Classic and 11-oxygenated androgens in serum and saliva across adulthood: a cross-sectional study analyzing the impact of age, body mass index, and diurnal and menstrual cycle variation

• Published in: European journal of endocrinology 2023-01, Vol.188 (1), p.86-100
• Main Authors: Schiffer, Lina, Kempegowda, Punith, Sitch, Alice J, Adaway, Joanne E, Shaheen, Fozia, Ebbehoj, Andreas, Singh, Sumitabh, McTaggart, Malcom P, O'Reilly, Michael W, Prete, Alessandro, Hawley, James M, Keevil, Brian G, Bancos, Irina, Taylor, Angela E, Arlt, Wiebke
• Format: Article
• Language: English
• Subjects: Adult; Androgens; Body Mass Index; Cross-Sectional Studies; Female; Humans; Male; Menstrual Cycle; Saliva - chemistry
• ISSN: 0804-4643; 1479-683X
• DOI: 10.1093/ejendo/lvac017

11-oxygenated androgens significantly contribute to the circulating androgen pool. Understanding the physiological variation of 11-oxygenated androgens and their determinants is essential for clinical interpretation, for example, in androgen excess conditions. We quantified classic and 11-oxygenated androgens in serum and saliva across the adult age and body mass index (BMI) range, also analyzing diurnal and menstrual cycle-dependent variation. Cross-sectional. Morning serum samples were collected from 290 healthy volunteers (125 men, 22-95 years; 165 women, 21-91 years). Morning saliva samples were collected by a sub-group (51 women and 32 men). Diurnal saliva profiles were collected by 13 men. Twelve women collected diurnal saliva profiles and morning saliva samples on 7 consecutive days during both follicular and luteal menstrual cycle phases. Serum and salivary steroids were quantified by liquid chromatography-tandem mass spectrometry profiling assays. Serum classic androgens decreased with age-adjusted BMI, for example, %change kg/m2 for 5α-dihydrotestosterone: men -5.54% (95% confidence interval (CI) -8.10 to -2.98) and women -1.62% (95%CI -3.16 to -0.08). By contrast, 11-oxygenated androgens increased with BMI, for example, %change kg/m2 for 11-ketotestosterone: men 3.05% (95%CI 0.08-6.03) and women 1.68% (95%CI -0.44 to 3.79). Conversely, classic androgens decreased with age in both men and women, while 11-oxygenated androgens did not. Salivary androgens showed a diurnal pattern in men and in the follicular phase in women; in the luteal phase, only 11-oxygenated androgens showed diurnal variation. Classic androgens decrease while active 11-oxygenated androgens increase with increasing BMI, pointing toward the importance of adipose tissue mass for the activation of 11-oxygenated androgens. Classic but not 11-oxygenated androgens decline with age.