criteria and monitoring protocols are followed, with special attention to the underlying cancer diagnosis.