Monograph: |
Human Menopausal Gonadotrophins
A purified extract of human postmenopausal urine
containing follicle-stimulating hormone (FSH) and
luteinising hormone (LH): the relative in-vivo activ-
ity is expressed as a ratio. Human menopausal gona-
dotrophins with a ratio of FSH:LH of 1:1 are known
as menotrophin .
Adverse Effects
Human menopausal gonadotrophins may cause
dose-related ovarian hyperstimulation varying from
mild ovarian enlargement and abdominal discomfort
to severe hyperstimulation with marked ovarian en-
largement or cyst formation, acute abdominal pain,
ascites, pleural effusion, hypovolemia, shock and
thrombo-embolic disorders. Rupture of the ovarian
cysts and intraperitoneal haemorrhage has occurred,
usually after pelvic examination. Fatalities have
been reported.
There is a risk of multiple births. Hypersensitivity
reactions and local reactions at the injection site
may occur.
Ovarian hyperstimulation syndrome occurring with human
menopausal gonadotrophins treatment in 4 women pro-
gressed to acute adnexal torsion and in another became se-
vere and was accompanied by deep venous thrombosis.
Precautions
Human menopausal gonadotrophins should not be
given to pregnant patients. Use should be avoided in
patients with abnormal genital bleeding, hormone
sensitive malignancies such as those of the breast
uterus, prostate, ovaries or testes, or ovarian cysts or
enlargement not caused by the polycystic ovary syn-
drome. Pituitary or hypothalamic lesions, adrenal or
thyroid disorders, and hyperprolactinemia should
be appropriately treated to exclude them as causes of
infertility before attempting therapy with human
menopausal gonadotrophins. Patients who experi-
ence ovarian enlargement are at risk of rupture; pel-
vic examinations should be avoided or carried out
with care and the recommendation has been made
that sexual intercourse should be avoided while
there is such a risk.
Interactions
In women who show evidence of excessive ovarian
stimulation while receiving human menopausal go-
nadotrophins the administration of drugs with
luteinising hormone (LH) activity increases the risk
of ovarian hyperstimulation syndrome.
Uses and Administration
Human menopausal gonadotrophins possess both
follicle-stimulating hormone (FSH) activity and luteinising
hormone (LH) activity .
Human menopausal gonadotrophins are used in the
treatment of male and female infertility due to hy-
pogonadism. In anovulatory infertility unresponsive
to clomiphene human menopausal gonadotrophins
are administered to induce follicular maturation and
are followed by treatment with chorionic gonado-
trophin to stimulate ovulation and corpus luteum
formation. In
women with polycystic ovary syndrome a gonadore-
lin analogue may be given beforehand to suppress
pituitary gonadotrophin production.
The dosage and schedule of treatment must be deter-
mined according to the needs of each patient: it is
usual to monitor response by studying the patient's
urinary oestrogen excretion or by ultrasonic visuali-
sation of follicles, or both. Human menopausal
gonadotrophins may be given daily by intramus-
cular injection to provide a dose of 75 to 150 units
of FSH and gradually adjusted if necessary until an
adequate response is achieved. Treatment is then
stopped and followed after I or 2 days by single
doses of chorionic gonadotrophin 5000 to 10,000
units. In menstruating patients treat-
ment should be started within the first 7 days of the
menstrual cycle. In the UK it has been suggested
that the treatment course should be abandoned if no
response is seen in 3 weeks although in the US the
manufacturers recommend that an individual course
of menotrophin should not exceed 12 days. This
course may be repeated at least twice more if neces-
sary.
An alternative schedule is to give three equal doses
of menotrophin. each providing 225 to 375 units of
FSH on alternate days followed by chorionic gona-
dotrophin one week after the first dose.
In in-vitro fertilisation procedures or other assisted
conception techniques human menopausal gonado-
trophins are used in conjunction with chorionic
gonadotrophin and sometimes also clomiphene cit-
rate or a gonadorelin analogue. Stimulation of
follicular growth is produced by human menopausal
gonadotrophins in a dose providing 75 to 300 units
of FSH daily, usually beginning on the 2nd or 3rd
day of the cycle. An example of a combined regimen
involves clomiphene citrate 100 mg on days 2 to 6,
with human menopausal gonadotrophins beginning
on day 5 in a dose providing 150 to 225 units of FSH
daily. Treatment is continued until an adequate re-
sponse is obtained and the final injection of human
menopausal gonadotrophins is followed I to 2 days
later with up to 10 000 units of chorionic gonado-
trophin. Oocyte retrieval is carried out about 32 to
36 hours later.
In men with hypogonadotrophic hypogonadism,
spermatogenesis is stimulated with chori-
onic gonadotrophin and then human menopausal
gonadotrophins are added in a dose of 75 or
150 units of FSH two or three times weekly. Treat-
ment should be continued for at least 3 or 4 months.
Infertility. References to the use of human menopausal
gonadotrophins in the management of female infertility
often with other agents including buserelin. chorionic
gonadotrophin, clomiphene citrate, leuprorelin, ethinyl-
oestradiol, and triptorelin. Anecdotal report suggests that
human menopausal gonadotrophins may be more effective
than urofollitrophin in treating anovulatory infertility, per-
haps because the luteinising hormone content plays some role
in follicular development. However, in contrast, others have
found the use of a pure recombinant follicle-stimulating hor-
mone to be associated with higher pregnancy rates than hu-
man menopausal gonadotrophins when employed in
regimens for in-vitro fertilisation.
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