Gonadotropin preparations

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

## Overview

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Gonadotropin preparations are drugs that mimic the physiological effects of gonadotropins, used therapeutically mainly as fertility medication for ovarian hyperstimulation and reversal of anovulation. For example, the so-called menotropins consist of LH and FSH extracted from human urine from menopausal women.[1] There are also recombinant variants.

## FSH and LH preparations

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hMG (human Menopausal Gonadotrophins), FSH and LH prepared from human urine collected from postmenopausal women. First extracted in 1953.[2] Injected intra-muscularily (IM) or subcutaneously (SC).

Generic

menotropins for injections, USP

Brands

* Menopur, 5 mL vials containing 75 IU FSH and 75 IU LH.
* Repronex, vials containing either 75 IU FSH and 75 IU LH, or 150 IU FSH and 150 IU LH.

The more common side effects of preparations containing FSH and LH are:[3]

* Mild bloating
* Pain, swelling, or irritation injection site
* Rash at injection site or other part of body
* Stomach pain or pelvic pain

## FSH preparations

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Preparations of follicle-stimulating hormone (FSH) mainly include those derived from the urine of menopausal women, as well as recombinant preparations. The recombinant preparations are more pure and more easily administered, but they are more expensive. The urinary preparations are equally effective and less expensive, but are not as convenient to administer as they are available in vials versus injection pens. One study reported that users of the purified urinary FSH preparation Bravelle experienced less injection site pain compared to the recombinant preparation Follistim.[4]

### Urinary preparations

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Purified urinary FSH (75 IU FSH and ≤ 2 IU of LH)

Generic

urofollitropin for injection, purified.

Brands

* Bravelle, U.S., (≤ 2 IU LH)
* Metrodin, U.S. and Canada, (≤ 1 IU LH)
* Fertinorm Hp, (Canada)

Highly purified urinary FSH (75 IU FSH and ≤ 0.1 IU LH/1000 IU FSH)

Generic

urofollitropin for injection, (highly) purified.

Dosage

typically 75 - 300, but as high as 600 IU / day

Brands

Fertinex (≤ 0.1 IU LH/1000 IU FSH)

### Recombinant preparations

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Follitropin alfa

Generic

Follitropin alfa injection

Brands

Gonal-F
Cinnal-f
Fertilex

Follitropin beta

Generic

follitropin beta injection

Brands

* Follistim
* Puregon

The package insert for Gonal-F states that based on physio-chemical tests and bioassays that follitropin beta and follitropin alfa are indistinguishable. Two studies showed no difference.[5][6] However, a more recent study showed there is may be a slight clinical difference, with the alfa form tending towards a higher pregnancy rate and the beta form tending towards a lower pregnancy rate, but with significantly higher estradiol (E2) levels.[7]

The package insert for Puregon states that structural analysis shows that the amino acid sequence of follitropin beta is identical to that of natural human follicle stimulating hormone (hFSH). Further, the ogliosaccharide side chains are very similar, but not completely identical to that of natural hFSH. However, these small differences do not affect the bioactivity compared to natural hFSH.

### Side effects of FSH preparations

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Side effects of FSH preparations include:[8]

* Local irritation at the injection site
* Feeling of fullness, bloating, and tenderness in the lower abdomen due to increasing size of the ovaries.
* Mood swings
* Fatigue

## FSH Analogs

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Corifollitropin alfa

Merck received approval on February 15, 2010 from the European Commission for ELONVA (corifollitropin alfa) a long lasting single injection fusion protein lacking LH activity. Only one injection is required for the first seven days, replacing the first seven daily injections of conventional FSH. Initial results demonstrates similar pregnancy rates as daily recombinant FSH injections.[9][10]

## LH (Luteinizing hormone) preparations

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Prepared from recombinant DNA.

Generic

lutropin alfa for injection
Brands

Luveris

## hCG (human Chorionic Gonadotropin) preparations

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Used to induce final maturation of follicle and subsequent ovulation. Also used for luteal phase support. Typically a single injection of 10,000 international units is used to induce ovulation. Recent data has shown that subcutaneous injection works as well as intramuscular injection, however this form of administration is not FDA approved.[11]

### Urinary preparations

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Derived from the urine of pregnant women.

