Intravenous lipid and heparin infusion-induced elevation in free fatty acids and triglycerides 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.


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


METHODS
This was a randomized, controlled, crossover trial.


METHODS
The study was conducted at an endocrinology center.


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


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


METHODS
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, 5alpha-dihydrotestosterone, estrone, and 17beta-estradiol. Urinary excretion of DHEA, DHEAS, 5-androstene-3beta,17beta-diol, and the sum of urinary excreted DHEA and its 16-hydroxylated downstream metabolites, 16alpha-hydroxy-DHEA and 5-androstene-3beta,16alpha,17beta-triol, were reduced.


CONCLUSIONS
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.
Mai
K
K
Department of Endocrinology, Diabetes, and Nutrition, Charité-Universitätsmedizin Berlin, Hindenburgdamm 30, 12200 Berlin, Germany.
Bobbert
T
T
Reinecke
F
F
Andres
J
J
Maser-Gluth
C
C
Wudy
S A
SA
Möhlig
M
M
Weickert
M O
MO
Hartmann
M F
MF
Schulte
H M
HM
Diederich
S
S
Pfeiffer
A F H
AF
Spranger
J
J
D000328:Adult; D000728:Androgens / Q000097:blood* / Q000378:metabolism; D000735:Androstenedione / Q000097:blood / Q000378:metabolism; D018592:Cross-Over Studies; D003687:Dehydroepiandrosterone / Q000097:blood / Q000378:metabolism; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood / Q000378:metabolism; D013196:Dihydrotestosterone / Q000097:blood / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005260:Female; D006493:Heparin / Q000008:administration & dosage*; D006801:Humans; D007262:Infusions, Intravenous; D008055:Lipids / Q000008:administration & dosage*; D011085:Polycystic Ovary Syndrome / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D012965:Sodium Chloride / Q000008:administration & dosage; D013739:Testosterone / Q000097:blood / Q000378:metabolism; D013997:Time Factors; D014280:Triglycerides / Q000097:blood*
D000728:Androgens; D005230:Fatty Acids, Nonesterified; D008055:Lipids; D014280:Triglycerides; D013196:Dihydrotestosterone; D013739:Testosterone; D000735:Androstenedione; D012965:Sodium Chloride; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate; D006493:Heparin