Androgens in Health and Disease.pdf - E Library

358 Tenover
be overcome with either a downward adjustment in the T dose or a switch to a form of
therapy that gives lower but more uniform levels of T.
ANDROGEN REPLACEMENT METHODS
To date, almost all of the ART trials have utilized T as the replacement androgen,
although the method of T replacement has varied. There is little experience with
nonaromatizable androgens, such as DHT, and this hormone is not commercially available
for clinical use in North America. Because it is not yet known how much of the effect
of ART on target organs such as bone are the result of the conversion of the T to
estrogens, at this time it is recommended that some form of T be the replacement androgen
for therapy.
The androgen dose–response of the various target organs in older men is not known,
but it has been shown that replacement of endogenous T with equivalent levels of exogenous
T has no measurable effect. Therefore, it should be the treatment goal to have some
significant increase in T over that at pretreatment while maintaining levels within the
physiological normal range for young adult men.
All methods for T replacement are probably efficacious if adequate serum T levels are
achieved. Selecting the form of therapy largely depends on recipient preference, but in
a few instances, selection on the basis of the possible relative side effects unique to the
T delivery form may be appropriate.
Listed in Table 7 are the major T delivery forms available in the United States that are
considered safe for use in older men. Because of the potential for liver toxicity, the oral
methylated testosterones are not considered in this category (95). Also in Table 7 are the
recommended starting doses for older men and the possible side effects unique to the
particular delivery form.
The injectable esters, T enanthate and T cypionate, have similar pharmacokinetics and
the recommended administration is every 1–2 wk. This form of T administration has
been around for over 50 yr, and if the man can learn to give himself the intramuscular
(im) injections or it can be administered by a family member, the cost of the therapy is
quite low. Although most men complain of little or no pain from T injections, some men
do not accept the idea of im injections, or because they are on warfarin, it is not appropriate
for them to receive the injections. In addition, the serum T levels obtained with this
method of therapy are far from physiologic. Especially with the every 2-wk dosing
regimen, T levels can be supraphysiologic within the first few days after injection and
fall to levels below the normal physiologic range just prior to the next dose. This form
of therapy often leads to a larger increase in hemoglobin and estradiol levels than seen
with other forms of T replacement, and in some men, the changes in T levels during the
dosing interval can be paralleled by changes in their libido and/or mood. As noted earlier,
however, the mood and libido changes with ART in older occur much less frequently
than with younger men. Because T metabolism slows with age, the recommended initial
doses of T for older men are lower than those usually used in younger adults.
The pellet form of T requires implantation with a trocar. Local extrusion of the pellets
and infection at the site of placement are possible problems. The pellets may be active
up to 6 mo, tend to give unpredictable plasma T levels, and require pellet removal if
dosage adjustment is necessary or adverse events occur. Therefore, it is a form of therapy
not generally recommended for use in most older men.