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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/11/10 05:06:42」(JST)

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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 of, and thus desensitizing, the GnRH receptors, it indirectly downregulates 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^[1] or uterine fibroids), to treat precocious puberty,^[2] and to control ovarian stimulation in In Vitro Fertilization (IVF). It is considered a possible treatment for paraphilias.^[3]

Leuprolide has been tested as a treatment for reducing sexual urges in pedophiles and other cases of paraphilia.^[4]^[5]

As of 2006 Leuprolide was under investigation for possible use in the treatment of mild to moderate Alzheimer's disease.^[6]

It also used for treatment of steroid abuse.^{[citation needed]}

Leuprolide, along with triptorelin and goserelin, are often used to delay puberty in transgender youth until they are old enough to begin hormone replacement therapy.^[7] They are also sometimes used as superior alternatives to anti-androgens like spironolactone and cyproterone acetate for suppressing testosterone production in trans women.

Veterinary use

Leuprolide has been used in two cases of ferrets with chronic adrenal disease, one with primary hyperaldosteronism,^[8] and one with hyperadrenocorticism ^[9]

Lupron protocol

A 2005 paper suggested leuprolide as a possible treatment for autism,^[10] 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.^[11] 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.^[12] This use has been termed the "Lupron protocol"^[13] 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^[14]^[15]^[16] and has had his medical license revoked.^[13] Medical experts have referred to Geier's claims as "junk science".^[17]

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 the world. It is used for palliative treatment of advanced prostate cancer, endometriosis and fibroids. It was approved by The Ministry of Health and Medical Education Of Iran.

Leuprolide acetate is marketed by Bayer AG under the brand name Viadur, by Tolmar under the brand name Eligard, and by TAP Pharmaceuticals (1985–2008), by Varian Darou Pajooh under the brand name Leupromer 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).

Adverse effects

Common side effects of Lupron Injection include redness/burning/stinging/pain/bruising at the injection site, hot flashes (flushing), increased sweating, night sweats, tiredness, headache, upset stomach, nausea, diarrhea, 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 2 months of leuprolide treatment, weakness, chills, clammy skin, skin redness, itching, or scaling, testicle pain, impotence, depression, or memory problems.^[18]

References

^ Crosignani PG, Luciano A, Ray A, Bergqvist A (January 2006). "Subcutaneous depot medroxyprogesterone acetate versus leuprolide acetate in the treatment of endometriosis-associated pain". Human reproduction (Oxford, England) 21 (1): 248–56. doi:10.1093/humrep/dei290. PMID 16176939.
^ 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): 1862–7. doi:10.1210/jc.2005-1500. PMID 16449344.
^ Saleh F, Niel T, Fishman M (2004). "Treatment of paraphilia in young adults with leuprolide acetate: a preliminary case report series". J Forensic Sci 49 (6): 1343–8. doi:10.1520/JFS2003035. PMID 15568711.
^ Schober JM, Byrne PM, Kuhn PJ. (2006). "Leuprolide acetate is a familiar drug that may modify sex-offender behaviour: the urologist's role.". BJU international 97 (4): 684–6. doi:10.1111/j.1464-410X.2006.05975.x. PMID 16536753.
^ Schober JM, Kuhn PJ, Kovacs PG, Earle JH, Byrne PM, Fries RA. (2005). "Leuprolide acetate suppresses pedophilic urges and arousability.". Archives of Sexual Behavior 34 (6): 691–705. doi:10.1007/s10508-005-7929-2. PMID 16362253.
^ Doraiswamy PM, Xiong GL. (2006). "Pharmacological strategies for the prevention of Alzheimer's disease". Expert Opin Pharmacother 7 (1): 1–10. doi:10.1517/14656566.7.1.1. PMID 16370917.
^ David A. Wolfe; Eric J. Mash (9 October 2008). Behavioral and Emotional Disorders in Adolescents: Nature, Assessment, and Treatment. Guilford Press. pp. 556–. ISBN 978-1-60623-115-9. Retrieved 24 March 2012.
^ Desmarchelier M, Lair S, Dunn M, Langlois I.Primary hyperaldosteronism in a domestic ferret with an adrenocortical adenoma. J Am Vet Med Assoc. 2008 Oct 15;233(8):1297-301.PMID:19180717
^ Boari A, Papa V, Di Silverio F, Aste G, Olivero D, Rocconi F. Type 1 diabetes mellitus and hyperadrenocorticism in a ferret. Vet Res Commun. 2010 Jun;34 Suppl 1:S107-10. doi: 10.1007/s11259-010-9369-2.PMID:20446034.
^ Geier M, Geier D (2005). "The potential importance of steroids in the treatment of autistic spectrum disorders and other disorders involving mercury toxicity". Med Hypotheses 64 (5): 946–54. doi:10.1016/j.mehy.2004.11.018. PMID 15780490.
^ Allen A (2007-05-28). "Thiomersal on trial: the theory that vaccines cause autism goes to court". Slate. Retrieved 2008-01-30.
^ "Testosterone regulation". Research Autism. 2007-05-07. Retrieved 2015-04-09.
^ ^a ^b "Maryland medical board upholds autism doctor's suspension". Chicago Tribune. May 11, 2011.
^ "John and Jane Doe v. Ortho-Clinical Diagnostics, Inc", US District Court for the Middle District of North Carolina, July 6, 2006
^ "Dr. Mark Geier Severely Criticized", Stephen Barrett, M.D., Casewatch.org
^ Mills S, Jones T (2009-05-21). "Physician team's crusade shows cracks". Chicago Tribune. Retrieved 2009-05-21.
^ 'Miracle drug' called junk science: Powerful castration drug pushed for autistic children, but medical experts denounce unproven claims, Chicago Tribune, May 21, 2009
^ http://www.rxlist.com/lupron-side-effects-drug-center.htm
^ https://nwhn.org/lupron®-–-what-does-it-do-women’s-health

