Leuprolide

Depending on the product, long-acting depot preparations use subcutaneous or intramuscular injection; the formulation determines the route and release interval.

Leuprolide acetate, also called leuprorelin, is a synthetic nine-amino-acid GnRH analog. Brands include Lupron, Lupron Depot, Eligard, Fensolvi and Camcevi. Natural GnRH is released in pulses and stimulates LH and FSH, which drive gonadal testosterone and estrogen production. Leuprolide is more potent and longer lasting; it was developed as TAP-144 and first approved in the US in 1985.

Its development followed identification of hypothalamic releasing hormones, work recognized in Andrew Schally and Roger Guillemin’s shared 1977 Nobel Prize. Chemists modified the known ten-amino-acid GnRH structure to improve receptor binding and resist degradation. Leuprolide has an amino-acid substitution and ethylamide tail. Its 1985 introduction helped establish medical hormone suppression as an alternative to surgical castration for prostate cancer.

Initial receptor stimulation briefly increases LH, FSH and testosterone—the flare. Continuous exposure then downregulates and desensitizes pituitary gonadotrophs. Over about two to four weeks, gonadotropin output falls and testosterone reaches castrate levels, or estrogen reaches a postmenopausal range.

• In hormone-sensitive prostate cancer, testosterone deprivation reduces a tumor-growth stimulus.
• In endometriosis and fibroids, estrogen reduction shrinks hormone-responsive tissue.
• In central precocious puberty, suppression interrupts premature sexual development and can help preserve adult height.

Early anti-androgen treatment is often used in advanced prostate cancer to limit transient flare-related worsening. Depots provide suppression for one, three, four or six months. A three-month pediatric depot registration program maintained stimulated-LH suppression in 78–95% of treated children.

FDA first approved daily subcutaneous leuprolide in 1985, followed by Lupron Depot in 1989. Additional strengths, indications and brands followed, including Eligard, pediatric Fensolvi and ready-to-use Camcevi. Formulations have different schedules and indications.

Uses include palliative hormone therapy for advanced or metastatic prostate cancer, endometriosis, central precocious puberty and uterine fibroids with anemia—often before surgery and together with iron. Pregnancy is a contraindication. Gynecologic and pediatric courses may be time limited partly because suppression can reduce bone density.

Expected effects of low sex hormones include hot flashes, sweating, reduced libido, erectile dysfunction, fatigue and mood changes. Injection discomfort and longer-term bone loss also occur. Important risks include early tumor flare, hyperglycemia, diabetes and cardiovascular events with prolonged androgen deprivation, rare seizures and severe skin reactions.

Pediatric labeling additionally warns about mood or behavioral changes and increased pressure around the brain, also called pseudotumor cerebri.