ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2008) 16 P22

Free fatty acids affect urinary excretion of androgen precursors thereby linking metabolism and hyperandrogenemia in vivo: results of a randomized, controlled trial

Knut Mai1, Thomas Bobbert1, Franziska Reinecke1, Janin Andres1, Volker Bähr1, Christiane Maser-Gluth4, Stefan Wudy5, Michaela Hartmann5, Matthias Möhlig1, Martin O Weickert2, Heinrich Schulte3, Sven Diederich3, Andreas Pfeiffer1 & Joachim Spranger1

1Department of Endocrinology, Diabetes and Nutrition, Charite – University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany; 2Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany; 3Endokrinologikum Berlin, Berlin, Germany; 4Steroid Laboratory, Department of Pharmacology, Ruprecht-Karls-University of Heidelberg, Heidelberg, Germany; 5Steroid Research Unit, Center of Child and Adolescent Medicine, Justus Liebig University, Giessen, Germany.

Context: The polycystic ovarian syndrome (PCOS) is characterized by hyperandrogenism and associated with obesity and impaired glucose metabolism. Despite the high prevalence of PCOS and the considerable clinical impact, the precise interplay between metabolism and hyperandrogenemia is not entirely clear. We therefore aimed to analyse the relation between circulating free fatty acids (FFAs) and androgen metabolism in vivo in women.

Design and participants: Twelve healthy young women during the early follicular phase of two subsequent cycles were investigated. A randomized controlled cross-over trial was performed. Following a 10-h overnight fast, 20% lipid/heparin or saline/heparin infusion was administered at a rate of 1.5 ml/min for 5 h.

Main outcome measures: Circulating androgens and their precursors as well as 24 h-urinary excretion of free DHEA, DHEAS, androstenedione, androsterone (An), etiocholanolone (Et), 5-androstene-3β,17α-diol, 5-androstene-3β,17β-diol, DHEA, 16α-hydroxy-DHEA, and 5-androstene-3β,16α,17β-triol) were measured.

Results: FFAs induced elevated circulating levels of androstenedione, DHEA, DHEAS, testosterone, DHT, estrone and 17β-estradiol. Urinary excretion of DHEA, free DHEAS, 5-androstene-3β,17α-diol and sum of urinary excreted DHEA and its 16-hydroxylated downstream metabolites 16α-hydroxy-DHEA and 5-androstene-3β,16α,17β-triol were reduced by FFAs.

Conclusions: Elevation of FFAs increases adrenal androgen precursors DHEA and DHEAS by lowering their urinary excretion in vivo in healthy young women. The here described mechanism might contribute to the development of hyperandrogenism in women with PCOS and suggests novel therapeutic targets to treat those patients.