From the Guidelines
Low SHBG levels are associated with a higher risk of metabolic and hormonal disorders, particularly in women with functional hypothalamic amenorrhoea (FHA) and polycystic ovarian morphology (PCOM), as evidenced by a recent study published in 2025 1. SHBG plays a crucial role in regulating the amount of sex hormones available to act on target tissues. In the context of FHA and PCOM, SHBG levels are significantly lower compared to those without PCOM, with a higher BMI, higher levels of anti-Müllerian hormone (AMH) and testosterone, and a higher increase in LH in the course of a GnRH test 1. Some key points to consider when evaluating SHBG levels include:
- SHBG levels can be influenced by various factors, including liver function, thyroid hormones, insulin levels, and medications like oral contraceptives.
- Low SHBG levels can lead to excess free testosterone, causing symptoms like acne, hirsutism, and irregular menstruation in women.
- The differential diagnosis between FHA-PCOM and PCOS can be challenging, and SHBG levels, along with other parameters like LH, testosterone, and the progestin challenge test, can be helpful in making an accurate diagnosis 1.
- Understanding SHBG levels is essential in interpreting total hormone measurements and developing appropriate treatment plans for hormonal disorders. Therefore, measuring SHBG levels is crucial in the evaluation and management of women with FHA and PCOM, as it can help identify those at higher risk of metabolic and hormonal disorders and guide treatment decisions 1.
From the Research
Definition and Function of SHBG
- Sex hormone-binding globulin (SHBG) is a serum glycoprotein that binds sex steroids with high affinity and specificity 2
- SHBG regulates the bioavailability of sex steroids in the bloodstream 2, 3
Factors Influencing SHBG Levels
- SHBG levels are regulated by androgens, estrogens, thyroid hormones, and other metabolic factors 2
- Liver fat content is a strong determinant of circulating SHBG, rather than body mass index (BMI) 3
- Proinflammatory cytokines may downregulate SHBG production 3
- Dietary factors may also influence SHBG regulation 3
Clinical Implications of SHBG
- Altered SHBG levels are associated with various disease conditions, including hyper- and hypoandrogenism, thyroid disorders, pituitary diseases, liver disorders, and breast and prostate cancer 2
- SHBG may be used as a surrogate marker for certain diseases, although its levels may not always be a specific result of the underlying pathology 2
- Low SHBG levels have been inversely linked to obesity, diabetes mellitus, and other cardiometabolic disorders 4
- SHBG may be used as a risk stratification tool for predicting ischemic stroke in women 4
SHBG in Specific Populations
- In HIV-infected men, SHBG and calculated free testosterone are important for the diagnosis of symptomatic hypogonadism 5
- Elevated SHBG values are found in one third of HIV-infected men, and are higher in men with compensated hypogonadism 5
- SHBG plays a central role in the pathogenesis of hypogonadism in HIV-infected men 5