Impact of acute biochemical castration on insulin sensitivity in healthy adult men.
BACKGROUND
Evidence supports an inverse relationship between serum testosterone (T) and insulin resistance in men. However, data with respect to causality are limited. The aim of this study was to explore the impact of acute biochemical castration on insulin sensitivity in healthy adult men.


METHODS
Ten healthy, adult males (mean age 41.0 +/- 3.9 yr) were studied. Subjects were studied at baseline and after 2 and 4 weeks of biochemical castration. Outpatient hospital research setting. Body composition (dual-energy x-ray absorptiometry), energy expenditure (indirect calorimetry), abdominal and visceral adiposity (MRI), skeletal muscle intramyocellular lipid content ([IMCL] (1)H-MR spectroscopy), and insulin sensitivity (hyperinsulinemic-euglycemic clamp) were assessed before and after 2 and 4 weeks of biochemical castration induced by a GnRH antagonist (acyline 300 mug/kg subcutaneous every 10-14 days). Serum T, insulin and glucose levels, body composition, abdominal visceral fat, IMCL, and glucose disposal rate (M) were measured.


CONCLUSIONS
Acyline administration suppressed serum T to frankly hypogonadal levels in all subjects for the duration of the study (P <0.009). No significant changes in body composition, energy expenditure, or M were observed at either 2 or 4 weeks of castration. Acyline is an effective GnRH antagonist inducing acute castration in all subjects. ii) Four weeks of biochemical castration has no impact on insulin sensitivity in healthy men likely due to unchanged body composition variables. iii) Insulin resistance associated with chronic low T levels may be largely driven by decreased fat free mass, increased percent body fat, and/or other metabolic regulatory factors.
Rabiee
Atoosa
A
Department of Surgery and Department of Medicine, Johns Hopkins Medical School, Baltimore, Maryland, USA.
Dwyer
Andrew A
AA
Caronia
Lisa M
LM
Hayes
Frances J
FJ
Yialamas
Maria A
MA
Andersen
Dana K
DK
Thomas
Bijoy
B
Torriani
Martin
M
Elahi
Dariush
D
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition / Q000502:physiology; D004958:Estradiol / Q000097:blood; D005640:Follicle Stimulating Hormone / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors; D006801:Humans; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance / Q000502:physiology*; D050152:Intra-Abdominal Fat / Q000378:metabolism; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism; D009842:Oligopeptides / Q000008:administration & dosage; D009919:Orchiectomy; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D050151:Subcutaneous Fat / Q000378:metabolism; D013739:Testosterone / Q000097:blood*; D055815:Young Adult
D001786:Blood Glucose; D007328:Insulin; D009842:Oligopeptides; D012738:Sex Hormone-Binding Globulin; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; C109238:acyline