1. Ovulation-Inducing Agent Presented by: Zinab Al-hajari

2. 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).

3. 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.

4. Pituitary hypothalamus Ovaries Estrogens FSH + LH Clomiphene Citrate -Ve + Ve

5. 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

7. 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 Does not occur The next course can be started (can be maintained for 6-12 m ) Double the dose to 100 mg/d Patients who don’t ovulate for 3 courses are unlikely to respond to CC

9. 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

10. Ovulation can be documented by using any one of a number of methods: Basal body temperature (BBT) Midcycle LH Serial transvaginal ultrasound

11. 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.

12. 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

13. Adverse effects: Multiple pregnancy Ovarian enlargement Abdominal distension Hot flushes Visual symptoms Nausea and Vomiting Headache

14. 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.

15. 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.

16. 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

17. Drug interaction: Danazole may reduce the response to clomiphene

18. Alternative and combination regimen: 1- With insuline sensitizing agent 2- With HCG 3- With glucocorticoid