Introduction

Men exhibit a higher mass of red blood cells than women, which had already been demonstrated by spectrophotometry in 900 subjects almost 100 years ago (Williamson 1916). This fact cannot totally be accounted for by menstrual blood loss occuring in women and has been shown to be caused by higher androgen levels present in men (Vahlquist 1950). The marked influence of androgens on erythropoiesis was a major endocrinological research topic during the 1970s (for review: Shahidi 1973). Although the prime time of androgen therapy for anemia passed with the introduction of recombinant erythropoietin (rhEPO) in 1987, androgens continue to be widely used for testosterone substitution therapy in hypogonadal men who often present with markedly lowered hemoglobin and erythrocyte concentrations. Nevertheless, the general issue of androgens in relation to erythropoiesis seems to be experiencing a current revival. The effects of androgens on erythropoiesis are exerted via several pathways which will be discussed. Safety aspects concerning increased red blood cell mass in terms of a putatively affected risk for ischemic vascular disease will also be considered.

Mechanisms of androgen action within the erythropoietic system

First intervention trials concerning androgens and erythropoiesis were performed in intact rats which exhibited a marked increase of hemoglobin concentrations and bone marrow activity upon testosterone administration (Vollmer and Gordon 1941). These results were confirmed in orchiectomized or hypophysectomized animals in which the resulting anemia could be successfully treated by injections with testosterone propionate (Crafts 1946; Steinglass et al. 1941).