Leuprorelin

Last updated

Leuprorelin
Leuprorelin.svg
Leuprorelin ball-and-stick.png
Clinical data
Trade names Lupron, Eligard, Lucrin, Lupaneta, others
Other namesleuprolide, leuprolidine, A-43818, Abbott-43818, DC-2-269, TAP-144
AHFS/Drugs.com Monograph
MedlinePlus a685040
License data
Pregnancy
category
  • AU:D
Routes of
administration 		implant, subcutaneous, intramuscular
Drug class GnRH analogue; GnRH agonist; Antigonadotropin
ATC code
Legal status
Legal status
Pharmacokinetic data
Elimination half-life 3 hours
Excretion Kidney
Identifiers
  • 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
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.161.466 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C59H84N16O12
Molar mass 1209.421 g·mol−1
3D model (JSmol)
  • CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](Cc2ccc(cc2)O)NC(=O)[C@H](CO)NC(=O)[C@H](Cc3c[nH]c4c3cccc4)NC(=O)[C@H](Cc5c[nH]cn5)NC(=O)[C@@H]6CCC(=O)N6
  • InChI=1S/C59H84N16O12/c1-6-63-57(86)48-14-10-22-75(48)58(87)41(13-9-21-64-59(60)61)68-51(80)42(23-32(2)3)69-52(81)43(24-33(4)5)70-53(82)44(25-34-15-17-37(77)18-16-34)71-56(85)47(30-76)74-54(83)45(26-35-28-65-39-12-8-7-11-38(35)39)72-55(84)46(27-36-29-62-31-66-36)73-50(79)40-19-20-49(78)67-40/h7-8,11-12,15-18,28-29,31-33,40-48,65,76-77H,6,9-10,13-14,19-27,30H2,1-5H3,(H,62,66)(H,63,86)(H,67,78)(H,68,80)(H,69,81)(H,70,82)(H,71,85)(H,72,84)(H,73,79)(H,74,83)(H4,60,61,64)/t40-,41-,42-,43+,44-,45-,46-,47-,48-/m0/s1 X mark.svgN
  • Key:GFIJNRVAKGFPGQ-LIJARHBVSA-N X mark.svgN
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Leuprorelin, also known as leuprolide, is a manufactured version of a hormone used to treat prostate cancer, breast cancer, endometriosis, uterine fibroids, as part of transgender hormone therapy, for early puberty, or to perform chemical castration of violent sex offenders. [9] [10] [11] It is given by injection into a muscle or under the skin. [9]

Contents

Leuprorelin is in the gonadotropin-releasing hormone (GnRH) analogue family of medications. [9] It works by decreasing gonadotropins and therefore decreasing testosterone and estradiol. [9] Common side effects include hot flashes, unstable mood, trouble sleeping, headaches, and pain at the site of injection. [9] Other side effects may include high blood sugar, allergic reactions, and problems with the pituitary gland. [9] Use during pregnancy may harm foetal development. [9]

Leuprorelin was patented in 1973 and approved for medical use in the United States in 1985. [9] [12] It is on the World Health Organization's List of Essential Medicines. [10] It is sold under the brand name Lupron among others. [9]

Medical use

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 [13] or uterine fibroids.

It may be used for precocious 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 may be used to reduce the risk of premature ovarian failure in women receiving cyclophosphamide for chemotherapy. [16]

Along with triptorelin and goserelin, it has been used to delay puberty in transgender youth until they are old enough to begin hormone replacement therapy. [17] Researchers have recommended puberty blockers after age 12, when the person has developed to Tanner stages 2–3, and then cross-sex hormones treatment at age 16. This use of the drug is off-label, however, not having been approved by the Food and Drug Administration and without data on long-term effects of this use.[ needs update ] [18]

They are also sometimes used as alternatives to antiandrogens like spironolactone and cyproterone acetate for suppressing testosterone production in transgender women. [19] [20] [21] It also is used for suppressing estrogen production in transgender men. [22]

