Androgens in Health and Disease.pdf - E Library

Chapter 12/Androgens and the Hematopoietic System 239
increase in hematocrit (mean 49.4%) and RBC volume while on androgens (48). To
further analyze the characteristics of the patients with different degrees of erythropoietic
response, patients were divided into two groups: those who achieved hematocrit level of
48% or greater (n = 9) and those achieving 48% group experienced cerebrovascular events while on testosterone
therapy, achieving hematocrits of 53%, 58%, and 64%, respectively. The incidence of
strokes in this group was 13%, much higher than in the general population (0.5–1.0%)
(48). No patient in the 48% is attained, a decision should be made regarding further
continuation of androgen therapy.
Elderly men are particularly susceptible to develop polycythemia. Drinka et al.
reported that two of eight hypogonadal elderly men developed polycythemia while
receiving testosterone enanthate 150 mg/70 kg every 2 wk (49). These two men had
the highest body mass index (BMI) in the group and their respective hematocrit levels
were 53.4% and 57.3%. Both patients developed sleep apnea and one was documented
to have nocturnal oxygen desaturation while on testosterone.
Androgens administered via different routes have a differential effect on hematopoietic
parameters. Therapy with Androderm, the transdermal testosterone patch, results in
a significantly lower rate of abnormal Hct elevations compared to intramuscular testosterone
(15.4% vs 43.8%) (50). This may be the result of less total area under the curve
in transdermal products. Similarly, in a recent study, none of the patients on transdermal
testosterone gel became symptomatic, discontinued therapy, or withdrew from the study
(51). These studies show that transdermal androgen preparations are less likely to result
in polycythemia compared to intramuscular preparations.
These studies show that polycythemia can be a dangerous complication of androgen
therapy. Although not studied prospectively, one should be cautious when giving androgens
to patients with relative erythrocytosis, on diuretics, and smokers.
HEMATOCRIT AND CARDIOVASCULAR DISEASE
The relationship between hematocrit and coronary heart disease (CHD) has been
known for a long time. An early autopsy study showed that patients with CHD had higher
premortem hematocrits (52). The Puerto Rico Heart Health Program (53) showed that
a higher hematocrit was associated with increased incidence of myocardial infarction
and CHD-related death. The Honolulu Heart Program studied more than 8000 Japanese
men prospectively for 10 yr (54) and found that subjects with hematocrit levels >45.4%
had a higher rate of death resulting from CHD compared to any other cause.
Similar to CHD, elevated hematocrit is also a risk factor for stroke. A retrospective
analysis of 500 patients found that men with hemoglobin of >15 g/dL or hematocrit of
>44% were twice as likely to get cerebral infarctions than patients with lower values
(55). For women, these values were >14 g/dL and >42%, respectively. Another study of
432 autopsy patients found that the risk of cerebral infarction increased steeply when the