Testosterone to Dihydrotestosterone Ratio as a New Biomarker for an Adverse Metabolic Phenotype in the Polycystic Ovary Syndrome

Context: Polycystic ovary syndrome (PCOS) 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. Objective: This study intended to determine the role of the testosterone (TT) to dihydrotestosterone (DHT) ratio (TT/DHT ratio) in PCOS patients and to further assess the correlation of this ratio with hormonal, anthropometric, and metabolic parameters. Design and Setting: Serum samples of 275 premenopausal PCOS patients fulfilling Rotterdam criteria and 35 BMI-matched, premenopausal, healthy controls were analyzed for testosterone, DHT, dehydroepiandrosterone (DHEA), and androstenedione using liquid chromatography/mass spectrometry. Main Outcome Measures: We measured total levels of testosterone and DHT and calculated un-bound hormone levels as well as the ratio of testosterone to DHT. Further, impaired glucose tolerance, basal and stimulated serum insulin levels, metabolic syndrome and insulin resistance according to the homeostatic model assessment (HOMA-IR) were assessed. Results: PCOS patients showed significantly higher levels of TT (P < .001), free testosterone (P < .001), and freeDHT(P < .001) compared to healthy controls. The TT/DHT ratio was significantly higher in PCOS patients (P < .001). No difference was found for total DHT levels (P < .072). In PCOS patients alone, the TT/DHT ratio was significantly higher in obese patients (P < .001) and patients with metabolic syndrome (P < .001), impaired glucose tolerance (IGT) (P < .001) or insulin resistance (P < .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 provide evidence for a strong link between a high TT/DHT ratio and an adverse metabolic phenotype in PCOS patients. This correlation was only found in PCOS patients, suggesting the TT/DHT ratio to be a new biomarker for an adverse metabolic phenotype in PCOS patients.