It is considered a possible treatment for paraphilias. [23] Leuprorelin has been tested as a treatment for reducing sexual urges in pedophiles and other cases of paraphilia. [24] [25]

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, [7] 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 of gynecomastia 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]

Pharmacology

Mechanism of action

Leuprorelin is a gonadotropin-releasing hormone (GnRH) analogue acting as an agonist at pituitary GnRH receptors. GnRH receptor agonists initially increase the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) by the anterior pituitary and increased serum estradiol and testosterone levels via the hypothalamic–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 to hypogonadism and a dramatic reduction in estradiol and testosterone levels regardless of sex. [29] [30]

Available forms

Leuprorelin is available in the following forms, among others: [31] [32] [33] [34] [35]

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. [42] [43] It was initially marketed only for daily injection, but a depot injection formulation was introduced in 1989. [43]

Approvals

Society and culture

On 24 March 2022, the Committee for Medicinal Products for Human Use (CHMP) of the European 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. [46] The applicant for this medicinal product is Accord Healthcare S.L.U. [46] Leuprorelin was approved for medical use in the European Union in May 2022. [8] [47]

Names

Leuprorelin is the generic name of the drug and its INN Tooltip International Nonproprietary Name and BAN Tooltip British Approved Name, while leuprorelin acetate is its BANM Tooltip British Approved Name and JAN Tooltip Japanese Accepted Name, leuprolide acetate is its USAN Tooltip United States Adopted Name and USP Tooltip United States Pharmacopeia, leuprorelina is its DCIT Tooltip Denominazione Comune Italiana, and leuproréline is its DCF Tooltip Dénomination Commune Française. [48] [49] [50] [51] It is also known by its developmental code names A-43818, Abbott-43818, DC-2-269, and TAP-144. [48] [49] [50] [51]

Leuprorelin is marketed by Bayer AG under the brand name Viadur, [6] by Tolmar under the brand names Eligard and Fensolvi, [4] [5] and by TAP Pharmaceuticals (1985–2008), by Varian Darou Pajooh under the brand name Leupromer and Abbott Laboratories (2008–present) under the brand name Lupron.

Controversy

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 state medicare fraud and illegal marketing of the drug leuprorelin. [52] TAP paid a total of $875 million, which was a record high at the time. [53] [54] 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. [54] The case arose under the False Claims Act with claims filed by Douglas Durand, a former TAP vice president of sales, and Joseph Gerstein, a doctor at Tufts University's HMO practice. [53] Durand, Gerstein, and Tufts shared $95 million of the settlement. [53]

There have since been various suits concerning leuprorelin use, none successful. [55] [56] 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. [57] 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. [58]

"Lupron protocol"

A 2005 paper in the controversial and non-peer reviewed journal Medical Hypotheses suggested leuprorelin as a possible treatment for autism, [59] 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 leuprorelin can help cure autism by lowering the testosterone levels and thereby mercury levels. [60] However, there is no scientifically valid or reliable research to show its effectiveness in treating autism. [61] This use has been termed the "Lupron protocol" [62] 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 [63] [64] [65] and has had his medical license revoked. [62] Medical experts have referred to Geier's claims as "junk science". [66]

Research

As of 2006, leuprorelin was under investigation for possible use in the treatment of mild to moderate Alzheimer's disease. [67] [ needs update ]

A by mouth formulation of leuprorelin is under development for the treatment of endometriosis. [68] It was also under development for the treatment of precocious puberty, prostate cancer, and uterine fibroids, but development for these uses was discontinued. [68] The formulation has the tentative brand name Ovarest. [68] As of July 2018, it is in phase II clinical trials for endometriosis. [68] [ needs update ]

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, [69] and one with concurrent diabetes mellitus. [70] It is also used to treat pet parrots with chronic egg laying behavior. [71]

Related Research Articles

<span class="mw-page-title-main">Antiandrogen</span> Class of pharmaceutical drugs

