Leuprolide
Encyclopedia
Leuprorelin or leuprolide acetate (USAN
) is a GnRH analog. Proper Sequence: Pyr-His-Trp-Ser-Tyr-D-Leu-Leu-Arg-Pro-NHEt (Pyr = L-Pyroglutamyl)
(LH) and follicle-stimulating hormone
(FSH) leading to hypogonadism
and thus a dramatic reduction in estradiol
and testosterone
levels in both sexes.
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 paraphilia
s.
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.
It also used for treatment of steroid abuse.
, 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".
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).
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.
United States Adopted Name
United States Adopted Names are unique nonproprietary names assigned to pharmaceuticals marketed in the United States. Each name is assigned by the USAN Council, which is co-sponsored by the American Medical Association , the United States Pharmacopeial Convention , and the American Pharmacists...
) 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 hormoneLuteinizing hormone
Luteinizing hormone is a hormone produced by the anterior pituitary gland. In females, an acute rise of LH called the LH surge triggers ovulation and development of the corpus luteum. In males, where LH had also been called interstitial cell-stimulating hormone , it stimulates Leydig cell...
(LH) and follicle-stimulating hormone
Follicle-stimulating hormone
Follicle-stimulating hormone is a hormone found in humans and other animals. It is synthesized and secreted by gonadotrophs of the anterior pituitary gland. FSH regulates the development, growth, pubertal maturation, and reproductive processes of the body. FSH and Luteinizing hormone act...
(FSH) leading to hypogonadism
Hypogonadism
Hypogonadism is a medical term for decreased functional activity of the gonads. Low testosterone is caused by a decline or deficiency in gonadal production of testosterone in males...
and thus a dramatic reduction in estradiol
Estradiol
Estradiol is a sex hormone. Estradiol is abbreviated E2 as it has 2 hydroxyl groups in its molecular structure. Estrone has 1 and estriol has 3 . Estradiol is about 10 times as potent as estrone and about 80 times as potent as estriol in its estrogenic effect...
and testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...
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 cancerProstate cancer
Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly...
or breast cancer
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
, estrogen-dependent conditions (such as endometriosis
Endometriosis
Endometriosis is a gynecological medical condition in which cells from the lining of the uterus appear and flourish outside the uterine cavity, most commonly on the ovaries. The uterine cavity is lined by endometrial cells, which are under the influence of female hormones...
or uterine fibroids
Uterine fibroids
A uterine fibroid is a benign tumor that originates from the smooth muscle layer and the accompanying connective tissue of the uterus.Fibroids are the most common benign tumors in...
), to treat precocious puberty
Precocious puberty
As a medical term, precocious puberty describes puberty occurring at an unusually early age. In most of these children, the process is normal in every respect except the unusually early age, and simply represents a variation of normal development. In a minority of children, the early development is...
, and to control ovarian stimulation in In Vitro Fertilization (IVF
In vitro fertilisation
In vitro fertilisation is a process by which egg cells are fertilised by sperm outside the body: in vitro. IVF is a major treatment in infertility when other methods of assisted reproductive technology have failed...
). It is considered a possible treatment for paraphilia
Paraphilia
Paraphilia is a biomedical term used to describe sexual arousal to objects, situations, or individuals that are not part of normative stimulation and that may cause distress or serious problems for the paraphiliac or persons associated with him or her...
s.
Leuprolide has been tested as a treatment for reducing sexual urges in pedophiles
Pedophilia
As a medical diagnosis, pedophilia is defined as a psychiatric disorder in adults or late adolescents typically characterized by a primary or exclusive sexual interest in prepubescent children...
and other cases of paraphilia
Paraphilia
Paraphilia is a biomedical term used to describe sexual arousal to objects, situations, or individuals that are not part of normative stimulation and that may cause distress or serious problems for the paraphiliac or persons associated with him or her...
. 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
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
.
Leuprolide is also used to treat chronic adrenal disease in ferrets.
It also used for treatment of steroid abuse.
Lupron protocol
A 2005 paper suggested leuprolide as a possible treatment for autismAutism
Autism is a disorder of neural development characterized by impaired social interaction and communication, and by restricted and repetitive behavior. These signs all begin before a child is three years old. Autism affects information processing in the brain by altering how nerve cells and their...
, the hypothetical method of action being the now defunct hypothesis
Thiomersal controversy
The thiomersal controversy describes claims that vaccines containing the mercury-based preservative thiomersal contribute to the development of autism and other brain development disorders...
that autism is caused by mercury
Mercury (element)
Mercury is a chemical element with the symbol Hg and atomic number 80. It is also known as quicksilver or hydrargyrum...
, with the additional unfounded assumption that mercury binds irreversibly to testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...
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
Mark Geier
Mark R. Geier is a self-employed American physician and controversial professional witness who has testified in more than 90 cases regarding allegations of injury or illness caused by vaccines....
, 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 cancerProstate cancerProstate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly...
on April 9, 1985. - Lupron Depot (7.5 mg/vial for monthly intramuscular depot injection) was first approved by the FDA for palliativePalliative carePalliative care is a specialized area of healthcare that focuses on relieving and preventing the suffering of patients...
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 endometriosisEndometriosisEndometriosis is a gynecological medical condition in which cells from the lining of the uterus appear and flourish outside the uterine cavity, most commonly on the ovaries. The uterine cavity is lined by endometrial cells, which are under the influence of female hormones...
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
Bayer
Bayer AG is a chemical and pharmaceutical company founded in Barmen , Germany in 1863. It is headquartered in Leverkusen, North Rhine-Westphalia, Germany and well known for its original brand of aspirin.-History:...
under the brand name Viadur, by Sanofi-Aventis
Sanofi-Aventis
Sanofi S.A. is a multinational pharmaceutical company headquartered in Paris, France, the world's fourth-largest by prescription sales. Sanofi engages in the research and development, manufacturing and marketing of pharmaceutical products for sale principally in the prescription market, but the...
under the brand name Eligard, and by TAP Pharmaceuticals
TAP Pharmaceuticals
TAP Pharmaceuticals was a Japanese pharmaceutical company.It was a joint venture between Abbott Laboratories and the Japanese Takeda Pharmaceutical Company, formed in 1977. The joint venture was dissolved in 2008 and most of the company merged with Takeda Pharmaceutical Co...
(1985–2008) and Abbott Laboratories
Abbott Laboratories
Abbott Laboratories is an American-based global, diversified pharmaceuticals and health care products company. It has 90,000 employees and operates in over 130 countries. The company headquarters are in Abbott Park, North Chicago, Illinois. The company was founded by Chicago physician, Dr....
(2008-current) under the brand name Lupron. It is available as a slow-release implant or subcutaneous
Subcutaneous injection
A subcutaneous injection is administered as a bolus into the subcutis, the layer of skin directly below the dermis and epidermis, collectively referred to as the...
/intramuscular injection
Intramuscular injection
Intramuscular injection is the injection of a substance directly into a muscle. In medicine, it is one of several alternative methods for the administration of medications . It is used for particular forms of medication that are administered in small amounts...
.
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. An AP article stated, "The hormone treatment was linked with a 96 percent higher risk of death after adjusting for other risk factors." 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. Women with endometriosis also suffer significant side effects.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 NetworkNational Women's Health NetworkThe National Women's Health Network is a non-profit women's health advocacy organization located in Washington, D.C.. It was founded in 1975 by Barbara Seaman, Alice Wolfson, Belita Cowan, Mary Howell, M.D., and Phyllis Chesler, Ph.D. The stated mission of the organization is to give women a...
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)