Pharmacodynamics of growth hormone abuse biomarkers and the influence of gender and testosterone: a randomized double-blind placebo-controlled study in young recreational athletes.
BACKGROUND
IGF axis proteins and collagen peptides are promising markers of GH abuse.


OBJECTIVE
Our objective was to investigate whether responses of serum IGF axis and collagen markers to GH differ between men and women, and are influenced by testosterone (T).


METHODS
This was a randomized, double-blind, placebo-controlled study of 8-wk treatment followed by 6-wk washout.


METHODS
The study was performed at a clinical research facility.


METHODS
A total of 96 recreationally trained healthy athletes (63 men, 33 women), aged 18-40 yr, were studied.


METHODS
All subjects received GH (2 mg/d sc) or placebo for 8 wk; men also received T (250 mg/wk im) or placebo for 5 wk.


METHODS
Serum IGF axis proteins (IGF-I, IGF binding protein-3, and acid labile subunit) and collagen peptides (N-terminal propeptide of type I procollagen, C-terminal telopeptide of type I collagen, and N-terminal propeptide of type III procollagen) were measured.


RESULTS
GH induced significant increases in IGF axis and collagen markers that were greater in men than women (P < 0.001). Of the IGF axis markers, IGF-I showed the greatest increase. The relative incremental responses of the collagen markers in general were greater than the IGF markers, especially for PIIINP. The collagen markers increased and decreased more slowly with most remaining elevated (P < 0.01) after 6 wk, in comparison to IGF markers, which returned to baseline within 1 wk. Addition of T to GH amplified the response of PIIINP by more than 1.5-fold but did not affect any other marker. T alone did not affect IGF axis markers but modestly increased collagen markers.


CONCLUSIONS
These markers of GH abuse are less responsive in women. The increases in collagen markers have a different time course to the IGF markers and extend the window of detection in both sexes. The response of PIIINP is increased by coadministration of T.
Nelson
Anne E
AE
Pituitary Research Unit, Garvan Institute of Medical Research, St. Vincent's Hospital, 384 Victoria Street, Darlinghurst 2010, Sydney, NSW, Australia.
Meinhardt
Udo
U
Hansen
Jennifer L
JL
Walker
Irene H
IH
Stone
Glenn
G
Howe
Christopher J
CJ
Leung
Kin-chuen
KC
Seibel
Markus J
MJ
Baxter
Robert C
RC
Handelsman
David J
DJ
Kazlauskas
Rymantas
R
Ho
Ken K
KK
D000293:Adolescent; D000328:Adult; D054316:Biomarkers, Pharmacological / Q000097:blood / Q000378:metabolism*; D002352:Carrier Proteins / Q000097:blood / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D006023:Glycoproteins / Q000097:blood / Q000378:metabolism; D012739:Gonadal Steroid Hormones / Q000097:blood; D013006:Growth Hormone / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D010919:Placebos; D012727:Sex Characteristics; D013177:Sports; D019966:Substance-Related Disorders / Q000175:diagnosis / Q000378:metabolism*; D013739:Testosterone / Q000008:administration & dosage / Q000494:pharmacology*
D054316:Biomarkers, Pharmacological; D002352:Carrier Proteins; D006023:Glycoproteins; D012739:Gonadal Steroid Hormones; D018972:Insulin-Like Growth Factor Binding Protein 3; D010919:Placebos; C075944:insulin-like growth factor binding protein, acid labile subunit; D013739:Testosterone; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D003094:Collagen