Can bilateral cryptorchidism cause hypogonadism?

Bilateral Cryptorchidism and Hypogonadism

Yes, bilateral cryptorchidism can cause hypogonadism, particularly primary hypogonadism due to testicular failure, which may require testosterone replacement therapy. 1

Pathophysiology and Risk

Bilateral cryptorchidism significantly impacts testicular function through several mechanisms:

• Impaired testicular development occurs when testes remain in a non-scrotal location, with damage proportional to the duration of the condition 2, 3
• Testicular hormone production is compromised, affecting both:
  • Sertoli cell function (long-term impairment)
  • Leydig cell function (may be affected in bilateral cases) 3

The risk of hypogonadism is particularly pronounced in bilateral cases:

• Men with a history of bilateral cryptorchidism show greatly reduced fertility compared to those with unilateral cryptorchidism or the general population 2
• Paternity rates are significantly lower (62% in formerly bilaterally cryptorchid men vs. 94% in control groups) 2
• Time to pregnancy is substantially longer (33.9 months for bilateral cases vs. 11.1 months for unilateral cases) 2

Evidence of Hypogonadism in Bilateral Cryptorchidism

Research demonstrates clear hormonal abnormalities:

• Lower plasma LH levels in high infertility risk groups suggest hypogonadotropic hypogonadism 4
• The FDA specifically recognizes cryptorchidism as a cause of primary hypogonadism requiring testosterone replacement therapy 1
• Up to 50% of boys with cryptorchidism may have defective mini-puberty, a critical period of hormonal activity in early infancy 4
• Bilateral testicular histology shows impaired transformation of Ad spermatogonia, which correlates with future sperm concentrations 5

Management Implications

The recognition of hypogonadism risk affects management:

1. Early detection and referral:

   • Refer infants with cryptorchidism by 6 months (corrected for gestational age) if no spontaneous descent occurs 2
   • Immediate specialist consultation for bilateral nonpalpable testes to rule out disorders of sex development 2

2. Surgical intervention:

   • Early orchidopexy (within first 18 months) is recommended to preserve fertility potential 2
   • Surgery cannot prevent infertility if Ad spermatogonia are absent 5

3. Hormonal evaluation:

   • Measure müllerian inhibiting substance or anti-müllerian hormone in boys with bilateral nonpalpable testes 2
   • Consider additional hormone testing to evaluate for anorchia 2
   • Monitor for hypogonadism, particularly in bilateral cases 4

4. Long-term follow-up:

   • Counsel patients and parents regarding potential long-term risks including infertility and cancer risk 2
   • Monitor for signs of hypogonadism during and after puberty 6

Clinical Pitfalls and Caveats

• Misdiagnosis risk: Bilateral nonpalpable testes may indicate disorders of sex development, including congenital adrenal hyperplasia in genetic females (46 XX) 2
• Imaging limitations: Ultrasound and other imaging modalities have poor sensitivity and specificity for nonpalpable testes and should not delay referral 2
• Treatment timing: Delay in orchidopexy increases the risk of testicular damage and subsequent hypogonadism 7
• Unilateral implications: Even unilateral cryptorchidism can have bilateral effects, as 70% of contralateral scrotal testes show impaired transformation of Ad spermatogonia 5
• Hormonal treatment limitations: Hormonal treatments with hCG or GnRH have low success rates for inducing testicular descent and are not recommended by current guidelines 3

While Leydig cell function is generally preserved in boys with a history of cryptorchidism, those with bilateral cryptorchidism treated with orchidopexy may show impaired hypothalamic-pituitary-gonadal function, particularly affecting Sertoli cells and germ cells 6.