ESPEYB20 12. The Year in Science and Medicine Steroids (3 abstracts)
12.6. 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
Schiffer L , Kempegowda P , Sitch AJ , Adaway JE , Shaheen F , Ebbehoj A , Singh S , McTaggart MP , O’Reilly MW , Prete A , Hawley JM , Keevil BG , Bancos I , Taylor AE & Arlt W
European Journal of Endocrinology, 2023, 188, 1–15. https://doi.org/10.1093/ejendo/lvac017
Brief summary: In this cross-sectional study, 11-oxygenated androgens were measured in morning serum samples from 290 healthy adults (125 men, age 22–95 years; 165 women, age 21–91 years) by LC–MSMS (liquid chromatography, tandem mass spectrometry) to generate normative values across the lifespan. In a subset of volunteers (n=83), additional measurements were performed in saliva to assess diurnal and menstrual cycle-dependent variation. In general, it was observed that classic but not 11-oxygenated androgens decline with age, and that with increasing BMI classic androgens decrease while active 11-oxygenated androgens increase.
In the last two decades, several studies showed that the circulating androgen pool results not only from classic androgen biosynthesis in the gonads and adrenals, but also from synthesis through alternative pathways and peripheral metabolism. Thereby 11-oxygenated androgens were found to play a key role, especially in androgen excess disorders such as PCOS (polycystic ovary syndrome) and congenital adrenal hyperplasia (e.g. due to 21-hydroxylase deficiency and P450 oxidoreductase deficiency), where they might be used as disease markers for diagnosis and monitoring. But so far, comprehensive data were missing to show the physiological levels and variability of these androgens in a larger cohort of healthy persons of both sexes with variable BMI, throughout life, menstrual cycles and diurnal rhythm. Therefore, this study provides much more than just normative values. It informs us about the physiology of these ‘new steroids’ which will likely soon also be used for routine clinical diagnostic and therapeutic control. In the study some of the androgen metabolites were also measured in saliva, which is an easy to obtain, alternative biomaterial to serum that might be difficult to obtain repetitively for questions regarding diurnal and cycle variabilities.
Lastly, in addition to the description of age, sex and cycle specific characteristics of circulating 11-oxygenated androgens in humans, the study provides important insight into the effect of body weight (BMI) on these androgens. Overall, an increase in BMI went parallel with an increase in 11- oxygenated androgens, with some sex specific differences. Furthermore, the observation that adrenal derived precursor 11- oxygenated androgens (11OHA4 and 11KA4) do not change with increasing BMI in females, while the activated products do, informs an important peripheral conversion in the adipose tissue.
Volume 20
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ESPE Yearbook of Paediatric Endocrinology
ISSN 1662-4009 (Online)
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