Can high Sex Hormone-Binding Globulin (SHBG) cause infertility if free testosterone levels are normal?

High SHBG and Male Fertility with Normal Free Testosterone

High Sex Hormone-Binding Globulin (SHBG) levels typically do not cause infertility when free testosterone levels are normal, as free testosterone is the key determinant of androgen status and reproductive function. 1

Understanding SHBG and Testosterone Relationship

• SHBG is a glycoprotein that binds to testosterone in the bloodstream
• Free testosterone (not bound to SHBG) is the biologically active form that affects spermatogenesis
• When free testosterone is normal, spermatogenesis typically proceeds normally regardless of SHBG levels 1
• The American Urological Association guidelines emphasize that free testosterone, not total testosterone or SHBG alone, is the critical factor for male reproductive health 1

Clinical Implications of High SHBG

When High SHBG Is Not a Concern

• If free testosterone levels are normal, high SHBG alone is unlikely to cause infertility 1
• In vivo studies have shown that higher SHBG levels do not necessarily lead to lower non-SHBG-bound testosterone levels 2
• Some research even indicates that higher SHBG may be associated with slightly higher non-SHBG-bound testosterone in adult men 2

When to Be Concerned

• High SHBG may indicate underlying conditions that could affect fertility:
  • Liver disease
  • Hyperthyroidism
  • Alcoholism
  • Medication effects (e.g., certain anticonvulsants, estrogens) 1, 3
• These underlying conditions, rather than the high SHBG itself, may be the actual cause of fertility issues

Evaluation Recommendations

1. Confirm free testosterone is normal

   • Morning measurement is essential due to diurnal variation 1
   • Free testosterone by equilibrium dialysis is the most accurate method

2. Evaluate for underlying causes of high SHBG

   • Liver function tests
   • Thyroid function tests
   • Medication review
   • Alcohol consumption assessment 1

3. Consider semen analysis

   • Direct assessment of fertility status is recommended if actively trying to conceive 4
   • Parameters to evaluate include sperm concentration, motility, and morphology

When to Seek Specialist Care

• If attempting conception for >12 months without success despite normal free testosterone
• If symptoms of hypogonadism persist despite normal free testosterone
• If semen analysis reveals abnormalities in sperm parameters 4, 1

Important Considerations

• Avoid exogenous testosterone therapy if fertility is desired, as it can suppress spermatogenesis 1
• The ratio of total testosterone to SHBG (free testosterone index) may provide additional insight into androgen status 1
• A testosterone/SHBG ratio ≥0.3 generally indicates normal gonadal function 1

In conclusion, while high SHBG can alter total testosterone measurements, it's the free testosterone level that determines reproductive function. As long as free testosterone remains within normal range, high SHBG alone is unlikely to be the cause of infertility.