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- May 15, 2018 -

After steroid hormones are secreted into the circulation, they are mostly bound to specific proteins, namely sex hormone-binding globulin (SHBG), corticosteroid-binding globulin (CBG), and/or albumin (Table 2).18 All steroids bind to albumin with low affinity but high capacity. In contrast, SHBG binds with high affinity but low capacity to the sex steroids, including DHT, testosterone, and estradiol. The binding of DHT to SHBG is approximately 3.5-times that of testosterone and eight-times that of estradiol. CBG binds with high affinity but low capacity to corticosteroids, progesterone, and 17-hydroxyprogesterone.


Table 2. Major steroid-binding proteins in blood

ProteinSteroid(s) BoundBinding AffinityBinding Capacity
AlbuminAll steroidsLowHigh
α1-Acid glycoprotein (orosomucoid)ProgesteroneLowHigh
Sex hormone-binding globulin (SHBG)Dihydrotestosterone, testosterone, estradiolHighLow
Corticosteroid-binding globulin (CBG)Corticosteroids, progesterone, 17α-hydroxyprogesteroneHighLow


Table 3 shows the binding distribution of important endogenous steroid hormones in normal women during the menstrual cycle.18 Each steroid is mostly protein-bound; only a small percentage is unbound or free. Free steroids are available for action in target cells and also for metabolism in peripheral tissues. Thus, SHBG and CBG play an important role in regulating the availability of steroid hormones for biologic action and clearance.


Table 3. Binding distribution of principle endogenous steroid hormones in normal women during the menstrual cycle*

SteroidSHBG-Bound (%)CBG-Bound (%)Albuin-Bound (%)Unbound (%)

*Follicular and luteal values were averaged.
(Westphal U. Steroid-Protein Interactions, p 259. Berlin, Springer-Verlag, 1986.)


Of clinical importance is free testosterone, which is often elevated in hyperandrogenic women with clinical manifestations of hirsutism. The free testosterone is regulated by the concentration of SHBG in blood. The higher the SHBG level, the lower the free testosterone level, and vice versa. A number of factors can affect SHBG concentrations in blood. They include obesity, menopause, insulin, and androgens, each of which decreases SHBG levels.19 In contrast, SHBG levels are increased by estrogens, thyroid hormone, liver cirrhosis, and prolonged stress.19