Antiandrogens, also known as androgen antagonists or testosterone blockers, are a class of drugs that prevent androgens like testosterone and dihydrotestosterone (DHT) from mediating their biological effects in the body. They act by blocking the androgen receptor (AR) and/or inhibiting or suppressing androgen production. They can be thought of as the functional opposites of AR agonists, for instance androgens and anabolic steroids (AAS) like testosterone, DHT, and nandrolone and selective androgen receptor modulators (SARMs) like enobosarm. Antiandrogens are one of three types of sex hormone antagonists, the others being antiestrogens and antiprogestogens.

<span class="mw-page-title-main">Diethylstilbestrol</span> Chemical compound

Diethylstilbestrol (DES), also known as stilbestrol or stilboestrol, is a nonsteroidal estrogen medication, which is presently rarely used. In the past, it was widely used for a variety of indications, including pregnancy support for those with a history of recurrent miscarriage, hormone therapy for menopausal symptoms and estrogen deficiency, treatment of prostate cancer and breast cancer, and other uses. By 2007, it was only used in the treatment of prostate cancer and breast cancer. In 2011, Hoover and colleagues reported on adverse health outcomes linked to DES including infertility, miscarriage, ectopic pregnancy, preeclampsia, preterm birth, stillbirth, infant death, menopause prior to age 45, breast cancer, cervical cancer, and vaginal cancer. While most commonly taken by mouth, DES was available for use by other routes as well, for instance, vaginal, topical, and by injection.

<span class="mw-page-title-main">Goserelin</span> Chemical compound

Goserelin, sold under the brand name Zoladex among others, is a medication which is used to suppress production of the sex hormones, particularly in the treatment of breast and prostate cancer. It is an injectable gonadotropin releasing hormone agonist.

<span class="mw-page-title-main">Bicalutamide</span> Prostate cancer treatment

Bicalutamide, sold under the brand name Casodex among others, is an antiandrogen medication that is primarily used to treat prostate cancer. It is typically used together with a gonadotropin-releasing hormone (GnRH) analogue or surgical removal of the testicles to treat metastatic prostate cancer (mPC). To a lesser extent, it is used at high doses for locally advanced prostate cancer (LAPC) as a monotherapy without castration. Bicalutamide was also previously used as monotherapy to treat localized prostate cancer (LPC), but authorization for this use was withdrawn following unfavorable trial findings. Besides prostate cancer, bicalutamide is limitedly used in the treatment of excessive hair growth and scalp hair loss in women, as a puberty blocker and component of feminizing hormone therapy for transgender girls and women, to treat gonadotropin-independent early puberty in boys, and to prevent overly long-lasting erections in men. It is taken by mouth.

<span class="mw-page-title-main">Nafarelin</span> Pharmaceutical drug

Nafarelin, sold under the brand name Synarel among others, is a gonadotropin-releasing hormone agonist medication which is used in the treatment of endometriosis and early puberty. It is also used to treat uterine fibroids, to control ovarian stimulation in in vitro fertilization (IVF), and as part of transgender hormone therapy. The medication is used as a nasal spray two to three times per day.

<span class="mw-page-title-main">Buserelin</span> Chemical compound

Buserelin, sold under the brand name Suprefact among others, is a medication which is used primarily in the treatment of prostate cancer and endometriosis. It is also used for other indications such as the treatment of premenopausal breast cancer, uterine fibroids, and early puberty, in assisted reproduction for female infertility, and as a part of transgender hormone therapy. In addition, buserelin is used in veterinary medicine. The medication is typically used as a nasal spray three times per day, but is also available for use as a solution or implant for injection into fat.

<span class="mw-page-title-main">Polyestradiol phosphate</span> Chemical compound

Polyestradiol phosphate (PEP), sold under the brand name Estradurin, is an estrogen medication which is used primarily in the treatment of prostate cancer in men. It is also used in women to treat breast cancer, as a component of hormone therapy to treat low estrogen levels and menopausal symptoms, and as a component of feminizing hormone therapy for transgender women. It is given by injection into muscle once every four weeks.

