GENDER DETERMINES SERUM FREE CORTISOL: HIGHER LEVELS IN MEN

Area of Science:

• Endocrinology
• Human Physiology
• Biochemistry

Background:

• Only the free fraction of serum cortisol (FC) is biologically active and accessible to glucocorticoid receptors.
• Understanding gender-specific differences in cortisol levels is crucial for interpreting physiological responses and potential health implications.

Purpose of the Study:

• To investigate potential gender-related differences in serum free cortisol (FC) levels.
• To compare basal and adrenocorticotropic hormone (ACTH)-stimulated FC between men and women.

Main Methods:

• Serum total cortisol (TC) and FC were measured in 323 healthy volunteers (175 men, 148 women).
• A low-dose 1-μg ACTH stimulation test was conducted in a subset of 56 participants (30 women, 26 men).
• Statistical analyses were performed to compare cortisol levels between genders, adjusting for age and body mass index (BMI).

Main Results:

• Men exhibited significantly higher basal serum TC (~18%) and FC (~33%) levels compared to women (P<.0001).
• The percentage of free cortisol (FC fraction) was also higher in men (5.4% vs. 4.8%, P = .046).
• ACTH-stimulated FC levels, measured by the area under the response curve, were significantly greater in men than in women (P = .0014).

Conclusions:

• Gender is a significant, previously unrecognized determinant of serum free cortisol (FC) levels in humans.
• The consistently higher bioactive cortisol fraction in men warrants further investigation into its role in gender-specific phenotypes like fat deposition and longevity.
• These findings highlight the importance of considering gender when evaluating cortisol dynamics and their physiological consequences.