Prospective Study of Effect of Androgens on Serum Inflammatory Markers in Men

Abstract

Objective-Because male sex is an independent risk factor for the severity of atherosclerosis, it is possible that androgens may be proatherogenic. There is evidence that sex hormones, particularly estrogens, regulate (or modulate) inflammation, a process integral to atherogenesis. Because levels of serum inflammatory markers predict cardiovascular outcomes, we prospectively assessed the effects of androgen therapy on these markers in older men. Methods and Results-Levels of high-sensitivity C-reactive protein (CRP), soluble intracellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1) were measured from sera collected at baseline and at the end of 2 randomized double-blind placebo-controlled trials evaluating the effects of 3 months of androgen treatment with either dihydrotestosterone (DHT) or recombinant human chorionic gonadotropin (rhCG) in healthy men aged Ͼ60 years with partial androgen deficiency (serum testosterone levels Ͻ15 nmol/L). For the DHT study (70 mg transdermally daily), 33 men completed 3 months of treatment (16 men were treated with DHT, and there were 17 controls). For the rhCG (250 g twice weekly) study, 20 men were treated with rhCG, and there were 20 controls. In both studies, groups were well matched for age and vascular risk factors. Androgen levels (DHT and testosterone) were consistently maintained at eugonadal levels throughout the trials, with estradiol markedly increased by rhCG but not DHT. Baseline CRP levels were 0.74 to 1.49 mg/L, sVCAM-1 levels were 847 to 950 ng/mL, and sICAM-1 levels were 256 to 292 ng/mL in all groups. Neither DHT nor rhCG resulted in significant changes in CRP, sVCAM-1, or sICAM-1 compared with placebo (PϾ0.3 in both studies). Conclusions-Exogenous androgen therapy with or without increased estradiol levels does not alter serum inflammatory markers in older men; this finding is in contrast to the effects of estrogens on inflammatory markers that have been found in postmenopausal women. These data provide a measure of reassurance concerning potential adverse cardiovascular effects of androgen therapy in older men.

The effect of testosterone replacement therapy on adipocytokines and C-reactive protein in hypogonadal men with type 2 diabetes

“…Others have similarly found no effect on IL-6 levels with testosterone therapy (29). Two studies in healthy men have found no effect of androgen therapy on CRP (50,51). Both these studies, similar to the present study, were short-duration studies over 3-6 months and the long-term effect of testosterone treatment on CRP has not been investigated.…”

The effects of short term (3 weeks) testosterone treatment on serum inflammatory markers in men undergoing coronary artery stenting

“…Testosterone has innate immune modulating properties [19]. There is, also, evidence that testosterone reduces inflammation and reduces inflammatory cytokines [16,20]. Hypogonadal or eugonadal men suffering with chronic inflammatory diseases have been shown to improve following testosterone administration [17,21].…”

Testosterone: a vascular hormone in health and disease

“…Conversely, a similar study demonstrated that testosterone therapy had no effect on serum TNFa concentrations in men with chronic heart failure (Pugh et al 2005) and testosterone replacement in hypogonadal men with T2DM had no effect on the TNFa, IL6 or CRP levels (Kapoor et al 2007). Likewise, in a prospective study of older men, the administration of DHT or human chorionic gonadotrophin (to stimulate testosterone synthesis from the Leydig cells) did not significantly alter the highsensitivity CRP, soluble vascular cell adhesion molecule 1 (sVCAM-1) or soluble intracellular adhesion molecule (sICAM) levels (Ng et al 2002).…”