Sex Hormone Binding Globulin (SHBG)

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Glycoprotein produced mainly by the liver that binds to sex hormones

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Sex Hormone Binding Globulin (SHBG) - Comprehensive Test Guide

Why is it done?
- Test Purpose: Measures the level of Sex Hormone Binding Globulin (SHBG), a protein produced primarily by the liver that binds to testosterone, estrogen, and other steroid hormones in the blood, regulating their availability and biological activity.
- Primary Indications: Evaluating hormonal imbalances, investigating infertility, assessing polycystic ovary syndrome (PCOS), evaluating hirsutism and acne, diagnosing hypogonadism or testosterone deficiency, and monitoring hormonal therapy effectiveness.
- Typical Circumstances: Often ordered as part of comprehensive hormone panel with testosterone and estrogen levels; performed during investigation of symptoms suggesting hormonal dysfunction; used in conjunction with other metabolic markers to assess insulin resistance and metabolic syndrome.
Normal Range
- Reference Values: Adults - 24-122 nmol/L (nanomoles per liter) or 7-36 ng/mL (nanograms per milliliter) Women: Typically 24-122 nmol/L or 7-36 ng/mL Men: Typically 10-57 nmol/L or 3-12 ng/mL Ranges vary by laboratory and may differ based on age, menopausal status, and hormonal contraceptive use.
- Units of Measurement: nmol/L (SI units - standard internationally) or ng/mL (conventional units used in some North American laboratories)
- Result Interpretation: Normal Range - SHBG within reference values indicates appropriate hormone-binding capacity Low SHBG - Below reference range; associated with increased free hormone levels High SHBG - Above reference range; associated with decreased free hormone availability Interpretation requires correlation with total and free testosterone/estrogen levels and clinical presentation.
- Clinical Significance: Normal SHBG suggests appropriate regulation of free hormone availability; abnormal values may explain symptoms despite normal total hormone levels; SHBG levels are more stable than fluctuating hormone levels and provide important context for interpreting hormone panel results.
Interpretation
- High SHBG Levels: Indicates increased binding of hormones, resulting in lower bioavailable (free) testosterone and estrogen; associated with hyperthyroidism, liver disease, estrogen use/therapy, pregnancy, and eating disorders; may contribute to symptoms of hormone deficiency despite normal total hormone levels.
- Low SHBG Levels: Indicates decreased binding capacity, resulting in increased free hormone levels; commonly associated with insulin resistance, PCOS, metabolic syndrome, obesity, type 2 diabetes, and hypothyroidism; may explain symptoms of androgen or estrogen excess; correlates with increased cardiovascular and metabolic risk.
- Factors Affecting Results: Insulin levels - inversely correlated; hyperinsulinemia decreases SHBG Body weight and composition - obesity lowers SHBG; weight loss increases SHBG Thyroid function - hyperthyroidism increases SHBG; hypothyroidism decreases SHBG Estrogen status - exogenous estrogen and pregnancy increase SHBG Liver function - liver disease may impair SHBG production Age - SHBG typically increases with age, especially in men Medications - corticosteroids, tamoxifen, and anticonvulsants can affect levels Ethnicity and genetic factors may influence baseline SHBG levels.
- Clinical Significance Patterns: Low SHBG + High Testosterone - Strongly suggestive of PCOS or androgen excess Low SHBG + Normal Total Testosterone - May indicate elevated free testosterone with clinical symptoms High SHBG + Low Free Testosterone - Suggests inadequate bioavailable hormone despite normal total levels SHBG changes over time - Progressive decline may indicate developing insulin resistance or metabolic syndrome SHBG in context of other markers - Most useful when interpreted with free testosterone, total testosterone, insulin, and metabolic markers.
Associated Organs
- Primary Organs Involved: Liver - Primary site of SHBG production and synthesis; liver dysfunction directly impacts SHBG levels Hypothalamus and Pituitary - Regulate gonadal hormone production, which indirectly affects SHBG metabolism Ovaries and Testes - Produce testosterone and estrogen that interact with SHBG Thyroid Gland - Thyroid hormones regulate SHBG production Pancreas - Insulin directly suppresses hepatic SHBG production, inversely correlating with SHBG levels.
- Conditions Associated with Abnormal SHBG: Polycystic Ovary Syndrome (PCOS) - Low SHBG with elevated free androgens Insulin Resistance - Hyperinsulinemia suppresses SHBG production Metabolic Syndrome - Multiple metabolic abnormalities associated with low SHBG Type 2 Diabetes - Insulin resistance leads to decreased SHBG Hypothyroidism - Reduced SHBG production Hyperthyroidism - Elevated SHBG levels Obesity - Associated with low SHBG and insulin resistance Fatty Liver Disease - Liver dysfunction may impair SHBG synthesis Cirrhosis and Hepatitis - Severe liver disease impairs SHBG production Hyperandrogenism - May result from or cause low SHBG Hypogonadism - High SHBG may mask low free testosterone Pregnancy - Physiologic elevation of SHBG Eating Disorders (Anorexia) - Malnutrition increases SHBG
- Associated Complications: Low SHBG complications - Increased cardiovascular risk, metabolic dysfunction, increased cancer risk (certain types), infertility issues, and difficulty managing hormonal symptoms High SHBG complications - Reduced bone density risk, hormonal deficiency symptoms despite normal total hormones, decreased sexual function, and reduced insulin sensitivity Diagnostic complications - May mask or misdiagnose hormonal disorders if total hormone levels are normal but free hormone levels are abnormal Treatment complications - Changes in SHBG during weight loss or hormone therapy can affect treatment efficacy and require dosage adjustments.
