Serum Testosterone to Androstenedione Ratio Predicts Metabolic Health in Normal-Weight Polycystic Ovary Syndrome Women.

Context: Increased aldo-keto reductase 1C3 (AKR1C3)-mediated conversion of androstenedione (A4) to testosterone (T) promotes lipid storage in subcutaneous (SC) abdominal adipose in overweight/obese polycystic ovary syndrome (PCOS) women.

Objective: This work examines whether an elevated serum T/A4 ratio, as a marker of enhanced AKR1C3 activity in SC abdominal adipose, predicts metabolic function in normal-weight PCOS women.

Methods: This prospective cohort study took place in an academic center and comprised 19 normal-weight PCOS women and 21 age- and body mass index-matched controls. Interventions included circulating hormone/metabolic determinations, intravenous glucose tolerance testing, total body dual-energy x-ray absorptiometry, and SC abdominal fat biopsy. Serum T/A4 ratios, hormone/metabolic measures, and expression of adipocytes matured in vitro were compared between female types; serum T/A4 ratios were correlated with serum lipids, adipose insulin resistance (adipose-IR), homeostatic model assessment of insulin resistance (HOMA-IR) and insulin sensitivity (Si).

Results: Increased serum T/A4 ratios ( = .040) and log adipose-IR values ( = .002) in PCOS women vs controls were accompanied by messenger RNA overexpression of PCOS adipocytes matured in vitro ( = .016). Serum T/A4 ratios in PCOS women, but not controls, negatively correlated with log triglycerides (TGs: R = -0.65,  = .002) and the TG index (R= -0.57,  = .011). Adjusting for serum free T, serum T/A4 ratios in PCOS women remained negatively correlated with log TG (R = -0.57,  = .013) and TG index (R = -0.50,  = .036), respectively, without significant relationships with other metabolic measures.

Conclusion: An elevated serum T/A4 ratio, as a marker of enhanced AKR1C3 activity in SC abdominal adipose, predicts healthy metabolic function in normal-weight PCOS women.