Steroid hormone analysis of adolescents and young women with polycystic ovarian syndrome and adrenocortical dysfunction using UPC²-MS/MS.

ABSTRACT:

Background

We recently identified 35 women with polycystic ovarian syndrome (PCOS) who exhibited features of micronodular adrenocortical hyperplasia. Steroid hormone analysis can be more accurate using state-of-the-art ultra-performance convergence chromatography-tandem mass spectrometry (UPC²-MS/MS). We hypothesized that UPC²-MS/MS may be used to better define hormonally this distinct subgroup of patients with PCOS.

Methods

Plasma from PCOS patients (n?=?35) and healthy volunteers (HVs, n?=?19) who all received dexamethasone testing was analyzed. Samples were grouped per dexamethasone responses and followed by UPC²-MS/MS analysis. When insufficient, samples were pooled from patients with similar responses to allow quantification over the low end of the assay.

Results

The C11-oxy C₁₉ (11?-hydroxyandrostenedione, 11keto-androstenedione, 11?-hydroxytestosterone, 11keto-testosterone):C₁₉ (androstenedione, testosterone) steroid ratio was decreased by 1.75-fold in PCOS patients compared to HVs. Downstream steroid metabolites 11?-hydroxyandrosterone and 11keto-androsterone were also measurable. The C11-oxy C₂₁ steroids, 11-hydroxyprogesterone and 11keto-dihydroprogesterone levels, were 1.2- and 1.7-fold higher in PCOS patients compared to HVs, respectively.

Conclusions

We hypothesized that UPC²-MS/MS may accurately quantify steroids, in vivo, and identify novel metabolites in a subgroup of patients with PCOS and adrenal abnormalities. Indeed, it appears that adrenal C11-oxy steroids have the potential of being used diagnostically to identify younger women and adolescents with PCOS who also have some evidence of micronodular adrenocortical hyperplasia.

Impact

Adrenal C11-oxy steroids may be clinically important in identifying young patients with PCOS and adrenal abnormalities. The steroids presented in our manuscript have not yet been considered in the clinical setting so far, and we believe that this study could represent a first focused step towards the characterization of a distinct subgroup of women with PCOS who may in fact be treated differently than the average patient with PCOS. This paper can change the understanding of PCOS as one disorder: it is in fact a heterogeneous condition. In addition, for the subgroup of patients with PCOS associated with adrenocortical dysfunction, our paper provides novel hormonal markers that can be used diagnostically. Finally, the paper also adds to the basic pathophysiological understanding of adrenocortical-ovarian interactions in steroidogenesis of young women and adolescent girls with PCOS.

SUBMITTER: Swart AC 

PROVIDER: S-EPMC7541460 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature