It may be used for
precocious puberty in both males and females,[15] 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.[16]
It is considered a possible treatment for
paraphilias.[24] Leuprorelin has been tested as a treatment for reducing sexual urges in
pedophiles and other cases of paraphilia.[25][26]
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,[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.[27] The rates of
gynecomastia with leuprorelin have been found to range from 3 to 16%.[28]
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.[29]
Pharmacology
Mechanism of action
Leuprorelin is a
gonadotropin-releasing hormone (GnRH)
analogue acting as an
agonist at
pituitaryGnRH 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.[30][31]
Available forms
Leuprorelin is available in the following forms, among others:[32][33][34][35][36]
Leuprorelin was discovered and first
patented in 1973 and was introduced for medical use in 1985.[43][44] It was initially marketed only for daily injection, but a
depot injection formulation was introduced in 1989.[44]
Lupron
depot for monthly intramuscular injection was approved by the FDA for
palliative treatment of advanced prostate cancer on 26 January 1989.[8]
Viadur was approved by the FDA for palliative treatment of advanced prostate cancer on 6 March 2000.[7]
Eligard was approved by the FDA for palliative treatment of advanced prostate cancer on 24 January 2002.[5]
Fensolvi was approved by the FDA for children with central precocious puberty on 4 May 2020.[6][46]
Society and culture
Legal status
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.[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]
Names
Leuprorelin is the
generic name of the drug and its
INNTooltip International Nonproprietary Name and
BANTooltip British Approved Name, while leuprorelin acetate is its
BANMTooltip British Approved Name and
JANTooltip Japanese Accepted Name, leuprolide acetate is its
USANTooltip United States Adopted Name and
USPTooltip United States Pharmacopeia, leuprorelina is its
DCITTooltip Denominazione Comune Italiana, and leuproréline is its
DCFTooltip 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 by
Bayer AG under the brand name Viadur,[7] by Tolmar under the brand names Eligard and Fensolvi,[5][6] 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.[53] TAP paid a total of $875 million, which was a
record 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 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.[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]
"Lupron protocol"
A 2005 paper in the controversial and non-
peer reviewed journal Medical Hypotheses suggested leuprorelin as a possible treatment for
autism,[60] 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.[61] However, there is no scientifically valid or reliable research to show its effectiveness in treating autism.[62] This use has been termed the "Lupron protocol"[63] 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[64][65][66] and has had his medical license revoked.[63] Medical experts have referred to Geier's claims as "junk science".[67]
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