In patients on testosterone replacement therapy (TRT) who report testicular atrophy, what treatment options are available?

Treatment for Testicular Atrophy During Testosterone Replacement Therapy

For patients on TRT experiencing testicular atrophy, the most effective treatment is to add human chorionic gonadotropin (hCG) therapy, which directly stimulates the testes and can restore testicular volume while maintaining testosterone levels. 1, 2

Understanding the Problem

Testicular atrophy on TRT is extremely common and predictable:

• Approximately 73% of men on testosterone therapy will experience testicular shrinkage at some point during treatment 3
• Testicular volume typically decreases by 16-23% after 4 months of weekly or biweekly testosterone injections 4
• The shrinkage occurs because exogenous testosterone suppresses luteinizing hormone (LH) secretion through negative feedback on the hypothalamic-pituitary-gonadal axis, and without LH stimulation, the Leydig cells atrophy 3, 4
• Injectable testosterone causes more severe testicular atrophy than transdermal preparations, with 22% of men maintaining suppressed LH levels throughout treatment 3

Primary Treatment Option: Add hCG Therapy

hCG is the only FDA-approved non-testosterone treatment for hypogonadism and works by mimicking LH to directly stimulate testicular Leydig cells 5:

• Typical dosing: 500-1,000 IU subcutaneously 2-3 times per week while continuing testosterone therapy 1
• hCG preserves testicular volume by maintaining Leydig cell function despite suppressed endogenous LH 5
• This approach allows patients to maintain the benefits of TRT while preventing or reversing testicular atrophy 1, 5
• The combination of testosterone plus hCG is particularly important for men who may desire fertility in the future, as it helps preserve spermatogenesis 1, 5

Expected Outcomes with hCG

• Testicular volume can be maintained or partially restored when hCG is added to ongoing TRT 4, 6
• The degree of recovery depends on duration of atrophy and individual response 4
• hCG is expensive and requires patient-administered injections, which may limit adherence 5

Alternative Approach: Discontinue TRT and Switch to Gonadotropin Therapy

If testicular atrophy is severe or fertility is a concern, completely stopping testosterone and switching to hCG plus FSH therapy is the guideline-recommended approach 1, 2:

• This strategy is mandatory for men actively seeking fertility, as exogenous testosterone causes azoospermia 1
• Combined hCG (1,000-2,500 IU 2-3 times weekly) plus recombinant FSH (75-150 IU 2-3 times weekly) provides optimal outcomes for both testosterone restoration and fertility preservation 1
• Recovery of testicular volume after stopping TRT can take 4-12 weeks or longer, with gradual return to normal size 4
• Spermatogenesis recovery may take months or rarely years after testosterone cessation 7

Monitoring and Assessment

Before initiating treatment for testicular atrophy:

• Perform testicular ultrasound to confirm atrophy, measure testicular volume (normal >12 mL), and rule out underlying pathology such as testicular cancer 2
• Check baseline LH, FSH, and total testosterone to assess the degree of hypothalamic-pituitary-gonadal axis suppression 2, 3
• If fertility is a concern, obtain semen analysis and consider sperm banking before any intervention 2

During treatment with hCG:

• Monitor testosterone levels every 2-3 months to ensure adequate replacement 1
• Reassess testicular volume clinically or by ultrasound at 3-6 month intervals 2
• Check hematocrit periodically, as hCG can stimulate testosterone production and increase erythrocytosis risk 1

Critical Pitfalls to Avoid

• Never ignore testicular atrophy in men who may desire future fertility—once spermatogenesis is severely suppressed, recovery can be prolonged or incomplete 7, 2
• Do not assume testicular atrophy is purely cosmetic—it reflects suppression of the entire testicular function, including both testosterone and sperm production 4
• Injectable testosterone causes more severe LH suppression and testicular atrophy than transdermal preparations (intramuscular route OR = 2.44 for LH suppression), so consider switching formulations if atrophy is problematic 3
• Failing to consider fertility preservation before definitive treatment decisions is a common error emphasized by multiple guideline societies 2

When Testicular Atrophy Is Not Reversible

If the patient has been on TRT for many years and has no fertility concerns:

• Testicular atrophy may be permanent despite hCG therapy, particularly if Leydig cells have undergone irreversible atrophy 6
• In such cases, reassure the patient that testosterone production is being maintained by exogenous therapy, and testicular size does not affect the efficacy of TRT 8
• Regular self-examination should be taught due to the theoretical increased risk of testicular cancer in atrophic testes, particularly in men with a history of cryptorchidism 2