Do reproductive hormones modify insulin sensitivity and metabolism in older men? A randomized, placebo-controlled clinical trial of recombinant human chorionic gonadotropin.
OBJECTIVE
In order to assess the hormonal determinants of insulin sensitivity and related components of the metabolic syndrome, we evaluated the effect of subcutaneous recombinant human chorionic gonadotropin (r-hCG; Ovidrel) on insulin sensitivity, vascular reactivity, leptin, insulin-like growth factor-I (IGF-I) and lipids in ambulant, community dwelling men >60 Years of age with serum testosterone <or= 15 nmol/l on two occasions.


METHODS
Forty eligible men were randomized to receive 250 microg (5000 IU) r-hCG subcutaneously twice each week (n=20) or placebo (n=20) injections for 3 Months, and all subjects (mean age 67 (range 60-85) Years) completed the study.


RESULTS
Groups were well matched for height, weight, anthropometry and insulin sensitivity. Insulin sensitivity was assessed by homeostasis model (HOMA) and euglycemic hyperinsulinemic clamp at baseline and at the end of the treatment period in the first 30 men who did not have diabetes mellitus. Insulin sensitivity (HOMA and euglycemic clamp) or beta cell function (HOMA) were not significantly changed by r-hCG despite a significant increase in lean body mass (approximately 2 kg, P<0.001) and reduced fat mass (approximately 1 kg, P<0.05). Subcutaneous fat (skinfold measurements), abdominal girth and serum leptin all decreased and IGF-I tended to increase, but these changes were not significant. Recombinant hCG significantly reduced total and low density lipoprotein cholesterol, and triglycerides, but did not significantly alter high density lipoprotein cholesterol. Endothelial function (vascular reactivity) was not significantly worsened. We conclude that three-Months of treatment with r-hCG demonstrates expected hormonal effects, improved lipids and did not worsen vascular endothelial function. Insulin sensitivity was not altered despite suggestive changes in body composition.


CONCLUSIONS
These findings suggest short-term metabolic and cardiovascular safety and argue against an important role for androgens in the hormonal control of insulin sensitivity in older men.
Liu
Peter Y
PY
Department of Andrology, Concord Hospital and ANZAC Research Institute, Concord, New South Wales 2139, Australia.
Wishart
Susan M
SM
Celermajer
David S
DS
Jimenez
Mark
M
Pierro
Irene Di
ID
Conway
Ann J
AJ
Handelsman
David J
DJ
D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D001823:Body Composition / Q000187:drug effects; D001916:Brachial Artery / Q000187:drug effects; D006063:Chorionic Gonadotropin / Q000008:administration & dosage*; D005640:Follicle Stimulating Hormone / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008055:Lipids / Q000097:blood; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D011994:Recombinant Proteins / Q000008:administration & dosage; D012039:Regional Blood Flow / Q000187:drug effects; D013739:Testosterone / Q000097:blood / Q000172:deficiency*
D006063:Chorionic Gonadotropin; D008055:Lipids; D011994:Recombinant Proteins; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone