Do severe varicoceles increase Sex Hormone-Binding Globulin (SHBG) levels and by how much do they decrease after correction?

Effect of Severe Varicoceles on SHBG and Changes After Correction

Severe varicoceles do not consistently increase Sex Hormone-Binding Globulin (SHBG) levels, but varicocele repair can decrease SHBG levels by approximately 13% (from 32.9 to 28.6 nmol/L) after treatment. 1

Varicocele and Hormonal Effects

• Varicoceles affect approximately 15% of the general male population but are present in 35-40% of men presenting with infertility, indicating a significant association between varicocele and fertility issues 2
• The pathophysiology of varicocele involves multiple mechanisms that can affect testicular function, including higher scrotal temperature, testicular hypoxia, and reflux of toxic metabolites 2
• Varicocele can lead to hormonal alterations that may contribute to fertility problems, though the literature shows contradictory results regarding specific hormonal changes 3

SHBG and Other Hormonal Changes in Varicocele

• Antiepileptic drugs can increase the production of sex hormone binding globulins (SHBG), but the direct effect of varicocele on SHBG is less clear 4
• In a study of 30 infertile men with varicocele, SHBG levels decreased significantly from 32.9 ± 3.5 to 28.6 ± 3.4 nmol/L after varicocele treatment, representing approximately a 13% reduction 1
• This decrease in SHBG was accompanied by a significant increase in the free androgen index from 66 ± 5.9 to 85 ± 6.8 after treatment 1

Hormonal Improvements After Varicocele Repair

• Varicocele repair can increase serum inhibin B levels, indicating improvement of spermatogenesis and Sertoli cell function 1
• Studies have shown that varicocelectomy can increase serum testosterone levels in men with varicoceles and testosterone deficiency 5
• In one study, mean serum testosterone increased from a preoperative level of 319 ± 12 to 409 ± 23 ng/dL postoperatively, representing a significant improvement 6
• Hormonal improvements typically parallel the timeline for semen parameter improvements, taking approximately 3-6 months (two spermatogenic cycles) to show enhancement 7

Treatment Recommendations

• 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 7, 2
• 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 8
• Microsurgical varicocele repair could be preferred to provide the best improvement in hormonal parameters 5

Clinical Considerations and Pitfalls

• The timing of surgery may influence outcomes, with earlier intervention potentially preventing permanent testicular damage 8
• An inverse correlation has been noted between preoperative testosterone levels and change in testosterone after varicocelectomy, suggesting that men with lower baseline testosterone may experience greater improvements 6
• Routine use of ultrasonography to identify non-palpable varicoceles is discouraged, as treatment of these subclinical varicoceles is not associated with improvement in either semen parameters or fertility rates 2
• Varicocele repair offers an advantage over exogenous testosterone treatment for hypogonadism by preserving fertility status in men who may desire children in the future 5