Gender Determines Serum Free Cortisol: Higher Levels in Men |
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| Institution: | 1. Institute of Endocrinology, Metabolism and Hypertension, Tel Aviv University, Israel.;2. Department of Internal Medicine D, Tel Aviv University, Israel.;3. Preventive Medicine Service, Tel Aviv-Sourasky Medical Center, Israel.;4. Sackler Faculty of Medicine, Tel Aviv University, Israel.;1. Institute of Brain Science, Department of Neurology, Medical School, Shanxi Datong University, Datong, China;2. Institute of Neurology, Huashan Hospital, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China;3. Department of Encephalopathy and National Major Clinical Department of Ministry of Health, Third Hospital, Department of Neurology, Shanxi University of Traditional Chinese Medicine, Taiyuan, China;1. Department of Pediatrics, School of Medicine, Shinshu University, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan;2. Department of Laboratory Medicine, Shinshu University Hospital, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan;3. Department of Pathology and Laboratory Medicine, Kariya Toyota General Hospital, 5-15 Sumiyoshi, Kariya, Aichi 448-8505, Japan;4. Biomedical Laboratory Sciences, Graduate School of Medicine, Shinshu University, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan;5. Child and Women''s Health Sciences, Graduate School of Medicine, Shinshu University, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan;1. Section of Endocrinology, Diabetes, and Nutrition, Boston University School of Medicine, Boston, Massachusetts;2. Boston University School of Public Health, Boston, Massachusetts;3. Department of Endocrinology, Diabetes, and Hypertension, Brigham and Women''s Hospital, Boston, Massachusetts;4. Department of Pharmacy, Boston Medical Center, Boston, Massachusetts. |
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| Abstract: | Objective: Because only the free fraction of serum cortisol can readily access glucocorticoid receptors, we investigated whether or not a gender-related difference in serum free cortisol (FC) exists in the basal and adrenocorticotropic hormone (ACTH)-stimulated state.Methods: Serum total cortisol (TC) and FC were measured in 323 subjects (175 men; 148 women). Additionally, the low-dose 1-μg ACTH test was performed in 56 subjects (30 women, 26 men). Subjects were healthy volunteers, recruited in a preventive medicine screening program and an outpatient clinic.Results: Overall, basal serum TC and FC level were ~18 and ~33%, respectively, higher in men than in women (TC, 14.5 ± 0.33 μg/dL vs. 12.3 ± 0.33 μg/dL; P<.0001; FC, 0.68 ± 0.02 μg/dL vs. 0.51 ± 0.02 μg/dL; P<.0001). The higher FC in men relative to women was apparent across a wide age range (17 to 86 years) and persisted after adjustment for age and body mass index. The FC fraction (%FC, out of TC) was concordantly higher in men (5.4 ± 0.09% vs. 4.8 ± 0.3%; P = .046). FC was not related to the estimated menopausal status (women age below and above 47, 50, or 53 years). ACTH-stimulated FC levels were significantly higher in men compared to women, as reflected by the area under the response curve (49.4 ± 3.4 μg × min vs. 39.6 ± 2.2 μg × min; P = .0014).Conclusion: Gender is an unrecognized determinant of serum FC in humans. The possibility of lifelong exposure to the higher bioactive fraction of cortisol under basal conditions or daily stress involving ACTH stimulation should be further investigated in the context of gender-related phenotypic features such as “android” (visceral) fat deposition and longevity.Abbreviations:ACTH = adrenocorticotropic hormoneBMI = body mass indexCBG = cortisol-binding globulinFC = free cortisolHPA = hypothalamic-pituitary-adrenalTC = total cortisol |
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