Leuprorelin

Leuprolide

Systematic (IUPAC) name
N-[1-[[1-[[1-[[1-[[1-[[1-[[5-(diaminomethylideneamino)-1- [2-(ethylcarbamoyl)pyrrolidin-1-yl]-1-oxo-pentan-2- yl]carbamoyl]-3-methyl-butyl]carbamoyl]-3-methyl- butyl]carbamoyl]-2-(4-hydroxyphenyl)ethyl] carbamoyl]-2-hydroxy-ethyl]carbamoyl]-2-(1H-indol-3- yl)ethyl]carbamoyl]-2-(3H-imidazol-4-yl)ethyl]-5-oxo- pyrrolidine-2-carboxamide
Clinical data
Trade names	Lupron
AHFS/Drugs.com	Consumer Drug Information
MedlinePlus	a685040
Pregnancy cat.	X
Legal status	℞ Prescription only
Routes	Implant / Injection
Pharmacokinetic data
Half-life	3 hours
Excretion	Renal
Identifiers
CAS number	53714-56-0 Y
ATC code	L02AE02
PubChem	CID 441410
DrugBank	DB00007
UNII	EFY6W0M8TG N
KEGG	D08113 Y
ChEMBL	CHEMBL1201199 N
Chemical data
Formula	C59H84N16O12
Mol. mass	1209.4 g/mol
N (what is this?)  (verify)

Leuprorelin (INN) or leuprolide acetate (USAN) is a GnRH analog. Proper Sequence: Pyr-His-Trp-Ser-Tyr-D-Leu-Leu-Arg-Pro-NHEt (Pyr = L-Pyroglutamyl)

Mode of action

Leuprolide acts as an agonist at pituitary GnRH receptors. By interrupting the normal pulsatile stimulation and the desensitization of the GnRH receptors; it indirectly down regulates the secretion of gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH) leading to hypogonadism and thus a dramatic reduction in estradiol and testosterone levels in both sexes.

Clinical use

An LH-RH (GnRH) analog, leuprolide may be used in the treatment of hormone-responsive cancers such as prostate cancer or breast cancer, estrogen-dependent conditions (such as endometriosis or uterine fibroids), to treat precocious puberty, and to control ovarian stimulation in In Vitro Fertilization (IVF). It is considered a possible treatment for paraphilias.

Leuprolide has been tested as a treatment for reducing sexual urges in pedophiles and other cases of paraphilia. High doses are sometimes used to chemically castrate sex offenders.

Leuprolide is also under investigation for possible use in the treatment of mild to moderate Alzheimer's disease.

Leuprolide is also used to treat chronic adrenal disease in ferrets.^{[citation needed]} It also used for treatment of steroid abuse.^{[citation needed]}

Lupron protocol

A 2005 paper suggested leuprolide as a possible treatment for autism, the hypothetical method of action being the now defunct hypothesis that autism is caused by mercury, with the additional unfounded assumption that mercury binds irreversibly to testosterone and therefore leuprolide can help cure autism by lowering the testosterone levels and thereby mercury levels. However, used on children or adolescents it could cause disastrous and irreversible damage to sexual functioning, and there is no scientifically valid or reliable research to show its effectiveness in treating autism. This use has been termed the "Lupron protocol" and Mark Geier, the proponent of the hypothesis, has frequently been barred from testifying in vaccine-autism related cases on the grounds of not being sufficiently expert in that particular issue and has had his medical license revoked. Medical experts have referred to Geier's claims as "junk science".

Approvals

• Lupron Injection (5 mg/mL for daily subcutaneous injection) was first approved by the FDA for treatment of advanced prostate cancer on April 9, 1985.
• Lupron Depot (7.5 mg/vial for monthly intramuscular depot injection) was first approved by the FDA for palliative treatment of advanced prostate cancer on January 26, 1989, and subsequently in 22.5 mg/vial and 30 mg/vial for intramuscular depot injection every 3 and 4 months, respectively. 3.75 mg/vial and 11.25 mg/vial dosage forms were subsequently approved for subcutaneous depot injection every month and every 3 months, respectively for treatment of endometriosis or fibroids. 7.5 mg/vial, 11.25 mg/vial, and 15 mg/vial dosage forms were subsequently approved for subcutaneous depot injection for treatment of children with central precocious puberty.
• Viadur (72 mg yearly subcutaneous implant) was first approved by the FDA for palliative treatment of advanced prostate cancer on March 6, 2000. Bayer will fulfill orders until current supplies are depleted, expected by the end of April 2008
• Eligard (7.5 mg for monthly subcutaneous depot injection) was first approved by the FDA for palliative treatment of advanced prostate cancer on January 24, 2002, and subsequently in 22.5 mg, 30 mg, and 45 mg doses for subcutaneous depot injection every 3, 4, and 6 months, respectively.
• Leupromer® 7.5 ( 7.5 mg, One month depot for subcutaneous injection) is the second In-situ forming injectable drug in world. it use for palliative treatment of advanced prostate cancer, endometriosis and fibroids. it approved by The Ministry of Health and Medical Education Of Iran.

Leuprolide acetate is marketed by Bayer AG under the brand name Viadur, by Sanofi-Aventis under the brand name Eligard, and by TAP Pharmaceuticals (1985–2008) and Abbott Laboratories (2008-current) under the brand name Lupron. It is available as a slow-release implant or subcutaneous/intramuscular injection.

In the UK and Ireland, leuprorelin is marketed by Takeda UK as Prostap SR (one-month injection) and Prostap 3 (three-month injection).

Warnings

A study that found that leuprorelin is very risky, especially for men with heart problems.^{[citation needed]} An AP article stated, "The hormone treatment was linked with a 96 percent higher risk of death after adjusting for other risk factors."^{[citation needed]} A similar study issued in JAMA in July 2008 also found that the drug offered no life-prolonging benefits in men with advanced prostate cancer vs. men who did not take any form of hormone therapy, or conservative management.^{[citation needed]} Women with endometriosis also suffer significant side effects.^{[citation needed]}

In June 2009 the label was changed again to warn about "convulsion" in the post-marketing surveillance. The label shows that 98% of women had adverse events including 65% suffering headache/migraine, 31% depression, 31% insomnia, and 25% Nausea/vomiting. Many other adverse events are listed in the label. The label also notes that women with no history of depression or psychiatric illness reported suicidal ideation and attempts.

Additionally, leuprolide therapy in conjunction with radiation has been shown to result in a statistically significant shortening of the penis.

See also

• National Women's Health Network article on Lupron Depot from November & December 2008.

External links

• Lupron Injection (package insert from abbott)
• Reforming (purportedly) Non-Punitive Responses to Sexual Offending (journal article discussing use of Lupron as a form of reforming sex offender law)