Renin-angiotensin blockade reduces serum free testosterone in middle-aged men on haemodialysis and correlates with erythropoietin resistance

Abstract

There are conflicting reports about the importance of the renin-angiotensin system (RAS) on erythropoietin (Epo) sensitivity in haemodialysis patients, but the role of gender has not been studied specifically. The hypothesis underlying this study is that Epo resistance associated with RAS blockade (RASB) is specific to men and related to drug-induced lowering of circulating testosterone. Men and women undergoing chronic haemodialysis were divided into groups according to whether or not they were receiving RASB. Serum was collected pre-dialysis for determination of free testosterone levels by enzyme immunoassay. Routine laboratory data and Epo doses were collated and analysed for the 3 month period prior to the measurement of the hormone level. Control women required more Epo than control men (P=0.002), but the Epo doses between men and women with RASB were similar. Men with RASB required more Epo than control men (P=0.002), but RASB had no effect on Epo requirements in women. There was a significant relationship between age and testosterone levels in control men (P=0.01) that was not present in men taking RASB. RASB was associated with lower levels of serum testosterone in men <60 years old (P=0.02), but had no effect on serum testosterone levels in older men or women. Multiple regression analysis demonstrated that serum testosterone negatively correlated with Epo dose (P=0.045) when all groups of patients were considered together. These data suggest that androgens may participate in Epo resistance associated with RASB in patients on haemodialysis, and that the effect is related to both gender and age.