Philipp Lachenmann: DELPHI Rationale


Schoeller Junkmann Preis 2008

Dr. Knut Mai

Charite – University Medicine Berlin, Campus Benjamin Franklin and German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal

Hyperlipidemia modifies circulating androgen levels in women: a randomized, controlled trial

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. Therefore we aimed to analyse the effects of hyperlipidemia on circulating androgen levels in healthy women.

Methods: In a randomized controlled cross-over trial, 12 healthy young women were investigated during the early follicular phase of two subsequent cycles. Following a 10-hour overnight fast, 20% lipid/heparin (LHI) or saline/heparin (SHI) infusion was given for 330 minutes.  Circulating androgens and their precursors as well as the 24 h-urinary androgen excretion were measured.

Results: As expected lipid infusion increased FFAs already after 1 hour and lead to an elevation of the adrenal androgen precursors androstenedione, DHEA and DHEAS compared to SHI. Accordingly a huge increase in testosterone, calculated free testosterone, DHT, estrone and 17β-estradiol levels could be detected during the LHI compared to SHI, whereas SHBG levels did not differ.

There was no indication for changed central stimulation. In addition the calculated activity of the hepatic sulfotransferase and 5a-reductase were not different. However the urinary excretion of DHEA, DHEAS, androstenediol, 16?-hydroxy-DHEA and androstenetriol were reduced.

Conclusion: Hyperlipidemia increases adrenal androgen precursors DHEA and DHEAS by lowering their urinary excretion in vivo in healthy young women. As the hyperlipidemia mediated effects on insulin sensitivity is usually not detectable within the first hour of a lipid infusion, these findings suggest an effect independent of insulin resistance. The here described mechanism of hyperlipidemia induced elevation of circulating androgens 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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