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Am J Physiol Endocrinol Metab. 2018 Dec 1;315(6):E1185-E1193. doi: 10.1152/ajpendo.00272.2018. Epub 2018 Oct 16.

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

Author information

1
Research Program in Men's Health: Aging and Metabolism, Brigham and Women's Hospital, Harvard Medical School , Boston, Massachusetts.
2
Department of Medicine and Department of Pathology, David Geffen School of Medicine at University of California , Los Angeles, California.
3
Program on Aging, Hebrew Senior Life, Roslindale, Massachusetts.
4
Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College , New York, New York.
5
Department of Radiation Oncology, Dana-Farber Cancer Institute , Boston, Massachusetts.
6
Department of Medical Oncology, Dana-Farber Cancer Institute , Boston, Massachusetts.
7
Division of Urology, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School , Boston, Massachusetts.
8
Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School , Boston, Massachusetts.

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.

KEYWORDS:

anemia; bone marrow; erythroferrone; erythropoietin; hepcidin; leukopenia

PMID:
30325657
PMCID:
PMC6336960
DOI:
10.1152/ajpendo.00272.2018

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