Sex Hormone Binding Globulin (SHBG) is a protein produced primarily by the liver that circulates throughout the bloodstream. This protein acts as a carrier molecule for sex hormones, regulating their availability to the body’s tissues. Testing SHBG is a common practice when evaluating hormonal health, especially when symptoms suggest an imbalance in testosterone or estrogen. Since it binds to these hormones, SHBG effectively controls the balance between active and inactive hormone fractions in the circulation.
The Role of SHBG in Hormone Regulation
SHBG operates like a transport system, binding tightly to sex hormones, most notably testosterone, dihydrotestosterone (DHT), and estradiol. Once these hormones are bound to SHBG, they are considered inactive because they cannot easily detach to enter cells and activate their specific receptors. This binding mechanism limits the immediate biological activity of sex hormones.
The concentration of SHBG directly determines the ratio of “free” versus “bound” hormones in the blood. Free hormones are those that are not attached to any transport protein, and only this small, unbound fraction is considered biologically active and accessible to target tissues. A hormone must be free to interact with cells, much like a key must be separate from its keychain to unlock a door.
A significant portion of total circulating sex hormones is bound to SHBG, with only about one to two percent circulating in the free state. SHBG’s high binding affinity for sex steroids, particularly testosterone, makes it the primary regulator of how much active hormone is available. Changes in SHBG levels can dramatically alter the amount of free hormone, even if the total amount of hormone in the bloodstream remains stable.
What Defines a “Normal” SHBG Range
Determining a “normal” SHBG level involves considering several factors, as the reference range is a statistical range that varies significantly. A person’s sex, age, and the phase of the menstrual cycle in pre-menopausal women influence what is considered a typical value. Because different laboratories use unique testing methods, the precise cutoffs can vary from one lab report to the next.
Generally, adult males often exhibit SHBG levels in a lower range compared to adult females. For example, typical adult male ranges might fall between 10 and 57 nanomoles per liter (nmol/L), while non-pregnant adult females may have a broader range, such as 18 to 144 nmol/L, though these specific numbers are examples and not universal. Levels also change across the lifespan; SHBG is high in childhood, decreases during puberty, and then tends to rise again in men as they age.
The SHBG result is rarely interpreted in isolation by medical professionals. Instead, it is commonly used alongside a total hormone measurement, such as Total Testosterone, to calculate the Free Androgen Index (FAI). The FAI provides an estimate of the biologically available testosterone, offering a more complete picture of hormonal status. This calculation is particularly useful in evaluating androgen status in women.
Understanding the Causes and Effects of Elevated SHBG
When SHBG levels are elevated, a greater number of sex hormone molecules are bound and rendered inactive. Common causes that stimulate the liver to produce more SHBG include hyperthyroidism and liver diseases, such as chronic hepatitis or cirrhosis. Certain medications, including anti-seizure drugs and estrogen-containing oral contraceptives, are known to raise SHBG levels. For men, a gradual increase in SHBG is a natural part of the aging process.
High SHBG results in a decrease in the concentration of free, active sex hormones available to tissues, even if the total hormone level is within the normal statistical range. The effect often manifests as symptoms of hormone deficiency. In men, this can lead to reduced libido, fatigue, and decreased muscle mass. Women may experience similar issues, along with irregular or absent menstrual cycles. High SHBG creates a condition of functional hormone deficiency by sequestering the hormones away from their target cells.
Understanding the Causes and Effects of Depressed SHBG
A low SHBG level signifies that fewer binding proteins are available to carry sex hormones, leaving a higher proportion of free, active hormone in the circulation. Low SHBG is strongly associated with conditions linked to metabolic dysfunction, including insulin resistance and obesity. Hypothyroidism is another condition that can suppress SHBG production.
Polycystic Ovary Syndrome (PCOS) in women is frequently associated with low SHBG due to accompanying hyperinsulinemia and high androgen levels. In women, this excess of free androgens can lead to symptoms of hyperandrogenism, such as acne, hirsutism, and menstrual irregularities.
Low SHBG is considered a reliable marker for metabolic syndrome and an increased risk of developing Type 2 diabetes. The resulting hormonal environment may contribute to elevated blood pressure and an unfavorable lipid profile.