Do varicoceles (varicose veins of the spermatic cord) increase sex hormone-binding globulin (SHBG) levels?

Do Varicoceles Increase Sex Hormone-Binding Globulin (SHBG) Levels?

Yes, varicoceles can increase sex hormone-binding globulin (SHBG) levels, though the relationship is complex and may vary depending on the severity of the condition and associated liver function. 1

Mechanism and Evidence

• In chronic liver disease, SHBG levels rise due to increased production, though the exact reasons remain unclear. This rise is stimulated by estrogens, which are also elevated in varicocele patients 1

• Varicoceles affect approximately 15% of the general male population but are present in 35-40% of men with infertility, indicating a significant association between varicocele and reproductive health issues 2, 3

• The pathophysiology of varicocele involves multiple mechanisms that affect testicular function, including:

  • Higher scrotal temperature
  • Testicular hypoxia
  • Reflux of toxic metabolites
  • Increased DNA damage 2, 3

• Studies have found that men with varicoceles and excessive gonadotropin responses to GnRH had higher than normal levels of SHBG compared to control groups 4

Effect of Varicocele Repair on SHBG Levels

• After varicocelectomy, there is a significant decrease in SHBG levels, with studies showing a mean decrease of 32.72 nmol/L post-surgery 2

• This decrease in SHBG following varicocele repair suggests that the elevated SHBG levels are directly related to the varicocele condition 2

• Hormonal improvements typically parallel improvements in semen parameters, taking approximately 3-6 months (two spermatogenic cycles) to show enhancement 2, 5

Hormonal Alterations in Varicocele Patients

• Varicocele patients often show multiple hormonal alterations beyond just SHBG changes:

  • Lower testosterone levels compared to men without varicoceles 6
  • Higher FSH and LH levels that may normalize after varicocelectomy 7
  • Lower circulating Anti-Müllerian Hormone and Inhibin-B levels 7

• In a study of men with bilateral grade 3 varicoceles, significant reduction in testicular function was observed with alterations in hormone levels 8

Clinical Implications

• The hormonal changes, including elevated SHBG, may contribute to the fertility issues and sexual dysfunction seen in varicocele patients 1, 2

• Treatment should be targeted to men with clinical varicoceles and abnormal semen parameters, as treatment of men with normal semen analysis or subclinical varicoceles is not recommended regardless of hormonal status 2, 3

• After varicocele repair, testosterone levels significantly increased in more than two-thirds of men in clinical studies, suggesting improvement in overall hormonal balance 6

Important Considerations

• The European Association of Urology strongly recommends surgery for varicocele when associated with a persistent small testis (size difference >2 mL or 20%), confirmed on two subsequent visits 6 months apart 2

• Routine use of ultrasonography to identify non-palpable varicoceles is discouraged, as treatment of these subclinical varicoceles is not associated with improvement in either hormonal parameters or fertility rates 2, 3

• When evaluating hormonal changes in varicocele patients, it's important to rule out other causes of hormonal alterations before attributing them solely to the varicocele 2