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

1124 detect the presence of an ectopic pregnancy, hydatidiform
mole, or choriocarcinoma. Such assays also are
used to follow the therapeutic response of malignancies
that secrete hCG, such as germ cell tumors.
Timing of Ovulation. Ovulation occurs ~36 hours after
the onset of the LH surge. Therefore urinary concentrations
of LH, as measured with an over-the-counter
radioimmunoassay kit, can be used to predict the
time of ovulation. Urine LH levels are measured every
12- 24 hours, beginning on day 10-12 of the menstrual
cycle (assuming a 28-day cycle), to detect the rise in
LH and estimate the time of ovulation. This estimate
facilitates the timing of sexual intercourse to optimize
the chance of achieving pregnancy.
Localization of Endocrine Disease. Measurements of
plasma LH and FSH levels with β subunit–specific
radioimmunoassays are useful in the diagnosis of
several reproductive disorders. Low or undetectable
levels of LH and FSH are indicative of hypogonadotropic
hypogonadism and suggest hypothalamic
or pituitary disease, whereas high levels of
gonadotropins suggest primary gonadal diseases. A
plasma FSH level of ≥10-12 mIU/mL on day 3 of the
menstrual cycle, indicative of decreased ovarian
reserve, is associated with reduced fertility, even if a
woman is menstruating normally, and predicts a lower
likelihood of success in assisted reproduction techniques
such as in vitro fertilization.
The administration of hCG can be used to stimulate
testosterone production and thus to assess Leydig
cell function in males suspected of having primary
hypogonadism (e.g., in delayed puberty). Serum testosterone
levels are assayed after multiple injections of
hCG. A diminished testosterone response to hCG indicates
Leydig cell failure; a normal testosterone response
suggests a hypothalamic-pituitary disorder and normal
Leydig cells.
Therapeutic Uses of the Gonadotropins
Male Infertility. In men with impaired fertility secondary
to gonadotropin deficiency (hypogonadotropic
hypogonadism), gonadotropins can establish or restore
fertility. Due to expense and to the occasional development
of antibody-mediated resistance to gonadotropins
with prolonged use, standard treatment has been to
induce sexual development with androgens, reserving
gonadotropins until fertility is desired.
SECTION V
HORMONES AND HORMONE ANTAGONISTS
Treatment typically is initiated with hCG (1500-2000 IUs
intramuscularly or subcutaneously) three times per week until clinical
parameters and the plasma testosterone level indicate full induction
of steroidogenesis. Thereafter, the dose of hCG is reduced to
2000 IU twice a week or 1000 IU three times a week, and
menotropins (FSH + LH) or recombinant FSH is injected three times
a week (typical dose of 150 IU) to fully induce spermatogenesis.
Based on the observation that the normal male infant is
exposed to high levels of gonadotropins during the first year of life, it
has been proposed that therapy with LH and FSH during infancy may
be associated with increased spermatogenesis later in life (Grumbach,
2005), and studies addressing this question are in progress.
The most common side effect of gonadotropin therapy in males
is gynecomastia, which occurs in up to a third of patients and presumably
reflects increased production of estrogens due to the induction of
aromatase. Maturation of the prepubertal testes typically requires treatment
for >6 months, and optimal spermatogenesis in some patients
may require treatment for up to 2 years. Once spermatogenesis has
been initiated, either by this combined therapy in patients with prepubertal
disease or in patients who developed hypogonadotropic hypogonadism
after sexual maturation, ongoing treatment with hCG alone
usually is sufficient to support sperm production.
Cryptorchidism. Cryptorchidism, the failure of one or
both testes to descend into the scrotum, affects up to
3% of full-term male infants and becomes less prevalent
with advancing postnatal age. Cryptorchid testes
have defective spermatogenesis and are at increased
risk for developing germ cell tumors. Hence the current
approach is to reposition the testes as early as possible,
typically at 1 year of age but definitely before 2 years
of age. The local actions of androgens stimulate descent
of the testes; thus hCG has been used by some to induce
testicular descent if the cryptorchidism is not secondary
to anatomical blockage.
Therapy usually consists of injections of hCG (3000 IU/m 2
body surface area) intramuscularly every other day for six doses. If
this does not induce testicular descent, orchiopexy should be performed.
Some experts prefer surgery as the initial approach based
on the association of hCG treatment with germ cell apoptosis in certain
experimental settings (Ritzen, 2008).
POSTERIOR PITUITARY HORMONES:
OXYTOCIN AND VASOPRESSIN
The structures of the neurohypophyseal hormones oxytocin
and arginine vasopressin (also called antidiuretic
hormone, or ADH) and the physiology and pharmacology
of vasopressin are presented in Chapter 25. The following
discussion emphasizes the physiology of
oxytocin. Therapeutic uses of synthetic oxytocin as a
uterine-stimulating agent to induce or augment labor in
selected pregnant women and to decrease postpartum
hemorrhage are described in Chapter 66.
Physiology of Oxytocin
Biosynthesis of Oxytocin. Oxytocin is a cyclic nonapeptide
that differs from vasopressin by only two amino