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)
Lupron victims hub, website against use of this drug.

UpToDate Contents

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1. 思春期における多嚢胞性卵巣症候群の診断的評価 diagnostic evaluation of polycystic ovary syndrome in adolescents
2. 転移性ホルモン受容体陽性乳癌に対する治療アプローチ：内分泌療法 treatment approach to metastatic hormone receptor positive breast cancer endocrine therapy
3. 子宮内膜症の長期治療を目的としたゴナドトロピン放出ホルモンアゴニスト gonadotropin releasing hormone agonists for long term treatment of endometriosis
4. 去勢感受性前立腺癌の初期全身療法 initial systemic therapy for castration sensitive prostate cancer
5. 思春期早発症の治療 treatment of precocious puberty

English Journal

Effects of chemical castration on sex offenders in relation to the kinetics of serum testosterone recovery: implications for dosing schedule.

Koo KC1, Ahn JH, Hong SJ, Lee JW, Chung BH.Author information 1Department of Urology and Urological Science Institute, Yonsei University College of Medicine, Seoul, Korea.AbstractINTRODUCTION: A growing number of countries are adopting chemical castration as treatment and penalty for sex offenders.
The journal of sexual medicine.J Sex Med.2014 May;11(5):1316-24. doi: 10.1111/jsm.12492. Epub 2014 Feb 27.
INTRODUCTION: A growing number of countries are adopting chemical castration as treatment and penalty for sex offenders.AIM: The aim of this study is to evaluate the outcome of chemical castration of sexual offenders with a focus on the kinetics of serum testosterone (T) recovery.METHODS: This prosp
PMID 24571582

Detection and effects on serum and urine steroid and LH of repeated GnRH analog (leuprolide) stimulation.

