Abstract
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
To examine 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.
Design
Prospective cohort study.
Setting
Academic center.
Patients
Nineteen normal-weight PCOS women; 21 age- and body mass index-matched controls.
Intervention(s)
Circulating hormone/metabolic determinations, intravenous glucose tolerance testing, total body dual-energy x-ray absorptiometry, SC abdominal fat biopsy.
Main Outcome Measure(s)
Serum T/A4 ratios, hormone/metabolic measures and AKR1C3 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 (P=0.040) and log adipose-IR values (P=0.002) in PCOS women versus controls were accompanied by AKR1C3 mRNA overexpression of PCOS adipocytes matured in vitro (P=0.016). Serum T/A4 ratios in PCOS women, but not controls, negatively correlated with log triglycerides (TG: R=-0.65, P=0.002) and the TG index (R=-0.57, P=0.011). Adjusting for serum free T, serum T/A4 ratios in PCOS women remained negatively correlated with log TG (R=-0.57, P=0.013) and TG index (R=-0.50, P=0.036), 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.
Serum Testosterone to Androstenedione Ratio Predicts Metabolic Health in Normal-Weight Polycystic Ovary Syndrome Women
