Endocrine Abstracts

Background: Excess testosterone in PCOS is accompanied by increased levels of other ovarian and adrenal androgens and precursors. Recently, 11-oxygenated adrenal androgens have been postulated as major components of the circulating androgen pool in PCOS. Obesity is strictly connected with androgen excess and with the derangement of hormone circadian rhythmicity. To date, it has not been clarified whether hyperandrogenism in PCOS, either complicated by obesity or not, is accompanied by the dysregulation of androgen biorhythm.

Objective: To investigate the daytime rhythmicity of androgens and precursors in saliva of women with PCOS fulfilling the three Rotterdam diagnostic criteria, according to their BMI status.

Methods: PCOS patients (age 15-34y) showed oligo-amenorrhea, polycystic ovarian morphology and either clinical (hirsutism) or biochemical (elevated serum testosterone) hyperandrogenism. These were subdivided in overweight/obese (OB-PCOS; BMI≥27 kg/m² n = 8) and non obese PCOS (NO-PCOS; BMI<27 kg/m² n = 8) and compared with age-matched non obese healthy women (NO-CTR; age: 23-32y; BMI<27 kg/m² n = 16). All were in follicular phase, had standardized meals and self-collected saliva every hour from 7 until 23am. Testosterone, androstenedione, 17OH-progesterone, dehydroepiandrosterone, 11OH-androstenedione and 11keto-testosterone were measured by LC-MS/MS.

Results: BMI was higher in OB-PCOS (31.1 (29.1-34.4)) compared to NO-PCOS (22.5 (20.2-27.2)) and NO-CTR (21.3 (20.7-22.9) kg/m²) (P<0.001), but similar between NO-PCOS and NO-CTR. All women showed higher androgen and precursor levels at awakening, which decreased until bedtime (all P<0.001). Testosterone and androstenedione, at each time point, and 17OH-progesterone, at most time points, were higher in OB-PCOS and NO-PCOS vs NO-CTR women (all P<0.050). Testosterone was higher in OB-PCOS vs NO-PCOS at 8, 10, 11, 16 and 17am (all P<0.050). Dehydroepiandrosterone was higher in OB-PCOS compared to both NO-PCOS and NO-CTR at 9-13 and 16-17am (all P<0.050). PCOS women showed a trend for high 11-oxygenated androgens at mid-morning and afternoon, but lower at late night, only achieving significance at 10am, with 11OH-androstenedione higher in OB-PCOS vs NO-CTR; at 17am, with 11-ketotestosterone higher in OB-PCOS and NO-PCOS vs NO-CTR; and at 23am, with 11OH-androstenedione lower in OB-PCOS vs NO-CTR (all P<0.050).

Conclusion: Androgen biorhythm was preserved in PCOS. Excess secretion of androgens originating from both ovary and adrenal was maintained throughout the day in both PCOS groups. The overweight/obese PCOS phenotype is featured by a partial rhythm derangement with a more severe testosterone excess and enhanced adrenal tone, as featured by dehydroepiandrosterone, at mid-morning and afternoon. Interestingly, 11-oxygenated androgens did not show a specific alteration in the examined PCOS phenotypes.