Monograph: |
Chorionic Gonadotrophin
A preparation of a glycoprotein substance secreted by the pla-
centa and obtained from the urine of pregnant women. It is a
white or almost while amorphous powder. The Ph. Eur. spec-
ifies a preparation containing not less than 2500 units per mg.
The USP specifies a potency of not less than 1500 USP units
per mg.
Soluble in water. Store at 2Β° to 8Β° in airtight containers: pro-
tect from light.
Units
650 units of human chorionic gonadotrophin are
contained in one ampoule of the third International
Standard (1986).
70 units of the alpha subunit of human chorionic go-
nadotrophin for immunoassay are contained in one
ampoule of the first International Reference Prepa-
ration (1975).
70 units of the beta subunit of human chorionic go-
nadotrophin for immunoassay are contained in one
ampoule of the first International Reference Prepa-
ration (1975).
Adverse Effects and Precautions
Side-effects that have been reported include head-
ache. tiredness, changes in mood, depression, rest-
lessness, oedema, (especially in males), and pain on
injection. Treatment for cryptorchidism may pro-
duce precociou~ puberty. Gynaecomastia has been
reported. Ovarian hyperstimulation may occur, with
marked ovarian enlargement or cyst formation,
acute abdominal pain, ascites, pleural effusion, hy-
povolaemia, shock, and thromboembolic disorders
in severe cases.
Chorionic gonadotrophin should be given with care
to patients in whom androgen-induced fluid reten-
tion might be a hazard as in asthma, epilepsy, mi-
graine, or cardiovascular disorders, including
hypertension, or renal disorders. Hypersensitivity
reactions may occur and it is recommended that pa-
tients suspected to be susceptible should be given
skin tests before treatment. It should not be given to
patients with disorders that might be exacerbated by
androgen release such as carcinoma of the prostate
or precocious puberty.
Pharmacokinetics
Following intramuscular administration peak con-
centrations of chorionic gonadotrophin occur about
6 hours after a dose. It is distributed primarily to the
gonads. Blood concentrations decline in a biphasic
manner, with half-lives of between about 6 and 11
hours, and 23 to 38 hours respectively. About 10 to
12% of an intramuscular dose is excreted in urine
within 24 hours.
Uses and Administration
Chorionic gonadotrophin is a hormone produced by
the placenta and obtained from the urine of pregnant
women. Its effects are predominantly those of the
gonadotrophin. luteinizing hormone ,
which is responsible for triggering ovulation and
formation of the corpus luteum in women, and stim-
ulates the production of testosterone by the testes in
men.
Chorionic gonadotrophin is given to women to in-
duce ovulation after follicular development has been
stimulated with follicle-stimulating hormone or hu-
man menopausal gonadotrophins in the treatment of
anovulatory infertility due to absent or low concen-
trations of gonadotrophins. A single dose of 5000 to
10000 units is given by intramuscular injection to
mimic the midcycle peak of luteinising hormone
which normally stimulates ovulation. Up to 3 repeat
injections of up to 5000 units each may be given
within the following 9 days to prevent insufficiency
of the corpus luteum. Chorionic gonadotrophin is
also given in conjunction with menotrophin and
sometimes also clomiphene citrate as an adjunct to
in vitro fertilisation procedures and other assisted
conception techniques involving superovulatior. and
oocyte collection.
In males it has been used in the treatment of prepu-
bertal cryptorchidism. Regimens vary wisely, but
doses usually range from 500 to 4000 units three
times weekly by intramuscular injection.
It is also given for male infertility associated with
hypogonadotrophic hypogonadism. Again, there is
considerable variation in the dosage regimen, and
doses have varied from 500 to 4000 units two to
three times weekly. An agent with follicle-stimulat-
ing activity such as menotrophin is often added to
enable normal spermatogenesis.
In the treatment of delayed puberty associated with
hypogonadism in males, an initial dose of 500 to
1500 units is given twice weekly; the dose should be
titrated against plasma-testosterone concentration.
Chorionic gonadotrophin has been used in the treat-
ment of obesity but there is no evidence to support
its value.
Cryptorchidism. Although surgery remains the treatment
with the best success rate in cryptorchidism it is often re-
served for boys who do not respond to a trial of hormonal
therapy . Gonadorelin or chorionic gonado-
trophin appear to be of some benefit, although only a
minority of cases will respond: they may be given in
combination.
Chorionic gonadotrophin is also used as an adjuvant to sur-
gery, to render the testis palpable.
Delayed puberty. Use of chorionic gonadotrophin may be
appropriate in boys with delayed puberty due to hypogonado-
trophic hypogonadism .
Infertility. In women with anovulatory infertility chorionic
gonadotrophin can be used to provoke ovulalion and provide
luteal support once maturation of a suitable number of folli
cles has been stimulated by other means. It is used
similarly in the various protocols for assisted reproduction. In
men with hypogonadotrophic hypogonadism it is employed to stimu-
late and maintain spermatogenesis.
Malignant neoplasms. Control of Kaposi's sarcoma
has been reported in a few patients given high-dose
intramuscular chorionic gonadotrophin. but regrowth oc-
curred when dosage was reduced or withdrawn. Another
study, using lower doses, was discontinued due to toxicity
and lack of benefit. but others have confirmed benefit
following intralesional injection. There is some suggestion
that preparations vary in their activity against the tumour,
and that it is
not chorionic gonadotrophin itself, but some impurity, (per-
haps a ribonuclease) which is the active principle.
Chorionic gonadotrophin CLDI-200) is also reported to be un-
der investigation in the treatment of acute leukaemia.
Obesity. A meta-analysis' involving 24 trials concluded that
there was no evidence that chorionic gonadotrophin was ef-
fective in the treatment of obesity .
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