Sex Hormone Binding Globulin (SHBG) is a protein synthesized predominantly by the liver that circulates throughout the bloodstream. This molecule acts as a transport vehicle for specific steroid hormones, primarily managing their delivery and availability to the body’s cells and tissues. By binding to these hormones, SHBG effectively regulates the proportion that is biologically available to exert effects. This mechanism ensures a controlled supply of hormonal signals, maintaining overall physiological balance.
How SHBG Controls Free Hormones
SHBG modulates the activity of sex hormones by binding to them with high affinity. The primary hormones it binds are testosterone, its potent metabolite dihydrotestosterone (DHT), and the estrogen estradiol. When these hormones are attached to SHBG, they are considered “bound” and are largely inactive, unable to interact with cellular receptors to trigger a biological response.
A small fraction of these hormones remains unbound or loosely attached to other proteins like albumin, termed “free” or “bioavailable.” Only these free hormones are structurally available to diffuse into target cells and activate signaling pathways. SHBG acts as a reservoir, regulating the amount of free hormone circulating at any given time. If SHBG levels are elevated, it sequesters a larger percentage of hormones, reducing the active free fraction.
Clinical Testing and Measurement
The measurement of SHBG is a standard procedure in clinical endocrinology, performed via a simple blood test. Clinicians typically order this test when investigating symptoms suggesting a sex hormone imbalance, even if total hormone levels appear normal. The concentration of SHBG in the serum helps interpret the true hormonal status of an individual.
The SHBG result is often mathematically combined with total testosterone to calculate the Free Androgen Index (FAI) or calculated free testosterone. This derived value provides a more accurate estimate of the biologically active hormone fraction than measuring total testosterone alone. This calculation is useful when symptoms of hormone excess or deficiency are present, such as hirsutism in women or unexplained low libido in men.
Factors Influencing SHBG Levels
The liver’s production of SHBG is highly responsive to metabolic and endocrine signals, leading to fluctuations in circulating levels.
Factors That Increase SHBG
Several factors increase SHBG production. These include elevated levels of estrogen, which is why women taking estrogen-containing oral contraceptives often exhibit higher concentrations. Hyperthyroidism, or an overactive thyroid, also stimulates the liver to produce more SHBG.
Age is another factor, as SHBG levels tend to increase naturally in men as they get older. Certain conditions like liver disease (specifically cirrhosis) and states of extreme low body weight (such as anorexia nervosa) are also associated with increased SHBG.
Factors That Decrease SHBG
A number of physiological states and conditions are linked to decreased SHBG levels. Obesity and high body mass index are strong inhibitors of SHBG synthesis. The presence of insulin resistance or hyperinsulinemia, often seen in Type 2 diabetes or metabolic syndrome, directly suppresses SHBG production.
High levels of androgens, whether produced naturally or introduced through external sources like anabolic steroids, can also decrease SHBG. Hypothyroidism (an underactive thyroid) and excessive growth hormone production are associated with a reduction in circulating SHBG.
Health Consequences of Imbalance
Consequences of High SHBG
When SHBG levels are abnormally high, they bind an excessive amount of sex hormones, leading to a deficiency of the free, active hormones. This reduction can manifest as fatigue, decreased libido, and difficulty maintaining muscle mass. In men, high SHBG often contributes to erectile dysfunction or hypogonadism symptoms despite normal total testosterone levels.
For women, excessively high SHBG can lead to a functional estrogen deficiency, potentially causing menstrual cycle irregularities or amenorrhea. The resulting low levels of free hormones can also negatively affect bone health, contributing to lower bone mineral density.
Consequences of Low SHBG
When SHBG levels are too low, the opposite effect occurs, resulting in an excess of free, biologically active sex hormones. In women, this is frequently a contributing factor in conditions like Polycystic Ovary Syndrome (PCOS). The resulting higher free androgen levels can cause symptoms such as acne, hirsutism, and irregular ovulation.
Low SHBG is a significant marker for metabolic dysfunction in both men and women. The strong association with insulin resistance and hyperinsulinemia means that low SHBG levels often correlate with an increased risk for developing Type 2 diabetes and metabolic syndrome.