Exp Clin Endocrinol Diabetes 2007; 115 - P02_042
DOI: 10.1055/s-2007-972449

Free fatty acids increase androgen precursors in vivo in young healthy women

K Mai 1, T Bobbert 1, F Reinecke 1, J Andres 1, V Bähr 1, C Maser-Gluth 2, H Schulte 3, S Diederich 3, AF Pfeiffer 1, J Spranger 1
  • 1Charité – University Medicine Berlin, Campus Benjamin Franklin, Dept. of Endocrinology, Diabetes and Nutrition, Berlin, Germany
  • 2Dept. of Pharmacology, Ruprecht-Karls-University of Heidelberg, Steroid Laboratory, Heidelberg, Germany
  • 3Endokrinologikum, Berlin, Germany

Objectives: Free fatty acids (FFA) are known to play an important role by inducing insulin resistance and metabolic disturbances in obesity and type 2 diabetes. In addition, FFAs seem to have a stimulatory effect on adrenal androgen precursors in men. However, the effect of FFAs on androgen precursors and androgens in women is yet unknown.

Methods: In a randomized controlled cross-over trial, 12 healthy female volunteers were investigated during the early follicular phase of two subsequent cycles. Following a 10-hour overnight fast, 20% lipid/heparin or saline/heparin infusion was given at a rate of 1.5ml/min for 5 hours. Serum levels of dihydroepiandrosterone (DHEA), dihydroepiandrosteronesulfate (DHEAS), androstenedione, 17-hydroxyprogesterone, progesterone, testosterone, dihydrotestosterone (DHT), androstanediolglucuronide (ADG), estrone, 17β-estradiol, SHBG, LH, FSH and ACTH were measured.

Results: The increase in FFAs was accompanied by enhanced levels of androstenedione, DHEA, DHEAS, testosterone, DHT, estrone, 17β-estradiol. These changes could be observed after 1 to 2 hours, while FFA induced insulin resistance is well known to occur not earlier than about 210 minutes after lipid infusion. Progesterone and 17-hydroxyprogesterone, ADG, SHBG and ACTH levels were not different. LH and FSH were slightly decreased by lipid/heparin infusion. This effect seems to be independent of subsequent changes in insulin resistance. Conversion of DHEA to DHEAS was not modified.

Conclusion: In summary, there is reasonable evidence that FFAs increase adrenal androgen precursors in healthy young women. These effects appear to be independent of a subsequently insulin resistance. The increased amount of DHEA seems to result in elevated androstenedione levels and hyperandrogenemia with increased testosterone and DHT levels. These effects appear to be independent of the pituitary axis. We propose that comparable mechanisms might be relevant in the development of hyperandrogenemia in women with PCOS.