How can testicular atrophy be prevented in patients undergoing Testosterone Replacement Therapy (TRT)?

Preventing Testicular Atrophy During Testosterone Replacement Therapy

Human chorionic gonadotropin (hCG) should be administered concurrently with testosterone replacement therapy to prevent testicular atrophy by maintaining intratesticular testosterone levels and preserving spermatogenesis.

Mechanism of Testicular Atrophy in TRT

Testosterone replacement therapy (TRT) causes testicular atrophy through:

• Suppression of the hypothalamic-pituitary-gonadal (HPG) axis
• Decreased luteinizing hormone (LH) and follicle-stimulating hormone (FSH) production
• Reduced intratesticular testosterone levels
• Impaired spermatogenesis 1

This feedback inhibition leads to decreased testicular size, function, and potential fertility issues.

Prevention Strategies

1. hCG Concurrent Therapy (First-Line)

hCG mimics LH and directly stimulates Leydig cells to produce testosterone within the testes.

Recommended Protocol:

• 500-1500 IU subcutaneously 2-3 times weekly while on TRT
• Dosage can be adjusted based on testicular size response and laboratory values
• Maintains intratesticular testosterone levels without disrupting exogenous testosterone benefits

2. Selective Estrogen Receptor Modulators (SERMs)

If hCG is unavailable or ineffective:

• Clomiphene citrate: 25-50 mg every other day
• Works by blocking estrogen receptors in the hypothalamus, increasing endogenous LH/FSH production 2, 3

3. Aromatase Inhibitors

For patients with elevated estrogen levels on TRT:

• Anastrozole: 0.5-1 mg twice weekly
• Reduces conversion of testosterone to estradiol, which can help maintain HPG axis function 3

Monitoring Protocol

1. Baseline Assessment (Before Starting TRT):

   • Testicular volume measurement (via orchidometer)
   • Semen analysis if fertility is a concern
   • Hormonal panel: Total testosterone, LH, FSH, estradiol

2. Follow-up Monitoring:

   • Testicular volume measurement every 3-6 months
   • Hormonal assessment every 3-6 months
   • Semen analysis if fertility is desired

Special Considerations

Fertility Preservation

For men who wish to preserve fertility while on TRT:

• Sperm banking before starting TRT is strongly recommended 4
• Consider using short-acting testosterone formulations (nasal or oral) that may have less suppressive effects on spermatogenesis 1

Important Warnings

• Exogenous testosterone can cause "testicular atrophy, subfertility, and infertility" as stated in the FDA label 5
• Recovery of spermatogenesis after TRT cessation is variable and may take 6-18 months
• Some patients may never fully recover normal spermatogenesis 3

Algorithm for Prevention of Testicular Atrophy on TRT

1. Assess fertility desires and baseline testicular function
2. If fertility preservation is important:
   • Offer sperm banking before TRT
   • Start hCG concurrently with TRT
3. If fertility is not a concern but preventing atrophy is desired:
   • Start hCG concurrently with TRT
4. If testicular atrophy develops despite hCG:
   • Increase hCG dose
   • Consider adding a SERM
   • Consider aromatase inhibitor if estradiol is elevated

By implementing these strategies, particularly concurrent hCG therapy, testicular atrophy can be effectively prevented in most men undergoing testosterone replacement therapy.