The effect of androgens in enhancing erythropoiesis is mediated primarily by the indirect stimulation of erythropoietin secretion from renal and extrarenal sources (see Chap. 212).72,73 Moreover, androgens act directly on the bone marrow to increase red blood cell production in response to erythropoietin. The demonstration that erythropoiesis was stimulated by replacement dosages of androgens in hypogonadal men prompted the use of androgens to treat a variety of other anemias. The anemia of chronic renal failure and hypoproliferative anemias due to bone marrow dysfunction (e.g., aplastic anemia, myelofibrosis, and anemia caused by hematologic malignancies) are the most common conditions in which androgen therapy has been used.

Androgens are beneficial in the treatment of anemia in patients with chronic renal failure who are on adequate maintenance hemodialysis and whose iron and folate stores are normal.80,81 and 82 Parenterally administered androgen preparations (e.g., testosterone enanthate and nandrolone decanoate) are more effective than oral androgens (e.g., fluoxymesterone and oxymetholone). Anephric patients do not respond to androgen treatment.81

The androgen formulations that are used to treat anemia in hemodialysis patients are intramuscular testosterone enanthate (4 mg/kg per week) or nandrolone decanoate (1.5 mg/kg per week for women; 3 mg/kg per week for men). Typical dosages are testosterone enanthate 200 to 250 mg intramuscularly weekly and nandrolone decanoate 100 to 200 mg intramuscularly weekly. The typical response to these pharmacologic doses is a rise in hemoglobin of 1 to 2 g/dL.80,81 Because nandrolone decanoate has reduced androgenic activity, it is the preferred preparation to treat women with renal failure. Long-term androgen therapy should be limited to patients who demonstrate symptomatic and hematologic responses after a 6-month trial of androgen treatment. Therapy should be stopped periodically in all patients to assess the continued need for treatment. In many instances, the anemia of chronic renal failure responds to androgen treatment because patients are relatively androgen deficient (i.e., men with hypogonadism commonly associated with uremia, or women).

Because it is more effective and does not cause virilization in women, in comparison with androgens, recombinant human erythropoietin is becoming the treatment of choice for the anemia of renal failure. Erythropoietin is expensive, however, and may be associated with significant side effects (e.g., severe hypertension and arteriovenous fistula thrombosis).83 Because androgens stimulate erythropoiesis directly, they have been used to augment the action of exogenous erythropoietin, so that lower doses of erythropoietin are needed to achieve an adequate hematopoietic response.84,85 Thus, androgens remain useful as a primary treatment (particularly in men) or adjunctive treatment for the anemia of end-stage kidney disease.

Androgen therapy has been useful in ameliorating some anemias resulting from bone marrow dysfunction, including aplastic anemia and primary refractory anemias; anemias secondary to hematologic malignancies, such as multiple myeloma and chronic lymphocytic leukemia; and myelophthisic anemias such as myelofibrosis.72,73 In unselected patients, the response rate of these anemias to androgens has been ˜50%.86 Patients with mild or moderate hypocellular bone marrows or myelofibrosis respond more consistently than those with severely aplastic bone marrows, hypercellular marrows (e.g., secondary to malignancies), or marrows demonstrating ineffective erythropoiesis (e.g., in primary refractory anemias or agnogenic myeloid metaplasia).
Because many of the acquired causes of hypoplastic or aplastic anemias resolve spontaneously, attributing the responses totally to androgen administration is difficult. In fact, two small, prospective, randomized trials of androgen therapy in patients with refractory or aplastic anemia did not demonstrate any benefit of androgen treatment.87,88

Androgens have been used as adjunctive therapy to stimulate erythropoiesis in patients with hemolysis due to sickle cell disease and paroxysmal nocturnal hemoglobinuria.73,89 In these conditions, androgens do not affect the hemolytic process. However, danazol, a weak oral 17α-alkylated androgen (600–800 mg per day), has been used successfully to treat patients with autoimmune hemolytic anemia and idiopathic thrombocytopenic purpura by directly lowering autoantibody titers.73,90 Maintenance therapy with low-dose danazol (50 mg per day) for the latter condition has been successful.90