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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Androgen Antagonists / pharmacology
  • Androgen Antagonists / therapeutic use*
  • Erythrocyte Count
  • Erythropoiesis / drug effects*
  • Erythropoietin / blood*
  • Ferritins / blood
  • Hepcidins / blood
  • Humans
  • Leuprolide / pharmacology
  • Leuprolide / therapeutic use*
  • Male
  • Middle Aged
  • Prospective Studies
  • Prostatic Neoplasms / blood*
  • Prostatic Neoplasms / drug therapy
  • Testosterone / blood*


  • Androgen Antagonists
  • EPO protein, human
  • Hepcidins
  • Erythropoietin
  • Testosterone
  • Ferritins
  • Leuprolide