Handelsman DJ1, Idan A2, Grainger J3, Goebel C3, Turner L2, Conway AJ4.Author information 1Andrology Department, Concord Hospital, Sydney, NSW 2139, Australia; ANZAC Research Institute, University of Sydney, Sydney, NSW 2139, Australia. Electronic address: djh@anzac.edu.au.2Andrology Department, Concord Hospital, Sydney, NSW 2139, Australia.3Australian Sports Drug Testing Laboratory, National Measurement Institute, Sydney, NSW 2139, Australia.4Andrology Department, Concord Hospital, Sydney, NSW 2139, Australia; ANZAC Research Institute, University of Sydney, Sydney, NSW 2139, Australia.AbstractNon-steroidal drugs that increase endogenous testosterone (T) may be used to exploit ergogenic effects of androgens in power sports. While superactive GnRH analog use is suspected, neither screening nor detection tests are developed. This study aimed to determine if (a) stimulation for 5 days by leuprolide (a superactive GnRH analog) of serum and urine steroids and urine LH is reproducible at a 2 week interval, (b) nandrolone decanoate (ND) co-administration masks responses to leuprolide administration, (c) performance of urine measurement of leuprolide and M1, its major metabolite, as a detection test. Healthy men were randomized into a 4 week parallel group, open label clinical study in which all men had daily sc injections of leuprolide (1mg) for 4 days in the 1st and 3rd weeks with hormone-free 2nd and 4th weeks. In the 3rd week, men were randomized to either ND injections or no extra treatment. Serum steroids were determined by liquid chromatography, tandem mass spectrometry (LC-MS), urine steroids by gas chromatography, mass spectrometry (GC-MS), urine leuprolide and M1 by high resolution LC-MS and urine LH by immunoassay. Leuprolide stimulated striking, reproducible increases in serum and urine LH and steroids (serum T, dihydroT (DHT), 3α diol; urine T, epitestosterone (E) and androsterone (A). ND suppressed basal serum T, E2, 3α diol, and urinary E but did not mask or change the magnitude of responses to leuprolide. Urine leuprolide and M1 measurement had 100% sensitivity and specificity in detecting leuprolide administration up to one day after cessation of injections with the detection window between 1 and 3 days after last dose. Screening using urine steroid and LH measurements, optimally by urinary log10(LHxT), correctly classified 82% of urine samples. It is concluded that leuprolide stimulation of endogenous testosterone is reproducible after a 10-day interval, is not masked by ND and is reliably detected by urine leuprolide or M1 measurement for at least 1 day after administration.
The Journal of steroid biochemistry and molecular biology.J Steroid Biochem Mol Biol.2014 May;141:113-20. doi: 10.1016/j.jsbmb.2014.01.011. Epub 2014 Feb 2.
Non-steroidal drugs that increase endogenous testosterone (T) may be used to exploit ergogenic effects of androgens in power sports. While superactive GnRH analog use is suspected, neither screening nor detection tests are developed. This study aimed to determine if (a) stimulation for 5 days by leu
PMID 24495617

Unrecognized kinetics of serum testosterone: impact on short-term androgen deprivation therapy for prostate cancer.

Koo KC1, Lee DH2, Kim KH2, Lee SH2, Hong CH2, Hong SJ2, Chung BH2.Author information 1Department of Urology and Urological Science Institute, Yonsei University College of Medicine, Seoul, Korea. ; Sex Offender Treatment and Rehabilitation Center, National Forensic Hospital, Gongju, Korea.2Department of Urology and Urological Science Institute, Yonsei University College of Medicine, Seoul, Korea.AbstractPURPOSE: To evaluate the kinetics of serum testosterone (T) recovery following short-term androgen deprivation therapy (ADT), as the understanding thereof is essential for the proper management of prostate cancer (PCa), especially intermittent ADT.
Yonsei medical journal.Yonsei Med J.2014 May 1;55(3):570-5. doi: 10.3349/ymj.2014.55.3.570. Epub 2014 Apr 1.
PURPOSE: To evaluate the kinetics of serum testosterone (T) recovery following short-term androgen deprivation therapy (ADT), as the understanding thereof is essential for the proper management of prostate cancer (PCa), especially intermittent ADT.MATERIALS AND METHODS: This prospective analysis inc
PMID 24719121

Japanese Journal

経尿道的膀胱腫瘍切除術及びホルモン療法にて治療を行った膀胱子宮内膜症の1例

小玉美智子,平松宏祐,金容輝,奥野健太郎,古元淑子,伏見博彰,竹村昌彦
日本産科婦人科内視鏡學會雜誌 = The journal of the Japan Endoscopy Society of Obstetrics and Gynecology 25(2), 395-398, 2009-12-01
… The administration of leuprolide acetate followed by genogest successfully reduced the tumor size and alleviated the symptoms for 14 months. …
NAID 10026519527

Comparison of the effects of cetrorelix, a GnRH antagonist, and leuprolide, a GnRH agonist, on experimental endometriosis

ALTINTAS Devrim,KOKCU Arif,TOSUN Migraci,CETINKAYA Mehmet B.,KANDEMIR Bedri
The journal of obstetrics and gynaecology research 34(6), 1014-1019, 2008-12-01
NAID 10023917711

Related Pictures

Leuprolide (leuproreline) Leuprolide Acetate Injection (Lupron) Leuprolide 2 Week Kit* leuprolide acetate leuprolide acetate Leuprolide Injection Medlineplus Drug Drugs reference index « leuprolide » Leuprolide acetate | Bad Drug LEUPROLIDE ACETATE (Sun Pharma Global Inc

★リンクテーブル★

リンク元	「ロイプロリド」「リュープロン」

「ロイプロリド」

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; category	X;
Legal status	℞ (Prescription only);
Routes of; administration	Implant / Injection
Pharmacokinetic data
Biological half-life	3 hours
Excretion	Renal
Identifiers
CAS Registry Number	53714-56-0
ATC code	L02AE02
PubChem	CID: 441410
IUPHAR/BPS	1175
DrugBank	DB00007
UNII	EFY6W0M8TG
KEGG	D08113
ChEMBL	CHEMBL1201199
Chemical data
Formula	C59H84N16O12
Molecular mass	1209.4 g/mol
(what is this?) (verify)

