What is the preferred formulation, injection or gel, for testosterone (testosterone) therapy in men with estrogen receptor-positive but human epidermal growth factor receptor 2 (HER2)-negative status?

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Critical Clarification: This Question Appears to Be About Male Breast Cancer, Not Testosterone Therapy

The question asks about testosterone formulations (injection vs gel) for men with estrogen receptor-positive, HER2-negative status—this terminology specifically refers to male breast cancer, not hypogonadism requiring testosterone replacement.

Testosterone Therapy is Absolutely Contraindicated in Men with Breast Cancer

Men with known or suspected breast cancer should NOT receive testosterone therapy in any formulation—neither injection nor gel. 1, 2, 3

Why This is an Absolute Contraindication

  • Testosterone can be aromatized to estradiol, potentially stimulating estrogen receptor-positive breast cancer cells and promoting disease progression or recurrence 4, 5
  • The FDA explicitly lists breast cancer as a contraindication for all testosterone products 3
  • ASCO guidelines for male breast cancer management specifically state that testosterone/androgen supplementation should not be used by men with breast cancer 2

The Correct Treatment Approach for These Patients

Men with hormone receptor-positive, HER2-negative breast cancer should receive endocrine therapy to BLOCK testosterone/estrogen, not supplement it:

First-Line Options for Advanced/Metastatic Disease:

  • Tamoxifen (most common first-line agent) 1, 2
  • Aromatase inhibitor PLUS GnRH agonist/antagonist (to suppress endogenous testosterone production) 1
  • Fulvestrant 1
  • CDK 4/6 inhibitors can be added to endocrine therapy as in women 1

Treatment Sequencing:

  • Endocrine therapy should be offered as first-line treatment except in visceral crisis or rapidly progressive disease 1
  • Men who progress on one endocrine agent should be switched to an alternative endocrine therapy 1
  • Treatment follows similar algorithms as in women with hormone receptor-positive breast cancer 1

If the Question Was Actually About Hypogonadism

If this question was mistakenly asking about testosterone replacement for hypogonadism (unrelated to breast cancer), the evidence shows:

  • Multiple testosterone formulations are available with selection based on clinical characteristics, availability, and patient preferences 1
  • No specific formulation (injection vs gel) is definitively superior in terms of efficacy for testosterone replacement 6
  • Both intramuscular and transdermal preparations effectively restore testosterone levels 6
  • The choice depends on patient preference, adherence considerations, cost, and side effect profile 6

However, this would be completely irrelevant for a man with breast cancer, where testosterone is contraindicated regardless of formulation.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Male Breast Cancer Management

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Testosterone Replacement Therapy in Females with History of Breast Cancer

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

MECHANISMS IN ENDOCRINOLOGY: Estradiol as a male hormone.

European journal of endocrinology, 2019

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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