<span class="mw-page-title-main">Triptorelin</span> GnRH-agonist

Triptorelin, sold under the brand name Decapeptyl among others, is a medication that acts as an agonist analog of gonadotropin-releasing hormone, repressing expression of luteinizing hormone (LH) and follicle-stimulating hormone (FSH).

<span class="mw-page-title-main">Gonadotropin-releasing hormone agonist</span> Drug class affecting sex hormones

A gonadotropin-releasing hormone agonist is a type of medication which affects gonadotropins and sex hormones. They are used for a variety of indications including in fertility medicine and to lower sex hormone levels in the treatment of hormone-sensitive cancers such as prostate cancer and breast cancer, certain gynecological disorders like heavy periods and endometriosis, high testosterone levels in women, early puberty in children, as a part of transgender hormone therapy, and to delay puberty in transgender youth among other uses. It is also used in the suppression of spontaneous ovulation as part of controlled ovarian hyperstimulation, an essential component in IVF. GnRH agonists are given by injections into fat, as implants placed into fat, and as nasal sprays.

<span class="mw-page-title-main">Gonadotropin-releasing hormone antagonist</span> Class of medications

Gonadotropin-releasing hormone antagonists are a class of medications that antagonize the gonadotropin-releasing hormone receptor and thus the action of gonadotropin-releasing hormone (GnRH). They are used in the treatment of prostate cancer, endometriosis, uterine fibroids, female infertility in assisted reproduction, and for other indications.

<span class="mw-page-title-main">Cetrorelix</span> Drug used in IVF procedures

Cetrorelix, or cetrorelix acetate, sold under the brand name Cetrotide, is an injectable gonadotropin-releasing hormone (GnRH) antagonist. A synthetic decapeptide, it is used in assisted reproduction to inhibit premature luteinizing hormone surges The drug works by blocking the action of GnRH upon the pituitary, thus rapidly suppressing the production and action of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). In addition, cetrorelix can be used to treat hormone-sensitive cancers of the prostate and breast and some benign gynaecological disorders. It is administered as either multiple 0.25 mg daily subcutaneous injections or as a single-dose 3 mg subcutaneous injection. The duration of the 3 mg single dose is four days; if human chorionic gonadotropin (hCG) is not administered within four days, a daily 0.25 mg dose is started and continued until hCG is administered.

<span class="mw-page-title-main">Abiraterone acetate</span> Chemical compound

Abiraterone acetate, sold under the brand name Zytiga among others, is a medication used to treat prostate cancer. Specifically it is used together with a corticosteroid for metastatic castration-resistant prostate cancer (mCRPC) and metastatic high-risk castration-sensitive prostate cancer (mCSPC). It should either be used following removal of the testicles or along with a gonadotropin-releasing hormone (GnRH) analog. It is taken by mouth.

Feminizing hormone therapy, also known as transfeminine hormone therapy, is hormone therapy and sex reassignment therapy to change the secondary sex characteristics of transgender people from masculine or androgynous to feminine. It is a common type of transgender hormone therapy and is used to treat transgender women and non-binary transfeminine individuals. Some, in particular intersex people, but also some non-transgender people, take this form of therapy according to their personal needs and preferences.

<span class="mw-page-title-main">Degarelix</span> Chemical compound

Degarelix, sold under the brand name Firmagon among others, is a hormonal therapy used in the treatment of prostate cancer.

<span class="mw-page-title-main">Deslorelin</span> Chemical compound

Deslorelin, sold under the brand names Ovuplant, SucroMate, and Suprelorin among others, is an injectable gonadotropin releasing hormone superagonist which is used in veterinary medicine for various indications.

