When Sex Hormone Binding Globulin Is Too High

Sex hormone binding globulin (SHBG), a transport protein for sex hormones, has a five-times stronger affinity for androgens such as testosterone and DHT than for estrogen. However, SHBG may have physiological roles beyond hormone transport (Goldstajn 2016).

SHBG production can be influenced by:

• Endocrine and liver disorders (Goldstajn 2016).
• Genetic factors (Simons 2021, Wallace 2013)
• Medications, alcohol intake, energy balance, physical activity, and dietary factors.
• A low-protein, low-fat diet can increase SHBG.
• Increased alcohol intake is associated with increased SHBG, while abstinence can reduce it (Ho 2023, Iturriaga 1999).
• Moderate alcohol intake can reduce SHBG, but excessive alcohol intake can increase it by 3-fold (Thaler 2015).
• A low SHBG is also associated with fatty liver, excess fructose intake obesity, glucose dysregulation, metabolic syndrome, PCOS, and increased risk of developing diabetes and cardiovascular disease (Goldstajn 2016).
• Elevated SHBG may be associated with decreased bone mineralization, increased fracture risk (Goldstajn 2016), hyperthyroidism, psychological stress, activation of the HPA axis (Thaler 2015), prostate cancer (Garcia-Cruz 2013, Thaler 2015), and CVD (Gyawali 2019).

The association between diet and SHBG levels is unclear and can vary. According to current research (Longcope 2000):

• SHBG increases as age increases.
• A high-fiber diet decreased SHBG in women, though increasing fiber has also been associated with increased SHBG.
• Vegetarian men and women were found to have increased SHBG levels compared to non-vegetarian.
• Increased caloric intake in people with anorexia decreased SHBG
• A very low-calorie diet doubled SHBG in women with PCOS.
• A high-fat diet decreased SHBG in men, and a low-fat diet increased it.
• Protein intake is negatively associated with SHBG; the lower the protein intake, the higher the SHBG level.
• A high-protein, high-fat diet may reduce elevated SHBG, which can also increase bioavailable testosterone in men.
• Protein intake increases insulin, which has an inhibitory effect on SHBG, lowering SHBG in the blood.

Some small-scale studies suggest that circulating SHBG levels may be (Gyawali 2018):

Inversely associated with

• Body composition
• C-reactive protein
• Estrogen
• Growth hormone
• Insulin
• Intrahepatic fat
• Moderate alcohol intake
• Monosaccharides
• Triglycerides

Positively associated with

• Adiponectin
• Follicle-stimulating hormone
• Physical activity and resistance training
• Total testosterone
• Thyroxine

Optimal Takeaways

Investigate and address potential causes of elevated SHBG, including

• Anorexia nervosa
• Excess alcohol intake
• Hyperthyroidism
• Inadequate protein intake
• Kwashiorkor
• Stress

Functional medicine approaches to lowering SHBG levels (Fork Clinic):

When estrogen or testosterone is low, and SHBG is elevated:

• Evaluate medication use that might influence SHBG. 
• Work to maintain a healthy body weight and eat enough food, including protein. Being underweight and having a low protein intake may be associated with higher SHBG and lower sex hormone levels. 
• Use natural remedies like nettle leaf to help decrease SHBG levels. 
• Support hormone levels with herbal medicine, supplements, bioidentical hormone replacement, or other strategies. 

References

Fork Clinic. Causes and Solutions for Elevated SHBG and TBG Levels. https://www.theforkclinic.com/post/causes-and-solutions-for-elevated-shbg-and-tbg-levels

Goldstajn, Marina Šprem et al. “Sex Hormone Binding Globulin (SHBG) as a Marker of Clinical Disorders.” Collegium antropologicum vol. 40,3 (2016): 211-8.

Gyawali, Prabin et al. “Cross-sectional and longitudinal determinants of serum sex hormone binding globulin (SHBG) in a cohort of community-dwelling men.” PloS one vol. 13,7 e0200078. 11 Jul. 2018, doi:10.1371/journal.pone.0200078

Ho, Ada Man-Choi et al. “Associations of sex-related steroid hormones and proteins with alcohol dependence: A United Kingdom Biobank study.” Drug and alcohol dependence vol. 244 (2023): 109781. doi:10.1016/j.drugalcdep.2023.109781

Iturriaga, H et al. “Sex hormone-binding globulin in non-cirrhotic alcoholic patients during early withdrawal and after longer abstinence.” Alcohol and alcoholism (Oxford, Oxfordshire) vol. 34,6 (1999): 903-9. doi:10.1093/alcalc/34.6.903

Longcope, C et al. “Diet and sex hormone-binding globulin.” The Journal of clinical endocrinology and metabolism vol. 85,1 (2000): 293-6. doi:10.1210/jcem.85.1.6291

Simons, Pomme I H G et al. “Sex hormone-binding globulin: biomarker and hepatokine?.” Trends in endocrinology and metabolism: TEM vol. 32,8 (2021): 544-553. doi:10.1016/j.tem.2021.05.002

Thaler, Markus A et al. “The biomarker sex hormone-binding globulin - from established applications to emerging trends in clinical medicine.” Best practice & research. Clinical endocrinology & metabolism vol. 29,5 (2015): 749-60. doi:10.1016/j.beem.2015.06.005

Wallace, Ian R et al. “Sex hormone binding globulin and insulin resistance.” Clinical endocrinology vol. 78,3 (2013): 321-9. doi:10.1111/cen.12086