Erythropoietin Resistance During Androgen Deficiency—Reply

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I thank Daniell for his interest in my editorial, but I cannot endorse his assertions. My editorial was not about the differential diagnosis of anemia in the elderly. Rather, it was about the impact of aging on red blood cell production within the context of 4 articles published simultaneously in the ARCHIVES. As discussed in the editorial, aging per se does not result in anemia, but the associated age-related fall in male androgen production is probably responsible for the mild decline in hemoglobin and hematocrit levels observed in otherwise healthy elderly men.¹ Unfortunately, Daniell has conflated this age-related process with the syndrome of hypogonadism, when in fact the two have never been demonstrated to be synonymous. As a corollary, there is no proof for his assertion that hypogonadism “develops frequently with advancing age.” Daniell's assertion that androgen therapy has a useful role in the management of anemia in end-stage renal disease also contradicts the known physiology of erythropoiesis. Androgens are neither necessary nor sufficient to sustain erythropoiesis and are not primarily involved in the elegant mechanism for oxygen sensing that regulates EPO production.² Indeed, chemical castration, which reduces serum testosterone to zero, has no effect on the serum erythropoietin level.³