Gonadotrophins Including Other Ovulation Stimulants

Usage

Gonadotropins are prescribed for the treatment of infertility in both men and women. In women, they are primarily used for ovulation induction in conditions like polycystic ovary syndrome (PCOS) or hypogonadotropic hypogonadism (HH), and for controlled ovarian stimulation in assisted reproductive technologies (ART) like in-vitro fertilization (IVF). In men, they are used to treat hypogonadotropic hypogonadism, which can cause low sperm production.

These medications are classified as gonadotropins and ovulation stimulators.

Gonadotropins mimic the action of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), stimulating the ovaries to develop follicles and produce eggs in women, and stimulating the testes to produce sperm in men.

Alternate Names

Gonadotropins are often referred to as ovulation stimulants. Brand names of gonadotropins include Gonal-f, Gonal-f RFF (follitropin alfa), Ovidrel, Novarel (choriogonadotropin alfa), and others.

How It Works

Pharmacodynamics: Gonadotropins bind to receptors in the gonads (ovaries and testes), mimicking the effects of FSH and LH. This leads to follicular development, oocyte maturation, and estrogen production in women, and spermatogenesis in men. Human chorionic gonadotropin (hCG) is often used to trigger final oocyte maturation and ovulation.

Pharmacokinetics: Gonadotropins are generally administered subcutaneously or intramuscularly. Absorption and distribution vary depending on the specific preparation. Metabolism and elimination pathways are not fully characterized, but a significant portion is likely excreted renally.

Mode of action: Gonadotropins interact with specific receptors on the surface of ovarian granulosa cells (FSH) and theca cells (LH), activating intracellular signaling pathways that promote follicular development, estrogen production, and oocyte maturation. hCG mimics LH’s action, triggering ovulation.

Receptor Binding: Gonadotropins bind to their respective gonadotropin receptors (FSH receptor and LH/hCG receptor) on the surface of gonadal cells.

Dosage

Standard Dosage

Adults:

• Ovulation induction: Initial dose is typically 75 IU daily, adjusted based on ovarian response, monitored via ultrasound and serum estradiol levels. Maximum dose is generally 300 IU daily.
• ART: Starting dose is typically 150-225 IU daily, adjusted based on ovarian response. Maximum dose is generally 450 IU daily.
• Male hypogonadotropic hypogonadism: Various regimens exist, often involving hCG and FSH, dosed multiple times per week.

Children:

Gonadotropins are not typically used in children except in specific cases like cryptorchidism, where hCG may be used. Dosing is weight-based and requires specialist guidance.

Special Cases:

• Elderly Patients: Dose adjustments may be needed based on ovarian reserve.
• Patients with Renal Impairment: Caution is advised, but specific dose adjustments are not typically necessary.
• Patients with Hepatic Dysfunction: Specific dose adjustments are not usually required.
• Patients with Comorbid Conditions: Caution is advised in patients with PCOS due to the risk of ovarian hyperstimulation syndrome (OHSS).

Clinical Use Cases

The dosage guidelines provided above encompass the clinical use cases for intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations are not relevant for gonadotropins.

Dosage Adjustments

Dose adjustments are based primarily on ovarian response as assessed by ultrasound and estradiol levels.

Side Effects

Common Side Effects

• Ovarian hyperstimulation syndrome (OHSS)
• Injection site reactions
• Headache
• Abdominal pain and bloating
• Mood swings

Rare but Serious Side Effects

• Severe OHSS (can be life-threatening)
• Multiple pregnancies
• Thromboembolism

Long-Term Effects

Long-term effects are rare, but prolonged use may increase the risk of ovarian tumors.

Adverse Drug Reactions (ADR)

Severe OHSS requires immediate medical attention.

Contraindications

• Pituitary tumors
• Ovarian cysts or enlargement unrelated to PCOS
• Prior ovarian hyperstimulation syndrome (OHSS)
• Unexplained vaginal bleeding
• Pregnancy and breastfeeding
• Hormone-dependent cancers

Drug Interactions

Clinically significant drug interactions are not well established.

Pregnancy and Breastfeeding

Gonadotropins are contraindicated in pregnancy and breastfeeding.

Drug Profile Summary

• Mechanism of Action: Stimulates follicular development and maturation in the ovaries and spermatogenesis in the testes.
• Side Effects: OHSS, injection site reactions, headache, abdominal pain, mood swings.
• Contraindications: Pituitary tumors, ovarian cysts, prior OHSS, vaginal bleeding, pregnancy, breastfeeding.
• Drug Interactions: Limited clinically significant interactions.
• Pregnancy & Breastfeeding: Contraindicated.
• Dosage: Varies based on indication and patient response. See detailed section above.
• Monitoring Parameters: Ultrasound, estradiol levels, follicular development.

Popular Combinations

Gonadotropins are often used in combination with hCG to trigger ovulation.

Precautions

• Careful monitoring of ovarian response is crucial.
• Patients with PCOS are at increased risk of OHSS.
• Multiple pregnancies are a risk.

FAQs

Q1: What is the recommended dosage for Gonadotrophins Including Other Ovulation Stimulants?

A: Dosage varies depending on the specific indication (ovulation induction, ART, male hypogonadotropic hypogonadism) and patient response. Initial doses typically range from 75 IU to 225 IU daily, with adjustments based on monitoring.

Q2: What are the signs and symptoms of OHSS?

A: Mild OHSS may present with abdominal bloating, discomfort, and nausea. Moderate OHSS may involve vomiting, diarrhea, and significant ovarian enlargement. Severe OHSS can cause rapid weight gain, ascites, pleural effusion, and difficulty breathing.

Q3: How is OHSS managed?

A: Management depends on the severity. Mild cases may require only supportive care. Moderate to severe OHSS may require hospitalization, fluid management, and careful monitoring.

Q4: What is the success rate of ovulation induction with gonadotropins?

A: Success rates vary depending on the cause of infertility and patient factors, but are generally good, especially in PCOS.

Q5: What are the risks of multiple pregnancies with gonadotropins?

A: The risk of multiple pregnancies is increased with gonadotropin use, particularly with higher doses and in patients with PCOS.

Q6: Can gonadotropins be used in men?

A: Yes, gonadotropins, often in combination with hCG, can be used to treat male hypogonadotropic hypogonadism, stimulating sperm production.

Q7: How are gonadotropins administered?

A: Gonadotropins are typically administered subcutaneously.

Q8: How long is a typical course of treatment with gonadotropins?

A: Treatment duration varies depending on the indication and patient response. For ovulation induction, treatment may last several days to weeks. For ART, treatment continues until sufficient follicular development is achieved. For male hypogonadotropic hypogonadism, treatment may be long-term.

Q9: Are there any alternatives to gonadotropins for ovulation induction?

A: Clomiphene citrate is a first-line oral medication for ovulation induction, but gonadotropins are often used when clomiphene is ineffective or contraindicated.