From the Guidelines
Elevated Sex Hormone-Binding Globulin (SHBG) levels are primarily caused by liver disease, hyperthyroidism, and high estrogen states, as well as certain medications and aging, with the most recent and highest quality evidence suggesting liver disease as a significant factor 1.
Causes of Elevated SHBG
Elevated SHBG levels can be caused by several physiological conditions and external factors. SHBG is a protein produced primarily in the liver that binds to sex hormones, particularly testosterone and estradiol, regulating their bioavailability in the bloodstream.
- Common causes of elevated SHBG include:
- Liver disease (such as hepatitis and cirrhosis) 1
- Hyperthyroidism
- Eating disorders
- Significant weight loss
- Hormonal factors also play a major role, with high estrogen states like pregnancy and oral contraceptive use frequently increasing SHBG levels 1
- Certain medications beyond contraceptives can raise SHBG, including anticonvulsants, some antipsychotics, and hormone replacement therapy
- Aging naturally increases SHBG levels, particularly in men
- Other factors include HIV infection, excessive alcohol consumption, and some genetic variations
Clinical Significance and Management
Elevated SHBG is clinically significant because it reduces the amount of free (bioavailable) testosterone and other sex hormones, potentially leading to symptoms of hormone deficiency despite normal total hormone levels.
- Management typically focuses on addressing the underlying cause rather than treating SHBG levels directly
- In cases of liver disease, management of the underlying liver condition is crucial, as SHBG levels can fluctuate with the progression of the disease 1
- For other causes, such as hormonal imbalances or medication-induced elevations, addressing the underlying issue or adjusting medications can help normalize SHBG levels
- In some cases, such as obesity-related hypogonadism, testosterone replacement therapy may be considered, but this should be individualized and monitored closely 1
From the Research
Causes of Elevated Sex Hormone-Binding Globulin (SHBG)
- Elevated SHBG levels can be caused by various factors, including:
- Thyroid status: Hyperthyroidism is associated with high SHBG levels, whereas hypothyroid patients have low or normal SHBG levels 2, 3
- Metabolic diseases: Certain metabolic diseases, such as obesity and metabolic syndrome, can result in changed SHBG serum levels 4, 5
- Endocrine disorders: Endocrine disorders that affect tissues involved in sex hormone regulation, such as polycystic ovary syndrome, can also impact SHBG levels 4
- Hormone levels: Changes in hormone levels, such as increased estrogen and thyroid hormone levels, can stimulate SHBG production 2, 5
- Age-related diseases: Elevated SHBG levels have been found in elderly women with Alzheimer's disease 6
- Drug interactions: Certain drugs, such as tamoxifen and genistein, can increase SHBG production and gene promoter activity 5
- The liver plays a crucial role in regulating SHBG levels, and factors that affect liver function, such as lipogenesis and free fatty acid biosynthesis, can impact SHBG expression 5
- SHBG levels can be used as a marker of certain pathological states, including metabolic syndrome and insulin resistance 4, 5