SHBG/9285 Overview: Sex Hormone-Binding Globulin (SHBG), Serum

Test Catalog

Test Name

Normal View

Sex Hormone-Binding Globulin (SHBG), Serum

Useful For Suggests clinical disorders or settings where the test may be helpful

Diagnosis and follow-up of women with symptoms or signs of androgen excess (eg, polycystic ovarian syndrome and idiopathic hirsutism)


An adjunct in monitoring sex-steroid and anti-androgen therapy


An adjunct in the diagnosis of disorders of puberty


An adjunct in the diagnosis and follow-up of anorexia nervosa


An adjunct in the diagnosis of thyrotoxicosis (tissue marker of thyroid hormone excess)


A possible adjunct in diagnosis and follow-up of insulin resistance and cardiovascular and type 2 diabetes risk assessment, particularly in women


In laboratories without access to bioavailable testosterone or equilibrium dialysis-based "true" free testosterone assays, sex hormone-binding globulin measurement is crucial in cases when assessment of the free testosterone fraction (aka free androgen index or calculated free testosterone) is required. At Mayo Medical Laboratories, both bioavailable testosterone (TTBS / Testosterone, Total and Bioavailable, Serum) and free testosterone (TGRP / Testosterone, Total and Free, Serum) measurements are available. Free testosterone (TGRP) is measured by equilibrium dialysis, obviating the need for sex hormone-binding globulin measurements to calculate free androgen fractions.

Method Name A short description of the method used to perform the test

Automated Chemiluminescent Immunometric Assay

NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.


Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name

Sex Hormone Binding Globulin, S

Aliases Lists additional common names for a test, as an aid in searching

Sex Steroid Binding Protein (SBP)
Testosterone-Estradiol Binding Globulin (TeBG)
Testosterone-Estradiol Binding Globulin (TeBG) Performed at Mayo New England

Specimen Type Describes the specimen type validated for testing


Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.


Preferred: Red top

Acceptable: Serum gel

Specimen Volume: 0.5 mL

Specimen Minimum Volume The amount of sample necessary to provide a clinically relevant result as determined by the Laboratory.

0.4 mL

Reject Due To Identifies specimen types and conditions that may cause the specimen to be rejected


Mild OK; Gross reject


Mild OK; Gross OK





Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperatures are also included.

Specimen TypeTemperatureTime
SerumRefrigerated (preferred)14 days
 Frozen 60 days

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Sex hormone-binding globulin (SHBG), a homodimeric 90,000 to 100,000 molecular weight glycoprotein, is synthesized in the liver. Metabolic clearance of SHBG is biphasic, with a fast initial distribution from vascular compartment into extracellular space (half-life of a few hours), followed by a slower degradation phase (half-life of several days).


SHBG binds sex steroids with high affinity (KD approximately 10[-10]M), dihydrotestosterone (DHT) ->testosterone (T) ->estrone/estradiol (E). Although each monomeric subunit contains 1 steroid binding site, the dimer tends to bind only a single sex-steroid molecule. The main function of SHBG is sex-steroid transport within the blood stream and to extravascular target tissues. SHBG also plays a key role in regulating bioavailable sex-steroid concentrations through competition of sex steroids for available binding sites and fluctuations in SHBG concentrations. Because of the higher affinity of SHBG for DHT and T, compared to E, SHBG also has profound effects on the balance between bioavailable androgens and estrogens. Increased SHBG levels may be associated with symptoms and signs of hypogonadism in men, while decreased levels can result in androgenization in women.


SHBG levels in prepubertal children are higher than in adults. With the increase in fat mass during early puberty they begin to fall, a process that accelerates as androgen levels rise. Men have lower levels compared with women and nutritional status is inversely correlated with SHBG levels throughout life, possibly mediated by insulin resistance. Insulin resistance, even without obesity, results in lower SHBG levels. This is associated with increased intra-abdominal fat deposition and an unfavorable cardiovascular risk profile. In postmenopausal women, it may also predict the future development of type 2 diabetes mellitus. Androgens and norethisterone-related synthetic progesterones also decrease SHBG in women.