Generic

(human) chorionic gonadotropin for injection, USP

Brands

* Pregnyl (Merck/Schering-Plough)
* Follutein
* Profasi
* Novarel

### Recombinant preparations

[edit | edit source]

Generic

choriogonadotropin alfa for injection (recombinant human Chorionic Gonadotropin, r-hCG).
Brands

Ovidrel

## References

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1. ↑ Menotropins at the US National Library of Medicine Medical Subject Headings (MeSH)
2. ↑ Ghumman, Surveen, 2006. Step by Step Ovulation Induction. Anshan Ltd, Kent, United Kingdom. ISBN 1-904798-96-9. Page 44.
3. ↑ Follicle Stimulating Hormone and Luteinizing Hormone (Intramuscular Route, Subcutaneous Route) Side effects. From Mayo Clinic. Last updated: Nov. 1, 2011
4. ↑ Dickey RP, Thornton M, Nichols J, Marshall DC, Fein SH, Nardi RV. Comparison of the efficacy and safety of a highly purified human follicle-stimulating hormone (Bravelle) and recombinant follitropin-beta for in vitro fertilization: a prospective, randomized study. Fertility and Sterility 2002 Jun;77(6): 1202-8.
5. ↑ Peter Brinsden, Fidelis Akagbosu, Lisa M Gibbons, Susan Lancaster, Dominique Gourdon, Patrick Engrand, Ernest Loumaye, 2000. "A comparison of the efficacy and tolerability of two recombinant human follicle-stimulating hormone preparations in patients undergoing in vitro fertilization-embryo transfer." Fertility and sterility, 73(1): 114-116.
6. ↑ R. Stan Williams, et al., 2003. "Pregnancy rates in varying age groups after in vitro fertilization: a comparison of follitropin alfa (Gonal F) and follitropin beta (Follistim)." American Journal of Obstetrics and Gynecology, 189(2):342-346.
7. ↑ Orvieto R, Nahum R, Rabinson J, Ashkenazi J, Anteby EY, Meltcer S., 2009. "Follitropin-alpha (Gonal-F) versus follitropin-beta (Puregon) in controlled ovarian hyperstimulation for in vitro fertilization: is there any difference?" Fertility and Sterility 2009 Apr;91(4 Suppl):1522-5. Epub 2008 Oct 11. PMID 18851846
8. ↑ Pharmacy FAQ from Regional Fertility Program, Cambrian Wellness Centre. Retrieved December 2013
9. ↑ N. P. Koper, R. Boostanfar, P. Devroey, B. C. Fauser, P. C. IJzerman-Boon, B. M. J. L. Mannaerts. Global ClinicalDevelopment, Organon, Part of Schering-Plough Corporation, Oss, Netherlands; Huntington Reproductive Center, Tarzana, CA; Center of Reproductive Medicine, Dutch-speaking Free University, Brussels, Belgium; University Medical Center Utrecht, Utrecht, Netherlands; Biometrics, NV Organon, Part of Schering-Plough Corporation, Oss, Netherlands. "Corifollitropin alfa demonstrates similar pregnancy rates as compared to daily recombinant FSH treatment in a controlled ovarian stimulation regimen for IVF/ICSI." Fertility and Sterility, 90:page S75.
10. ↑ Devroey P, Boostanfar R, Koper NP, Mannaerts BM, Ijzerman-Boon PC, Fauser BC, 2009. "A double-blind, non-inferiority RCT comparing corifollitropin alfa and recombinant FSH during the first seven days of ovarian stimulation using a GnRH antagonist protocol." Human Reproduction, 2009, August 14, [Epub ahead of print]. PMID 19684043.
11. ↑ http://www.washivf.com/GWIVF-GWIVF_Content_C-Index_Page_Template_1143644788329.html

Template:Gonadotropins and GnRH

* v
* t
* e

Signaling peptide/protein receptor modulators

Adiponectin|

| AdipoR1|

* Agonists: Peptide: Adiponectin
* ADP-355
* ADP-399; Non-peptide: AdipoRon
* (–)-Arctigenin
* Arctiin
* Gramine
* Matairesinol

* Antagonists: Peptide: ADP-400

|

AdipoR2|

* Agonists: Peptide: Adiponectin
* ADP-355
* ADP-399; Non-peptide: AdipoRon
* Deoxyschizandrin
* Parthenolide
* Syringing
* Taxifoliol

* Antagonists: Peptide: ADP-400

Angiotensin|

* See here instead.

