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

Authors: Gagliano-Jucá, T.; Pencina, K. M.; Ganz, T.; Travison, T. G.; Kantoff, P. W.; Nguyen, P. L.; Taplin, M. E.; Kibel, A. S.; Li, Z.; Huang, G.; Edwards, R. R.; Nemeth, E.; Basaria, S.
Article Title: Mechanisms responsible for reduced erythropoiesis during androgen deprivation therapy in men with prostate cancer
Abstract: Androgen deprivation therapy (ADT) is a mainstay of treat-ment 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-mo 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 wk, and 24 wk 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106 cells/l, 95%CI = 0.3 to 0.1106 cells/l, P  0.001), hematocrit (1.9%, 95%CI = 2.7 to 1.1%, P  0.001), and hemoglobin (0.6 g/dl, 95%CI = 0.8 to 0.3 g/dl, P  0.001). Serum hepcidin concentration increased in the ADT-group (18 ng/ml, P  0.001); however, iron concentrations did not change (1.1 g/dl, P = 0.837). Ferritin levels increased in men on ADT (60 ng/ml, P  0.001). Iron binding capacity, transferrin saturation, erythroferrone, and erythropoietin did not 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. © 2018 the American Physiological Society.
Keywords: erythropoietin; anemia; bone marrow; hepcidin; erythroferrone; leu-kopenia
Journal Title: American Journal of Physiology - Endocrinology and Metabolism
Volume: 315
Issue: 6
ISSN: 0193-1849
Publisher: American Physiological Society  
Date Published: 2018-12-01
Start Page: E1185
End Page: E1193
Language: English
DOI: 10.1152/ajpendo.00272.2018
PROVIDER: scopus
PUBMED: 30325657
Notes: Article -- Export Date: 1 February 2019 -- Source: Scopus
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  1. Philip Wayne Kantoff
    62 Kantoff