From the Guidelines
Elevated sex hormone binding globulin (SHBG) capacity is primarily caused by conditions that affect liver function, such as advanced liver disease, which can lead to an increase in SHBG production, as seen in patients with cirrhosis 1. The causes of elevated SHBG can be multifactorial, including:
- Liver diseases, such as hepatitis and cirrhosis, which can affect SHBG production and lead to an increase in SHBG levels 1
- Hormonal imbalances, such as hyperthyroidism, which can increase SHBG production
- Estrogen excess from medications like oral contraceptives, hormone replacement therapy, or pregnancy
- Certain medications, including anticonvulsants, phenytoin, and some antipsychotics, which can raise SHBG levels
- Aging, which naturally increases SHBG in men
- Low body weight, caloric restriction, and excessive exercise, which can elevate SHBG levels in both sexes It is essential to address the underlying condition causing elevated SHBG, rather than targeting SHBG directly, to return SHBG to normal levels and alleviate symptoms of hormone deficiency. For example, normalizing thyroid function in hyperthyroidism or adjusting estrogen-containing medications can help return SHBG to normal levels. Elevated SHBG is clinically significant because it reduces the amount of free (bioavailable) sex hormones in circulation, potentially causing symptoms of hormone deficiency despite normal total hormone levels. According to a recent study, SHBG levels ultimately decline with further progression from compensated to decompensated cirrhosis 1.
From the Research
Causes of Elevated Sex Hormones Binding Capacity
Elevated sex hormones binding capacity, also known as elevated sex hormone-binding globulin (SHBG), can be caused by various factors, including:
- Thyroid hormones: Thyrotoxicosis is associated with high SHBG levels 2, 3, 4
- Estrogens and androgens: SHBG levels are regulated by these sex steroids 2
- Metabolic factors: Certain metabolic diseases, such as obesity and metabolic syndrome, can affect SHBG levels 5
- Liver disorders: The liver is the main organ responsible for producing SHBG, and liver diseases can alter SHBG levels 5
- Endocrine disorders: Diseases that affect tissues involved in sex hormone regulation, such as polycystic ovary syndrome (PCOS), can impact SHBG levels 5, 6
- Medications and alcohol consumption: Certain drugs and alcohol can influence SHBG levels 2
Disease Conditions Associated with Altered SHBG Levels
Several disease conditions are accompanied by altered SHBG levels, including:
- Hyper- and hypoandrogenism 2
- Thyroid disorders 2, 3, 4
- Pituitary diseases 2
- Liver disorders 2, 5
- Breast and prostate cancer 2, 5
- PCOS 6
- Obesity and metabolic syndrome 5
- Osteoporosis 5
SHBG as a Biomarker
SHBG can be used as a biomarker for certain disease conditions, including: