Histrelin

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.

Histrelin

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	L02AE05 (WHO)
Legal status
Legal status	US: ℞-only
Pharmacokinetic data
Bioavailability	92%
Protein binding	70%
Metabolism	Hepatic
Elimination half-life	4.0 hours
Identifiers
IUPAC name 5-oxo-L-prolyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-1-benzyl-D-histidyl-L-leucyl-N^5-(diaminomethylene)-L-ornithyl-N-ethyl-L-prolinamide
CAS Number	76712-82-8
PubChem CID	25077993
IUPHAR/BPS	3884
ChemSpider	10482012
UNII	H50H3S3W74
KEGG	D02369
ChEMBL	ChEMBL1201255
CompTox Dashboard (EPA)	DTXSID50227543
ECHA InfoCard	100.163.860
Chemical and physical data
Formula	C66H86N18O12
Molar mass	1323.528 g·mol^−1
3D model (JSmol)	Interactive image
SMILES CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC2=CN(C=N2)CC3=CC=CC=C3)NC(=O)[C@H](CC4=CC=C(C=C4)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC5=CNC6=CC=CC=C65)NC(=O)[C@H](CC7=CNC=N7)NC(=O)[C@@H]8CCC(=O)N8
InChI 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 Key:HHXHVIJIIXKSOE-QILQGKCVSA-N
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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.

Side effects

Side effects are mainly due to low testosterone levels and include headache, hot flashes, reduced libido, and erectile dysfunction.[6]

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.[7][8]

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

• Gonadotropin-releasing hormone receptor § Agonists

References

1. Histrelin acetate (Vantas) - New Drug Bulletins
2. Histrelin consumer information
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): 1697–704. doi:10.1210/jc.2006-2479. PMID 17327379.
4. "Primary Care Protocol for Transgender Patient Care: Hormone Administration". transhealth.ucsf.edu. Archived from the original on 2012-01-17. Retrieved 2015-09-29.
5. Cohen, Deborah; Barnes, Hannah (20 September 2019). "Gender dysphoria in children: puberty blockers study draws further criticism". BMJ. doi:10.1136/bmj.l5647. Retrieved 3 February 2021.
6. Drugs.com: Histrelin Monograph
7. Mutschler E, Schäfer-Korting M (2001). Arzneimittelwirkungen (in German) (8th ed.). Stuttgart: Wissenschaftliche Verlagsgesellschaft. pp. 372–3. ISBN 3-8047-1763-2.
8. 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. PMID 8917899.

External links

• Central Precocious Puberty