What are the causes of Sex Hormone-Binding Globulin (SHBG) elevation in females?

From the Guidelines

Elevated Sex Hormone Binding Globulin (SHBG) in females should be addressed through lifestyle modifications and treating underlying causes, with a focus on weight normalization, dietary changes, and regular strength training, as these interventions can help optimize hormone balance and reduce the risk of associated morbidities, such as breast cancer and metabolic syndrome, as suggested by recent studies 1. The management of elevated SHBG in women typically involves addressing the underlying cause, such as adjusting estrogen-containing medications, treating thyroid disorders, or modifying diet and exercise habits.

• Common causes of elevated SHBG in women include oral estrogen therapy, hyperthyroidism, liver disease, anorexia nervosa, and certain medications like anticonvulsants, as noted in studies 1.
• Symptoms may include decreased libido, vaginal dryness, and irregular menstruation due to reduced free testosterone.
• Dietary changes that may help include increasing protein intake, moderating carbohydrate consumption, and ensuring adequate caloric intake.
• Laboratory testing should include thyroid function tests, liver function tests, and free hormone levels in addition to SHBG to properly assess the hormonal status and guide treatment.
• Recent studies have highlighted the importance of lifestyle modifications in improving breast cancer prognosis and reducing the risk of metabolic syndrome, which is associated with elevated SHBG levels 1.
• The relationship between SHBG and breast cancer is complex and influenced by various factors, including estrogen levels, insulin-like growth factor-1, and inflammatory markers, as illustrated in Figure 1 of the study 1.

From the Research

SHBG Elevation in Female

• SHBG (Sex Hormone Binding Globulin) is a protein that plays a crucial role in transporting sex steroids in the body 2, 3, 4.
• In females, SHBG levels can be influenced by various factors such as nutritional factors, body mass index (BMI), and polycystic ovary syndrome (PCOS) 2.
• Studies have shown that SHBG concentrations are negatively correlated with BMI and central adiposity, and insulin may be the humoral mediator of the weight-dependent changes in SHBG 2.
• Elevated SHBG levels have been observed in elderly women with Alzheimer's disease, suggesting an abnormal increase in its production and regulation 5.
• SHBG levels can also be affected by various diseases, including hyperthyroidism, hypogonadism, androgen insensitivity, and hepatic cirrhosis 4.
• The combination of Anti-Müllerian hormone (AMH) and SHBG levels has been suggested as a diagnostic biomarker for polycystic ovary syndrome (PCOS) 6.

Factors Influencing SHBG Levels

• Nutritional factors: calorie restriction can lead to an increase in SHBG levels, while an isocaloric, low-fat diet has no significant effect 2.
• Body mass index (BMI): SHBG concentrations are negatively correlated with BMI and central adiposity 2.
• Insulin: insulin may be the humoral mediator of the weight-dependent changes in SHBG 2.
• Polycystic ovary syndrome (PCOS): SHBG levels are lower in women with PCOS, and the combination of AMH and SHBG levels can be used as a diagnostic biomarker for PCOS 2, 6.

Clinical Significance of SHBG

• SHBG levels can be used to evaluate mild disorders of androgen metabolism and identify women with hirsutism who are more likely to respond to estrogen therapy 4.
• The combination of AMH and SHBG levels can be used as a diagnostic biomarker for PCOS 6.
• Elevated SHBG levels have been observed in elderly women with Alzheimer's disease, suggesting a potential link between SHBG and neurodegenerative diseases 5.