Endogenous or exogenous thyroid hormones or estrogens increase SHBG levels. In men, there is also an age-related gradual rise, possibly secondary to the mild age-related fall in testosterone production. This process can result in bioavailable testosterone levels that are much lower than would be expected based on total testosterone measurements alone.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.



Tanner Stages*

Mean Age

Reference Range (nmol/L)

Stage I



Stage II



Stage III



Stage IV



Stage V



*Puberty onset (transition from Tanner stage I to Tanner stage II) occurs for boys at a median age of 11.5 (+/-2) years. For boys, there is no definite proven relationship between puberty onset and body weight or ethnic origin. Progression through Tanner stages is variable. Tanner stage V (young adult) should be reached by age 18.



Tanner Stages*

Mean Age

Reference Range (nmol/L)

Stage I



Stage II



Stage III



Stage IV



Stage V



*Puberty onset (transition from Tanner stage I to Tanner stage II) occurs for girls at a median age of 10.5 (+/-2) years. There is evidence that it may occur up to 1 year earlier in obese girls and in African American girls. Progression through Tanner stages is variable. Tanner stage V (young adult) should be reached by age 18.



Males: 10-57 nmol/L

Females (non-pregnant): 18-144 nmol/L

Interpretation Provides information to assist in interpretation of the test results

Many conditions of mild-to-moderate androgen excess in women, particularly polycystic ovarian syndrome, are associated with low sex hormone-binding globulin (SHBG) levels. Most of these women are also insulin resistant and many are obese. A defect in SHBG production could lead to bioavailable androgen excess, in turn causing insulin resistance that depresses SHBG levels further. There are rare cases of SHBG mutations that clearly follow this pattern. SHBG levels are typically very low in these individuals. However, in most patients, SHBG levels are mildly depressed or even within the lower part of the normal range. In these patients, the primary problem may be androgen overproduction, insulin resistance, or both. A definitive cause cannot be usually established. Any therapy that either increases SHBG levels (eg, estrogens or weight loss), reduces bioactivity of androgens (eg, androgen receptor antagonists, alpha-reductase inhibitors), or reduces insulin resistance (eg, weight loss, metformin, peroxisome proliferator-activated receptor [PPAR] gamma agonists), can be effective. Improvement is usually associated with a rise in SHBG levels, but bioavailable or free testosterone levels should also be monitored.


The primary method of monitoring sex-steroid or antiandrogen therapy is direct measurement of the relevant sex-steroids and gonadotropins. However, for many synthetic androgens and estrogens (eg, ethinyl-estradiol) clinical assays are not available. In those instances, rises in SHBG levels indicate successful anti-androgen or estrogen therapy, while falls indicate successful androgen treatment.


Adult SHBG levels in boys with signs of precocious puberty support that the condition is testosterone driven, rather than representing premature adrenarche.


Patients with anorexia nervosa have high SHBG levels. With successful treatment, levels start to fall as nutritional status improves. Normalization of SHBG precedes, and may be predictive of, future normalization of reproductive function.


Thyrotoxicosis increases SHBG levels. In situations when assessment of true functional thyroid status may be difficult (eg, patients receiving amiodarone treatment, individuals with thyroid hormone transport-protein abnormalities, patients with suspected thyroid hormone resistance or suspected inappropriate thyroid-stimulating hormone [TSH] secretion such as a TSH-secreting pituitary adenoma), an elevated SHBG level suggests tissue thyrotoxicosis, while a normal level indicates euthyroidism or near-euthyroidism. In patients with gradual worsening of thyrotoxicosis (eg, toxic nodular goiter), serial SHBG measurement, in addition to clinical assessment, thyroid hormone, and TSH measurement, may assist in the timing of treatment decisions. Similarly, SHBG measurement may be of value in fine-tuning suppressive TSH therapy for patients with nodular thyroid disease or treated thyroid cancer. Results are not definitive in the short-term in patients receiving drugs that displace total thyroxine (T4) from albumin.


