What studies investigate elevated levels of Sex Hormone-Binding Globulin (SHBG)?

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Last updated: May 28, 2025View editorial policy

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From the Guidelines

High levels of sex hormone-binding globulin (SHBG) are often associated with liver disease, and research suggests that SHBG synthesis is stimulated by estrogens, although the reasons for SHBG rise in chronic liver disease remain unclear 1. To find relevant studies about high levels of SHBG, I recommend searching medical databases like PubMed, Google Scholar, or MEDLINE using terms such as "elevated SHBG," "high sex hormone-binding globulin," or "SHBG hypersecretion." Some key points to consider when reviewing studies on high SHBG levels include:

  • The relationship between SHBG and hormonal imbalances, particularly in the context of liver disease 1
  • The impact of SHBG on reproductive health, including menstrual irregularities and infertility in women, and low testosterone levels and erectile dysfunction in men 1
  • The role of estrogens in stimulating SHBG synthesis, and the subsequent effects on the hypothalamic-pituitary axis 1
  • The clinical outcomes associated with high SHBG levels, including decreased libido, fatigue, and reproductive issues 1 By examining these aspects, you can gain a comprehensive understanding of the condition and its implications for patient health and quality of life. It is essential to prioritize the most recent and highest-quality studies, such as the 2021 practice guidance by the American Association for the Study of Liver Diseases 1, to ensure that your understanding is based on the latest evidence.

From the Research

Studies on High Levels of Sex Hormone Binding Globulin (SHBG)

  • High levels of SHBG have been associated with various clinical disorders, including metabolic syndrome, obesity, and polycystic ovary syndrome 2.
  • SHBG is a reliable marker of insulin resistance and can serve as a predictor of type 2 diabetes 3, 4.
  • The production of SHBG is mainly regulated by sex steroids and thyroxine, and its levels are also influenced by metabolic factors such as obesity and lipogenesis 5, 4.
  • Altered SHBG levels have been observed in various disease conditions, including hyper- and hypoandrogenism, thyroid disorders, pituitary diseases, liver disorders, and breast and prostate cancer 5.
  • SHBG has been recognized as a potential drug candidate for the treatment of liver-related metabolic disorders, including non-alcoholic fatty liver disease (NAFLD) and insulin resistance 3.

Regulation of SHBG Levels

  • SHBG levels are regulated by hormones such as thyroid and estrogenic hormones, as well as by nutritional factors and certain drugs 4.
  • Monosaccharides such as glucose or fructose can decrease SHBG expression by inducing lipogenesis, which reduces hepatic HNF-4alpha levels 4.
  • Thyroid hormones and PPARgamma antagonists have been shown to increase SHBG expression by diminishing hepatic lipogenesis and free fatty acid liver biosynthesis 4.

Clinical Significance of SHBG

  • SHBG has been established as a reliable marker of certain pathological states, including metabolic syndrome, obesity, and polycystic ovary syndrome 2, 6.
  • SHBG levels have been correlated with cardiovascular risk, thyroid function, gynecological conditions, and carcinogenesis 6.
  • Genetic alterations in the SHBG gene have been identified as a potential new diagnostic marker for various clinical disorders 6.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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