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

Daniel A Dumesic; Ayli Tulberg; Megan McNamara; Tristan R Grogan; David H Abbott; Rajanigandha Naik; Gwyneth Lu; Gregorio D Chazenbalk

doi:10.1210/jendso/bvab158

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

J Endocr Soc. 2021 Oct 1;5(11):bvab158. doi: 10.1210/jendso/bvab158. eCollection 2021 Nov 1.

Authors

Daniel A Dumesic¹, Ayli Tulberg¹, Megan McNamara¹, Tristan R Grogan², David H Abbott³, Rajanigandha Naik¹, Gwyneth Lu¹, Gregorio D Chazenbalk¹

Affiliations

¹ Department of Obstetrics and Gynecology, University of California, Los Angeles, Los Angeles, California 90095, USA.
² Department of Medicine Statistics Core, University of California, Los Angeles, Los Angeles, California 90095, USA.
³ OB/GYN, Wisconsin National Primate Research Center, University of Wisconsin, Madison, Madison, Wisconsin 53715, USA.

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: 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 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 = .040) and log adipose-IR values (P = .002) in PCOS women vs controls were accompanied by AKR1C3 messenger RNA overexpression of PCOS adipocytes matured in vitro (P = .016). Serum T/A4 ratios in PCOS women, but not controls, negatively correlated with log triglycerides (TGs: R = -0.65, P = .002) and the TG index (R = -0.57, P = .011). Adjusting for serum free T, serum T/A4 ratios in PCOS women remained negatively correlated with log TG (R = -0.57, P = .013) and TG index (R = -0.50, P = .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.

Keywords: AKR1C3; adipocyte; adipose; androstenedione; polycystic ovary syndrome; testosterone.

; The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.

Abstract

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