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Free Fatty Acids Increase Androgen Precursors in Vivo

Department of Endocrinology, Diabetes and Nutrition (K.M., T.B., V.K., J.A., H.R., M.O., M.O.W., V.B., M.M., A.F.H.P., S.D., J.S.), Charite–University Medicine Berlin, Campus Benjamin Franklin, 12200 Berlin, Germany; Department of Clinical Nutrition (K.M., T.B., V.K., J.A., H.R., M.O., M.O.W., V.B., M.M., A.F.H.P., S.D., J.S.), German Institute of Human Nutrition Potsdam-Rehbrücke, 14558 Nuthetal, Germany; and Endokrinologikum (S.D.), 10117 Berlin, Germany

Address all correspondence and requests for reprints to: Joachim Spranger, M.D., Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbrücke, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany. E-mail: spranger{at}mail.dife.de or joachim.spranger{at}charite.de.

Context: There is considerable evidence that metabolic factors such as insulin resistance may induce hyperandrogenemia in polycystic ovary syndrome. However, other metabolic factors such as free fatty acids (FFAs) may also contribute to androgen excess.

Objective: The objective was to study effects of FFAs on adrenal production of androgen precursors in vivo.

Design and Participants: We investigated eight healthy young men, because male individuals produce the androgen precursors dehydroepiandrosterone (DHEA), DHEA sulfate, and androstenedione predominantly in the adrenal gland. A randomized controlled crossover trial was performed.

Intervention: After a 10-h overnight fast, 20% lipid/heparin or saline/heparin infusion was given at a rate of 1.5 ml/min. Four hours after start of lipid infusion, a euglycemic hyperinsulinemic clamp was performed.

Main Outcome Measures: DHEA, androstenedione, 17-OH-progesterone, testosterone, estrone, LH, FSH, ACTH, and cortisol were measured.

Results: The adrenal androgen precursors DHEA and androstenedione showed a circadian decline during saline/heparin infusion (P < 0.05 vs. baseline, respectively), whereas no significant changes were observed during lipid/heparin infusion (P = not significant vs. baseline, respectively). Correspondingly, DHEA and androstendione values were significantly elevated during lipid compared with saline infusion (P < 0.05, respectively), and areas under curve of both androgen precursors were significantly increased with lipid compared with saline infusion. Notably, all changes were detected before induction of insulin resistance.

Conclusions: This study demonstrates that FFAs increase production of androgen precursors in vivo in men. These data tentatively suggest that hyperandrogenemia in polycystic ovary syndrome may be induced, at least in part, by elevated FFAs.

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