Sex Hormone-Binding Globulin (SHBG)
SHBG is a hepatic homodimeric glycoprotein that binds sex steroids with high affinity, regulating the equilibrium between free and protein-bound testosterone and estradiol.
Standard vs. Optimal Reference Rangesnmol/L
Standard reference intervals represent the statistical 95% distribution of unselected commercial populations. Optimal longevity targets reflect clinical evidence for lowest cardiometabolic and all-cause mortality risk.
Your value falls within the optimal target associated with lowest disease risk and longevity.
10 - 57 nmol/L (Male), 18 - 144 nmol/L (Female)
General reference distribution across unselected commercial populations.
25 - 45 nmol/L (Male)
Concentration target associated with minimal all-cause cardiometabolic mortality.
Molecular Mechanism & Clinical Purpose
Hepatic SHBG transcription is stimulated by estrogens and thyroid hormones but powerfully downregulated by insulin, IGF-1, and hepatic lipogenesis.
Differential Diagnosis
Elevated Levels (SHBG High)
- •Aging in men
- •Hyperthyroidism
- •Caloric restriction / Anorexia nervosa
- •Oral estrogen administration
Low Levels (SHBG Low)
- •Metabolic syndrome, insulin resistance, and visceral adiposity
- •Hypothyroidism
- •Exogenous androgen or growth hormone use
Technical Reference & Deep Dive
Biochemistry & Enzymatic Pathways
Longevity Risk Architecture & Epidemiology
Pre-Analytical Caveats & Diagnostic Workup
Pre-Analytical Considerations:
Blood draw must occur strictly between 7:00 AM and 9:00 AM to account for steep circadian cortisol and testosterone peaks. Ensure 8 hours of restful sleep prior; night shift work or sleep deprivation severely blunts endocrine pulsatility. Discontinue biotin supplements for 72 hours before thyroid or steroid testing to prevent false immunoassay results. For reproductive hormones in premenopausal females, precisely document the day of the menstrual cycle (Day 3 for baseline follicular, Day 21 for luteal).
Reflexive Testing Protocol:
- Free Hormone Equilibrium Dialysis or LC-MS/MS assay for direct bioavailable hormone quantification
- Pituitary trophic hormone panel (TSH, LH, FSH, ACTH, Prolactin) to differentiate primary vs central secondary endocrinopathies
- Autoantibody quantification (Thyroid Peroxidase Antibodies, Thyroglobulin Antibodies, 21-Hydroxylase Antibodies)
- Pelvic, testicular, or thyroid high-resolution ultrasound imaging to assess glandular parenchymal architecture
- Dynamic endocrine stimulation testing (Cosyntropin/ACTH stimulation test, Dexamethasone suppression test, GnRH test)
Clinical Citations & Primary Literature (1)
- [1]Sex Hormone-Binding Globulin as an Independent Biomarker of Metabolic Health - Nature Reviews Endocrinology (2021). PMID: 34188701
Associated Longevity Guides & Clinical Calculators
Medicine 3.0Explore comprehensive evidence-based clinical protocols, testing costs, and algorithmic calculators that incorporate Sex Hormone-Binding Globulin (SHBG) into overall healthspan optimization.