Histrelin

Last updated
Histrelin
Histrelin.svg
Clinical data
Trade names Vantas, Supprelin LA, others
AHFS/Drugs.com Monograph
MedlinePlus a601146
Routes of
administration 		Subcutaneous implant
Drug class GnRH analogue; GnRH agonist; Antigonadotropin
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 92%
Protein binding 70%
Metabolism Hepatic
Elimination half-life 4.0 hours
Identifiers
  • 5-oxo-L-prolyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-1-benzyl-D-histidyl-L-leucyl-N5-(diaminomethylene)-L-ornithyl-N-ethyl-L-prolinamide
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.163.860 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C66H86N18O12
Molar mass 1323.528 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](Cc1cn(Cc2ccccc2)cn1)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CO)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@@H]1CCC(=O)N1
  • InChI=1S/C66H86N18O12/c1-4-70-64(95)55-17-11-25-84(55)65(96)48(16-10-24-71-66(67)68)76-58(89)49(26-38(2)3)77-62(93)53(30-43-34-83(37-74-43)33-40-12-6-5-7-13-40)81-59(90)50(27-39-18-20-44(86)21-19-39)78-63(94)54(35-85)82-60(91)51(28-41-31-72-46-15-9-8-14-45(41)46)79-61(92)52(29-42-32-69-36-73-42)80-57(88)47-22-23-56(87)75-47/h5-9,12-15,18-21,31-32,34,36-38,47-55,72,85-86H,4,10-11,16-17,22-30,33,35H2,1-3H3,(H,69,73)(H,70,95)(H,75,87)(H,76,89)(H,77,93)(H,78,94)(H,79,92)(H,80,88)(H,81,90)(H,82,91)(H4,67,68,71)/t47-,48-,49-,50-,51-,52-,53+,54-,55-/m0/s1 Yes check.svgY
  • Key:HHXHVIJIIXKSOE-QILQGKCVSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Histrelin acetate, sold under the brand names Vantas and Supprelin LA among others, is a nonapeptide analogue of gonadotropin-releasing hormone (GnRH) with added potency. [1] When present in the bloodstream, it acts on particular cells of the pituitary gland called gonadotropes. Histrelin stimulates these cells to release luteinizing hormone and follicle-stimulating hormone. Thus it is considered a gonadotropin-releasing hormone agonist or GnRH agonist.

Contents

Medical uses

Histrelin is used to treat hormone-sensitive cancers of the prostate in men and uterine fibroids in women. In addition, histrelin has been proven to be highly effective in treating central precocious puberty in children. [2] [3]

It is available as a daily intramuscular injection.

Histrelin is also available in a 12-month subcutaneous implant (Vantas) for the palliative treatment of advanced prostate cancer, since 2005 in the US, and since Jan 2010 in the UK.

A 12-month subcutaneous implant (Supprelin LA) for central precocious puberty (CPP) was approved on May 3, 2007 by the U.S. Food and Drug Administration.

Histrelin can be part of the primary care protocol in transgender children/youth, which is an off-label use in the USA [4] and the UK, [5] and is used in suppressing cis-sex puberty, until the patient is ready to begin cross-sex hormonal therapy. It is also sometimes prescribed to transgender adults who benefit from having their sex hormone production halted. In this application, patients often keep the implant for two years before replacing, with regular blood tests to monitor the hormone levels. Implants left too long are more difficult to replace. [6]

Since 2020, Vantas is not available anymore. Endo, its manufacturer said batches of the medication were not coming out right. They added that although Supprelin and Vantas were manufactured in the same facility, they were not identical product (though both contain 50 mg of histrelin acetate.) As of 2023, Vantas is still not available and the only available implant is Supprelin LA. [7]

Vantas was priced around $4400 in 2004 while Supprelin LA was priced at $37,000 in 2007. [8]

Side effects

Common side effects include headache, hot flashes, constipation, reduced libido, gynecomastia, insomnia, renal impairment, weight loss, testicular atrophy, and erectile dysfunction. [9]

Pharmacology

In a process known as downregulation, daily stimulation of pituitary gonadotropes causes them to become desensitized to the effects of histrelin. As a consequence, levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) fall after a short period of time. From that point forward, as long as histrelin is administered, the levels of LH and FSH in the blood remain low. [10] [11]

This prolonged lowering of LH and FSH levels is the rationale for therapy using GnRH agonists. Since LH and FSH stimulate the gonads to produce estrogens and androgens in females and males respectively, histrelin can effectively be used to decrease the sex steroids in the blood of patients.

