Endocrine Abstracts

Introduction: Clinical and laboratory hyperandrogenisms indistinctly contribute to PCOS diagnosis; however, they differ in hormonal and metabolic correlates and require proper therapeutic strategies. Circulating biomarkers of hirsutism were not identified so far, with elevated testosterone being observed only in half of hirsute patients. Reasons for such inconsistencies possibly relies in previously used immunoassays, nowadays recognized as not adequate because of poor reliability and limited steroid panel. The present study aimed at defining the circulating steroid fingerprint that specifically distinguishes hirsutism by LC-MS/MS profiling of a broad steroid panel.

Methods: Sixteen serum steroids were determined in 352 patients (age 14–49 years) in follicular phase. The independent effect of ovarian dysfunction (OD; oligo-amenorrhea and/or PCO morphology), hyperandrogenemia (testosterone≥1.56 nmol/L and/or androstenedione≥5.72 nmol/L) and hirsutism (modified-Ferriman-Gallway score≥8) on circulating steroids was valued. Moreover, hirsute (n=74) vs not-hirsute (n=47) women were compared within patients showing both OD and hyperandrogenemia.

Results: OD directly associated with LH (P=0.048) and LH/FSH (P<0.001), and negatively with FSH (P<0.001). OD positively associated with androstenedione (P=0.002), 17OHprogesterone/progesterone (P<0.001), 17OHprogesterone/17OHpregnenolone (P=0.004), androstenedione/dehydroepiandrosterone (P<0.001), and negatively with progesterone (P=0.026), dehydroepiandrosterone (P=0.029), dehydroepiandrosterone-sulfate (P=0.034) and 11deoxycortisol/17OHprogesterone (P=0.003). Hyperandrogenemia positively associated with mFG-score (P=0.012), ACTH, LH and LH/FSH (all P<0.001), insulin (P=0.025) and HOMA-IR (P=0.045). Hyperandrogenemia positively associated with 17OHpregnenolone, progesterone, dehydroepiandrosterone, 17OHprogesterone, estrone (all P<0.001), dehydroepiandosterone-sulfate (P=0.004), dihydrotestosterone (P=0.009), corticosterone, 11deoxycortisol, cortisol (all P<0.001), cortisone (P=0.009), 17OHprogesterone/progesterone (P<0.001) and androstenedione/dehydroepiandrosterone (P=0.014), and negatively with dehydroepiandrosterone-sulfate/dehydroepiandrosterone, testosterone/androstenedione, estrone/androstenedione, estradiol/testosterone, dihydrotestosterone/testosterone and cortisol/11deoxycortisol (all P<0.001). Hirsutism directly associated with BMI (P=0.014) and inversely with HDL (P=0.041). Hirsutism also associated with lowering progesterone (P=0.007) and 17OHprogesterone (P=0.003) and increasing androstenedione/17OHprogesterone (P<0.001) and 11deoxycortisol/17OHprogesterone (P=0.021). Compared with not-hirsute, hirsute women with OD and hyperandrogenemia exhibited higher BMI (P=0.002) and dehydroepiandrosterone/17OHpregnenolone (P=0.011), and lower SHBG (P=0.001), 17OHprogesterone (P=0.030), testosterone (P=0.004), androstenedione/dehydroepiandrosterone (P=0.024) and testosterone/androstenedione (P=0.039).

Conclusions: Androstenedione excess in OD apparently originates by gonads, as indicated by imbalanced gonadotropin, low progesterone, increased 17hydroxylase activity and reduced adrenal secretion. Hyperandrogenemia is featured by insulin resistance, combined ovarian and adrenal hypersecretion of the overall steroid profile, and reduced precursors’ conversion in downstream active steroids. Hirsutism is characterized by obesity and dyslipidemia, by low 17OHprogesterone and, in the PCOS context, by mild hypertestosteronemia and reduced SHBG, overall suggesting that this phenotype could result by increased free-androgens at the pilosebaceous unit.