Leuprorelin

What is Leuprorelin?

Leuprorelin, also known as leuprolide, is a synthetic nonapeptide analog of naturally occurring gonadotropin-releasing hormone (GnRH). It is a type of hormone (endocrine) therapy used to treat various conditions by suppressing the production of certain hormones in the body, specifically testosterone in males and estrogen in females.

Leuprorelin acts as a potent inhibitor of gonadotropin secretion when given continuously. After an initial transient increase in circulating levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), chronic administration of leuprorelin results in a significant reduction of LH and FSH. This leads to the suppression of ovarian and testicular steroidogenesis, reducing testosterone levels to castrate levels in males and estrogen levels to post-menopausal levels in pre-menopausal females. This effect is reversible upon discontinuation of the drug.

Different Names

Leuprorelin is marketed under various brand names, including:

• Lupron Depot

• Eligard

• Fensolvi

• Camcevi

• Prostap (UK)

• Lutrate Depot

Side Effects and Benefits

Benefits:

• Treatment of hormone-sensitive cancers: Leuprorelin is highly effective in treating advanced prostate cancer and pre-menopausal breast cancer by suppressing the hormones that fuel their growth.

• Managing other conditions: It is used to treat endometriosis, uterine fibroids, and central precocious puberty (early puberty) in children.

• Transgender hormone therapy: It can be used as part of transgender hormone therapy to suppress natal hormones.

• Chemical castration: It can be used for chemical castration of violent sex offenders.

Side Effects:

• Hormonal side effects: Many side effects are a result of the intended hormonal suppression. These include:

  • Hot flashes or sweats

  • Decreased libido and impotence

  • Testicular shrinkage or atrophy

  • Gynecomastia (breast tenderness or pain and increase in breast tissue) in males

  • Vaginal dryness in females

• Other common side effects:

  • Injection site reactions (pain, redness, or irritation)

  • Fatigue or weakness

  • Headache

  • Joint, muscle, or bone pain

  • Mood swings or depression

• More serious side effects (less common):

  • Tumor Flare: When treatment is initiated, there can be a temporary increase in testosterone levels, which may cause a temporary worsening of cancer symptoms.

  • Cardiovascular risks: There is an increased risk of heart attack, stroke, and other cardiovascular events.

  • Metabolic changes: Increased blood sugar, increased risk of diabetes, and high lipids (e.g., cholesterol) can occur.

  • Bone weakening: Long-term use can lead to bone thinning (osteoporosis).

  • Severe skin reactions: In rare cases, life-threatening skin reactions have been reported.

  • Seizures: Convulsions have been observed in some patients.

Pros and Cons

Pros:

• Highly effective: Leuprorelin is a very effective treatment for the conditions it is prescribed for, particularly in suppressing hormone-sensitive cancers.

• Convenient dosing: The depot (sustained-release) formulations allow for less frequent injections (monthly, every 3 months, every 4 months, or even every 6 months), which is convenient for patients.

• Non-surgical alternative: It provides a non-surgical alternative to procedures like orchiectomy (surgical removal of the testes) for testosterone suppression.

• Reversible: The effects of leuprorelin are generally reversible upon discontinuation of treatment.

Cons:

• Significant side effects: The side effects can be severe and can significantly impact a person's quality of life.

• Initial "flare" effect: The initial surge in hormones can temporarily worsen a patient's condition.

• Not a cure: For cancers like prostate cancer, it is a palliative treatment that manages the disease but does not cure it.

• Long-term risks: Long-term use is associated with a greater risk of bone loss and cardiovascular problems.

• Requires injections: The medication is not active orally and must be administered via injection, which may be uncomfortable for some people.

Dosage and Frequency

The dosage and frequency of leuprorelin depend on the condition being treated and the specific formulation used (e.g., depot for 1, 3, 4, or 6-month administration).

• For advanced prostate cancer:

  • A common dose is 7.5 mg injected intramuscularly every 4 weeks.

  • Other formulations include 22.5 mg every 3 months, 30 mg every 4 months, or 45 mg every 6 months.

• For other conditions:

  • Dosages vary, and a doctor will determine the appropriate dose and frequency based on the patient's age, weight, and clinical response.

Half-Life and Detection Time

• Half-life: The terminal elimination half-life of leuprorelin is approximately 3 hours. However, this refers to the short-acting, non-depot formulation. The depot formulations release the drug over a much longer period. After an initial "burst" of release, the drug is released at a constant rate for the duration of the intended dosing interval (e.g., 1, 3, or 6 months).

• Detection time: Due to the sustained-release nature of the depot formulations, leuprorelin can be detectable in the body for a considerable amount of time after the last injection. While the short half-life of the active substance is 3 hours, a study found that sustained-release leuprolide levels were detectable more than 14 days longer than the expected treatment duration. Normal hormonal function is usually restored within 4 to 12 weeks after treatment is discontinued. The presence of the drug can be detected for an extended period, potentially for several months, depending on the dose and formulation.

Sterogenic, Progestogenic, Prolactin, and Anabolic Androgenic Effects

• Sterogenic Effects: Leuprorelin is not a steroid. It is a peptide that works by altering the production of sex steroids (testosterone and estrogen). As an LH-RH agonist, it initially stimulates the production of these steroids, but prolonged use leads to a significant decrease in their levels, effectively shutting down steroidogenesis.

• Progestogenic Effects: Leuprorelin does not have progestogenic effects. It is not a progestin. It works on the GnRH receptors in the pituitary gland, not on progesterone receptors.

• Prolactin Affects: Leuprorelin can stimulate prolactin release, particularly during ovarian stimulation. However, studies have shown that while it may elevate prolactin levels, this does not always have apparent clinical consequences.

• Anabolic Androgenic Ratio: Leuprorelin is an androgen-deprivation therapy. It suppresses androgen production. Therefore, it does not have an anabolic or androgenic ratio. Its mechanism of action is the complete opposite of an anabolic steroid. It leads to a catabolic state by drastically reducing testosterone levels, which can result in a loss of muscle mass and bone density over time.