<span class="mw-page-title-main">Cyproterone acetate</span> Chemical compound

Cyproterone acetate (CPA), sold alone under the brand name Androcur or with ethinylestradiol under the brand names Diane or Diane-35 among others, is an antiandrogen and progestin medication used in the treatment of androgen-dependent conditions such as acne, excessive body hair growth, early puberty, and prostate cancer, as a component of feminizing hormone therapy for transgender individuals, and in birth control pills. It is formulated and used both alone and in combination with an estrogen. CPA is taken by mouth one to three times per day.

<span class="mw-page-title-main">Relugolix</span> Chemical compound

Relugolix, sold under the brand names Orgovyx and Relumina among others, is a gonadotropin-releasing hormone antagonist medication which is used in the treatment of prostate cancer in men and uterine fibroids in women. It is taken by mouth.

The medical uses of bicalutamide, a nonsteroidal antiandrogen (NSAA), include the treatment of androgen-dependent conditions and hormone therapy to block the effects of androgens. Indications for bicalutamide include the treatment of prostate cancer in men, skin and hair conditions such as acne, seborrhea, hirsutism, and pattern hair loss in women, high testosterone levels in women, hormone therapy in transgender women, as a puberty blocker to prevent puberty in transgender girls and to treat early puberty in boys, and the treatment of long-lasting erections in men. It may also have some value in the treatment of paraphilias and hypersexuality in men.

Drugs and sexual desire is about sexual desire being manipulated through drugs from various approaches. Sexual desire is generated under the effects from sex hormones and microcircuits from brain regions. Neurotransmitters play essential roles in stimulating and inhibiting the processes that lead to libido production in both men and women. For instance, a positive stimulation is modulated by dopamine from the medial preoptic area in the hypothalamus and norepinephrine. At the same time, inhibition occurs when prolactin and serotonin are released for action.

Leuprorelin/norethisterone acetate, also known as leuprolide/norethindrone acetate and sold under the brand name Lupaneta Pack, is a co-packaged medication used to treat endometriosis. It contains leuprorelin as the acetate, a gonadotropin-releasing hormone agonist, and norethisterone acetate, a progestin. The leuprorelin is given by intramuscular injection and the norethisterone acetate is taken by mouth.

