Usage
Recombinant follicle stimulating hormone (rFSH) is a gonadotropin used to treat infertility in both men and women.
- In women: It is prescribed for anovulation (including polycystic ovary syndrome) when clomiphene citrate is ineffective and for controlled ovarian hyperstimulation to induce the development of multiple follicles in assisted reproductive technologies (ART) like in vitro fertilization (IVF), gamete intrafallopian transfer (GIFT), and intracytoplasmic sperm injection (ICSI). In women with severe LH and FSH deficiency (serum LH level < 1.2 IU/L), it is used in conjunction with luteinizing hormone (LH).
- In men: rFSH is prescribed for stimulating spermatogenesis in men with congenital or acquired hypogonadotropic hypogonadism, and is administered concomitantly with human chorionic gonadotropin (hCG).
- Pharmacological classification: Gonadotropin
Alternate Names
Recombinant human follicle stimulating hormone, follitropin alfa, follitropin beta
Brand Names: Follistim AQ, Gonal-F, Puregon, Bemfola, Afolia
How It Works
Pharmacodynamics: rFSH binds to FSH receptors in the ovaries and testes, mimicking the action of endogenous FSH. In women, this leads to follicular growth and development and estrogen production. In men, rFSH stimulates Sertoli cells in the testes, which support sperm production.
Pharmacokinetics:
- Absorption: rFSH is readily absorbed following subcutaneous (SC) or intramuscular (IM) administration. Bioavailability is approximately 76% for IM and 78% for SC routes.
- Distribution: The volume of distribution is ~8L in females.
- Metabolism: Not extensively metabolized.
- Elimination: rFSH is eliminated via renal and hepatic pathways. The half-life is approximately 44 hours after a single IM dose, 27-30 hours after multiple IM doses, and around 33 hours after a single SC dose. It is not known if it is excreted in breastmilk.
Mode of Action: Receptor binding at FSH receptors in the gonads.
Dosage
Standard Dosage
Adults:
- Anovulation: Starting dose of 75-150 IU daily, increased by 37.5-75 IU every 7-14 days if necessary, to a maximum of 225 IU daily, until adequate follicular development.
- Controlled Ovarian Hyperstimulation for ART: Starting dose of 150-225 IU daily on day 2 or 3 of the cycle, adjusted up to 450 IU daily based on ovarian response.
- Hypogonadotropic Hypogonadism (Men): 150 IU three times weekly, concomitantly with hCG, for at least 4 months, potentially up to 18 months.
Children: Not recommended.
Special Cases: Dose adjustment may be necessary based on ovarian response, patient characteristics, and clinical indication. Specific dosage guidelines for elderly, renally impaired, or hepatically impaired patients are not explicitly defined, but careful monitoring is recommended.
Clinical Use Cases
rFSH is not typically used in clinical scenarios like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. It is specifically indicated for infertility treatment.
Side Effects
Common Side Effects:
Headache, nausea, vomiting, diarrhea, abdominal pain, bloating, injection site reactions (redness, swelling, bruising), breast pain or swelling, acne, stuffy nose.
Rare but Serious Side Effects:
Ovarian hyperstimulation syndrome (OHSS) (severe lower stomach pain, nausea, vomiting, diarrhea, bloating, rapid weight gain, decreased urination, breathing problems), blood clots, allergic reactions (hives, difficulty breathing, swelling).
Long-Term Effects: Not well established.
Contraindications
Untreated endocrine disorders; abnormal vaginal bleeding; ovarian cysts or enlargement (not due to polycystic ovary syndrome); tumors of the breast, ovary, uterus, testicle, hypothalamus, or pituitary gland; hypersensitivity to rFSH products, streptomycin, or neomycin; pregnancy.
Drug Interactions
Clinically significant drug interactions are not well characterized. Potential interactions with GnRH agonists/antagonists should be considered in ART. Limited information is available about potential interactions with other medications, OTC drugs, supplements, or food/lifestyle factors.
Pregnancy and Breastfeeding
Contraindicated in pregnancy (Pregnancy Category X). Excretion in breast milk is unknown, but use is not recommended due to the potential for adverse effects in infants.
Drug Profile Summary
- Mechanism of Action: Stimulates follicular development and estrogen production in women, stimulates spermatogenesis in men.
- Side Effects: Common: Headache, nausea, injection site reactions. Serious: OHSS, blood clots.
- Contraindications: Pregnancy, tumors of reproductive organs, untreated endocrine disorders.
- Drug Interactions: Limited data available.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: Variable depending on indication and individual patient response.
- Monitoring Parameters: Follicle size, estrogen levels, sperm count.
Popular Combinations
rFSH is commonly used in combination with hCG in male hypogonadotropic hypogonadism and to trigger ovulation in women. In women with severe LH and FSH deficiency, it is combined with LH preparations.
Precautions
Pre-existing medical conditions (thyroid, adrenal, or pituitary disorders) should be assessed before starting treatment. Pregnancy should be excluded in women before starting rFSH. Careful monitoring of ovarian response is essential during treatment.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Recombinant follicle stimulating hormone?
A: Dosage varies based on the indication and patient response. Starting doses typically range from 75-150 IU daily, with adjustments made based on monitoring.
Q2: What are the most common side effects of rFSH?
A: Headache, nausea, vomiting, abdominal discomfort, and injection site reactions.
Q3: Can rFSH be used in pregnant women?
A: No, rFSH is contraindicated in pregnancy.
Q4: How is rFSH administered?
A: Subcutaneously or intramuscularly.
Q5: What is the role of hCG in conjunction with rFSH treatment?
A: hCG triggers ovulation in women and supports spermatogenesis in men when used with rFSH.
Q6: What is OHSS, and how is it managed?
A: Ovarian hyperstimulation syndrome (OHSS) is a serious side effect characterized by ovarian enlargement and fluid shifts. Treatment involves discontinuing rFSH and hCG, supportive care, and close monitoring.
Q7: Can rFSH be used in patients with polycystic ovary syndrome?
A: Yes, rFSH is indicated for ovulation induction in women with polycystic ovary syndrome who have not responded to clomiphene citrate.
Q8: How is ovarian response monitored during rFSH treatment?
A: Ultrasound monitoring of follicle size and estradiol levels.
Q9: What is the difference between follitropin alfa and follitropin beta?
A: Both are recombinant forms of FSH, with slight differences in their carbohydrate side chains. They are clinically comparable in terms of efficacy and safety.
