Androgens in Health and Disease.pdf - E Library

Chapter 12/Androgens and the Hematopoietic System 235
Iron Incorporation
Testosterone stimulates iron (Fe) incorporation into red blood cells (RBCs). Administration
of androgens along with intravenous 59 Fe results in an increase in Fe uptake by
the erythrocytes (16). Administration of testosterone propionate three times a week to
female mice increases RBC 59 Fe incorporation by 100% (17). However, there is a delay
of 96 h between the administration of testosterone and the maximal uptake of 59 Fe.
Red Cell Glycolysis
After entering the cells, androgens enhance the intracellular uptake of glucose. This
leads to glycolysis (18), resulting in the formation of high-energy phosphate bonds
leading to DNA transcription and synthesis of mRNA in the erythroid cells. Erythropoiesis
is seen after 6–12 h of glucose utilization (18). This mechanism is believed to be
independent of Epo.
ERYTHROPOIETIC RESPONSE
TO TESTOSTERONE IN NORMAL MEN
Before discussing the therapeutic efficacy of androgens in different disease states, it
is important to study the erythropoietic response to androgens in a normal man. In one
study, administration of 250 mg of testosterone enanthate for 5 mo to normal men failed
to demonstrate any significant changes in blood parameters (19). Palacios et al. conducted
a study on 53 young men and administered testosterone with different dosing
schedules (20). Subjects were divided into two groups: The first group received 200 mg
testosterone enanthate weekly and the second group received the same dose every 2 wk
for 16 wk. Significant increase in RBC and white blood cell (WBC) counts were seen in
the weekly group with no significant increase in the bimonthly group. Mild increases in
hemoglobin and hematocrit were seen in both groups. This study showed that administration
of twice the normal replacement dose to healthy young men results in a significant
increase in red cell and white cell mass.
THERAPEUTIC USES OF ANDROGENS
IN VARIOUS FORMS OF ANEMIAS
Anemia of Renal Failure
Patients with renal failure are anemic because of decreased production of Epo (21).
Despite adequate hemodialysis, defective erythropoiesis does not normalize in this
patient population (22). Because humans have an extrarenal site for Epo synthesis, Epo
levels have been detected in the plasma of anephric patients (23). Androgens have been
employed in the past for the treatment of anemia of end-stage renal disease (ESRD);
however, with the introduction of rhEpo in the late 1980s, androgens have lost popularity.
However, recent studies have shown that androgens may still have a role in erythropoiesis
in these patients. In addition to their erythropoietic effect, androgens are
cost-effective and have an anabolic effect. Initial studies reported that administration of
200 mg testosterone enanthate twice weekly in two ESRD patients resulted in an increase
in Epo and hemoglobin levels and increased 59 Fe incorporation into erythrocytes (24).
In one of these patients, the transfusion requirements also significantly decreased.
Richardson and Weinstein administered 400–600 mg testosterone enanthate weekly to