Mechanisms responsible for reduced erythropoiesis during androgen deprivation therapy in men with prostate cancer

Androgen deprivation therapy (ADT) is a mainstay of treatment for prostate cancer (PCa). As androgens stimulate erythropoiesis, ADT is associated with a reduction in hematocrit, which in turn contributes to fatigue and related morbidity. However, the mechanisms involved in ADT-induced reduction in erythropoiesis remain unclear. We conducted a 6-month prospective cohort study and enrolled men with PCa about to undergo ADT (ADT-Group) and a control group of men who had previously undergone prostatectomy for localized PCa and were in remission (Non-ADT Group). All participants had normal testosterone levels at baseline. Fasting blood samples were collected at baseline, 12 weeks and 24 weeks after initiation of ADT; samples were obtained at the same intervals from enrollment in the Non-ADT group. Blood count, iron studies, erythropoietin, erythroferrone and hepcidin levels were measured. Seventy participants formed the analytical sample (31 ADT, 39 Non-ADT). ADT was associated with a significant reduction in erythrocyte count (estimated mean difference = -0.2 x 10(6)cells/mu l; 95%CI = -0.3 to -0.1 x 10(6)cells/mu l; p < 0.001), hematocrit (-1.9%; 95%CI = -2.7 to -1.1%; p < 0.001) and hemoglobin (-0.6g/dl; 95%CI = -0.8 to -0.3g/dl; p < 0.001). Serum hepcidin concentration increased in the ADT-group (18ng/ml; p<0.001); however, iron concentrations did not change (-1.1 mu g/dl; p = 0.837). Ferritin levels increased in men on ADT (60ng/ml; p < 0.001). Iron binding capacity, transferrin saturation, erythroferrone and erythropoietin didn't change. Nine men undergoing ADT developed new-onset anemia. In conclusion, reduced proliferation of marrow erythroid progenitors leads to ADT-induced reduction in erythropoiesis. Future studies should evaluate the role of selective androgen receptor modulators in the treatment of ADT-induced anemia.