Androgens in Health and Disease.pdf - E Library

352 Tenover
studies in which eugonadal men have been supplemented with androgens have shown
an increase in hematocrit with therapy (65). Healthy older men tend to have similar or
slightly lower hematocrits compared with normal young adult men (61,66).
Cardiovascular Disease
Androgens often have been categorized as having a negative impact on cardiovascular
health. This has been based on the higher incidence of cardiovascular disease (CVD) in
men compared to women of the same age, the decrease of high-density lipoprotein
(HDL) cholesterol levels at puberty in boys (67), the worsening of the atherogenic lipid
profile in young adult men who are taking nonaromatizable androgens (68), and the
increase in HDL cholesterol seen when either young or old men are made hypogonadal
(69). On the other hand, epidemiological studies have reported a positive correlation
between free T and HDL cholesterol levels (70) and a negative correlation with fibrinogen
and plasminogen activator inhibitor levels (71). Short-term infusion studies with T
have shown a direct arterial vasodilatory effect (72) and prolongation of time until
ischemia during exercise testing in men with known CVD (73).
Prostate
Androgens have a role in promoting both benign prostate hyperplasia (BPH) and
prostate adenocarcinoma, two independently distributed, but common, diseases in older
men. Although epidemiological studies have not demonstrated that circulating levels of
androgens are implicated in the etiology of either disease, androgen deprivation therapy
has been used for the treatment of both. Serum prostate-specific antigen (PSA) levels and
prostate volumes are lower in hypogonadal nonelderly adult men, and both these parameters
increase to normal, but not above normal, following T replacement (74). Older men
with prostate cancer may have low T levels (75).
CLINICAL STUDIES OF ART
As with any therapy, knowledge of the possible benefits and potential adverse
effects of treatment, characteristics of the persons for whom those benefits and risks
are most likely to occur, the dose–response profile of the target organ(s) of interest,
and the relative benefit–to–risk ratio for the hormone doses to be utilized are all
important information. Unfortunately, these data for ART are limited at this time, and
therapeutic decisions are being made, by necessity, without complete information.
Limitations in using the data from currently available trials to assist with making
decisions about utilization of ART in a clinical practice include (1) the lack of uniformity
in the hormonal values used as study entrance criterion, (2) the variety of treatment
modalities utilized and the androgen levels obtained with therapy, (3) the diversity
in outcome parameters measured, (4) the relatively small number of participants who
have been studied, (5) the short periods of treatment that have been evaluated (most
studies are 12 mo or less in duration), and (6) the lack of experience with the use of
ART in men other than those with robust health and who are less than 75 yr of age.
Direct extrapolation of the current clinical ART data obtained from generally healthy
men to what might be expected to occur in more frail populations should be done with
caution; although the benefits of ART may be more pronounced in this latter group,
the risks may also increase.