Insulin sensitivity during combined androgen blockade for prostate cancer.
BACKGROUND
GnRH agonists markedly increase fat mass in men with prostate cancer, but little is known about the effects of treatment on insulin sensitivity.


OBJECTIVE
The objective of the study was to assess the effects of short-term GnRH agonist treatment on insulin sensitivity.


METHODS
This was a prospective 12-wk study.


METHODS
The study was conducted at a general clinical research center.


METHODS
We studied 25 men with locally advanced or recurrent prostate cancer, no radiographic evidence of metastases, no history of diabetes mellitus, and no evidence of diabetes mellitus at baseline visit.


METHODS
Leuprolide depot and bicalutamide were used in the study.


METHODS
Oral glucose tolerance tests and body composition assessment by dual-energy x-ray absorptiometry were performed at baseline and wk 12. The primary study outcome was change in insulin sensitivity index.


RESULTS
Mean (+/- se) percentage fat body mass increased by 4.3 +/- 1.3% from baseline to wk 12 (P = 0.002). Insulin sensitivity index decreased by 12.9 +/- 7.6% (P = 0.02). Insulin sensitivity by homeostatic model assessment decreased by 12.8 +/- 5.9% (P = 0.02). Fasting plasma insulin levels increased by 25.9 +/- 9.3% (P = 0.04). Mean glycosylated hemoglobin also increased significantly (P < 0.001).


CONCLUSIONS
Short-term treatment with leuprolide and bicalutamide significantly increased fat mass and decreased insulin sensitivity in men with prostate cancer. These observations suggest that GnRH agonists may increase the risk of diabetes mellitus and cardiovascular disease in older men.
Smith
Matthew R
MR
Massachusetts General Hospital, Cox 640, 100 Blossom Street, Boston, MA 02114, USA. smith.matthew@mgh.harvard.edu
Lee
Hang
H
Nathan
David M
DM
D015502:Absorptiometry, Photon; D000273:Adipose Tissue / Q000187:drug effects; D000328:Adult; D000726:Androgen Antagonists / Q000009:adverse effects* / Q000627:therapeutic use*; D000886:Anthropometry; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects* / Q000627:therapeutic use*; D015415:Biomarkers; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition / Q000187:drug effects; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D008055:Lipids / Q000097:blood; D008297:Male; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D013739:Testosterone / Q000097:blood; D016896:Treatment Outcome
D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D015415:Biomarkers; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007987:Gonadotropin-Releasing Hormone; D007328:Insulin; D008055:Lipids; D013739:Testosterone