Interpretation

Many conditions of mild-to-moderate androgen excess in women, particularly polycystic ovarian syndrome, are associated with low sex hormone-binding globulin (SHBG) concentrations. A defect in SHBG production could lead to bioavailable androgen excess, in turn causing insulin resistance that depresses SHBG concentrations further. There are rare cases of SHBG variants that follow this pattern. SHBG concentrations are typically very low in these individuals. However, in most patients, SHBG concentrations are mildly depressed or possibly within the lower part of the reference interval. In these patients, the primary problem may be androgen overproduction, insulin resistance, or both.

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

Therapies/behavior alterations that may potentially increase SHBG concentrations include reducers of bioactivity of androgens (eg, androgen receptor antagonists, alpha-reductase inhibitors) or reduction of insulin resistance (eg, weight loss, metformin, peroxisome proliferator-activated receptor gamma agonists). Clinical assays may not be available for many therapeutic synthetic androgens and estrogens (eg, ethinyl-estradiol). In those instances, increasing SHBG concentrations may be associated with anti-androgen or estrogen therapy, while SHBG reduction can be associated with androgen treatment.

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

Thyrotoxicosis increases SHBG concentrations. 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 thyrotropin [TSH] secretion, such as a TSH-secreting pituitary adenoma), elevated SHBG concentrations suggest tissue thyrotoxicosis, while normal levels indicate euthyroidism or near-euthyroidism.

SHBG is also produced by placental tissue and, therefore, values will be elevated during pregnancy. Reference ranges for pregnant women have not been established at 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 concentrations may predict progressive insulin resistance, cardiovascular complications, and progression to type 2 diabetes. An increase in SHBG concentrations 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 concentrations for any given level of other factors influencing SHBG.

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 (free androgen index or calculated free testosterone) is required. At Mayo Clinic 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.