What factors lower Sex Hormone-Binding Globulin (SHBG) levels?

Factors That Lower Sex Hormone-Binding Globulin (SHBG) Levels

Several factors can lower SHBG levels, including obesity, insulin resistance, high-dose glucocorticoids, growth hormone, testosterone, and certain medications. 1, 2

Primary Factors That Decrease SHBG

• Medications and hormones:

  • Glucocorticoids (such as prednisone) 1
  • Growth hormone 2
  • Testosterone and other androgens 1, 2
  • Certain anticonvulsants 2

• Metabolic conditions:

  • Obesity (particularly central/abdominal obesity) 1, 2, 3
  • Insulin resistance and hyperinsulinemia 2, 3
  • Type 2 diabetes 3
  • Metabolic syndrome 2

• Growth factors:

  • Insulin-like growth factor-1 (IGF-1) 4
  • Epidermal growth factor (EGF) 4
  • Transforming growth factor alpha (TGF-alpha) 4

Physiological and Pathological States Associated with Low SHBG

• Endocrine disorders:

  • Polycystic ovary syndrome (PCOS) 1
  • Cushing's syndrome 1, 5
  • Acromegaly 1

• Other conditions:

  • Non-alcoholic fatty liver disease 2
  • Hypothyroidism (opposite of hyperthyroidism, which increases SHBG) 2, 3

Mechanisms of SHBG Regulation

• Insulin and insulin resistance play a key role in lowering SHBG levels, which explains why obesity, metabolic syndrome, and type 2 diabetes are associated with reduced SHBG 6, 3

• Growth factors have been demonstrated to significantly decrease SHBG production in hepatic cells (the liver is the primary site of SHBG production) 4

• Androgens traditionally were thought to lower SHBG levels, though research shows this relationship is complex and may be indirect through other metabolic pathways 6, 5

Clinical Implications

• Low SHBG increases free (bioavailable) testosterone and other sex hormones, which can lead to symptoms of hyperandrogenism in women 1, 3

• In men, low SHBG with normal total testosterone may not require treatment if free testosterone levels are adequate 2

• Weight loss and improved insulin sensitivity through lifestyle modifications can help normalize SHBG levels in those with obesity or metabolic syndrome 2, 3

• When evaluating testosterone status, both total and free testosterone (or calculated free testosterone index) should be measured, especially when SHBG levels may be abnormal 2

Common Pitfalls in SHBG Assessment

• Focusing only on total hormone levels without considering SHBG can lead to misdiagnosis of hormone deficiencies or excesses 2, 3

• Not recognizing that SHBG changes can occur independently of sex steroid alterations in certain conditions 5

• Failing to consider non-steroidal factors (like insulin and growth factors) when evaluating causes of low SHBG 6, 4

• Not accounting for age-related changes in SHBG levels, which typically increase with aging in both men and women 2, 5