　　[★]

英: leuprolide
同: リュープロリド
化: leuprolide acetate
関: リュープロレリン、リュープロン

[show details]

ロイプロリド : 約 5,100 件
リュープロリド : 約 1,420 件

「リュープロン」

　　[★]

商: Lupron
関: リュープロレリン leuprorelin、ロイプロリド leuprolide

商品名
LH-RH作動薬;前立腺癌および閉経前乳癌治療;子宮内膜症治療
日本での販売なし？

[pmid16176939-1] Crosignani PG, Luciano A, Ray A, Bergqvist A (January 2006). "Subcutaneous depot medroxyprogesterone acetate versus leuprolide acetate in the treatment of endometriosis-associated pain". Human reproduction (Oxford, England) 21 (1): 248–56. doi:10.1093/humrep/dei290. PMID 16176939.

[pmid16449344-2] 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): 1862–7. doi:10.1210/jc.2005-1500. PMID 16449344.

[3] Saleh F, Niel T, Fishman M (2004). "Treatment of paraphilia in young adults with leuprolide acetate: a preliminary case report series". J Forensic Sci 49 (6): 1343–8. doi:10.1520/JFS2003035. PMID 15568711.

[4] Schober JM, Byrne PM, Kuhn PJ. (2006). "Leuprolide acetate is a familiar drug that may modify sex-offender behaviour: the urologist's role.". BJU international 97 (4): 684–6. doi:10.1111/j.1464-410X.2006.05975.x. PMID 16536753.

[5] Schober JM, Kuhn PJ, Kovacs PG, Earle JH, Byrne PM, Fries RA. (2005). "Leuprolide acetate suppresses pedophilic urges and arousability.". Archives of Sexual Behavior 34 (6): 691–705. doi:10.1007/s10508-005-7929-2. PMID 16362253.

[6] Doraiswamy PM, Xiong GL. (2006). "Pharmacological strategies for the prevention of Alzheimer's disease". Expert Opin Pharmacother 7 (1): 1–10. doi:10.1517/14656566.7.1.1. PMID 16370917.

[WolfeMash2008-7] David A. Wolfe; Eric J. Mash (9 October 2008). Behavioral and Emotional Disorders in Adolescents: Nature, Assessment, and Treatment. Guilford Press. pp. 556–. ISBN 978-1-60623-115-9. Retrieved 24 March 2012.

[8] Desmarchelier M, Lair S, Dunn M, Langlois I.Primary hyperaldosteronism in a domestic ferret with an adrenocortical adenoma. J Am Vet Med Assoc. 2008 Oct 15;233(8):1297-301.PMID:19180717

[9] Boari A, Papa V, Di Silverio F, Aste G, Olivero D, Rocconi F. Type 1 diabetes mellitus and hyperadrenocorticism in a ferret. Vet Res Commun. 2010 Jun;34 Suppl 1:S107-10. doi: 10.1007/s11259-010-9369-2.PMID:20446034.

[10] Geier M, Geier D (2005). "The potential importance of steroids in the treatment of autistic spectrum disorders and other disorders involving mercury toxicity". Med Hypotheses 64 (5): 946–54. doi:10.1016/j.mehy.2004.11.018. PMID 15780490.

[11] Allen A (2007-05-28). "Thiomersal on trial: the theory that vaccines cause autism goes to court". Slate. Retrieved 2008-01-30.

[12] "Testosterone regulation". Research Autism. 2007-05-07. Retrieved 2015-04-09.

[chicagotribune-13] "Maryland medical board upholds autism doctor's suspension". Chicago Tribune. May 11, 2011.

[14] "John and Jane Doe v. Ortho-Clinical Diagnostics, Inc", US District Court for the Middle District of North Carolina, July 6, 2006

[15] "Dr. Mark Geier Severely Criticized", Stephen Barrett, M.D., Casewatch.org

[16] Mills S, Jones T (2009-05-21). "Physician team's crusade shows cracks". Chicago Tribune. Retrieved 2009-05-21.

[17] 'Miracle drug' called junk science: Powerful castration drug pushed for autistic children, but medical experts denounce unproven claims, Chicago Tribune, May 21, 2009

[18] ttp://www.rxlist.com/lupron-side-effects-drug-center.htm

[19] ttps://nwhn.org/lupron®-–-what-does-it-do-women’s-health

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leuprolide