Sex Hormone Binding Globulin (SHBG) is a glycoprotein produced primarily in the liver. This protein acts as a transport mechanism in the bloodstream for sex hormones, including Testosterone, Dihydrotestosterone (DHT), and Estradiol. By binding to these hormones, SHBG controls the amount of active hormone available to interact with target tissues throughout the body. When a hormone is bound to SHBG, it is considered inactive, regulating the proportion of sex hormones that are biologically active.
Lifestyle and Nutritional Factors That Elevate SHBG
Several non-disease factors related to daily habits and physiology can lead to an increase in SHBG levels in men. The aging process is a common physiological contributor, as SHBG levels tend to increase progressively in men over the age of 60. This rise is often associated with the natural decline in testosterone production that occurs with advancing age.
Significant changes in body composition and diet can also affect SHBG synthesis in the liver. Severe caloric restriction, rapid weight loss, or being significantly underweight, such as in cases of anorexia nervosa, consistently elevates SHBG concentrations. This dietary stress signals metabolic changes that increase the binding protein’s production.
Chronic, heavy consumption of alcohol is another factor linked to elevated SHBG levels. Excessive alcohol intake can disrupt normal liver function, leading to increased SHBG production. Specific dietary patterns, such as very low-fat or high-fiber diets, have also been observed to increase SHBG concentrations.
Underlying Medical Conditions and Medications as Causes
Several medical conditions and pharmaceutical agents can increase SHBG production. Hyperthyroidism, characterized by an overactive thyroid gland, is a common cause. The excessive production of thyroid hormone directly enhances the synthesis of SHBG by the liver.
Chronic liver disease, particularly cirrhosis or chronic hepatitis, can lead to elevated SHBG levels. Liver dysfunction often results in altered regulatory signals, contributing to increased synthesis of the binding globulin. Conditions that result in chronically low testosterone levels, such as certain forms of hypogonadism, can also indirectly drive SHBG up.
Certain medications are also known to influence SHBG production. Anticonvulsant drugs used to manage seizures are linked to elevated levels. Exposure to high doses of exogenous estrogens or synthetic hormones can stimulate the liver’s output of SHBG, mimicking estrogenic states.
Clinical Manifestations of High SHBG
When SHBG levels are high, they bind an excessive proportion of circulating testosterone, reducing the “free” or unbound fraction of the hormone. Free testosterone is the biologically active form that exerts effects on cells. High SHBG leads to functional hypogonadism, even if total testosterone levels are normal, resulting in symptoms associated with testosterone deficiency.
Sexual health is often impacted, with common complaints including reduced libido or loss of interest in sex. Men may notice a decline in the quality of erections, experiencing erectile dysfunction or a decreased frequency of spontaneous morning erections. These symptoms arise because the active hormone required for normal sexual function is effectively “locked up” by the elevated SHBG.
Systemic effects of low free testosterone are also evident, presenting as persistent and unexplained fatigue or low energy levels. Men may observe a reduction in muscle mass and strength, even with consistent exercise, alongside an increase in body fat accumulation. Over time, chronically low free testosterone can contribute to a decrease in bone mineral density, raising the risk of developing osteoporosis and fractures.
Diagnostic Testing and Management Strategies
The investigation of suspected high SHBG begins with a blood test to measure the Total Testosterone, Free Testosterone, and SHBG levels. Measuring SHBG directly allows a healthcare provider to calculate the Free Androgen Index or the bioavailable testosterone, which provides a more accurate picture of hormone availability than total testosterone alone. These tests are often performed in the morning, as testosterone levels exhibit a diurnal variation.
If elevated SHBG is confirmed, comprehensive testing is required to identify the underlying cause, which is the primary focus of management. This includes evaluating thyroid function with tests like TSH and free T4, and assessing liver function with enzyme panels. A thorough review of all medications and a discussion of lifestyle factors like alcohol intake, diet, and weight fluctuations are also necessary.
Treatment centers on addressing the root pathology, such as managing a thyroid disorder or treating chronic liver disease. For cases linked to dietary habits or alcohol consumption, management involves nutritional counseling and lifestyle modification to normalize metabolic balance. If the underlying cause cannot be fully corrected and the man remains symptomatic with low free testosterone, therapeutic options like testosterone replacement therapy may be considered to overcome the binding effect of the high SHBG.