Skip to main content

What is SHBG?

Updated

Sex hormone-binding globulin (SHBG) is a glycoprotein that plays a crucial role in the transport and regulation of sex hormones in the bloodstream. It primarily binds to androgens, such as testosterone, and estrogens, thereby regulating their bioavailability and activity in the body. SHBG binds to sex hormones, particularly testosterone and estradiol, and transports them in the bloodstream. This binding regulates the amount of free (bioavailable) hormones that can interact with target tissues and exert biological effects. By binding to sex hormones, SHBG controls their access to tissues and cells. Only the unbound (free) fraction of these hormones is biologically active and can interact with hormone receptors. Additionally, SHBG levels have been associated with various metabolic and renal functions. For instance, lower SHBG levels have been linked to worse biometric, lipid, liver, and renal function parameters in women with polycystic ovary syndrome (PCOS). Moreover, SHBG levels have been found to be associated with kidney function in both men and women, with lower levels correlating with lower estimated glomerular filtration rate (eGFR) and higher risk of chronic kidney disease (CKD).

SHBG is clinically relevant in various health contexts. Certain chemicals, such as hexaconazole, have been shown to interact with SHBG, potentially disrupting normal endocrine functions. Hexaconazole, a fungicide, has demonstrated stable molecular interaction with SHBG, which may interfere with the binding of natural hormones and lead to endocrine disruption. Studies have shown that SHBG levels are positively associated with kidney function, with higher levels associated with better eGFR and lower risk of CKD in men. In women, SHBG levels have also been linked to kidney function, although the associations can vary based on other factors such as age and metabolic health. Additionally, SHBG levels are associated with lipid profiles and cardiometabolic health. Higher SHBG levels have been linked to better lipid profiles, including higher high-density lipoprotein cholesterol (HDL-C) and lower triglycerides and non-HDL cholesterol.

Further Reading:

  1. Alquraini, A. (2023). Potency of Hexaconazole to Disrupt Endocrine Function with Sex Hormone-Binding Globulin. International Journal of Molecular Sciences, 24(4), 3882–3882. https://doi.org/10.3390/ijms24043882
  2. Zhang, H., Chen, C., Zhang, X., Wang, Y., Wan, H., Chen, Y., Zhang, W., Xia, F., Lu, Y., & Wang, N. (2022). Association between sex hormone-binding globulin and kidney function in men: results from the SPECT-China study. Chinese Medical Journal, 135(17), 2083–2088. https://doi.org/10.1097/cm9.0000000000002046
  3. Hui, L., Nano, J., Prehn, C., Cecil, A., Rathmann, W., Zeller, T., Lechner, A., Adamski, J., Peters, A., & Thorand, B. (2022). Associations of endogenous androgens and sex hormone-binding globulin with kidney function and chronic kidney disease. Frontiers in Endocrinology, 13. https://doi.org/10.3389/fendo.2022.1000650
  4. Azene, Z. N., Davis, S. R., McNeil, J. J., Tonkin, A. M., Handelsman, D. J., & Islam, R. M. (2023). Estrone, sex hormone binding globulin and lipid profiles in older women: an observational study. Climacteric: The Journal of the International Menopause Society, 26(2), 114–120. https://doi.org/10.1080/13697137.2023.2165908
  5. Zhao, J. V., & Schooling, C. M. (2020). Sex-specific Associations of Sex Hormone Binding Globulin with CKD and Kidney Function: A Univariable and Multivariable Mendelian Randomization Study in the UK Biobank. Journal of the American Society of Nephrology, 32(3), 686–694. https://doi.org/10.1681/asn.2020050659
  6. Luo, X., Yang, X.-M., Cai, W.-Y., Chang, H., Ma, H.-L., Peng, Y., & Wu, X.-K. (2020). Decreased Sex Hormone-Binding Globulin Indicated Worse Biometric, Lipid, Liver, and Renal Function Parameters in Women with Polycystic Ovary Syndrome. International Journal of Endocrinology, 2020, 1–6. https://doi.org/10.1155/2020/7580218
  7. N. Narinx, David, K., J. Walravens, Vermeersch, P., Claessens, F., Fiers, T., B. Lapauw, Antonio, L., & D. Vanderschueren. (2022). Role of sex hormone-binding globulin in the free hormone hypothesis and the relevance of free testosterone in androgen physiology. Cellular and Molecular Life Sciences, 79(11). https://doi.org/10.1007/s00018-022-04562-1