DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

1202 A
Testosterone Enanthate
enjoyed popularity among athletes who seek to enhance
2000
their performance. Another alkylated androgen, 7αmethyl-19-nortestosterone,
is poorly converted to dihy-
200 mg
1600
drotestosterone.
SECTION V
HORMONES AND HORMONE ANTAGONISTS
B
Serum Testosterone (ng/dL)
C
1200
800
400
0
1000
800
600
400
200
0
1000
800
600
400
200
0
0
One patch (5 mg)
0 4 8 12 16 20 24
Testosterone Gel
100 mg
50 mg
2 4 6 8 10 12 14
Time (days)
Testosterone Patch
Time (hours)
0 4 8 12 16 20 24
Time (hours)
Figure 41–7. Pharmacokinetic profiles of three testosterone
preparations during their chronic administration to hypogonadal
men. Doses of each were given at time 0. Shaded areas indicate
range of normal levels. [Data adapted from A. Snyder and
Lawrence (1980); B. Dobs et al. (1999); C. Swerdloff et al.
(2000)]
Selective Androgen-Receptor Modulators. Stimulated by the development
of selective estrogen receptor modulators, which have estrogenic
effects in some tissues but not others (Chapter 40),
investigators are attempting to develop selective androgen receptor
modulators. Another stimulus is the desirable effects of testosterone
in some tissues, such as muscle and bone, and the undesirable effects
in other tissues, such as the prostate. Nonsteroidal molecules have
been developed that bind to the androgen receptor and have greater
effect on muscle and bone than on the prostate. Some of these compounds
have begun trials in humans (Narayanan et al., 2008).
Therapeutic Uses of Androgens
Male Hypogonadism. The best established indication
for administration of androgens is testosterone deficiency
in men (i.e., treatment of male hypogonadism).
Any of the testosterone preparations or testosterone
esters just described can be used to treat testosterone
deficiency. Monitoring treatment for beneficial and
deleterious effects differs somewhat in adolescents and
the elderly from that in other men.
Monitoring for Efficacy. The goal of administering testosterone to a
hypogonadal man is to mimic as closely as possible the normal serum
concentration. Therefore, measuring the serum testosterone concentration
during treatment is the most important aspect of monitoring
testosterone treatment for efficacy. When the serum testosterone concentration
is measured depends on the testosterone preparation used
(Figure 41–7). Occasional random fluctuations can occur, however,
so measurements should be repeated for any dose. When the enanthate
or cypionate esters of testosterone are administered once every
2 weeks, the serum testosterone concentration measured midway
between doses should be normal; if not, the dosage schedule should
be adjusted accordingly. If testosterone deficiency results from testicular
disease, as indicated by an elevated serum LH concentration,
adequacy of testosterone treatment also can be judged indirectly by
the normalization of LH within 2 months of treatment initiation
(Findlay et al., 1989; Snyder and Lawrence, 1980).
Normalization of the serum testosterone concentration
induces normal virilization in prepubertal boys and restores virilization
in men who became hypogonadal as adults. Within a few
months, and often sooner, libido, energy, and hematocrit return to
normal. Within 6 months, muscle mass increases and fat mass
decreases. Bone density, however, continues to increase for 2 years
(Snyder et al., 2000).
Monitoring for Deleterious Effects. When testosterone itself is administered,
as in one of the transdermal preparations or as an ester that
is hydrolyzed to testosterone, it has no “side effects” (i.e., no effects
that endogenously secreted testosterone does not have), as long as
the dose is not excessive. Modified testosterone compounds, such as
the 17α-alkylated androgens, do have undesirable effects even when
dosages are targeted at physiological replacement. Some of these