Transcript Ovulation-Inducing Agent Presented by: Zinab Al

Ovulation-Inducing Agent
Presented by:
Zinab Al-hajari
Chemical structure:
Clomiphene citrate is a
a non-steroidal selective
estrogen receptor modulator
(SERM) related structurally
to triphenylethylene.
It is available as a racemic
mixture of
cis (zuclomiphene) and trans
form (enclomipene).
OCH2CH2N
CH2CH3
CH2CH3
Cl
Mechanism of action:
Clomiphene is a partial agonist at oestrogen
receptor.
It leads to an increase in the secretion of
gonadotropins and oestrogen by inhibiting
estradiol’s feedback effect on the
gonadotropins.
Clomiphene Citrate
hypothalamus
Pituitary
+ Ve
-Ve
FSH + LH
+ Ve
Estrogens
Ovaries
Pharmacokinetics:
Clomiphene is readily absorbed orally.
Has a very large volume of distribution
high bioavailability
It reaches peak plasma concentration within 6h
Its half-life of an oral dose is about 5 days.
Metabolized in the liver by the cytochrome P-450
pathway and there is evidence of enterohepatic
recycling
Excreted principally in the feces and minimally in
the urine
Dosage:
• The recommended dosage at the beginning of therapy
is 50 mg/d for 5 days, Starting on day 2–5 of the
cycle .
ovulation
occurs
The next course can be started
(can be maintained for 6-12 m )
Does not occur
Patients
who don’t
ovulate for
3 courses
are
unlikely to
respond to
CC
Double the dose to 100 mg/d
Effects:
Stimulate ovulation in women with
oligomenorrhea or amenorrhea due to
ovulatory dysfunction.
The majority of patients suffer from
polycystic ovary syndrome( 7% ), which is
characterized by
Ovarian hyperandrogenism
Olig- or anovulation
Infertility
Ovulation can be documented by using
any one of a number of methods:
Basal body temperature (BBT)
Midcycle LH
Serial transvaginal ultrasound
Clinical uses:
Used for treatment of disorders of
ovulation in patients wishing to become
pregnant.
It is not used in patient with pituitary or
hypothalamic failure
Treatment of gynecomastia.
Treatment results:
About 80% can be expected to
respond by having ovulatory cycles.
Approximately half of these patient
become pregnant
clomiphene resistant are likely to be
• obese
• insuline resistant
• hyperandrogenic
Adverse effects:
Multiple pregnancy
Ovarian enlargement
Abdominal distension
Hot flushes
Visual symptoms
Nausea and Vomiting
Headache
Serious medical conditions:
Ovarian hyperstimulation syndrome (OHSS):
Ovulation induction with injectable
gonadotropins is a more common cause of
OHSS than is clomiphene
serious medical complication
characterized by:
cystic enlargement of ovaries
A marked increase in vascular permeability.
Overdose:
•
•
•
•
As a result of the use of more than the
recommended dose during clomiphene
citrate therapy.
Symptoms:
Nausea, vomiting
Vasomotor flushes
visual blurring
Ovarian enlargement with pelvic or
abdominal pain.
Contraindication and cautions:
Pregnancy
Nursing mother
Ovarian cyst or enlargement not due to PCOS
Liver disease
Any patient who complains of abdominal symptoms
should be examined carefully
Special precaution must be taken in patient who
have visual symptoms
Organic intracranial lesion such as pituitary tumor
Hypersensitivity to the drug
Drug interaction:
Danazole may reduce the response to
clomiphene
Alternative and
combination regimen:
1- With insuline sensitizing agent
2- With HCG
3- With glucocorticoid