Serophene (clomiphene citrate) is a selective estrogen receptor modulator (SERM) indicated for the treatment of ovulatory dysfunction in women desiring pregnancy. It represents a first-line pharmacological intervention for anovulatory infertility, particularly in cases of polycystic ovary syndrome (PCOS). By competitively binding to estrogen receptors in the hypothalamus, it disrupts negative feedback, leading to increased secretion of gonadotropin-releasing hormone (GnRH). This subsequently stimulates the pituitary gland to release follicle-stimulating hormone (FSH) and luteinizing hormone (LH), thereby promoting follicular development and ovulation. Its established efficacy, favorable safety profile, and oral administration route make it a cornerstone of fertility treatment protocols.

Features

• Active ingredient: Clomiphene citrate 50 mg
• Pharmacologic class: Selective estrogen receptor modulator (SERM)
• Administration: Oral tablet
• Standard packaging: 10 tablets per blister strip
• Bioavailability: Approximately 85-90% following oral administration
• Half-life: 5-7 days for zuclomiphene (active isomer)
• Metabolism: Hepatic, via cytochrome P450 system
• Excretion: Primarily fecal (approximately 42-48%), with urinary elimination of metabolites

Benefits

• Effectively induces mono-follicular or oligo-follicular development in anovulatory women
• Restores hypothalamic-pituitary-ovarian axis function to achieve physiological ovulation
• Offers non-invasive oral administration compared to injectable gonadotropins
• Demonstrates cumulative conception rates of approximately 70-80% over 6 treatment cycles in appropriate candidates
• Provides cost-effective first-line treatment for ovulatory disorders
• Enables timed intercourse or intrauterine insemination cycles with predictable follicular growth

Common use

Serophene is primarily prescribed for the induction of ovulation in women with ovulatory dysfunction who wish to achieve pregnancy. Its most frequent application is in patients with polycystic ovary syndrome (PCOS) characterized by oligo-ovulation or anovulation. It is also utilized in cases of hypothalamic amenorrhea, though response may be less predictable than in PCOS. Additionally, Serophene may be used off-label for ovarian stimulation in ovulatory women undergoing superovulation with intrauterine insemination (IUI) and for the evaluation of ovarian reserve through the clomiphene citrate challenge test (CCCT). Treatment is typically initiated after exclusion of other causes of infertility, including male factor, tubal pathology, and uterine abnormalities.

Dosage and direction

The recommended initial dosage is 50 mg (one tablet) daily for 5 days, beginning on day 3, 4, or 5 of the menstrual cycle following spontaneous or progestin-induced withdrawal bleeding. Treatment should be started at the lowest effective dose to minimize the risk of multiple gestation and ovarian hyperstimulation syndrome (OHSS). If ovulation does not occur at the initial dose, the dosage may be increased to 100 mg daily for 5 days in subsequent cycles. Doses exceeding 100 mg daily are not recommended due to anti-estrogenic effects on the endometrium which may impair implantation. The maximum recommended daily dose is 150 mg. Treatment beyond 6 cycles is generally discouraged due to potential increased risk of ovarian cancer with prolonged use. Ultrasound monitoring of follicular development is advised, particularly during the first treatment cycle or following dosage adjustments.

Precautions

Prior to initiating Serophene therapy, complete evaluation of the infertile couple should be performed, including assessment of ovarian, tubal, uterine, and male factors. Liver function tests should be considered in patients with history of hepatic impairment. Patients should be advised of the risk of multiple gestation (approximately 5-10%, predominantly twins) and ovarian hyperstimulation syndrome (OHSS). Visual symptoms such as blurring, scotomas, or photophobia may occur and warrant immediate discontinuation and ophthalmologic evaluation. Long-term use (≥12 cycles) may be associated with increased risk of borderline ovarian tumors. Careful monitoring is required in patients with polycystic ovary syndrome due to increased sensitivity to gonadotropins. Thyroid and adrenal disorders should be ruled out or adequately treated before initiation of therapy.

