Interplay of Cortisol, Testosterone, and Abdominal Fat Mass in Normal-weight Women With Polycystic Ovary Syndrome

Daniel A Dumesic; Adina F Turcu; Haiping Liu; Tristan R Grogan; David H Abbott; Gwyneth Lu; Devyani Dharanipragada; Gregorio D Chazenbalk

doi:10.1210/jendso/bvad079

Interplay of Cortisol, Testosterone, and Abdominal Fat Mass in Normal-weight Women With Polycystic Ovary Syndrome

J Endocr Soc. 2023 Jun 7;7(8):bvad079. doi: 10.1210/jendso/bvad079. eCollection 2023 Jul 3.

Authors

Daniel A Dumesic¹, Adina F Turcu², Haiping Liu², Tristan R Grogan³, David H Abbott⁴, Gwyneth Lu¹, Devyani Dharanipragada¹, Gregorio D Chazenbalk¹

Affiliations

¹ Department of Obstetrics and Gynecology, University of California, Los Angeles, 1Los Angeles, CA 90095, USA.
² Division of Metabolism, Endocrinology, Nutrition and Diabetes, University of Michigan, Ann Arbor, MI 48103, USA.
³ Department of Medicine Statistics Core, University of California, Los Angeles, Los Angeles, CA 90024, USA.
⁴ Department of Obstetrics and Gynecology, Wisconsin National Primate Research Center, University of WI-Madison, Madison, WI 53715, USA.

Abstract

Context: Ovarian and adrenal steroidogenesis underlie endocrine-metabolic dysfunction in polycystic ovary syndrome (PCOS). Adipocytes express aldo-keto reductase 1C3 and type 1 11β-hydroxysteroid dehydrogenase, which modulate peripheral androgen and cortisol production.

Objectives: To compare serum adrenal steroids, including 11-oxygenated androgens (11-oxyandrogens), cortisol, and cortisone between normal-weight women with PCOS and body mass index- and age-matched ovulatory women with normal-androgenic profiles (controls), and assess whether adrenal steroids associate with abdominal adipose deposition.

Design: Prospective, cross-sectional, cohort study.

Setting: Academic medical center.

Patients: Twenty normal-weight women with PCOS and 20 body mass index-/age-matched controls.

Interventions: Blood sampling, IV glucose tolerance testing, and total-body dual-energy x-ray absorptiometry.

Main outcome measures: Clinical characteristics, hormonal concentrations, and body fat distribution.

Results: Women with PCOS had higher serum total/free testosterone (T) and androstenedione (A4) levels and a greater android/gynoid fat mass than controls (androgens P < .001; android/gynoid fat mass ratio, P = .026). Serum total/free T and A4 levels correlated positively with android/gynoid fat mass ratio in all women combined (P < .025, all values). Serum 11ß-hydroxyA4, 11-ketoA4, 11ß-hydroxyT, 11-ketoT, cortisol, and cortisone levels were comparable between female types and unrelated to body fat distribution. Serum 11-oxyandrogens correlated negatively with % total body fat, but lost significance adjusting for cortisol. Serum cortisol levels, however, correlated inversely with android fat mass (P = .021), with a trend toward reduced serum cortisol to cortisone ratio in women with PCOS vs controls (P = .075), suggesting diminished 11β-hydroxysteroid dehydrogenase activity.

Conclusion: Reduced cortisol may protect against preferential abdominal fat mass in normal-weight PCOS women with normal serum 11-oxyandrogens.

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

Abstract

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