See also

Related Research Articles

<span class="mw-page-title-main">Gonadotropin-releasing hormone</span> Mammalian protein found in Homo sapiens

Gonadotropin-releasing hormone (GnRH) is a releasing hormone responsible for the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary. GnRH is a tropic peptide hormone synthesized and released from GnRH neurons within the hypothalamus. The peptide belongs to gonadotropin-releasing hormone family. It constitutes the initial step in the hypothalamic–pituitary–gonadal axis.

Gonadotropins are glycoprotein hormones secreted by gonadotropic cells of the anterior pituitary of vertebrates. This family includes the mammalian hormones follicle-stimulating hormone (FSH) and luteinizing hormone (LH), the placental/chorionic gonadotropins, human chorionic gonadotropin (hCG) and equine chorionic gonadotropin (eCG), as well as at least two forms of fish gonadotropins. These hormones are central to the complex endocrine system that regulates normal growth, sexual development, and reproductive function. LH and FSH are secreted by the anterior pituitary gland, while hCG and eCG are secreted by the placenta in pregnant humans and mares, respectively. The gonadotropins act on the gonads, controlling gamete and sex hormone production.

Gonadarche refers to the earliest gonadal changes of puberty. In response to pituitary gonadotropins, the ovaries in females and the testes in males begin to grow and increase the production of the sex steroids, especially estradiol and testosterone. The ovary and testis have receptors, follicle cells and leydig cells, respectively, where gonadotropins bind to stimulate the maturation of the gonads and secretion of estrogen and testosterone. Certain disorders can result in changes to timing or nature of these processes.

<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">Gonadorelin</span> Chemical compound

Gonadorelin is a gonadotropin-releasing hormone agonist which is used in fertility medicine and to treat amenorrhea and hypogonadism. It is also used in veterinary medicine. The medication is a form of the endogenous GnRH and is identical to it in chemical structure. It is given by injection into a blood vessel or fat or as a nasal spray.

<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">Hypothalamic–pituitary–gonadal axis</span> Concept of regarding the hypothalamus, pituitary gland and gonadal glands as a single entity

The hypothalamic–pituitary–gonadal axis refers to the hypothalamus, pituitary gland, and gonadal glands as if these individual endocrine glands were a single entity. Because these glands often act in concert, physiologists and endocrinologists find it convenient and descriptive to speak of them as a single system.

<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">Familial male-limited precocious puberty</span> Medical condition

Familial male-limited precocious puberty, often abbreviated as FMPP, also known as familial sexual precocity or gonadotropin-independent testotoxicosis, is a form of gonadotropin-independent precocious puberty in which boys experience early onset and progression of puberty. Signs of puberty can develop as early as an age of 1 year.

The gonadotropin-releasing hormone receptor (GnRHR), also known as the luteinizing hormone releasing hormone receptor (LHRHR), is a member of the seven-transmembrane, G-protein coupled receptor (GPCR) family. It is the receptor of gonadotropin-releasing hormone (GnRH). The GnRHR is expressed on the surface of pituitary gonadotrope cells as well as lymphocytes, breast, ovary, and prostate.

<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">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.

An antigonadotropin is a drug which suppresses the activity and/or downstream effects of one or both of the gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH). This results in an inhibition of the hypothalamic-pituitary-gonadal (HPG) axis, and thus a decrease in the levels of the androgen, estrogen, and progestogen sex steroids in the body. Antigonadotropins also inhibit ovulation in women and spermatogenesis in men. They are used for a variety of purposes, including for the hormonal birth control, treatment of hormonally-sensitive cancers, to delay precocious puberty and puberty in transgender youth, as a form of chemical castration to reduce the sex drives of individuals with hypersexuality or pedophilia, and to treat estrogen-associated conditions in women such as menorrhagia and endometriosis, among others. High-dose antigonadotropin therapy has been referred to as medical castration.

