Characterisation of the daily rhythm of salivary androgens in healthy women and in women with polycystic ovary syndrome by liquid chromatography-tandem mass spectrometry

Laura Rotolo; Alessandra Gambineri; Valentina Bissi; Francesca Zauli; Greta Galante; Carolina Cecchetti; Paola Dionese; Elisabetta Belardinelli; Beatrice Solmi; Uberto Pagotto; Flaminia Fanelli

doi:10.1530/endoabs.99.RC1.7

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Endocrine Abstracts (2024) 99 RC1.7 | DOI: 10.1530/endoabs.99.RC1.7

ECE2024 Rapid Communications Rapid Communications 1: Reproductive and Developmental Endocrinology (7 abstracts)

Characterisation of the daily rhythm of salivary androgens in healthy women and in women with polycystic ovary syndrome by liquid chromatography-tandem mass spectrometry

Laura Rotolo ^1,2 , Alessandra Gambineri ^1,2 , Valentina Bissi ¹ , Francesca Zauli ^1,2 , Greta Galante ¹ , Carolina Cecchetti ^1,2 , Paola Dionese ^1,2 , Elisabetta Belardinelli ^1,2 , Beatrice Solmi ^1,2 , Uberto Pagotto ^1,2 & Flaminia Fanelli ¹

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¹Center for Applied Biomedical Research, Dept. Of Medical and Surgical Sciences, Alma Mater Studiorum - Bologna University, Bologna, Italy; ²Endocrinology and Diabetes Prevention and Care Unit, IRCCS Azienda Ospedaliero-Universitaria, Bologna, Italy

Background: PCOS is characterised by increased production of ovarian and adrenal androgens. Obesity is closely connected to excess androgens and to the disruption of hormone circadian rhythmicity. To date, it is not clear whether hyperandrogenism in PCOS, complicated or not by obesity, is associated with androgen rhythm dysregulation.

Aim: To investigate androgen diurnal rhythmicity and overall daily androgen exposure by measuring testosterone(T), androstenedione(A4) and dehydroepiandrosterone(DHEA) in saliva of healthy women(HW) and women with PCOS fulfilling the three Rotterdam diagnostic criteria, according to their BMI status.

Methods: HW (n=24), aged 23-37 y, showed no PCO morphology (PCOm), menstrual irregularity or hyperandrogenism. PCOS (n=18) were 15-38 y old and showed oligo-amenorrhea, PCOm and either clinical or biochemical hyperandrogenism. Both groups were subdivided into normal weight (NW:BMI<25kg/m²; HW:n=20, PCOS:n=5) and overweight/obese (OW/OB:BMI≥25kg/m²; HW:n=4, PCOS:n=13). All were in early follicular phase, had standardised meals at 8, 13 and 20am, and self-collected saliva hourly from 7 until 23am. Salivary T, A4 and DHEA were measured by a validated LC-MS/MS method.

Results: All women presented elevated androgen levels upon awakening, decreasing until bedtime (all P<0.001). Compared to HW, PCOS displayed higher T and A4 levels at each time point, and higher DHEA at 9, 11 and 16 am (all P<0.050). Throughout the day, minor androgen peaks were detected at 14 (A4,DHEA), 18 (DHEA) and 23 (T,A4,DHEA) am in HW, and at 11 (T,A4,DHEA), 17 (T,A4,DHEA) and 23 (T) am in PCOS. The AUC for daily T and A4 profiles was significantly greater in PCOS vs HW, irrespectively of BMI, whereas DHEA AUC was higher in OW/OB PCOS compared to NW PCOS and to both NW and OW/OB HW (all P<0.050). Multiple regression, including androgen AUC as the dependent variable and age, BMI and PCOS status as covariates, showed an independent impact of PCOS on T and A4 (both P<0.001) and of BMI on DHEA (P=0.031).

Conclusions: Our study provides novel insights into circadian androgen regulation in healthy and PCOS women, enabled by a highly sensitive and specific LC-MS/MS technology. While overall diurnal androgen rhythmicity was preserved, PCOS exhibited a time-specific dysregulation of small androgen surges. Excess T and A4 were detectable in saliva throughout the day in PCOS, whereas DHEA excess was only noticeable in the mid-morning and afternoon. While increased T and A4 secretion characterised PCOS condition regardless of BMI, excess DHEA specifically typified the obese PCOS phenotype, smggesting a specific adrenal contribution to PCOS-related dysmetabolic sequelae.