Sex Hormone Binding Globulin (SHBG)
SHBG is a protein made by the liver that binds sex hormones (testosterone, estradiol). Bound hormones are inactive — only FREE hormones work. High SHBG = less free hormone available (symptoms despite normal total levels). Low SHBG = more free hormone (symptoms of excess, or adequate levels despite low totals). Low SHBG is also a metabolic marker — strongly associated with insulin resistance, metabolic syndrome, diabetes risk, and PCOS. Always interpret testosterone with SHBG for the complete picture.
Sex Hormone Binding Globulin (SHBG) is a protein produced by the liver that binds to sex hormones — primarily testosterone and estradiol — in the bloodstream. When hormones are bound to SHBG, they’re inactive and unavailable to tissues. Only the unbound “free” hormones can enter cells and exert effects. SHBG essentially acts as a hormone reservoir and regulator, controlling how much active hormone is available at any given time.
Why does this matter? SHBG levels significantly affect how sex hormones function in your body, even when total hormone levels appear normal. High SHBG binds more hormone, reducing the amount available to tissues — you might have normal total testosterone but experience low testosterone symptoms because most of it is bound up. Low SHBG means more free hormone is available, potentially causing symptoms of hormone excess. Understanding SHBG helps interpret hormone tests accurately and explains why symptoms don’t always match total hormone levels.
Key Benefits of Testing
SHBG testing clarifies confusing hormone situations. When total testosterone is normal but symptoms suggest deficiency (or excess), SHBG often explains the discrepancy. It helps calculate free and bioavailable testosterone — the fractions that actually matter for tissue effects.
SHBG is also a metabolic health marker. Low SHBG is associated with insulin resistance, metabolic syndrome, type 2 diabetes, and fatty liver disease. It can be an early indicator of metabolic problems even before glucose abnormalities appear, offering an opportunity for early intervention.
What Does This Test Measure?
The SHBG test measures the concentration of sex hormone binding globulin protein in your blood. SHBG is a glycoprotein produced primarily by the liver. It has binding sites that attach to sex hormones with different affinities — it binds testosterone more tightly than estradiol, and binds dihydrotestosterone (DHT) most tightly of all.
How SHBG Affects Hormone Availability
Sex hormones in blood exist in three forms. Tightly bound to SHBG (about 40-60% of testosterone, 40% of estradiol), these hormones are essentially inactive. Loosely bound to albumin (about 40-50%), these hormones can dissociate and become available. Free/unbound (about 1-3% of testosterone, 2-3% of estradiol), these hormones are immediately available to enter cells. The free plus albumin-bound portions together constitute “bioavailable” hormone — the amount that can actually affect tissues.
When SHBG is high, more hormone is tightly bound and less is free. Total hormone might look normal, but free hormone is low, causing symptoms of deficiency. When SHBG is low, less is bound and more is free. Total hormone might look normal, but free hormone is elevated, potentially causing symptoms of excess.
What Regulates SHBG
Multiple factors influence SHBG production by the liver. Estrogen increases SHBG — this is why women have higher SHBG than men, and why SHBG rises with estrogen-containing medications. Thyroid hormone increases SHBG — hyperthyroidism raises it, hypothyroidism lowers it. Insulin decreases SHBG — insulin resistance and high insulin states lower SHBG, which is why it’s a metabolic marker. Androgens decrease SHBG — testosterone tends to lower SHBG. Liver health affects SHBG — liver disease can either raise or lower it depending on the type. Age and body composition also play roles.
Why This Test Matters
For Women
Evaluates androgen excess symptoms. Women with acne, hirsutism, or hair loss may have normal total testosterone but low SHBG, resulting in elevated free testosterone that causes symptoms. SHBG helps identify this pattern, common in PCOS.
Helps diagnose PCOS. Low SHBG is common in polycystic ovary syndrome, contributing to the androgen excess that characterizes the condition. SHBG testing is part of comprehensive PCOS evaluation.
Assesses metabolic risk. Low SHBG in women is associated with insulin resistance, metabolic syndrome, and increased diabetes risk. It can be an early warning sign prompting lifestyle intervention.
For Men
Clarifies testosterone status. Total testosterone alone doesn’t tell the whole story. A man with normal total testosterone but high SHBG may have low free testosterone and genuine symptoms. Conversely, low-normal total testosterone with low SHBG may provide adequate free testosterone.
Calculates free testosterone. Free testosterone is difficult to measure directly. More commonly, it’s calculated from total testosterone, SHBG, and albumin. SHBG is essential for this calculation.
Guides testosterone therapy decisions. Understanding SHBG helps interpret testosterone levels during treatment. Some men have SHBG changes that affect how much testosterone is bioavailable.
Metabolic Health Marker
Indicates insulin resistance. SHBG is inversely related to insulin levels — higher insulin drives SHBG lower. Low SHBG often appears before fasting glucose abnormalities, making it an early metabolic warning sign.
Predicts diabetes risk. Multiple studies show low SHBG independently predicts future type 2 diabetes, even after accounting for other risk factors.