Hypogonadotropic hypogonadism (HH), is due to problems with either the hypothalamus or pituitary gland affecting the hypothalamic-pituitary-gonadal axis. Hypothalamic disorders result from a deficiency in the release of gonadotropic releasing hormone (GnRH), while pituitary gland disorders are due to a deficiency in the release of gonadotropins from the anterior pituitary. GnRH is the central regulator in reproductive function and sexual development via the HPG axis. GnRH is released by GnRH neurons, which are hypothalamic neuroendocrine cells, into the hypophyseal portal system acting on gonadotrophs in the anterior pituitary. The release of gonadotropins, LH and FSH, act on the gonads for the development and maintenance of proper adult reproductive physiology. LH acts on Leydig cells in the male testes and theca cells in the female. FSH acts on Sertoli cells in the male and follicular cells in the female. Combined this causes the secretion of gonadal sex steroids and the initiation of folliculogenesis and spermatogenesis. The production of sex steroids forms a negative feedback loop acting on both the anterior pituitary and hypothalamus causing a pulsatile secretion of GnRH. GnRH neurons lack sex steroid receptors and mediators such as kisspeptin stimulate GnRH neurons for pulsatile secretion of GnRH.

<span class="mw-page-title-main">Premature thelarche</span> Medical condition

Premature thelarche (PT) is a medical condition, characterised by isolated breast development in female infants. It occurs in females younger than 8 years, with the highest occurrence before the age of 2. PT is rare, occurring in 2.2-4.7% of females aged 0 to 2 years old. The exact cause of the condition is still unknown, but it has been linked to a variety of genetic, dietary and physiological factors.

<span class="mw-page-title-main">Gonadotropin-releasing hormone modulator</span> Type of medication which modulates the GnRH receptor

A GnRH modulator, or GnRH receptor modulator, also known as an LHRH modulator or LHRH receptor modulator, is a type of medication which modulates the GnRH receptor, the biological target of the hypothalamic hormone gonadotropin-releasing hormone. They include GnRH agonists and GnRH antagonists. These medications may be GnRH analogues like leuprorelin and cetrorelix – peptides that are structurally related to GnRH – or small-molecules like elagolix and relugolix, which are structurally distinct from and unrelated to GnRH analogues.

References

  1. ↑ Davis M (25 February 2005). Chandramouli J (ed.). "Histrelin acetate (Vantas)". New Drug Bulletins. University of Utah Hospitals & Clinics. Archived from the original on 10 May 2006.
  2. ↑ "Histrelin consumer information". Drugs.com.
  3. ↑ Eugster EA, Clarke W, Kletter GB, Lee PA, Neely EK, Reiter EO, et al. (May 2007). "Efficacy and safety of histrelin subdermal implant in children with central precocious puberty: a multicenter trial". The Journal of Clinical Endocrinology and Metabolism. 92 (5): 1697–1704. doi:10.1210/jc.2006-2479. PMID   17327379.
  4. ↑ "Primary Care Protocol for Transgender Patient Care: Hormone Administration". Center of Excellence for Transgender Health. University of California, San Francisco, Department of Family and Community Medicine. April 2011. Archived from the original on 2012-01-17. Retrieved 2015-09-29.
  5. ↑ Cohen D, Barnes H (September 2019). "Gender dysphoria in children: puberty blockers study draws further criticism". BMJ. 366: l5647. doi:10.1136/bmj.l5647. PMID   31540909. S2CID   202711942.
  6. ↑ Marinkovic M, Carswell J, Roberts SA (2019). "Emerging Developments in Pubertal Suppression for Gender Incongruent/Gender Dysphoric Youth". In Finlayson C (ed.). Pubertal Suppression in Transgender Youth. pp. 95–100. doi:10.1016/B978-0-323-56963-7.00012-0. ISBN   978-0-323-56963-7. S2CID   186736821.
  7. ↑ Lupkin S (6 November 2021). "Drugmaker drops cheaper version of drug, leaving patients stuck with pricier one". National Public Radio (NPR).
  8. ↑ Lupkin S (24 February 2020). "Hormone Blocker Sticker Shock: Kids Drug Costs 8 Times More Than One For Adults". National Public Radio (NPR).
  9. ↑ Drugs.com: Histrelin Monograph
  10. ↑ Mutschler E, Schäfer-Korting M (2001). Arzneimittelwirkungen (in German) (8th ed.). Stuttgart: Wissenschaftliche Verlagsgesellschaft. pp. 372–3. ISBN   3-8047-1763-2.
  11. ↑ 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): 707–713. PMID   8917899.
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.