References

  1. ↑ ELIGARD (Mundipharma Pty Ltd) Department of Health and Aged Care. Retrieved 30 March 2023
  2. ↑ "Product monograph brand safety updates". Health Canada. February 2024. Retrieved 24 March 2024.
  3. 1 2 3 "Lupron- leuprolide acetate lupron- leuprolide acetate injection, solution". DailyMed. Archived from the original on 27 May 2021. Retrieved 27 May 2021.
  4. 1 2 3 4 "Eligard- leuprolide acetate kit". DailyMed. 26 March 2020. Archived from the original on 10 August 2020. Retrieved 20 August 2020.
  5. 1 2 3 4 "Fensolvi- leuprolide acetate kit". DailyMed. 3 June 2020. Archived from the original on 26 October 2020. Retrieved 20 August 2020.
  6. 1 2 3 4 "Viadur- leuprolide acetate". DailyMed. Archived from the original on 27 May 2021. Retrieved 26 May 2021.
  7. 1 2 3 4 "Lupron Depot- leuprolide acetate kit". DailyMed. Archived from the original on 27 May 2021. Retrieved 27 May 2021.
  8. 1 2 "Camcevi EPAR". European Medicines Agency (EMA). 22 March 2022. Retrieved 21 June 2022.
  9. 1 2 3 4 5 6 7 8 9 "Leuprolide Acetate". The American Society of Health-System Pharmacists. Archived from the original on 23 December 2016. Retrieved 8 December 2016.
  10. 1 2 World 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.
  11. ↑ Silvani M, Mondaini N, Zucchi A (September 2015). "Androgen deprivation therapy (castration therapy) and pedophilia: What's new". Archivio Italiano di Urologia, Andrologia. 87 (3): 222–226. doi: 10.4081/aiua.2015.3.222 . hdl: 11568/1073189 . PMID   26428645. S2CID   5181746.
  12. ↑ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 514. ISBN   978-3-527-60749-5. Archived from the original on 20 June 2021. Retrieved 19 September 2020.
  13. ↑ 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. 21 (1): 248–56. doi: 10.1093/humrep/dei290 . PMID   16176939.
  14. ↑ 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. PMID   16449344.
  15. ↑ "Lupron, used to halt puberty in children, may cause lasting health problems". STAT. 2 February 2017. Archived from the original on 7 December 2020. Retrieved 7 December 2020.
  16. ↑ Clowse ME, Behera MA, Anders CK, Copland S, Coffman CJ, Leppert PC, Bastian LA (March 2009). "Ovarian preservation by GnRH agonists during chemotherapy: a meta-analysis". Journal of Women's Health. 18 (3): 311–19. doi:10.1089/jwh.2008.0857. PMC   2858300 . PMID   19281314.
  17. ↑ Wolfe DA, Mash EJ (2008). Behavioral and Emotional Disorders in Adolescents: Nature, Assessment, and Treatment. Guilford Press. pp. 556–. ISBN   978-1-60623-115-9. Archived from the original on 2 July 2014. Retrieved 24 March 2012.
  18. ↑ 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. PMID   19213192. S2CID   22526704.
  19. ↑ Gava G, Mancini I, Alvisi S, Seracchioli R, Meriggiola MC (December 2020). "A comparison of 5-year administration of cyproterone acetate or leuprolide acetate in combination with estradiol in transwomen". European Journal of Endocrinology. 183 (6): 561–569. doi: 10.1530/EJE-20-0370 . PMID   33055297. S2CID   222832326.
  20. ↑ 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. PMID   26932202. S2CID   30150360.
  21. ↑ "Hormone Therapy in Gender Dysphoria" (PDF). NHS Guideline. Table 1
  22. ↑ "Hormone Therapy in Gender Dysphoria" (PDF). NHS Guideline. Table 1
  23. ↑ 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. PMID   15568711.
  24. ↑ 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): 684–86. doi:10.1111/j.1464-410X.2006.05975.x. PMID   16536753. S2CID   19365144.
  25. ↑ 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. S2CID   24065433.
  26. ↑ "Common Side Effects of Lupron (Leuprolide Acetate Injection) Drug Center". Archived from the original on 29 July 2015. Retrieved 26 July 2015.[ full citation needed ]
  27. ↑ 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. PMID   16321765.
