Leuprolide acetate
Overview
Leuprolide acetate is a synthetic nonapeptide analogue of the naturally occurring gonadotropin‑releasing hormone (GnRH) that acts as a long‑acting GnRH receptor agonist. When administered continuously by injection, leuprolide acetate initially stimulates the release of pituitary gonadotropins luteinizing hormone (LH) and follicle‑stimulating hormone (FSH), followed by downregulation of their secretion and significant suppression of gonadal steroid hormone synthesis. This results in reduced production of testosterone in males and estrogen in females, producing a reversible medical castration state that is useful in managing hormone‑dependent diseases. Leuprolide acetate is most commonly delivered as intramuscular or subcutaneous depot injections with dosing intervals ranging from monthly to once every six months depending on the formulation and indication. Its mechanism and hormonal effects have made it a cornerstone therapy for advanced prostate cancer, symptomatic endometriosis, uterine fibroids, and central precocious puberty, reflecting its broad application in both oncology and endocrinology.
Background and Date of Approval
Leuprolide acetate was first approved for medical use in the United States in 1985 as a daily subcutaneous injection under the brand name Lupron, for the palliative treatment of advanced prostate cancer, introducing the first long‑acting GnRH agonist into clinical practice. Over time, depot formulations were developed and approved to allow sustained release and less frequent administration, with monthly, three‑month, four‑month, and six‑month depot injections. These developments expanded the usability of leuprolide acetate in hormone‑dependent conditions. Multiple formulations of leuprolide acetate have been approved by the FDA for advanced prostate cancer, endometriosis, and central precocious puberty. A pediatric formulation for central precocious puberty in children two years and older received approval in 2020. Regulatory authorities in Europe and other regions have likewise approved leuprolide acetate for similar indications.
Uses
Leuprolide acetate is indicated for the palliative treatment of advanced hormone‑dependent prostate cancer in adult males by suppressing testosterone to castrate levels. It is also indicated for management of endometriosis in women, including relief of associated pelvic pain and reduction of endometriotic lesions, and for preoperative hematologic improvement of patients with anemia due to uterine fibroids in combination with iron therapy. In pediatric patients, it is indicated for the treatment of central precocious puberty to delay premature sexual development. The choice of formulation and dosing interval is tailored to the specific indication, patient age, and clinical goals.
Administration
Leuprolide acetate is administered by injection, either subcutaneously or intramuscularly, depending on the formulation. Depot preparations provide sustained release over defined intervals. Common dosing regimens include monthly injections as well as longer intervals of three, four, or six months. In central precocious puberty, pediatric formulations are dosed according to body weight and age to achieve suppression of pubertal hormones. Treatment duration is based on clinical response, desired hormonal suppression, and tolerability, with regular clinical and laboratory monitoring to assess hormone levels and adjust dosing if necessary.
Side Effects
Common side effects are largely related to induced hypogonadism and hormone suppression. In males, typical effects include hot flashes, loss of libido, erectile dysfunction, and fatigue. In females, decreased estrogen levels may lead to hot flashes, vaginal dryness, mood changes, and menstrual changes. Other frequently observed effects include headache, injection site reactions such as pain and swelling, nausea, and weight changes. The frequency and severity vary among patients and are managed under clinical supervision.
Warnings
Serious adverse events include a transient initial flare of symptoms due to the early surge in gonadotropin release, which may exacerbate underlying conditions such as bone pain or urinary obstruction in prostate cancer. Long‑term suppression can lead to decreased bone mineral density and increased risk of osteoporosis, metabolic changes including insulin resistance, and cardiovascular effects. Hypersensitivity reactions and rare events involving pituitary apoplexy have been reported. Leuprolide acetate is contraindicated during pregnancy due to potential fetal harm. Careful evaluation and monitoring are required in patients with a history of cardiovascular disease, depression, or metabolic disorders.
Precautions
Baseline assessments should include hormone levels, bone density evaluation, and cardiovascular risk assessment. Special caution is needed in patients with pre-existing osteoporosis or metabolic conditions. Live vaccines should be avoided during significant immunosuppression. Drug interactions are generally limited but monitoring is advised when used with medications that affect hormone metabolism or cardiovascular risk. Regular follow-up is essential to adjust therapy based on hormone suppression and side effects.
Expert Tips
Patient selection involves confirming a hormone-dependent condition and assessing baseline bone health and metabolic status. Baseline and ongoing monitoring of testosterone or estrogen levels is critical to ensure adequate suppression. Patients should be counseled on potential initial symptom flare, the importance of adherence to injection schedules, and lifestyle measures to support bone health, including calcium and vitamin D intake. Depot formulations should be properly reconstituted and injected with rotation of sites to minimize local reactions. Coordination with supportive care measures such as bone density monitoring and cardiovascular risk management enhances outcomes.