Bradykinin|

* Agonists: Bradykinin
* Kallidin

* Antagonists: FR-173657
* Icatibant
* LF22-0542

CGRP|

* Agonists: Amylin
* CGRP
* Pramlintide

* Antagonists: Atogepant
* BI 44370 TA
* CGRP (8-37)
* MK-3207
* Olcegepant
* Rimegepant
* SB-268262
* Telcagepant
* Ubrogepant

* Antibodies: Eptinezumab
* Erenumab
* Fremanezumab
* Galcanezumab

Cholecystokinin|

| CCKA|

* Agonists: Cholecystokinin

* Antagonists: Amiglumide
* Asperlicin
* Devazepide
* Dexloxiglumide
* Lintitript
* Lorglumide
* Loxiglumide
* Pranazepide
* Proglumide
* Tarazepide
* Tomoglumide

|

CCKB|

* Agonists: Cholecystokinin
* CCK-4
* Gastrin
* Pentagastrin (CCK-5)

* Antagonists: Ceclazepide
* CI-988 (PD-134308)
* Itriglumide
* L-365,360
* Netazepide
* Proglumide
* Spiroglumide

Unsorted|

* Antagonists: Nastorazepide

CRH|

| CRF1|

* Agonists: Cortagine
* Corticorelin
* Corticotropin releasing hormone
* Sauvagine
* Stressin I
* Urocortin

* Antagonists: Antalarmin
* Astressin-B
* CP-154,526
* Emicerfont
* Hypericin
* LWH-234
* NBI-27914
* NBI-74788
* Pexacerfont
* R-121919
* TS-041
* Verucerfont

|

CRF2|

* Agonists: Corticorelin
* Corticotropin releasing hormone
* Sauvagine
* Urocortin

* Antagonists: Astressin-B

Cytokine|

See here instead.

Endothelin|

* Agonists: Endothelin 1
* Endothelin 2
* Endothelin 3
* IRL-1620

* Antagonists: A-192621
* ACT-132577
* Ambrisentan
* Aprocitentan
* Atrasentan
* Avosentan
* Bosentan
* BQ-123
* BQ-788
* Clazosentan
* Darusentan
* Edonentan
* Enrasentan
* Fandosentan
* Feloprentan
* Macitentan
* Nebentan
* Sitaxentan
* Sparsentan
* Tezosentan
* Zibotentan

Galanin|

| GAL1|

* Agonists: Galanin
* Galanin (1-15)
* Galanin-like peptide
* Galmic
* Galnon
* NAX 810-2

* Antagonists: C7
* Dithiepine-1,1,4,4-tetroxide
* Galantide (M15)
* M32
* M35
* M40
* SCH-202596

|

GAL2|

* Agonists: Galanin
* Galanin (1-15)
* Galanin (2-11)
* Galanin-like peptide
* Galmic
* Galnon
* J18
* NAX 810-2

* Antagonists: C7
* Galantide (M15)
* M32
* M35
* M40
* M871

GAL3|

* Agonists: Galanin
* Galanin (1-15)
* Galmic
* Galnon

* Antagonists: C7
* Galantide (M15)
* GalR3ant
* HT-2157
* M32
* M35
* M40
* SNAP-37889
* SNAP-398299

Ghrelin/GHS|

* See here instead.

GH|

* See here instead.

GHRH|

* See here instead.

GLP|

| GLP-1|

* Agonists: Albiglutide
* Beinaglutide
* Dulaglutide
* Efpeglenatide
* Exenatide
* GLP-1
* Langlenatide
* Liraglutide
* Lixisenatide
* Oxyntomodulin
* Pegapamodutide
* Semaglutide
* Taspoglutide

|

GLP-2|

* Agonists: Apraglutide
* Elsiglutide
* Glepaglutide
* GLP-2
* Teduglutide

Others|

* Propeptides: Preproglucagon
* Proglucagon

Glucagon|

* Agonists: Dasiglucagon
* Glucagon
* Oxyntomodulin

* Antagonists: Adomeglivant
* L-168,049
* LGD-6972

* Propeptides: Preproglucagon
* Proglucagon

GnRH|

* See here instead.

Gonadotropin|

* See here instead.

Growth factor|

See here instead.

Insulin|

* Agonists: Chaetochromin (4548-G05)
* Insulin-like growth factor 1
* Insulin-like growth factor 2
* Insulin
* Insulin aspart
* Insulin degludec
* Insulin detemir
* Insulin glargine
* Insulin glulisine
* Insulin lispro
* Mecasermin
* Mecasermin rinfabate

* Antagonists: BMS-754807
* S661
* S961

* Kinase inhibitors: Linsitinib

* Antibodies: Xentuzumab (against IGF-1 and IGF-2)

Kisspeptin|

* Agonists: Kisspeptin
* Kisspeptin-10

* Antagonists: Kisspeptin-234

Leptin|

* Agonists: Leptin
* Metreleptin

MCH|

| MCH1|

* Agonists: Melanin concentrating hormone

* Antagonists: ATC-0065
* ATC-0175
* GW-803430
* NGD-4715
* SNAP-7941
* SNAP-94847

|

MCH2|

* Agonists: Melanin concentrating hormone

Melanocortin|

* See here instead.

