What is the management approach for a patient with low Sex Hormone-Binding Globulin (SHBG) and hypogonadism?

Management of Low SHBG and Hypogonadism

For patients with low Sex Hormone-Binding Globulin (SHBG) and hypogonadism, testosterone replacement therapy should be initiated after confirming the diagnosis with two separate morning total testosterone measurements below 300 ng/dL, calculating the free testosterone index (total testosterone/SHBG ratio <0.3), and ensuring the presence of clinical symptoms.

Diagnostic Approach

Laboratory Assessment

• Measure morning total testosterone levels on at least two separate occasions (both <300 ng/dL indicates testosterone deficiency) 1
• Calculate free testosterone index (total testosterone/SHBG ratio) - a ratio <0.3 confirms hypogonadism 1, 2
• Measure serum luteinizing hormone (LH) to determine if hypogonadism is primary or secondary 1, 2
• Consider measuring free testosterone, especially in:
  • Obese patients
  • Older men (>60 years)
  • Conditions affecting SHBG levels 3, 4

Clinical Evaluation

• Assess for specific symptoms of hypogonadism:
  • Sexual symptoms: reduced libido, erectile dysfunction, decreased spontaneous/morning erections
  • Physical symptoms: decreased energy, fatigue, decreased physical strength
  • Psychological symptoms: low mood, decreased motivation, concentration difficulties 1
• Evaluate for conditions that affect SHBG levels:
  • SHBG increases: hepatic disease, hyperthyroidism, aging, smoking, HIV/AIDS
  • SHBG decreases: obesity, hypothyroidism, insulin resistance, metabolic syndrome, type 2 diabetes 1

Treatment Approach

Testosterone Replacement Therapy (TRT)

• Initiate testosterone replacement therapy in men with confirmed hypogonadism (symptoms plus low testosterone) 2, 5
• Dosing options:
  • Testosterone enanthate: 50-400 mg intramuscular injection every 2-4 weeks 5
  • Transdermal preparations (gel, patch) for more stable levels 2
• Target mid-normal range testosterone levels (500-600 ng/dL) 2
• Monitor response by checking testosterone levels 2-3 months after initiation 2

Special Considerations for Low SHBG

• Low SHBG increases free testosterone relative to total testosterone, which may mask hypogonadism if only total testosterone is measured 3, 6
• In patients with low SHBG:
  • Free testosterone or free testosterone index is more reliable than total testosterone alone 4, 6
  • Symptoms may be present despite "normal" total testosterone levels 4
  • Adjust treatment based on both clinical symptoms and free testosterone levels 6

Monitoring

• Check testosterone levels 2-3 months after initiating therapy 2
• Monitor for adverse effects:
  • Polycythemia (check hematocrit)
  • Prostate issues (PSA)
  • Cardiovascular effects 2
• Discontinue oxandrolone if used, as it can further decrease SHBG levels 7

Contraindications and Cautions

• Known or suspected prostate or breast cancer 2, 5
• Desire for fertility (testosterone suppresses spermatogenesis) 2
• Severe lower urinary tract symptoms
• Erythrocytosis (hematocrit >54%)
• Untreated obstructive sleep apnea
• Uncontrolled heart failure 5

Lifestyle Modifications

• Weight loss in obese patients (improves testosterone bioavailability) 2
• Regular physical exercise (improves testosterone levels) 2
• Smoking cessation 2
• Reduction of alcohol consumption 2

Clinical Pearls and Pitfalls

• Pitfall: Relying solely on total testosterone to diagnose hypogonadism in patients with conditions affecting SHBG
  • Up to 17.2% of men with erectile dysfunction have normal total testosterone but low free testosterone 3
  • This issue is particularly common in men over 60 years (26.3%) 3
• Pearl: Calculate free testosterone index (total testosterone/SHBG ratio) to improve diagnostic accuracy
• Pearl: Symptoms of hypogonadism develop only when both total and free testosterone decline 4
• Caution: Testosterone therapy may cause hypercalcemia, peliosis hepatis, venous thromboembolism, and cardiovascular events in susceptible individuals 5