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.

Adipocytokines, Obesity, and Insulin Resistance During Combined Androgen Blockade for Prostate Cancer

“…9 GnRH agonists also increase serum triglycerides and low density lipoprotein cholesterol. 5,8,10 Consistent with these adverse metabolic effects, GnRH agonists are associated with greater risk of incident diabetes mellitus and cardiovascular disease in men with prostate cancer. 11…”

Relationship between insulin and hypogonadism in men with metabolic syndrome

“…It has been proposed that the hypogonadism resultant from prostate cancer treatment, by the blockage of gonadotrophins by GnRH-agonists (50,51) or by castration (52), could be associated with an increase in insulin levels.…”

Androgen deprivation therapy through bilateral orchiectomy: increased metabolic risks

“…These findings are in agreement with previous studies. Dockery et al 25 reported elevated total cholesterol and high-density lipoprotein 3 months after the beginning of ADT. In another short-term study, increased total cholesterol, triglycerides and high-density lipoprotein were observed.…”

“…Similar results were observed in other studies. 24,25 Moreover, a low level of adiponectin and elevated inflammatory markers characterize classic metabolic syndrome. Conversely, it is reported that ADT increases the serum adiponectin level and does not change the level of C-reactive protein.…”