SHBG is also produced by placental tissue and therefore values will be elevated during pregnancy. Reference ranges for pregnant females have not been established in our institution.


In patients with known insulin resistance, "metabolic syndrome," or high risk of type 2 diabetes (eg, women with a history of gestational diabetes), low SHBG levels may predict progressive insulin resistance, cardiovascular complications, and progression to type 2 diabetes. An increase in SHBG levels may indicate successful therapeutic intervention.


A genetic variant of SHBG (Asp327->Asn) introduces an additional glycosylation site in 10% to 20% of the population, resulting in significantly slower degradation. These individuals tend to have higher SHBG levels for any given level of other factors influencing SHBG.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Human antimouse antibodies may be present in specimens from patients who have received immunotherapy utilizing monoclonal antibodies. Other heterophile antibodies may also be present in patient specimens. This assay has been specifically formulated to minimize the effects of these antibodies on the assay. However, results from patients known to have such antibodies must be carefully evaluated.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Pugeat M, Crave JC, Tourniare J, Forest MG: Clinical utility of sex hormone-binding globulin measurement. Horm Res 1996;45:148-155

2. Tehernof A, Despres JP: Sex steroid hormone, sex hormone-binding globulin, and obesity in men and women. Horm Metab Res 2000;32:526-536

3. Kahn SM, Hryb DJ, Nakhle AM, Romas NA: Sex hormone-binding globulin is synthesized in target cells. J Endocrinol 2002;175:113-120

4. Hammond GL: Access of reproductive steroids to target issues. Obstet Gynecol Clin North Am 2002;29:411-423

5. Elmlinger MW, Kuhnel W, Ranke MB: Reference ranges for serum concentrations of lutropin (LH), follitropin (FSH), estradiol (E2), prolactin, progesterone, sex hormone binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEA-S), cortisol and ferritin in neonates, children, and young adults. Clin Chem Lab Med 2002;40(11):1151-1160

Method Description Describes how the test is performed and provides a method-specific reference

IMMULITE 2000 sex hormone-binding globulin (SHBG) is a solid-phase, 2-site chemiluminescent immunoassay. A polystyrene bead is coated with a monoclonal antibody specific for sex hormone-binding globulin (SHBG). The patient sample, diluted 1 in 20, and alkaline phosphatase-conjugated anti-SHBG (polyclonal) are added to the bead and incubated. SHBG in the sample is bound to form an antibody sandwich complex. Unbound conjugate is then removed by washing, after which substrate is added. The chemiluminescent substrate, a phosphate ester of adamantly dioxetane, undergoes hydrolysis in the presence of alkaline phosphatase to yield an unstable intermediate. The continuous production of this substance results in the sustained emission of light. The photon output is proportional to the concentration of SHBG in the sample.(Package insert: IMMULITE SHBG 2000, July 2008)

PDF Report Indicates whether the report includes an additional document with charts, images or other enriched information


Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.

Monday through Friday; 5 a.m.-12 a.m., Saturday; 6 a.m.-6 p.m.

Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.

Same day/1 day

Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result

3 days

Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

14 days

Performing Laboratory Location The location of the laboratory that performs the test


Test Classification Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturers instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.

This test has been cleared or approved by the U.S. Food and Drug Administration and is used per manufacturer's instructions. Performance characteristics were verified by Mayo Clinic in a manner consistent with CLIA requirements.

CPT Code Information Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.


LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and result codes of this test.

LOINC codes are provided by the performing laboratory.

Test IDTest Order NameOrder LOINC Value
SHBGSex Hormone Binding Globulin, S13967-5


Result IDTest Result NameResult LOINC Value
SHBGSex Hormone Binding Globulin, S13967-5