Follow-up Tests
- Recommended Additional Tests: Free Testosterone - Essential for interpreting SHBG results and assessing bioavailable hormone levels Total Testosterone - Comprehensive hormone assessment; interpret in context of SHBG Free Estradiol - Evaluate free estrogen levels if SHBG abnormalities are identified Total Estradiol - Complete hormonal picture in women Luteinizing Hormone (LH) - Assess pituitary function and reproductive hormone axis Follicle Stimulating Hormone (FSH) - Evaluate gonadal function Insulin Fasting - Assess insulin resistance given inverse relationship with SHBG Glucose (Fasting) - Screen for diabetes and metabolic dysfunction Thyroid Stimulating Hormone (TSH) - Evaluate thyroid function as it affects SHBG Free T4 and T3 - If TSH abnormal, assess thyroid hormone levels Liver Function Panel - Assess hepatic synthetic function if SHBG abnormal Lipid Panel - Evaluate cardiovascular risk in metabolic syndrome Hemoglobin A1C - Assess long-term glucose control Prolactin - Evaluate if reproductive dysfunction present Androstenedione and DHEA-S - Further androgen assessment if hyperandrogenism suspected
- Further Investigations: Pelvic Ultrasound - If PCOS suspected (look for ovarian cysts) Transvaginal Ultrasound - Detailed ovarian and uterine assessment in women Abdominal Ultrasound - Assess for fatty liver disease if metabolic dysfunction Oral Glucose Tolerance Test (OGTT) - If insulin resistance or prediabetes suspected Continuous Glucose Monitoring - In selected cases with metabolic dysfunction Imaging Studies - May be indicated if pituitary or hypothalamic pathology suspected Genetic Testing - In selected cases where genetic hormonal disorders suspected
- Monitoring Frequency: Initial Diagnosis - Baseline SHBG with comprehensive hormone panel With Treatment Initiation - Recheck 6-8 weeks after starting therapy to assess response With Lifestyle Modifications - Retest 3-6 months after weight loss, exercise, or dietary changes Chronic Management - Annual or biannual testing for patients with PCOS, metabolic syndrome, or hypogonadism Hormone Replacement Therapy - Every 6-12 months to assess adequacy of dosing Response Monitoring - Variable frequency based on clinical response and symptoms Long-term Surveillance - Regular monitoring if conditions associated with significant health risks
- Related Complementary Tests: Testosterone/SHBG Ratio - Provides estimate of free testosterone when direct free testosterone measurement unavailable Free Androgen Index (FAI) - Calculated as (total testosterone/SHBG) × 100; useful PCOS marker Metabolic Markers - Adiponectin, leptin, inflammatory markers (CRP, TNF-alpha) Bone Markers - If hypogonadism or hormone deficiency affecting bone health Cardiovascular Risk Markers - Lipoprotein(a), homocysteine, if metabolic dysfunction Body Composition Analysis - DEXA scan, bioimpedance analysis for comprehensive metabolic assessment
Fasting Required?
- Fasting Status: No - Fasting is NOT required for SHBG testing SHBG levels are relatively stable throughout the day and unaffected by food or drink intake May be drawn fasting or non-fasting without affecting result accuracy.
- Special Timing Considerations: Morning testing preferred - Best to draw in early morning (8-10 AM) when hormone levels are typically more stable Menstrual cycle timing - In women with regular cycles, testing is ideally performed in follicular phase (days 2-5 of cycle) for standardized results Consistent timing - If retesting for comparison, try to draw at similar time of day as initial test Avoid testing timing post-exercise - Some recommend avoiding testing immediately after vigorous exercise
- Medications to Avoid or Consider: Oral Contraceptives - Increase SHBG; may need to note on lab requisition; consider timing of testing in relation to pill use Hormone Replacement Therapy - Will affect SHBG levels; note dosage and duration on requisition Corticosteroids - May alter SHBG; document use with lab Anticonvulsants (Phenytoin) - May affect SHBG; inform laboratory Estrogen-containing products - Including patches, creams, topical formulations Androgens/Testosterone - Will affect SHBG through feedback mechanisms Tamoxifen - May increase SHBG Anabolic Steroids - Will suppress SHBG Other medications - Generally do not require discontinuation; inform provider and laboratory of all current medications
- Patient Preparation Requirements: General Preparation - No special preparation needed beyond standard venipuncture requirements Hydration - Normal fluid intake is acceptable; not necessary to drink extra water Activity Level - No need to restrict exercise; avoid strenuous activity immediately before test only if possible Stress Management - Minimize stress if possible, but not a strict requirement Clothing - Wear loose, comfortable clothing for easy blood draw Identification - Bring photo ID and insurance information to lab Appointment Timing - Plan appointment for early morning if possible (8-10 AM preferred) Women - Note first day of last menstrual period and current cycle day if applicable Medication List - Bring complete list of all current medications and supplements Lab Requisition - Ensure provider completes lab order with relevant clinical information including symptoms, suspected diagnoses, and current treatments to aid in result interpretation

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