How should I evaluate and manage low sexual desire caused by elevated sex‑hormone‑binding globulin (SHBG)?

Evaluation and Management of Low Libido Caused by Elevated SHBG

Measure both morning total testosterone AND free testosterone (or calculate free androgen index) to confirm functional hypogonadism, then identify and treat the underlying cause of elevated SHBG before considering testosterone replacement therapy. 1, 2

Initial Diagnostic Workup

Hormone Testing Protocol

• Obtain morning total testosterone (between 8:00-10:00 AM) using an accurate, reliable assay 1, 2
• Measure free testosterone using equilibrium dialysis (gold standard) or calculate the free androgen index (total testosterone/SHBG ratio) 1, 2
• A free testosterone index <0.3 confirms hypogonadism despite potentially normal total testosterone 2
• Measure luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to distinguish primary from secondary hypogonadism 1

Critical pitfall: Relying solely on total testosterone will miss functional hypogonadism when SHBG is elevated, as the bound testosterone is biologically inactive despite appearing "normal" on lab results. 2

Identify the Underlying Cause of Elevated SHBG

The European Association of Urology identifies these specific conditions that increase SHBG: 1

Endocrine disorders:

• Hyperthyroidism—check TSH, free T4 1
• Aging (physiological increase) 1

Hepatic disease:

• Check liver function tests (AST, ALT, alkaline phosphatase, bilirubin, albumin) 1, 2
• Hepatic cirrhosis markedly elevates SHBG 3

Medications causing SHBG elevation:

• Anticonvulsants (phenytoin, carbamazepine) 1
• Estrogens (including oral contraceptives in transgender patients) 1
• Thyroid hormone replacement (excessive dosing) 1

Other conditions:

• HIV/AIDS—consider HIV testing in appropriate clinical contexts 1, 2
• Smoking history 1

Management Algorithm

Step 1: Treat the Underlying Condition First

This is the most effective approach to lowering SHBG and should always be attempted before testosterone replacement. 2

• If hyperthyroid: Correct thyroid dysfunction with antithyroid medications, radioactive iodine, or surgery as indicated 2
• If hepatic disease: Manage liver disease appropriately based on etiology 2
• If medication-induced: Discontinue or substitute the offending medication if clinically safe 1
• If HIV-related: Optimize antiretroviral therapy 1

Step 2: Consider Testosterone Replacement Therapy

Testosterone replacement is appropriate in symptomatic men with documented low free testosterone, even when total testosterone appears normal. 1, 2

Indications for testosterone therapy:

• Confirmed low free testosterone or free androgen index <0.3 2
• Persistent symptoms (decreased libido, erectile dysfunction, reduced muscle mass, fatigue) 1
• Failed correction of underlying SHBG-elevating condition 2

Benefits of testosterone replacement:

• Improved sexual function and libido 1
• Enhanced well-being 1
• Increased muscle mass and strength 1
• Improved bone density 1

Monitoring requirements for testosterone therapy:

• Baseline digital rectal exam and PSA before initiating therapy 2
• Check PSA every 3-6 months during the first year, then annually 2
• Monitor hematocrit/hemoglobin regularly (risk of polycythemia) 2
• Assess for urinary symptoms, sleep apnea exacerbation, and gynecomastia 2
• Consider prostate biopsy if PSA rises >1.0 ng/mL in any year 2
• Recheck testosterone levels to ensure therapeutic range 2

Important caveat: Testosterone replacement will suppress the hypothalamic-pituitary-gonadal axis and compromise fertility, so this must be discussed with patients of reproductive age. 1

Understanding the Pathophysiology

Why High SHBG Causes Low Libido Despite "Normal" Total Testosterone

• SHBG binds testosterone with high affinity, reducing free (bioavailable) testosterone 2, 3
• The pituitary gland senses free testosterone levels, not total testosterone, when regulating hormone production 2
• When SHBG increases, more testosterone becomes bound and biologically inactive 2, 3
• This creates functional hypogonadism—adequate total testosterone but insufficient free testosterone for normal sexual function 2
• Patients exhibit androgen-deficiency symptoms (reduced libido, fatigue, erectile dysfunction) despite laboratory values showing "normal" total testosterone 2

Compensatory Mechanisms

• Reduced free testosterone decreases negative feedback on the pituitary 2
• This triggers increased LH and FSH secretion to stimulate more testosterone production 2
• However, if SHBG remains elevated, the additional testosterone produced also becomes bound, perpetuating the cycle 2

Key Clinical Pearls

• Never interpret total testosterone in isolation when evaluating hypogonadism—always measure or calculate free testosterone, especially when SHBG abnormalities are suspected 1, 2
• The testosterone:SHBG ratio correlates well with free testosterone and helps discriminate patients with androgen deficiency from normal individuals 3, 4
• SHBG levels around 74 nmol/L can conceal functional hypogonadism by making total testosterone appear falsely reassuring 2
• Obesity paradoxically lowers SHBG (through insulin resistance), so elevated SHBG in an obese patient suggests a different underlying etiology 1, 5