It may be used forprecocious puberty in both males and females,[14] 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.[15]
It is considered a possible treatment forparaphilias.[23] Leuprorelin has been tested as a treatment for reducing sexual urges inpedophiles and other cases of paraphilia.[24][25]
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,[8] 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, testicle pain, impotence, depression, or memory problems.[26] The rates ofgynecomastia with leuprorelin have been found to range from 3 to 16%.[27]
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.[28]
During the initial phase of luteinizing hormone-releasing hormone (LHRH) agonist therapy in individualsassigned male at birth, there is a notable phenomenon known as the "flare." This occurs when testosterone levels temporarily surge by approximately 50% within the first 1 to 2 weeks of therapy. This increase is a response to the initial stimulation of luteinizing hormone (LH) by the LHRH agonist, leading to a rise in testosterone levels before they begin to decrease as intended. For individuals receiving LHRH agonists as part of gender-affirming care, this temporary increase in testosterone can be particularly distressing, exacerbating gender dysphoria and discomfort. To manage and mitigate these effects, healthcare providers often prescribe antiandrogens during this phase to help block the unwanted increase in testosterone and alleviate the associated distress.[29]
Leuprorelin is agonadotropin-releasing hormone (GnRH)analogue acting as anagonist atpituitaryGnRH receptors. GnRH receptor agonists initially increase the secretion ofluteinizing hormone (LH) andfollicle-stimulating hormone (FSH) by theanterior pituitary and increased serumestradiol andtestosterone levels via thehypothalamic–pituitary–gonadal axis (HPG axis). However, normal functioning of this axis requires pulsatile release of GnRH from the hypothalamus. Continuous exposure to an agonist such as leuprorelin for several weeks causes pituitary GnRH receptors to become desensitised and no longer responsive. This desensitisation is the objective of leuprorelin therapy because it ultimately reduces LH and FSH secretion, leading tohypogonadism and a dramatic reduction in estradiol and testosterone levels regardless of sex.[30][31]
Leuprorelin was discovered and firstpatented in 1973 and was introduced for medical use in 1985.[43][44] It was initially marketed only for daily injection, but adepot injection formulation was introduced in 1989.[44]
On 24 March 2022, theCommittee for Medicinal Products for Human Use (CHMP) of theEuropean Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Camcevi, intended for the treatment of the cancer of the prostate in adult men when the cancer is "hormone-dependent", which means that it responds to treatments that reduce the levels of the hormone testosterone.[47] The applicant for this medicinal product is Accord Healthcare S.L.U.[47] Leuprorelin was approved for medical use in the European Union in May 2022.[9][48]
Leuprorelin is thegeneric name of the drug and itsINNTooltip International Nonproprietary Name andBANTooltip British Approved Name, while leuprorelin acetate is itsBANMTooltip British Approved Name andJANTooltip Japanese Accepted Name, leuprolide acetate is itsUSANTooltip United States Adopted Name andUSPTooltip United States Pharmacopeia, leuprorelina is itsDCITTooltip Denominazione Comune Italiana, and leuproréline is itsDCFTooltip Dénomination Commune Française.[49][50][51][52] It is also known by its developmental code names A-43818, Abbott-43818, DC-2-269, and TAP-144.[49][50][51][52]
Leuprorelin is marketed byBayer AG under the brand name Viadur,[7] by Tolmar under the brand names Eligard and Fensolvi,[5][6] and byTAP Pharmaceuticals (1985–2008), by Varian Pharmed( Previously named Varian Darou Pajooh) under the brand name Leupromer andAbbott Laboratories (2008–present) under the brand name Lupron.
In October 2001, the US Department of Justice, states attorneys general, and TAP Pharmaceutical Products, a subsidiary of Abbott Laboratories, settled criminal and civil charges against TAP related to federal and statemedicare fraud and illegal marketing of the drug leuprorelin.[53] TAP paid a total of $875 million, which was arecord high at the time.[54][55] The $875 million settlement broke down to $290 million for violating the Prescription Drug Marketing Act, $559.5 million to settle federal fraud charges for overcharging Medicare, and $25.5 million reimbursement to 50 states and Washington, D.C., for filing false claims with the states' Medicaid programs.[55] The case arose under theFalse Claims Act with claims filed by Douglas Durand, a former TAP vice president of sales, and Joseph Gerstein, a doctor atTufts University's HMO practice.[54] Durand, Gerstein, and Tufts shared $95 million of the settlement.[54]
There have since been various suits concerning leuprorelin use, none successful.[56][57] They either concern the oversubscription of the drug or undue warning about the side effects. Between 2010 and 2013, the FDA updated the Lupron drug label to include new safety information on the risk of thromboembolism, loss of bone density and convulsions.[58] The FDA then asserted that the benefits of leuprorelin outweigh its risks when used according to its approved labeling. Since 2017, the FDA has been evaluating leuprorelin's connection to pain and discomfort in musculoskeletal and connective tissue.[59]
^abcdefghi"Leuprolide Acetate". The American Society of Health-System Pharmacists.Archived from the original on 23 December 2016. Retrieved8 December 2016.
^abWorld Health Organization (2019).World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization.hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
^Badaru A, Wilson DM, Bachrach LK, et al. (May 2006). "Sequential comparisons of one-month and three-month depot leuprolide regimens in central precocious puberty".The Journal of Clinical Endocrinology and Metabolism.91 (5):1862–67.doi:10.1210/jc.2005-1500.PMID16449344.
^Dreger A (January–February 2009). "Gender identity disorder in childhood: inconclusive advice to parents".The Hastings Center Report.39 (1):26–9.doi:10.1353/hcr.0.0102.PMID19213192.S2CID22526704.
^Gava G, Cerpolini S, Martelli V, Battista G, Seracchioli R, Meriggiola MC (August 2016). "Cyproterone acetate vs leuprolide acetate in combination with transdermal oestradiol in transwomen: a comparison of safety and effectiveness".Clinical Endocrinology.85 (2):239–246.doi:10.1111/cen.13050.PMID26932202.S2CID30150360.
^Saleh FM, Niel T, Fishman MJ (2004). "Treatment of paraphilia in young adults with leuprolide acetate: a preliminary case report series".Journal of Forensic Sciences.49 (6):1343–48.doi:10.1520/JFS2003035.PMID15568711.
^Di Lorenzo G, Autorino R, Perdonà S, De Placido S (December 2005). "Management of gynaecomastia in patients with prostate cancer: a systematic review".Lancet Oncol.6 (12):972–79.doi:10.1016/S1470-2045(05)70464-2.PMID16321765.
^Mutschler E, Schäfer-Korting M (2001).Arzneimittelwirkungen (in German) (8 ed.). Stuttgart: Wissenschaftliche Verlagsgesellschaft. pp. 372–73.ISBN978-3-8047-1763-3.
^ab"Camcevi: Pending EC decision".European Medicines Agency (EMA). 24 March 2022. Archived fromthe original on 29 March 2022. Retrieved28 March 2022. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
^Desmarchelier M, Lair S, Dunn M, Langlois I (2008). "Primary hyperaldosteronism in a domestic ferret with an adrenocortical adenoma".Journal of the American Veterinary Medical Association.233 (8):1297–301.doi:10.2460/javma.233.8.1297.PMID19180717.
Shajnfeld A, Krueger RB (July 2006). "Reforming (Purportedly) Non-Punitive Responses to Sexual Offending".Developments in Mental Health Law.25: 81.SSRN1077282.
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