Contraindications

Serophene is contraindicated in patients with: pregnancy; liver disease or history of hepatic dysfunction; abnormal uterine bleeding of undetermined origin; ovarian cysts not associated with polycystic ovary syndrome; uncontrolled thyroid or adrenal dysfunction; organic intracranial lesions such as pituitary tumors; hypersensitivity to clomiphene citrate or any component of the formulation. It is also contraindicated in patients with endometrial carcinoma and those who are not attempting to achieve pregnancy. The medication should not be administered simultaneously with other fertility medications except under specialized supervision.

Possible side effects

The most common adverse reactions (>10%) include vasomotor flushes (10-20%), abdominal discomfort (5-10%), and ovarian enlargement (5-10%). Less frequent side effects (1-10%) comprise nausea/vomiting, breast tenderness, visual disturbances (blurred vision, photophobia, diplopia), headache, and abnormal uterine bleeding. Rare adverse events (<1%) include ovarian hyperstimulation syndrome, weight gain, allergic reactions, and reversible hair loss. Visual symptoms typically resolve following discontinuation but necessitate permanent cessation of therapy. Most side effects are dose-dependent and reversible upon discontinuation of treatment.

Drug interaction

Serophene may interact with several medications: Danazol may inhibit ovulation induced by clomiphene. Estrogen-containing medications may antagonize the therapeutic effect. Tamoxifen may have additive estrogenic/anti-estrogenic effects. Medications affecting cytochrome P450 2D6 metabolism (e.g., fluoxetine, paroxetine, quinidine) may alter clomiphene levels. Thyroxine replacement therapy may require adjustment as clomiphene may increase thyroxine-binding globulin levels. Anticoagulant therapy may require monitoring as clomiphene may potentially affect coagulation parameters. Concomitant use with other ovulation induction agents (e.g., gonadotropins) significantly increases the risk of ovarian hyperstimulation syndrome and multiple gestation.

Missed dose

If a dose is missed, it should be taken as soon as remembered unless it is nearly time for the next dose. Doubling of doses to make up for a missed dose is not recommended. Consistent timing of administration is important for maintaining stable drug levels. If multiple doses are missed, consultation with the prescribing physician is advised as the treatment cycle may need to be restarted. The impact of missed doses depends on the timing within the 5-day treatment course, with missed doses in the first three days having greater potential impact on follicular development.

Overdose

There have been no reports of serious adverse effects from massive overdosage of Serophene. Doses as high as 2 g daily for 30 days have been administered without apparent toxicity. However, symptoms of overdose would be expected to be an exaggeration of known adverse effects, particularly severe vasomotor symptoms, visual disturbances, abdominal pain, and ovarian enlargement. In case of suspected overdose, symptomatic and supportive measures should be instituted. There is no specific antidote. Gastric lavage may be considered if ingestion occurred within a short time frame. Medical attention should be sought immediately for proper evaluation and management.

Storage

Store at controlled room temperature 20°-25°C (68°-77°F), with excursions permitted between 15°-30°C (59°-86°F). Keep in the original container with the lid tightly closed to protect from light and moisture. Do not store in bathroom or other areas with high humidity. Keep out of reach of children and pets. Do not use after the expiration date printed on the packaging. Properly discard any unused medication after treatment completion. Do not flush medications down the toilet or pour into drain unless instructed to do so.

Disclaimer

This information is provided for educational purposes only and does not constitute medical advice. Treatment with Serophene should only be undertaken under the supervision of a qualified healthcare provider specializing in reproductive medicine. Individual response to therapy may vary based on numerous factors including age, diagnosis, and concomitant medical conditions. The prescribing physician should be consulted for complete information regarding indications, contraindications, warnings, precautions, and adverse reactions. Patients should thoroughly discuss the risks and benefits of treatment with their healthcare provider before initiating therapy.

Reviews

Clinical studies demonstrate ovulation rates of approximately 60-85% and pregnancy rates of 30-50% per ovulatory cycle in appropriately selected patients with World Health Organization (WHO) Group II anovulation. Systematic reviews indicate cumulative pregnancy rates of 70-80% after 6 treatment cycles. Patient satisfaction surveys report high acceptability of oral administration compared to injectable alternatives. Specialist evaluations consistently position Serophene as first-line therapy for ovulatory disorders due to its established efficacy, manageable side effect profile, and cost-effectiveness. Long-term follow-up studies confirm safety with appropriate cycle limitation, though continued monitoring is recommended given potential associations with borderline ovarian tumors with prolonged use.