  28. ↑ Jewett C (2 February 2017). "Women Fear Drug They Used To Halt Puberty Led To Health Problems". Kaiser Health Network. Retrieved 17 November 2022.
  29. ↑ Mutschler E, Schäfer-Korting M (2001). Arzneimittelwirkungen (in German) (8 ed.). Stuttgart: Wissenschaftliche Verlagsgesellschaft. pp. 372–73. ISBN   978-3-8047-1763-3.
  30. ↑ Wuttke W, Jarry H, Feleder C, Moguilevsky J, Leonhardt S, Seong JY, Kim K (1996). "The neurochemistry of the GnRH pulse generator". Acta Neurobiologiae Experimentalis. 56 (3): 707–13. doi:10.55782/ane-1996-1176. PMID   8917899. Archived from the original on 8 December 2015.
  31. ↑ Teutonico D, Montanari S, Ponchel G (March 2012). "Leuprolide acetate: pharmaceutical use and delivery potentials". Expert Opin Drug Deliv. 9 (3): 343–54. doi:10.1517/17425247.2012.662484. PMID   22335366. S2CID   30843402.
  32. ↑ Butler SK, Govindan R (2010). Essential Cancer Pharmacology: The Prescriber's Guide. Lippincott Williams & Wilkins. pp. 262–. ISBN   978-1-60913-704-5. Archived from the original on 13 June 2021. Retrieved 29 August 2018.
  33. ↑ Lehne RA, Rosenthal R (2014). "Anticancer drugs II: Hormonal agents, targeted drugs, and other noncytotoxic anticancer drugs". Pharmacology for Nursing Care. Elsevier Health Sciences. pp. 1296–. ISBN   978-0-323-29354-9. Archived from the original on 11 August 2021. Retrieved 29 August 2018.
  34. ↑ Su X, Hapani S, Wu S (2011). "An Update on Androgen-Deprivation Therapy for Advanced Prostate Cancer". Prostate Cancer. Demos Medical Publishing. pp. 503–512. ISBN   978-1-935281-91-7. Archived from the original on 13 June 2021. Retrieved 29 August 2018.
  35. ↑ "Leuprolide Long-acting – Medical Mutual" (PDF). 21 May 2020. Archived from the original on 11 August 2021. Retrieved 11 August 2021.
  36. ↑ "Lupron Depot- leuprolide acetate kit". DailyMed. Archived from the original on 27 May 2021. Retrieved 27 May 2021.
  37. ↑ "Lupron Depot- leuprolide acetate kit". DailyMed. Archived from the original on 27 May 2021. Retrieved 27 May 2021.
  38. ↑ "Lupron Depot-Ped- leuprolide acetate kit". DailyMed. Archived from the original on 27 May 2021. Retrieved 27 May 2021.
  39. ↑ Ibrahim A (25 May 2021). "Camcevi (leuprolide) NDA Approval" (PDF). U.S. Food and Drug Administration. Archived (PDF) from the original on 27 May 2021. Retrieved 27 May 2021.
  40. ↑ "Lupaneta Pack- leuprolide acetate and norethindrone acetate kit". DailyMed. Archived from the original on 27 May 2021. Retrieved 27 May 2021.
  41. ↑ "Lupaneta Pack- leuprolide acetate and norethindrone acetate kit". DailyMed. Archived from the original on 27 May 2021. Retrieved 27 May 2021.
  42. 1 2 Jamil GL (2013). Rethinking the Conceptual Base for New Practical Applications in Information Value and Quality. IGI Global. pp. 111–. ISBN   978-1-4666-4563-9. Archived from the original on 13 June 2021. Retrieved 27 August 2018.
  43. 1 2 3 Hara T (2003). Innovation in the Pharmaceutical Industry: The Process of Drug Discovery and Development. Edward Elgar Publishing. pp. 106–07. ISBN   978-1-84376-566-0. Archived from the original on 13 June 2021. Retrieved 27 August 2018.
  44. ↑ Esber EC (21 May 1985). "Lupron (Leuprolide acetate) NDA approval" (PDF). U.S. Food and Drug Administration. Archived (PDF) from the original on 10 April 2021. Retrieved 27 May 2021.
  45. ↑ Ernst D (4 May 2020). "Fensolvi Approved for Central Precocious Puberty". MPR. Archived from the original on 5 November 2020. Retrieved 19 August 2020.
  46. 1 2 "Camcevi: Pending EC decision". European Medicines Agency (EMA). 24 March 2022. Retrieved 28 March 2022. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  47. ↑ "Camcevi Product information". Union Register of medicinal products. Retrieved 3 March 2023.
  48. 1 2 Elks J (2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 730–. ISBN   978-1-4757-2085-3. Archived from the original on 13 June 2021. Retrieved 25 February 2018.
