10
nmol/L
2
%
490
ng/dL
—
10
nmol/L
2
%
490
ng/dL
—
The SHBG Calculator estimates Sex Hormone-Binding Globulin (SHBG) concentration from total and free testosterone measurements using the Vermeulen mass action model in reverse. SHBG is a critical glycoprotein produced primarily by the liver that regulates the bioavailability of sex hormones by binding testosterone and estradiol with high affinity. Understanding SHBG levels is essential for accurate interpretation of testosterone measurements and for diagnosing conditions associated with hormonal imbalance.
SHBG is a homodimeric protein with a molecular weight of approximately 90 kDa. Each SHBG dimer can bind one molecule of testosterone or dihydrotestosterone (DHT) with high affinity (Ka ~1 x 10^9 L/mol) or estradiol with slightly lower affinity. Normal SHBG levels are 20-60 nmol/L in men and 40-120 nmol/L in women, though values vary with age, body composition, and metabolic status.
SHBG levels are regulated by a complex interplay of hormonal and metabolic factors. Factors that increase SHBG: aging, estrogen (oral contraceptives, HRT), hyperthyroidism, liver cirrhosis, anticonvulsants (phenytoin), low body weight, and HIV infection. Factors that decrease SHBG: obesity, insulin resistance/type 2 diabetes, hypothyroidism, androgens (exogenous testosterone, anabolic steroids), glucocorticoids, growth hormone, and nephrotic syndrome.
The clinical significance of SHBG extends beyond hormone transport. Low SHBG is now recognized as an independent risk factor for type 2 diabetes, metabolic syndrome, and cardiovascular disease. Prospective studies have demonstrated that each standard deviation decrease in SHBG is associated with a 1.3-1.8 fold increased risk of developing type 2 diabetes, independent of obesity and testosterone levels. SHBG may also play a direct role in cellular signaling through a putative membrane receptor.
This calculator uses the inverse Vermeulen approach: given known total testosterone, free testosterone, and albumin, it back-calculates the SHBG concentration required to produce the observed free testosterone fraction. This is useful when SHBG measurement is not available but both total and free testosterone have been measured, or for validating laboratory SHBG results against the expected value based on the testosterone measurements.
The calculator reverses the Vermeulen equation to estimate SHBG:
Step 1: Convert total T and free T to nmol/L (x 0.0347). Convert albumin to mol/L.
Step 2: Calculate albumin-bound T: Alb_bound = [Albumin] x Ka_alb x [FT] / (1 + Ka_alb x [FT])
Step 3: Calculate SHBG-bound T: SHBG_bound = Total_T - Free_T - Albumin_bound
Step 4: Solve for SHBG: SHBG = SHBG_bound x (1 + Ka_SHBG x [FT]) / (Ka_SHBG x [FT])
Association constants: Ka_SHBG = 1.0 x 10^9 L/mol; Ka_albumin = 3.6 x 10^4 L/mol.
SHBG Status: 1 = Low (<20 nmol/L), 2 = Normal (20-60 nmol/L), 3 = High (>60 nmol/L).
Status 1 (Low SHBG, <20 nmol/L): Associated with insulin resistance, obesity, metabolic syndrome, type 2 diabetes, hypothyroidism, and androgen use. Screen for metabolic disease. Free testosterone may be deceptively normal despite low total T. Status 2 (Normal, 20-60 nmol/L): SHBG is within the expected range for adult males. Testosterone distribution is likely normal. Status 3 (High SHBG, >60 nmol/L): Associated with aging, liver disease, hyperthyroidism, estrogen therapy, and low BMI. Total testosterone may appear normal while free/bioavailable T is actually low. Consider free T when evaluating symptoms.
Inputs
Results
With total T 500, free T 10 (2.0%), the calculated SHBG is ~40 nmol/L — solidly normal. Testosterone distribution is balanced.
Inputs
Results
Despite low total T of 320, free T is 11 ng/dL (3.4%) due to very low SHBG (~15). This pattern is typical of obesity with insulin resistance. Total T underestimates androgen status.
Sex Hormone-Binding Globulin is a glycoprotein made by the liver that binds sex hormones (testosterone, DHT, estradiol) in the blood. It regulates how much hormone is free and bioavailable. About 45% of testosterone is bound to SHBG and is considered biologically inactive while bound.
Normal SHBG for adult males is 20-60 nmol/L. For adult females, it is 40-120 nmol/L. SHBG rises with age in both sexes. Postmenopausal women often have lower levels. Values vary by laboratory, assay method, and clinical context.
SHBG determines how much testosterone is bioavailable. Two men with identical total T can have very different free T if their SHBG levels differ. High SHBG masks true androgen deficiency (low free T with normal total T). Low SHBG can mask true androgen adequacy. SHBG is also an independent metabolic risk marker.
The most common cause is obesity/insulin resistance, which directly suppresses hepatic SHBG production. Other causes: hypothyroidism, nephrotic syndrome, exogenous androgens, glucocorticoids, growth hormone excess, and acromegaly. Low SHBG is a marker for metabolic syndrome and future type 2 diabetes risk.
Aging is the most common cause in men. Other causes: liver cirrhosis, hyperthyroidism, estrogen therapy (oral contraceptives in women), anticonvulsants (phenytoin, carbamazepine), anorexia nervosa, HIV infection, and some genetic variants. High SHBG lowers bioavailable testosterone.
Insulin directly suppresses hepatic SHBG production. Hyperinsulinemia (from insulin resistance) leads to low SHBG. This is why SHBG is inversely correlated with BMI, waist circumference, and HOMA-IR. Weight loss and insulin sensitizers (metformin) can increase SHBG levels.
Yes. SHBG binds estradiol with slightly lower affinity than testosterone. Changes in SHBG affect both testosterone and estradiol bioavailability. In states of low SHBG, both free testosterone and free estradiol are elevated. This is particularly relevant in PCOS and obesity.
SHBG itself is not directly treated — the underlying cause is addressed. For low SHBG: treat insulin resistance, lose weight, optimize thyroid function. For high SHBG: address the cause (liver disease, thyroid disorder). In some cases, adjusting testosterone replacement approach is needed.
Exogenous testosterone typically lowers SHBG because androgens suppress hepatic SHBG production. This means more of the administered testosterone remains bioavailable. However, excessive SHBG suppression may indicate supraphysiologic dosing. Monitor SHBG during TRT.
Partially. Twin studies show SHBG has a heritability of about 50-65%. Several genetic variants (particularly in the SHBG gene on chromosome 17) affect SHBG levels. However, metabolic and hormonal factors (BMI, insulin, thyroid hormones) also have major effects and are modifiable.
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