Endocrine Abstracts

Context: Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder in women of classic androgen synthesis. Recent work has highlighted that impaired DHEA sulfation results in enhanced androgen production. Here, we evaluated the relationship between DHEA and DHEAS and androgen excess and metabolic phenotype in PCOS.

Patients and methods: We compared 65 women with PCOS to 35 healthy women matched for age and body mass index (BMI). All subjects underwent measurement of fasting glucose and insulin for Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). Androgen status was assessed in serum and 24-h urine by mass spectrometry. Pearson product-moment correlation coefficient analysis, Fishers exact test and one-way ANOVA were used for statistical analysis.

Results: Women with PCOS showed evidence of impaired DHEA sulfation as indicated by a significantly higher DHEA/DHEAS ratio (median 6.9 (range 0.4–28.0) vs 1.8 (0.5–3.7) nmol/μmol in controls, P<0.0001). For further analysis, we divided the PCOS patients according to whether their DHEA/DHEAS ratio was normal, i.e. similar to controls, (<5 nmol/μmol, n=24) or increased (≥5 nmol/μmol, n=41). The two PCOS groups did not differ with regard to BMI or HOMA-IR. PCOS patients with an increased DHEA/DHEAS ratio had significantly increased excretion of both major androgen metabolites, androsterone and etiocholanolone, reflective of total androgen production (androsterone (median 2496 (IQR 1645–4350) μg/24 h vs 1214 (827–1815) μg/24 h in controls, P=0.0002; etiocholanolone (2076 (1483–3005) μg/24 h vs 1133 (717.5–1910) μg/24 h in controls, P=0.0069). By contrast, androgen production in PCOS patients with normal DHEA/DHEAS ratio did not differ significantly from controls.

Conclusion: The DHEA/DHEAS ratio is an independent and sensitive indicator of androgen excess in PCOS. Impaired DHEA sulfation is much more prevalent in PCOS than previously assumed, with two thirds of PCOS patients showing an increased DHEA/DHEAS ratio closely linked to total androgen production.