Testosterone/dihydrotestosterone ratio as a new biomarker for PCOS

Introduction: Polycystic ovary syndrome is a heterogeneous disease with many different aspects including hyperandrogenism and metabolic disturbances. Clinical phenotypes show different patterns of steroid hormones that have been investigated to some extent. The steroid hormone cascade involves the metabolic activity of different enzymes, e.g. 5alpha-reductase, responsible for the conversion of testosterone (TT) to dihydrotestosterone (DHT).

This study intended to determine the 5alpha-reductase activity in PCOS patients by calculating the TT/DHT ratio and to further assess the correlation of this ratio with hormonal, anthropometric and metabolic parameters.

Methods: Serum samples of 275 PCOS patients fulfilling Rotterdam criteria and 35 BMI-matched, healthy controls were analysed for testosterone, dihydrotestosterone, dehydroepiandrosterone and androstenedione using liquid chromatography/mass spectrometry. TT/DHT ratio was calculated in order to reflect 5alpha-reductase activity.

Result: PCOS patients showed significantly higher levels of total testosterone (p < 0.001), free testosterone (p < 0.001) and free DHT (p < 0.001) compared to controls. TT/DHT ratio was significantly higher in PCOS patients (p < 0.001), indicating a lower 5alpha-reductase activity. No difference was found for total DHT levels (p = 0.072). In PCOS patients alone, TT/DHT ratio was significantly higher in obese patients (p < 0.001) and patients with metabolic syndrome (p < 0.001), pathologic oGTT (p < 0.001) or insulin resistance (p < 0.001). Significant correlations of the TT/DHT ratio with various adverse anthropometric, hormonal, lipid and liver parameters and parameters of glucose metabolism were found.

Conclusion: Our data show a higher TT/DHT ratio in serum of PCOS patients, indicating a lower 5alpha-reductase activity and adverse effects on the clinical and metabolic appearance.