Why do females have low bioavailable testosterone?

Why Females Have Low Bioavailable Testosterone

Females naturally have low bioavailable testosterone due to a combination of lower total testosterone production and higher sex hormone-binding globulin (SHBG) levels compared to males, which together significantly reduce the amount of free testosterone available for tissue action. 1

Physiological Basis for Low Bioavailable Testosterone in Females

Production Differences

• Females produce approximately 15-25 times less total testosterone than males 2
• Primary production sites differ:
  • In males: Primarily synthesized in the testes
  • In females: Minor amounts produced in the ovaries with additional contribution from adrenal androgen precursors that undergo peripheral conversion 2

Binding Protein Dynamics

• Sex hormone-binding globulin (SHBG) is a critical regulator of testosterone bioavailability:

  • SHBG is a glycoprotein primarily synthesized in the liver
  • It binds with high affinity to testosterone, making it unavailable to tissues
  • Only 0.5-3% of circulating testosterone is unbound (free) and biologically active 3

• Females typically have higher SHBG levels than males, which further reduces their bioavailable testosterone 1, 4

Factors Affecting SHBG and Bioavailable Testosterone

Hormonal Influences

• Estrogen increases SHBG production, while androgens decrease it 1, 4
• Females have higher estrogen-to-androgen ratios, promoting higher SHBG levels
• Exogenous estrogen (e.g., oral contraceptives) further increases SHBG, which reduces free testosterone 5

Other Physiological Regulators

• SHBG levels are also regulated by:
  • Thyroid hormones (hypothyroidism decreases SHBG)
  • Insulin (insulin resistance decreases SHBG)
  • Nutritional status and dietary factors 1, 4

Clinical Significance of Low Bioavailable Testosterone in Females

Normal Female Physiology

• Low bioavailable testosterone is normal in females and contributes to female-typical characteristics
• Even at these lower levels, testosterone plays important roles in:
  • Sexual desire and response
  • Maintenance of bone density
  • Muscle mass preservation
  • Overall sense of well-being 5

Pathological States

• Abnormally low testosterone in females may result in:

  • Decreased libido
  • Reduced sense of well-being
  • Persistent fatigue
  • Decreased motivation 5

• Abnormally high bioavailable testosterone (despite potentially normal total testosterone) can occur in conditions like PCOS due to decreased SHBG levels 1

Measurement Considerations

• When assessing testosterone status in females, measurement of bioavailable or free testosterone is more clinically relevant than total testosterone 1, 2

• Preferred methods for accurate assessment:

  • Free testosterone by equilibrium dialysis (gold standard)
  • Calculated free testosterone using accurate formulas that include total testosterone, SHBG, and albumin
  • Bioavailable testosterone (free + albumin-bound) 1, 2

• Caution: Free testosterone measurements by analog methods are often inaccurate, especially when SHBG levels are altered 3

Clinical Implications

• Understanding the naturally low bioavailable testosterone state in females is important for:

  • Proper interpretation of laboratory values
  • Appropriate diagnosis of androgen deficiency or excess
  • Guiding hormone replacement decisions in specific clinical scenarios 1, 5

• The testosterone:SHBG ratio (<0.3) can help identify true hypogonadism despite potentially misleading total testosterone levels 1