Can inhibin B (Inhibin B) levels be abnormal in patients with normal Follicle-Stimulating Hormone (FSH) levels?

Inhibin B Levels in Patients with Normal FSH Levels

Yes, inhibin B levels can be abnormal even when FSH levels are normal, particularly in cases of early or subtle testicular dysfunction where the hypothalamic-pituitary-gonadal feedback system is not yet fully compromised.

Relationship Between Inhibin B and FSH

Inhibin B is a dimeric glycoprotein produced primarily by Sertoli cells in the testes and serves as a direct marker of testicular function, particularly spermatogenesis. While FSH and inhibin B typically have an inverse relationship, this relationship is not absolute, and discrepancies can occur for several reasons:

• Inhibin B directly reflects Sertoli cell function and spermatogenesis, while FSH reflects the pituitary response to gonadal feedback
• Early testicular dysfunction may affect inhibin B production before FSH levels rise
• Some conditions can affect one hormone independently of the other

Clinical Scenarios Where Normal FSH Can Occur with Abnormal Inhibin B

1. Early Spermatogenic Dysfunction:

   • Subtle testicular damage may cause decreased inhibin B while FSH remains within normal range
   • This represents an early stage before the feedback mechanism fully activates 1

2. Varicocele:

   • Some patients with varicocele may have reduced inhibin B with normal FSH levels 2, 3
   • This suggests that inhibin B may be more sensitive to early spermatogenic changes

3. Cryptorchidism History:

   • Men with history of cryptorchidism may show discordant inhibin B and FSH levels 2

4. Partial Hypospermatogenesis:

   • Some forms of partial spermatogenic failure may affect inhibin B production while FSH remains normal 2

5. Post-Chemotherapy/Radiation:

   • According to ESMO guidelines, testicular irradiation leads to a rapid decrease in inhibin B before FSH changes become evident 4

Diagnostic Implications

The AUA guidelines suggest that in cases of bilateral nonpalpable testes, measuring Müllerian inhibiting substance (MIS) or anti-Müllerian hormone (AMH) along with inhibin B provides valuable diagnostic information 4. When evaluating male fertility:

• Combined Testing: Using both inhibin B and FSH together provides more sensitive and specific assessment of spermatogenesis than either marker alone 1

• Predictive Value: Inhibin B shows positive correlation with:

  • Testicular volume
  • Sperm count
  • Overall spermatogenic status 5, 2

• Limitations: Inhibin B alone cannot reliably predict the presence of sperm in testicular biopsy samples for extraction 1

Clinical Applications

For men with suspected fertility issues:

1. Early Detection: Abnormal inhibin B with normal FSH may represent the earliest detectable sign of spermatogenic dysfunction

2. Monitoring Treatment: Inhibin B can be used to monitor response to hormonal treatments for infertility 6

3. Differential Diagnosis: In azoospermia, inhibin B levels help distinguish between obstructive and non-obstructive causes

4. Predictive Testing: According to the EAU guidelines, inhibin B levels (along with FSH, LH, and AMH) can be used to predict sperm retrieval outcomes in men with non-obstructive azoospermia, though with limited accuracy 4

Common Pitfalls

• Overreliance on FSH alone: Assuming normal spermatogenesis based solely on normal FSH levels may miss early testicular dysfunction
• Isolated Testing: Using either inhibin B or FSH alone rather than in combination reduces diagnostic accuracy
• Timing Variations: Inhibin B shows diurnal variation similar to testosterone, so timing of sample collection matters 1
• Misinterpretation: Some cases of Sertoli-cell-only syndrome paradoxically show normal inhibin B levels for unknown reasons 1

In summary, while FSH and inhibin B typically show an inverse relationship, normal FSH levels do not guarantee normal inhibin B levels. Measuring both hormones provides complementary information about the status of the hypothalamic-pituitary-gonadal axis and spermatogenesis.