  49. 1 2 Index Nominum 2000: International Drug Directory. Taylor & Francis. 2000. pp. 599–. ISBN   978-3-88763-075-1. Archived from the original on 13 June 2021. Retrieved 25 February 2018.
  50. 1 2 Morton IK, Hall JM (2012). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 164–. ISBN   978-9-401144-39-1. Archived from the original on 13 June 2021. Retrieved 25 February 2018.
  51. 1 2 "Leuprorelin". Drugs.com. Archived from the original on 25 February 2018. Retrieved 25 February 2018.
  52. ↑ Charatan F (October 2001). "Drug companies defrauded Medicare of millions". BMJ. 323 (7317): 828. doi:10.1136/bmj.323.7317.828a. PMC   1121385 . PMID   11597964.
  53. 1 2 3 Petersen M (4 October 2001). "2 Drug Makers to Pay $875 Million to Settle Fraud Case". The New York Times. ISSN   0362-4331 . Retrieved 24 January 2022.
  54. 1 2 "#513: 10-03-01 TAP PHARMACEUTICAL PRODUCTS INC. AND SEVEN OTHERS CHARGED WITH HEALTH CARE CRIMES COMPANY AGREES TO PAY $875 MILLION TO SETTLE CHARGES". www.justice.gov. Retrieved 24 January 2022.
  55. ↑ "What You Should Know About Lupron Class Action Lawsuit". Law Answer. 8 May 2021. Retrieved 28 February 2022.
  56. ↑ "Abbott, AbbVie Defeat Long-Running Lupron Bone, Joint Suit (1)". news.bloomberglaw.com. Retrieved 28 February 2022.
  57. ↑ "More women come forward with complaints about Lupron side effects". KTNV. 12 February 2019. Retrieved 28 February 2022.
  58. ↑ Center for Drug Evaluation and Research (30 September 2019). "January - March 2017 | Potential Signals of Serious Risks/New Safety Information Identified by the FDA Adverse Event Reporting System (FAERS)". FDA.
  59. ↑ 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.
  60. ↑ Allen A (28 May 2007). "Thiomersal on trial: the theory that vaccines cause autism goes to court". Slate. Archived from the original on 3 February 2008. Retrieved 30 January 2008.
  61. ↑ "Testosterone regulation". Research Autism. 7 May 2007. Archived from the original on 18 April 2015. Retrieved 9 April 2015.
  62. 1 2 Tsouderos T, Cohn M (11 May 2011). "Maryland medical board upholds autism doctor's suspension". Chicago Tribune . Archived from the original on 21 October 2011.
  63. ↑ "John and Jane Doe v. Ortho-Clinical Diagnostics, Inc" (PDF). US District Court for the Middle District of North Carolina. 6 July 2006. Archived from the original (PDF) on 6 March 2008.
  64. ↑ Barrett S (11 July 2012). "Dr. Mark Geier Severely Criticized". Casewatch.net. Archived from the original on 23 December 2020.
  65. ↑ Mills S, Jones T (21 May 2009). "Physician team's crusade shows cracks". Chicago Tribune. Archived from the original on 25 May 2009. Retrieved 21 May 2009.
  66. ↑ "'Miracle drug' called junk science: Powerful castration drug pushed for autistic children, but medical experts denounce unproven claims". Chicago Tribune . 21 May 2009. Archived from the original on 3 December 2013.
  67. ↑ Doraiswamy PM, Xiong GL (2006). "Pharmacological strategies for the prevention of Alzheimer's disease". Expert Opinion on Pharmacotherapy. 7 (1): 1–10. doi:10.1517/14656566.7.1.S1. PMID   16370917. S2CID   5546284.
  68. 1 2 3 4 "Leuprorelin oral - Enteris BioPharma". Adis Insight. Springer Nature Switzerland AG. Archived from the original on 4 November 2017. Retrieved 16 July 2018.
  69. ↑ 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. PMID   19180717.
  70. ↑ Boari A, Papa V, Di Silverio F, Aste G, Olivero D, Rocconi F (2010). "Type 1 diabetes mellitus and hyperadrenocorticism in a ferret". Veterinary Research Communications. 34 (Suppl 1): S107–10. doi: 10.1007/s11259-010-9369-2 . PMID   20446034.
  71. ↑ "Treatment of Chronic Egg Laying". Yarmouth Veterinary Center. Archived from the original on 24 November 2020. Retrieved 29 December 2020.

Further reading

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.