Sex Hormone-Binding Globulin (SHBG) is a protein produced primarily by the liver that travels through the bloodstream. Its main role is to bind and transport sex hormones, specifically testosterone, dihydrotestosterone (DHT), and estradiol. A high SHBG result indicates that the body is producing more of this carrier protein than expected. This elevation is a sign that a physiological change or external factor is influencing liver function, often leading to hormonal imbalance.
The Function of SHBG and Its Impact on Free Hormones
SHBG regulates the bioavailability of sex hormones within the body. When SHBG binds to a hormone molecule, that hormone becomes temporarily inactive and cannot interact with cell receptors to exert its effects. These hormones are considered “bound” and are essentially in a storage or transport state.
Only a small fraction of sex hormones remains unbound, or “free,” and this fraction is biologically active and able to enter tissues. High levels of SHBG mean that a larger proportion of your total sex hormones are being tightly bound and sequestered. This reduction in the bioavailable or “free” hormone fraction is the central issue associated with elevated SHBG.
Even if total testosterone or total estradiol levels are within the normal range, high SHBG can lead to symptoms of hormone deficiency. The tissues in your body rely on the free hormones to function correctly. When too many hormones are trapped by SHBG, symptoms like low libido, chronic fatigue, decreased muscle mass, and mood changes can occur.
Primary Medical Conditions That Elevate SHBG
Internal physiological changes often signal the liver to increase its production of SHBG. One of the most common medical causes of elevated SHBG is hyperthyroidism, or an overactive thyroid gland. High levels of thyroid hormones stimulate the liver cells to synthesize and release more SHBG into circulation. Treating the underlying thyroid condition typically leads to the normalization of SHBG levels.
Conditions affecting the liver itself can also cause an elevation, particularly in cases of cirrhosis. Although the liver is the site of SHBG production, damage from chronic disease can sometimes lead to an overproduction. Genetic factors also play a part, with specific variations in the SHBG gene accounting for a portion of the natural variation seen in the population.
In some individuals, especially women, certain endocrine states can drive SHBG up significantly. Pregnancy, for instance, dramatically increases SHBG due to high estrogen production, which is a normal and temporary state. Furthermore, severe caloric restriction or eating disorders, like anorexia nervosa, can lead to very high SHBG levels due to low body weight and nutritional deficiencies. Low levels of growth hormone can also be associated with increased SHBG levels in both men and women.
Lifestyle and Medication Factors Influencing SHBG Levels
External factors, including diet and pharmaceutical interventions, can significantly influence the liver’s production of SHBG. A high intake of synthetic estrogen, most commonly found in oral contraceptive pills, is one of the most potent stimulators of SHBG synthesis. The estrogen component in these medications sends a strong signal to the liver, causing a substantial increase in the binding protein. Similarly, some forms of hormone replacement therapy can have the same effect.
Certain anticonvulsant and anti-epileptic medications are also known to raise SHBG levels over time. These drugs can interfere with the liver’s normal metabolic processes, indirectly promoting the production of the globulin. If you have recently started a new medication, it is important to discuss its potential hormonal side effects with your prescribing physician.
Dietary and body composition changes are another significant set of factors. Chronic, excessive alcohol consumption can burden the liver and alter its hormone-regulating capacity. Furthermore, a consistently low-calorie intake, a very low-fat diet, or rapid weight loss can all contribute to elevated SHBG levels, as the body interprets these states as periods of nutritional stress.
Clinical Management of Elevated SHBG
The management of high SHBG focuses primarily on identifying and treating the underlying cause, as there is no specific medication approved to directly lower SHBG levels. A healthcare provider will likely begin by conducting a thorough diagnostic workup, including a review of your medication history. This evaluation will often involve tests for thyroid-stimulating hormone (TSH) to check for hyperthyroidism and liver enzyme panels to assess liver function.
If a medical condition is identified, such as an overactive thyroid, treating that condition is the most effective way to restore SHBG to a healthy range. In cases where medication is the cause, your doctor may suggest an alternative treatment or a modification of the current dosage. For instance, switching from an oral estrogen contraceptive to a non-oral form can sometimes mitigate the SHBG-raising effect.
Lifestyle modifications are often recommended. Ensuring adequate caloric and protein intake is important, as severe dietary restriction can be a driving factor. Addressing any nutritional deficiencies and maintaining a healthy body weight can help regulate the liver’s hormone-binding protein synthesis.