Can high sex hormone-binding globulin (SHBG) increase follicle-stimulating hormone (FSH) levels?

Relationship Between High SHBG and FSH Levels

High sex hormone-binding globulin (SHBG) levels can increase follicle-stimulating hormone (FSH) levels through an inverse relationship between SHBG and testosterone bioavailability. 1

Mechanism of SHBG's Effect on FSH

• SHBG is a liver-derived protein that binds to sex hormones, particularly testosterone and to a lesser extent estradiol, reducing their bioavailability
• When SHBG is elevated:
  • Less free testosterone is available in circulation
  • This reduced free testosterone decreases negative feedback on the hypothalamic-pituitary axis
  • The decreased negative feedback results in increased FSH secretion from the pituitary

Evidence Supporting This Relationship

• In women with functional hypothalamic amenorrhea (FHA), those with higher SHBG levels demonstrate higher FSH levels compared to those with lower SHBG levels 2, 1
• The inverse relationship between SHBG and testosterone bioavailability is well-documented, with SHBG effectively reducing the amount of biologically active testosterone 3
• Studies show that SHBG concentrations correlate negatively with both body mass index and fasting insulin levels, suggesting metabolic factors also influence this relationship 3

Clinical Relevance

• The free testosterone index (ratio of total testosterone to SHBG) is a crucial indicator of gonadal function:

  • A ratio ≥0.3 indicates normal gonadal function
  • A ratio <0.3 suggests hypogonadism, which may be associated with altered FSH levels 1

• In postmenopausal women, FSH has been shown to have a stronger association with metabolic syndrome than SHBG, highlighting the complex interplay between these hormones 4

Factors That Influence SHBG Levels

• Increase SHBG:

  • Estrogens
  • Thyroid hormones (particularly thyroxine)
  • Glucocorticoids

• Decrease SHBG:

  • Androgens
  • Insulin and insulin resistance
  • Growth hormone (GH) 5
  • Obesity

Clinical Applications

• Measuring SHBG is useful for:
  1. Correctly interpreting testosterone and estradiol serum concentrations
  2. Investigating androgen-estrogen balance in gonadal and sexual dysfunctions
  3. Assessing the peripheral effect of hormones that regulate SHBG production
  4. Evaluating insulin resistance and cardiovascular risk 3

Common Pitfalls in Assessment

• Relying solely on total testosterone measurements without considering SHBG levels can lead to misinterpretation of hormone status
• Failing to consider the impact of liver disease, which can alter SHBG production 2
• Not accounting for medications that may affect SHBG levels (e.g., oral estrogens, certain anticonvulsants)
• Overlooking the impact of thyroid dysfunction on SHBG levels, which can indirectly affect FSH 2

In conclusion, elevated SHBG can increase FSH levels by reducing free testosterone availability, thereby decreasing negative feedback on the hypothalamic-pituitary axis. This relationship is important to consider when evaluating reproductive and metabolic disorders.