Associates with fatty liver. Non-alcoholic fatty liver disease (NAFLD) is associated with low SHBG, reflecting both the metabolic dysfunction and potentially altered liver protein synthesis.
Value of Testing for Complete Picture
SHBG transforms how we interpret sex hormone levels. Testing SHBG alongside total testosterone or estradiol provides much more clinical information than total hormones alone. For anyone with hormone-related symptoms that don’t match their total hormone levels, or anyone concerned about metabolic health, SHBG adds crucial context. It helps avoid both undertreatment (missing low free hormones despite normal totals) and overtreatment (treating based on total levels when free hormones are adequate).
What Can Affect SHBG Levels?
Causes of High SHBG
- Estrogen therapy (oral contraceptives, hormone replacement)
- Pregnancy — estrogen increases drive SHBG up
- Hyperthyroidism — thyroid hormone increases SHBG production
- Liver disease (cirrhosis, hepatitis — certain types)
- Anorexia nervosa and low body weight
- Aging — SHBG tends to increase with age
- HIV infection
- Anticonvulsant medications
Causes of Low SHBG
- Insulin resistance and hyperinsulinemia
- Metabolic syndrome
- Type 2 diabetes
- Obesity — especially central/abdominal obesity
- Polycystic ovary syndrome (PCOS)
- Hypothyroidism
- Non-alcoholic fatty liver disease (NAFLD)
- Androgen excess or androgen therapy
- Growth hormone excess (acromegaly)
- Cushing’s syndrome
- Nephrotic syndrome
Medications Affecting SHBG
Oral estrogens raise SHBG more than transdermal (patch/gel) estrogens because oral estrogens pass through the liver first. This “first-pass effect” stimulates SHBG production. Androgens and anabolic steroids lower SHBG. Some anticonvulsants and other medications also affect SHBG levels.
When Should You Get Tested?
For Women
Symptoms of androgen excess: Hirsutism (excess facial/body hair), acne, or hair loss with normal total testosterone — low SHBG might explain the symptoms.
PCOS evaluation: SHBG is commonly tested as part of comprehensive PCOS workup.
Metabolic concerns: Family history of diabetes, signs of insulin resistance, or metabolic syndrome evaluation.
For Men
Low testosterone symptoms with normal total testosterone: Fatigue, low libido, erectile dysfunction when total T is normal — high SHBG might be reducing free testosterone.
Calculating free testosterone: When accurate assessment of bioavailable testosterone is needed.
Before or during testosterone therapy: Understanding SHBG helps interpret treatment response.
For Both Sexes
Metabolic health assessment: As part of comprehensive metabolic evaluation, especially with obesity, prediabetes, or metabolic syndrome.
Thyroid disorder evaluation: When hormone symptoms don’t match thyroid treatment expectations.
Unexplained hormone symptoms: When symptoms don’t match total hormone levels.
Understanding Your Results
SHBG interpretation depends on clinical context, sex, and what symptoms or conditions are being evaluated.
High SHBG
In men, high SHBG reduces free testosterone even when total testosterone is normal. This can cause low testosterone symptoms (fatigue, low libido, erectile dysfunction) despite normal total T. The solution might involve addressing underlying causes (hyperthyroidism, liver disease, medications) rather than simply adding testosterone.
In women, high SHBG generally isn’t problematic for androgen-related symptoms — it reduces free androgens, which can actually be beneficial. However, very high SHBG might contribute to low free estradiol symptoms in some cases.
Low SHBG
In men, low SHBG increases free testosterone relative to total testosterone. A man with low-normal total testosterone but low SHBG may have adequate free testosterone. However, low SHBG often indicates metabolic problems that deserve attention.
In women, low SHBG increases free androgens, potentially causing hirsutism, acne, and other androgen excess symptoms even with normal total testosterone. Low SHBG is also a metabolic warning sign associated with insulin resistance and diabetes risk.
Using SHBG to Calculate Free Testosterone
Free testosterone is difficult to measure directly — most labs calculate it from total testosterone, SHBG, and albumin. This calculated value helps assess true androgen status when SHBG is abnormal.
What to Do About Abnormal Results
For High SHBG
Identify underlying causes: Check thyroid function (hyperthyroidism raises SHBG), review medications (oral estrogens, anticonvulsants), evaluate liver function, and consider other causes.
In men with symptoms: Calculate free testosterone. If free testosterone is low despite normal total testosterone, address reversible causes first. If hyperthyroidism is present, treating it will lower SHBG. If medications are responsible, alternatives might be considered.
Consider clinical significance: High SHBG itself isn’t dangerous — the question is whether it’s causing symptoms through reduced free hormone.
For Low SHBG
Assess metabolic health: Low SHBG is strongly associated with insulin resistance. Check fasting glucose, HbA1c, and lipids. Consider metabolic syndrome evaluation.
In women with androgen symptoms: Calculate free testosterone. Androgen excess symptoms with normal total testosterone but low SHBG confirms that free androgens are elevated. Treatment targets the underlying condition (often PCOS) and may include medications that raise SHBG (oral contraceptives) or reduce androgen effects.
