title: Testosterone suppression in men with prostate cancer leads to an increase in arterial stiffness and hyperinsulinaemia.
abstract: The role of androgens in cardiovascular disease is uncertain. We aimed to determine the vascular effects of androgen suppression in men with prostate cancer. Arterial stiffness (or 'compliance') was measured in 16 men (71+/-9 years, mean+/-S.D.) prior to, and 3 months after, complete androgen suppression with gonadotrophin-releasing hormone analogues as treatment for prostate cancer. Fifteen control men (70+/-7 years) also had arterial stiffness studies at baseline and 3 months later. Two measures of arterial stiffness were employed: systemic arterial compliance (SAC) was measured by simultaneous recording of aortic flow and carotid artery pressure ('area method'), and pulse wave velocities (PWVs) were recorded with the 'Complior' system. The 16 cases underwent glucose-tolerance and fasting-lipids tests on both visits. After 3 months of testosterone suppression, there was a significant fall in SAC, which was not seen in the controls [mean change+/-S.E.M., -0.26+/-0.09 a.c.u. (arbitrary compliance unit) in the cases versus +0.06+/-0.11 in the controls; P =0.03). Central, but not peripheral, PWVs tended to increase in the cases (mean change+/-S.E.M. for aorto-femoral PWV, +0.5+/-0.4 m/s for cases versus -0.3+/-0.3 m/s for controls; P =0.08). After testosterone suppression, fasting insulin levels increased from 6.89+/-4.84 m-units/l to 11.34+/-8.16 m-units/l (mean+/-S.D.), total cholesterol increased from 5.32+/-0.77 mmol/l to 5.71+/-0.82 mmol/l and high-density lipoprotein cholesterol increased from 1.05+/-0.24 mmol/l to 1.26+/-0.36 mmol/l; P <0.005 for all. No significant change occurred in body-mass index, serum glucose, low-density lipoprotein cholesterol or triacylglycerol (triglyceride) levels. Our results indicate that loss of androgens in men leads to an increase in aortic stiffness and serum insulin levels, and may therefore adversely affect cardiovascular risk.
authors.affiliation: Section of Geriatric Medicine, Imperial College Faculty of Medicine, Hammersmith Hospital, London W12 0NN, UK. f.dockery@ic.ac.uk
authors.forename: Frances
authors.initials: F
authors.lastname: Dockery
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Bulpitt
authors.forename: Sanjiv
authors.initials: S
authors.lastname: Agarwal
authors.forename: Mandy
authors.initials: M
authors.lastname: Donaldson
authors.forename: Chakravarthi
authors.initials: C
authors.lastname: Rajkumar
mesh_terms: D000368:Aged; D000726:Androgen Antagonists / Q000009:adverse effects*; D000886:Anthropometry; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects; D001011:Aorta / Q000503:physiopathology; D002339:Carotid Arteries / Q000503:physiopathology; D003187:Compliance / Q000187:drug effects; D017273:Goserelin / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006946:Hyperinsulinism / Q000139:chemically induced*; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D013739:Testosterone / Q000037:antagonists & inhibitors*; D014655:Vascular Resistance / Q000187:drug effects*
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D007328:Insulin; D017273:Goserelin; D013739:Testosterone