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Intravenous Lipid and Heparin Infusion-Induced Elevation in Free Fatty Acids and Triglycerides Modifies Circulating Androgen Levels in Women: A Randomized, Controlled Trial

Department of Endocrinology, Diabetes, and Nutrition (K.M., T.B., F.R., J.A., M.M., M.O.W., S.D., A.F.H.P., J.S.), Charite-Universitätsmedizin Berlin, Campus Benjamin Franklin, 12200 Berlin, Germany; Department of Clinical Nutrition (K.M., T.B., F.R., J.A., M.M., M.O.W., S.D., A.F.H.P., J.S.), German Institut of Nutrition, 14558 Potsdam, Germany; Endokrinologikum Berlin (H.M.S., S.D.), 10117 Berlin, Germany; Steroid Laboratory (C.M.-G.), Department of Pharmacology, Ruprecht-Karls-University of Heidelberg, D-69117 Heidelberg, Germany; and Steroid Research and Mass Spectrometry Unit (S.A.W., M.F.H.), Center of Child and Adolescent Medicine, Justus Liebig University, 35385 Giessen, Germany

Address all correspondence and requests for reprints to: Joachim Spranger, M.D., Department of Endocrinology, Diabetes, and Nutrition, Charité-Universitätsmedizin Berlin, Hindenburgdamm 30, 12200 Berlin, Germany. E-mail: joachim.spranger{at}charite.de.

Background: 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.

Objective: The objective of the study was to analyze the effects of iv lipid and heparin infusion on circulating androgen levels in healthy women.

Design: This was a randomized, controlled, crossover trial.

Setting: The study was conducted at an endocrinology center.

Patients: Patients included 12 healthy young women during the early follicular phase of two subsequent cycles.

Intervention: After an overnight fast, a 20% lipid/heparin or a saline/heparin infusion was administered in random order for 330 min.

Main Outcome Measures: A detailed characterization of androgen metabolism was performed.

Results: Elevations in free fatty acids and triglycerides, induced by lipid/heparin infusion, elevates the levels of androstenedione, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), testosterone, 5-dihydrotestosterone, estrone, and 17β-estradiol. Urinary excretion of DHEA, DHEAS, 5-androstene-3β,17β-diol, and the sum of urinary excreted DHEA and its 16-hydroxylated downstream metabolites, 16-hydroxy-DHEA and 5-androstene-3β,16,17β-triol, were reduced.

Conclusion: The mechanism of iv lipid and heparin infusion-induced elevation of circulating androgens described here might contribute to the development of hyperandrogenism in women with PCOS and suggests that lowering of hyperlipidemia might be a potential therapeutic target in patients with PCOS to treat hyperandrogenemia.

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