Leuprorelin

Leuprorelin, also known as leuprolide, is a manufactured version of a hormone used to treat prostate cancer, breast cancer, endometriosis, uterine fibroids, for early puberty, as part of transgender hormone therapy, or to perform chemical castration of violent sex offenders.[5][6] It is given by injection into a muscle or under the skin.[5]

Leuprorelin is in the gonadotropin-releasing hormone (GnRH) analogue family of medications.[5] It works by decreasing gonadotropins, thereby decreasing testosterone and estradiol.[5] Common side effects include hot flashes, unstable mood, trouble sleeping, headaches, and pain at the site of injection.[5] Other side effects may include high blood sugar, allergic reactions, and problems with the pituitary gland.[5] Use during pregnancy may harm foetal development.[5]

Leuprorelin was patented in 1973 and approved for medical use in the United States in 1985.[5][7] It is on the World Health Organization's List of Essential Medicines.[8] It is sold under the brand name Lupron, among others.[5]

Medical uses

Leuprorelin may be used in the treatment of hormone-responsive cancers such as prostate cancer and breast cancer. It may also be used for estrogen-dependent conditions such as endometriosis[9] or uterine fibroids.

It may be used for precocious puberty in both males and females,[10] and to prevent premature ovulation in cycles of controlled ovarian stimulation for in vitro fertilization (IVF). This use is controversial since the Lupron label advises against using the drug when one is considering pregnancy, due to a risk of birth defects.[11]

It may be used to reduce the risk of premature ovarian failure in women receiving cyclophosphamide for chemotherapy.[12]

Side effects

Common side effects of leuprorelin injection include redness/burning/stinging/pain/bruising at the injection site, hot flashes (flushing), increased sweating, night sweats, tiredness, headache, upset stomach, nausea, diarrhea, impotence, testicular shrinkage, constipation, stomach pain, breast swelling or tenderness, acne, joint/muscle aches or pain, trouble sleeping (insomnia), reduced sexual interest, vaginal discomfort/dryness/itching/discharge, vaginal bleeding, swelling of the ankles/feet, increased urination at night, dizziness, breakthrough bleeding in a female child during the first two months of leuprorelin treatment, weakness, chills, clammy skin, skin redness, itching, or scaling, testicular pain, impotence, depression, or memory problems.[21] The rates of gynecomastia with leuprorelin have been found to range from 3 to 16%.[22]

A cohort of women that were prescribed leuprorelin to delay precocious puberty as children has developed osteoporosis and brittle teeth at an unexpected rate; However, the FDA has not established that these conditions were caused by leuprorelin.[23]

Pharmacology

Chemistry

The peptide sequence is Pyr-His-Trp-Ser-Tyr- D -Leu-Leu-Arg-Pro-NHEt (Pyr = L -pyroglutamyl).

History

Leuprorelin was discovered and first patented in 1973 and was introduced for medical use in 1985.[40][41] It was initially marketed only for daily injection, but a depot injection formulation was introduced in 1989.[41]

Society and culture

Research

As of 2006, leuprorelin was under investigation for possible use in the treatment of mild to moderate Alzheimer's disease.[60]

A by mouth formulation of leuprorelin is under development for the treatment of endometriosis.[61] It was also under development for the treatment of precocious puberty, prostate cancer, and uterine fibroids, but development for these uses was discontinued.[61] The formulation has the tentative brand name Ovarest.[61] As of July 2018, it is in phase II clinical trials for endometriosis.[61]

Veterinary use

Leuprorelin is frequently used in ferrets for the treatment of adrenal disease. Its use has been reported in a ferret with concurrent primary hyperaldosteronism,[62] and one with concurrent diabetes mellitus.[63] It is also used to treat pet parrots with chronic egg laying behavior.[64]

Further reading