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Drug:
Clomiphene (Serophene, Clomid)
What is clomiphene
and when is it prescribed
Clomiphene is the drug of choice
for patients whose ovulation defect is associated with normal levels of
estrogen. Generally these are the women who will have a positive Progesterone
Challenge Test in that they have a withdrawal bleed after taking progesterone
tablets.
How does clomiphene
work?
Clomiphene is very similar to Estrogen
in its structure, so that feed back receptors in the brain are misled to
take up clomiphene instead of estrogen. As a result, the brain is unable
to perceive the normal estrogen levels and thinking these are now low,
activates the release of F.S.H. from the pituitary. Clomiphene therefore
leads to a "knock-on" effect, by stimulating the brain to stimulate the
pituitary and so lead to ovarian stimulation and ovulation.
What kinds of patients
benefit from clomiphene?
Clomiphene is beneficial in 4 groups
of patients:
-
Women with amenorrhoea and normal levels
of estrogen; e.g. after stopping the contraceptive pill, many women can
experience months of delay before their periods become re-established.
-
Women with oligomenorrhoea and normal
levels of estrogen; e.g. if you are only having 3 periods a year.
-
In women who have periods with ovulation
but consistently inadequate luteal phases; i.e. your B.B.T. Chart shows
that after ovulation the temperature rise is usually maintained for less
than 11 days, and the progesterone level on day 21 may also be reduced.
-
In women receiving donor insemination;
it can be very helpful in regulating ovulation in such cases especially
if the cycle is a little erratic.
How is clomiphene
administered
Treatment begins within five days
of the commencement of menstrual bleeding. A single 50 mg clomiphene tablet
has to be taken daily for 5 days. This is regardless of whether the period
has been a spontaneous one or resulting from a Progesterone Challenge Test.
Ovulation will usually occur 5-13 days after the last tablet of clomiphene.
While taking this treatment, it is advisable to maintain a B.B.T. Chart.
The dosage of clomiphene may need
to be increased. The dosage can be safely increased at a rate of one tablet
per day each cycle until there is evidence of ovulation or until a maximum
dose of 200mg (4 tablets) per day is reached. The average patient
normally ovulates with a dosage of 50-100 mg per day for 5 days. Once ovulation
has been achieved as indicated by a luteal phase of more than 11 days and
an adequate day-21 progesterone level, treatment is maintained at the same
dosage levels for 6 cycles.
How effective is the
clomiphene therapy
80-90% of the patients who take clomiphene
therapy should ovulate and 55% of this group should get pregnant. The reason
for the difference in percentages between ovulation and pregnancy is that
for a number of patients an ovulatory defect is not the only contributory
factor in their infertility. If, however, one selects the patients for
whom ovulation disorder is the sole cause of infertility, their pregnancy
rate is almost as high as the ovulation rate.
There is a 1 in 16 chance (approximately
6%) that clomiphene therpay will result in multiple pregnancies in most
cases these will be twins. Patients are not an increased risk of miscarriage.
In fact, the miscarriage rate appears to be lower than for the general
population. There is no increase in the incidence of abnormalities in the
resulting babies.
Does the clomiphene
therapy have any side effects
Treatment with clomiphene is very
safe. Side effects, if they occur, are mild and only rarely require that
treatment be discontinued. The commonest side effect occurring in 10% of
women is the symptom of "hot flushes". There is no need to panic. Clomiphene
does not trigger menopause. These "hot flushes" are due to the anti-estrogenic
effect of clomiphene. Other less frequent symptoms include abdominal distension,
breast discomfort, headaches, mild depression and occasional blurring of
vision. Clomiphene treatment will have to be discontinued if it results
in enlargement of the ovaries. Moderate pelvic pain is a symptom of this
condition. Treatment is stopped until the ovaries have returned to normal
size.
Is any other test or
medication required in addition to clomiphene
It is worth the effort to repeat
the post-coital test for patients taking clomiphene, although this test
may have been previously normal. This is because clomiphene works by being
an anti-estrogen, and sometimes this can result in the mucus becoming much
stickier than normal. The additional administration of a short course of
a natural estrogen between the last day of clomiphene and the expected
time of ovulation can reverse this effect.
If ovulation does not occur
even after taking the maximum dosage of clomiphene, or if the luteal
phase remains inadequate, human chorionic gonadotrophin (H.C.G.) is given
in addition to the clomiphene.
(Note: A number of specialists use
a drug very similar to clomiphene called tamoxifen.)
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