Mechanisms responsible for reduced erythropoiesis during androgen deprivation therapy in men with prostate cancer.
Am J Physiol Endocrinol Metab
; 315(6): E1185-E1193, 2018 12 01.
Article
en En
| MEDLINE
| ID: mdl-30325657
ABSTRACT
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-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/µl, 95%CI = -0.3 to -0.1×106 cells/µl, 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 µg/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.
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Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias de la Próstata
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Testosterona
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Eritropoyetina
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Leuprolida
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Eritropoyesis
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Antagonistas de Andrógenos
Tipo de estudio:
Observational_studies
Límite:
Aged
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Humans
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Male
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Middle aged
Idioma:
En
Año:
2018
Tipo del documento:
Article