**10. Androgens**

There is no literature available in CKD patients not on dialysis. Before EPO was available, androgens (which may increase endogenous EPO production, sensitivity of erythroid progenitors to the effects of EPO, and red blood cell survival) were used regularly in the treatment of anemia in dialysis patients.**43-46** Their use for anemia in dialysis patients has declined markedly since EPO was approved.

EPO and androgen's combination in hemodialysis patients has been studied:

Ballal et.al. performed a study in a group of 15 adult male hemodialysis patients.**47** Seven patients were treated with EPO alone at a dose of 2,000 U intravenously (IV) three times a week. An additional group of eight patients was treated with 2,000 U of EPO three times a week and also received 100 mg of nandrolone decanoate intramuscularly (IM) each week. After 12 weeks of therapy, HCT values increased slightly in the group receiving EPO alone, from 25.3+/-0.8 to 27.4+/-1.5. In contrast, EPO in combination with nandrolone decanoate resulted in a greater increase in HCT values, from 24.4+/-1.4 to 32.9 +/-1.8 (p < 0.001). The results showed that the groups receiving low-dose EPO alone had a poor erythropoietic response. In contrast, patients receiving androgen in addition to EPO had a significantly greater increase in HCT values with treatment. These data show that androgen therapy significantly augments the action of exogenous EPO such that lower doses of EPO may be sufficient for an adequate hematopoietic response.

In a prospective, randomized study by Berns et al. in a chronic hemodialysis population, patients received EPO 40 U/kg intravenously three times weekly either alone (Group 1, n = 6) or with weekly intramuscular injection of 2 mg/kg nandrolone decanoate (Group 2, n = 6) for up to 16 weeks. Baseline HCT, ferritin, N-terminal parathyroid hormone, and aluminum levels were similar. The mean weekly rate of rise in HCT was 0.32+/-0.13% in Group 1 and 0.37+/-0.11% in Group 2, (p = NS). Three of 6 patients in Group 1, but only 1 of 6 patients in Group 2, reached the target HCT of 30% within 16 weeks. Two patients in Group 2 requested that the nandrolone decanoate be stopped prior to reaching target HCT because of unacceptable side effects (acne). **48** Nandrolone decanoate did not enhance the response rate to this EPO dose and is associated with significant side effects.

In a longer open-label study with low-dose EPO therapy, 19 chronic hemodialysis patients were randomly assigned to receive EPO (1,500 units IV at each HD treatment) either alone or with nandrolone decanoate (100 mg intramuscularly weekly) for 26 weeks.**49** The mean increase in HCT and the final achieved HCT were greater in the nandrolone decanoate treated group (8.2 and 33.2 percent, respectively) than in the group treated with EPO alone (3.5 percent and 28.3 percent, respectively). No serious side effects were reported.

Thirty two hemodialysis patients were randomly assigned to receive low dose EPO therapy (1,000 units SC at each HD treatment) either alone or with nandrolone decanoate 50 mg intramuscularly twice weekly for six months.**50** The increase in Hb in the nandrolone decanoate treated group (from 7.5 to 10.4 g/dL) was not statistically different from the control group (7.3 to 10.0 g/dL). Side effects, including gynecomastia, hirsutism, menstrual irregularity, and increases in liver enzymes and triglyceride levels, were common.

The limiting factor in these studies was small size and relatively short follow ups, and none attempted to maintain currently recommended Hb levels. The 2006 K DOQI guidelines for anemia in CKD stated that androgens should not be used as an adjuvant to EPO.
