From the Guidelines
A sharp rise in Sex Hormone-Binding Globulin (SHBG) levels can be caused by estrogen-containing medications, hyperthyroidism, liver disease, significant caloric restriction, aging, certain medications like anticonvulsants, and pregnancy. The most recent and highest quality study, 1, suggests that liver disease, particularly cirrhosis, can cause a rise in SHBG levels, although the reasons for this rise remain unclear. Some key factors that can cause a sharp rise in SHBG levels include:
- Estrogen-containing medications, which stimulate SHBG production in the liver
- Hyperthyroidism, which enhances hepatic SHBG synthesis
- Liver disease, particularly cirrhosis, which can disrupt the liver's ability to regulate SHBG production
- Significant caloric restriction and anorexia nervosa, which can cause a spike in SHBG levels as part of the body's response to malnutrition
- Aging, which naturally increases SHBG levels, especially in men after age 50
- Certain medications like anticonvulsants (phenytoin, carbamazepine) and HIV medications, which can also elevate SHBG
- Pregnancy, which causes dramatic increases in SHBG levels due to rising estrogen levels, as noted in 1. It's worth noting that the study 1 from 2002 found that antiepileptic drugs, including carbamazepine and phenytoin, can induce hepatic cytochrome P450 dependent steroid hormone breakdown and the production of sex hormone binding globulins (SHBG), thereby reducing biologically active sex hormone serum concentrations. However, the most recent study 1 provides more insight into the causes of a sharp rise in SHBG levels, particularly in the context of liver disease. Therefore, liver disease, particularly cirrhosis, should be considered as a potential cause of a sharp rise in SHBG levels, as it is a significant factor that can disrupt the liver's ability to regulate SHBG production, as noted in 1.
From the Research
Causes of a Sharp Rise in SHBG Levels
Several factors can contribute to a sharp rise in Sex Hormone-Binding Globulin (SHBG) levels, including:
- Thyroid hormones: Studies have shown that thyroid hormones can increase SHBG production indirectly by increasing hepatocyte nuclear factor-4alpha (HNF-4alpha) gene expression and reducing cellular palmitate levels 2.
- Certain medications: Tamoxifen, a drug used to treat breast cancer, has been shown to increase SHBG levels in patients with carcinoma of the breast 3.
- Thyrotoxicosis: Children and adolescents with thyrotoxicosis have been found to have elevated SHBG levels, which normalize after antithyroid therapy 4.
- Metabolic factors: SHBG levels are also regulated by metabolic factors, such as liver function and nutritional status 5.
- Hormonal changes: SHBG levels can be influenced by changes in androgen and estrogen levels, as well as other hormonal factors 5, 6.
Disease Conditions Associated with Altered SHBG Levels
Certain disease conditions can also be associated with altered SHBG levels, including:
- Hyper- and hypoandrogenism
- Thyroid disorders
- Pituitary diseases
- Liver disorders
- Breast and prostate cancer 5 These conditions can lead to changes in SHBG levels, which can be used as a biomarker to diagnose and monitor disease progression.