Address modifiable factors: Weight loss, exercise, and dietary improvements can raise SHBG by improving insulin sensitivity. Treating hypothyroidism if present will raise SHBG.
Consider it a metabolic warning: Low SHBG may appear before diabetes develops. It’s an opportunity for early lifestyle intervention.
Related Health Conditions
Polycystic Ovary Syndrome (PCOS)
Low SHBG is characteristic of PCOS, contributing to the androgen excess that causes many PCOS symptoms. The insulin resistance common in PCOS drives SHBG down, increasing free testosterone. SHBG testing helps confirm androgen excess even when total testosterone is normal. Treatments that improve insulin sensitivity (metformin, weight loss) tend to raise SHBG.
Metabolic Syndrome
Low SHBG is associated with metabolic syndrome — the cluster of conditions including abdominal obesity, high blood pressure, elevated glucose, and abnormal cholesterol that increase cardiovascular and diabetes risk. SHBG is inversely related to insulin levels and may be an early marker of metabolic dysfunction.
Type 2 Diabetes
Low SHBG independently predicts future type 2 diabetes development, even after accounting for BMI and other risk factors. The relationship reflects SHBG’s inverse correlation with insulin levels. Testing SHBG can identify diabetes risk early, prompting preventive lifestyle intervention.
Male Hypogonadism
In evaluating low testosterone symptoms, SHBG helps determine true androgen status. High SHBG can cause symptoms even with normal total testosterone by reducing free testosterone. Conversely, low SHBG might mean adequate free testosterone despite low-normal total testosterone. Accurate assessment prevents both undertreatment and overtreatment.
Hyperthyroidism
Excess thyroid hormone increases hepatic SHBG production, raising SHBG levels. This can reduce free sex hormones and contribute to symptoms. In women, it may cause menstrual irregularities. In men, it can contribute to low free testosterone symptoms. Treating hyperthyroidism normalizes SHBG.
Hypothyroidism
Low thyroid hormone reduces SHBG production. In women, this can increase free androgens, potentially contributing to hirsutism or acne. Hypothyroidism is one cause of low SHBG to consider in evaluation. Thyroid hormone replacement normalizes SHBG.
Non-Alcoholic Fatty Liver Disease (NAFLD)
NAFLD is associated with low SHBG, reflecting both the metabolic dysfunction underlying fatty liver and potentially altered liver protein production. Low SHBG in the context of metabolic risk factors should prompt consideration of liver health evaluation.
Related Biomarkers Often Tested Together
Total Testosterone — SHBG determines what fraction of total testosterone is bioavailable.
Free Testosterone — Often calculated using SHBG and total testosterone.
Estradiol — Also bound by SHBG; relevant for complete hormone assessment.
TSH — Thyroid disorders affect SHBG; check thyroid if SHBG is abnormal.
Fasting Insulin — Insulin inversely affects SHBG; relevant for metabolic assessment.
HbA1c — Low SHBG predicts diabetes; check metabolic markers together.
Note: Information provided in this article is for educational purposes and doesn’t replace personalized medical advice.
Frequently Asked Questions
Sex Hormone Binding Globulin is a protein made by the liver that binds sex hormones (mainly testosterone and estradiol) in the blood. Hormones bound to SHBG are inactive. Only free (unbound) hormones can enter cells and have effects. SHBG controls how much active hormone is available.
Total testosterone includes both bound and free hormone. Only free testosterone is active. If SHBG is high, more testosterone is bound up and less is free — you might have low testosterone symptoms despite normal total testosterone. SHBG explains this discrepancy.
The most common cause is insulin resistance — high insulin suppresses SHBG production. This makes low SHBG common in obesity, metabolic syndrome, PCOS, and type 2 diabetes. Hypothyroidism, androgen use, and certain other conditions also lower SHBG.
Estrogen increases SHBG, so pregnancy and oral contraceptives/hormone therapy raise it. Hyperthyroidism, liver disease, aging, and certain medications also increase SHBG.
Low SHBG itself isn’t harmful, but it’s a warning sign for metabolic problems. It’s associated with insulin resistance and predicts future diabetes risk. It also means more free androgens, which can cause symptoms in women (hirsutism, acne).
Yes. Weight loss and improved insulin sensitivity (through diet, exercise, or sometimes medication) can raise SHBG. Treating hypothyroidism raises SHBG. In women, oral contraceptives raise SHBG and can help with androgen excess symptoms.
Not usually in basic panels, but it’s valuable when hormone symptoms don’t match total hormone levels, when evaluating PCOS, when assessing metabolic health, or when calculating free testosterone in men.
References
Key Sources:
- Hammond GL. Plasma steroid-binding proteins: primary gatekeepers of steroid hormone action. J Endocrinol. 2016;230(1):R13-25.
- Ding EL, et al. Sex hormone-binding globulin and risk of type 2 diabetes in women and men. N Engl J Med. 2009;361(12):1152-1163.
- Wallace IR, et al. Sex hormone binding globulin and insulin resistance. Clin Endocrinol. 2013;78(3):321-329.
