From the Guidelines
Low sex hormone-binding globulin (SHBG) levels can be caused by several factors, including obesity, insulin resistance, metabolic syndrome, and type 2 diabetes, as well as polycystic ovarian morphology (PCOM) in women with functional hypothalamic amenorrhoea (FHA) 1.
Causes of Low SHBG
The causes of low SHBG are multifactorial and can include:
- Obesity and insulin resistance, which lead to increased insulin levels that suppress SHBG production in the liver
- Metabolic syndrome and type 2 diabetes
- Hypothyroidism, as thyroid hormones normally stimulate SHBG production
- Certain medications like glucocorticoids, growth hormone, and anabolic steroids
- Genetic factors, with some individuals having naturally lower SHBG levels
- Excessive alcohol consumption, liver disease, and high-protein diets
- PCOM in women with FHA, which is associated with lower SHBG levels, higher BMI, and higher levels of anti-Müllerian hormone (AMH) and testosterone 1
Clinical Significance
Low SHBG is clinically significant because it increases the amount of free (unbound) sex hormones in the bloodstream, potentially leading to symptoms of hormone excess in both men and women.
Management
Addressing the underlying cause is key to managing low SHBG, which might involve:
- Weight loss through diet and exercise for obesity-related cases
- Better management of diabetes or thyroid conditions
- Adjusting medications under medical supervision
- Considering the diagnosis of FHA-PCOM in women with amenorrhoea and PCOM, and using parameters such as serum levels of LH, testosterone, and SHBG to differentiate between FHA-PCOM and PCOS 1
From the Research
Causes of Low SHBG
- Low Sex Hormone-Binding Globulin (SHBG) is associated with various diseases, including polycystic ovary syndrome (PCOS), obesity, insulin resistance, metabolic syndrome, and diabetes type II 2.
- Emerging evidence suggests that liver fat content, rather than body mass index (BMI), is a strong determinant of circulating SHBG levels 3.
- Risk factors for low SHBG include higher body mass index, diabetes, ethnicity, chronic obstructive pulmonary disease, coronary heart disease, and smoking 4.
- SHBG levels correlate with insulin resistance in postmenopausal women, and may be a useful index of hyperinsulinemia and/or insulin resistance in this population 5.
- In women with PCOS, SHBG levels are negatively associated with fasting blood sugar, fasting insulin, and triglyceride levels, and may be a helpful biomarker for the diagnosis of PCOS 6.
Metabolic and Hormonal Associations
- Low SHBG levels are associated with metabolic disturbances, including insulin resistance, glucose intolerance, and dyslipidemia 2, 5.
- SHBG levels are negatively correlated with free androgen index (FAI) in both pre- and postmenopausal women 5.
- Dehydroepiandrosterone sulfate (DHEA-S) levels are positively associated with fasting insulin levels in women with PCOS 6.
- Triglyceride levels are positively associated with fasting blood sugar and HOMA-IR, and negatively associated with SHBG levels in women with PCOS 6.
Clinical Implications
- Therapeutic interventions that improve SHBG levels may reduce PCOS-associated complications 2.
- SHBG levels may be a useful biomarker for the diagnosis and treatment of PCOS, as well as for identifying individuals at risk of metabolic disturbances 2, 6.
- Further research is needed to fully understand the mechanisms underlying the regulation of SHBG levels and their relationship to metabolic and hormonal disturbances 3.