Investigation of circulating androgens

Federico Ponzetto; Caprino Mirko Parasiliti; Lorenzo Campioni; Lorenzo Marinelli; Fabio Settanni; Antonello Nonnato; Giulio Mengozzi; Roberta Giordano; Ezio Ghigo

doi:10.1530/endoabs.99.P563

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Endocrine Abstracts (2024) 99 P563 | DOI: 10.1530/endoabs.99.P563

ECE2024 Poster Presentations Reproductive and Developmental Endocrinology (45 abstracts)

Investigation of circulating androgens’ circadian variations: expanding the knowledge by monitoring phase II metabolites

Federico Ponzetto ¹ , Mirko Parasiliti Caprino ¹ , Lorenzo Campioni ¹ , Lorenzo Marinelli ¹ , Fabio Settanni ² , Antonello Nonnato ² , Giulio Mengozzi ¹ , Roberta Giordano ¹ & Ezio Ghigo ¹

Err

Author affiliations

¹University of Turin, Department of Medical Sciences, Turin; ²City of Health and Science University Hospital, Clinical Biochemistry, Turin

Background: Many endogenous steroid hormones are reported to be subjected to distinct circadian rhythms, which are driven by central regulators, hormonal bioavailability and half-life. Recently, the measurement of androgens phase II metabolites has gained interest in the diagnosis and management of different endocrinological pathologies, such as polycystic ovarian syndrome (PCOS), female adrenal hyperandrogenism and hirsutism, prostate cancer, but their circadian patterns have not yet been characterized.

Methods: Serum samples were collected at six different time points across 24 hours (8:00, 10:00, 12:00; 16:00, 20:00, 8:00) from 19 healthy volunteer males. In-house UHPLC-MS/MS method was used for measuring in a single analysis circulating concentrations of 13 steroid hormones together with 13 androgens phase II metabolites (7 glucuronides and 6 sulphates). Cosinor analysis was performed to obtain diurnal models including mesor (rhythm adjusted median), zenith, and nadir concentrations, to measure rhythm’s acrophase and amplitude as well as to test variations’ statistical significance.

Results: The monitoring of target steroids’ circadian rhythmicity highlighted that among endogenous hormones, all ACTH-related steroids showed significant fluctuations throughout the 24-hours period, with the highest concentrations measured in early morning samples then decreasing until afternoon collection. Concerning androgens, for testosterone a less pronounced but significant circadian rhythm was observed, while DHT did not show any variation during the day. A similar pattern was obtained by investigating phase II metabolites: the absence of diurnal fluctuations was noticed for both sulpho- and glucuro-conjugated androgens, with the latter owning a shifted zenith at 10 a.m.

Conclusions: The outcomes of this study highlighted that, in contrast with the majority of circulating steroid hormones, androgens phase II metabolites have satisfactory performance in terms of intra-day stability of circulating levels. For this reason, their introduction in clinical practice as biomarkers of pathological conditions to be monitored with longitudinal monitoring in the context of individualized precision medicine could be envisaged.