Neuropeptide FF|

* Agonists: Neuropeptide AF
* Neuropeptide FF
* Neuropeptide SF (RFRP-1)
* Neuropeptide VF (RFRP-3)

* Antagonists: BIBP-3226
* RF9

Neuropeptide S|

* Agonists: Neuropeptide S

* Antagonists: ML-154
* SHA-68

Neuropeptide Y|

| Y1|

* Agonists: Neuropeptide Y
* Peptide YY

* Antagonists: BIBO-3304
* BIBP-3226
* BVD-10
* GR-231118
* PD-160170

|

Y2|

* Agonists: 2-Thiouridine 5'-triphosphate
* Neuropeptide Y
* Neuropeptide Y (13-36)
* Peptide YY
* Peptide YY (3-36)

* Antagonists: BIIE-0246
* JNJ-5207787
* SF-11

Y4|

* Agonists: GR-231118
* Neuropeptide Y
* Pancreatic polypeptide
* Peptide YY

* Antagonists: UR-AK49

Y5|

* Agonists: BWX-46
* Neuropeptide Y
* Peptide YY

* Antagonists: CGP-71683
* FMS-586
* L-152,804
* Lu AA-33810
* MK-0557
* NTNCB
* Velneperit (S-2367)

Neurotensin|

| NTS1|

* Agonists: Neurotensin
* Neuromedin N

* Antagonists: Meclinertant
* SR-142948

|

NTS2|

* Agonists: Neurotensin

* Antagonists: Levocabastine
* SR-142948

Opioid|

See here instead.

Orexin|

| OX1|

* Agonists: Orexin (A, B)

* Antagonists: ACT-335827
* ACT-462206
* Almorexant
* Filorexant
* Lemborexant
* Nemorexant
* RTIOX-276
* SB-334867
* SB-408124
* SB-649868
* Suvorexant
* TCS-1102

|

OX2|

* Agonists: Orexin (A, B)
* SB-668875

* Antagonists: ACT-335827
* ACT-462206
* Almorexant
* EMPA
* Filorexant
* JNJ-10397049
* Lemborexant
* MK-1064
* SB-649868
* Seltorexant
* Suvorexant
* TCS-1102
* TCS-OX2-29

Oxytocin|

* See here instead.

Prolactin|

* Agonists: Growth hormone
* Human placental lactogen
* Placental growth hormone (growth hormone variant)
* Prolactin
* S179D-hPRL
* Somatotropin

* Antagonists: Δ1–9-G129R-hPRL
* Δ1–14-G129R-hPRL
* G120K-hGH
* G129R-hPRL

* Prolactin modulators: Prolactin inhibitors: D2 receptor agonists (e.g., bromocriptine, cabergoline); Prolactin releasers: D2 receptor antagonists (e.g., domperidone, metoclopramide, risperidone)
* Estrogens (e.g., estradiol)
* Progestogens (e.g., progesterone)

PTH|

* Agonists: Abaloparatide
* Parathyroid hormone
* Parathyroid hormone-related protein (PTHrP)
* Semparatide
* Teriparatide

Relaxin|

* Agonists: Insulin-like factor 3
* Relaxin (1, 2, 3)
* Serelaxin

Somatostatin|

* See here instead.

Tachykinin|

* See here instead.

TRH|

* Agonists: Azetirelin
* Fertirelin
* Montirelin
* Orotirelin
* Posatirelin
* Protirelin
* Rovatirelin
* Taltirelin
* TRH (TRF)

TSH|

* Agonists: Thyrotropin alfa
* TSH (thyrotropin)

Vasopressin|

* See here instead.

VIP/PACAP|

| VIPR1|

* Agonists: Peptide: Bay 55-9837
* LBT-3393
* PACAP
* VIP

|

VIPR2|

* Agonists: Peptide: LBT-3627
* PACAP
* VIP

PAC1|

* Agonists: PACAP
* PACAP (1-27)
* PACAP (1-38)

* Antagonists: PACAP (6-38)

Unsorted|

* PHI
* PHM
* PHV

Others|

* Endogenous: Adrenomedullin
* Apelin
* Asprosin
* Bombesin
* Calcitonin
* Carnosine
* CART
* CLIP
* DSIP
* Enteroglucagon
* Formyl peptide
* GALP
* GIP
* GRP
* Integrin ligands (collagens, fibrinogen, fibronectin, laminins, ICAM-1, ICAM-2, osteopontin, VCAM-1, vitronectin)
* Kininogens
* Motilin
* Natriuretic peptides (ANP, BNP, CNP, urodilatin)
* Nesfatin-1
* Neuromedin B
* Neuromedin N
* Neuromedin S
* Neuromedin U
* Obestatin
* Osteocalcin
* Resistin
* Secretin
* Thymopoietin
* Thymosins
* Thymulin
* Urotensin-II
* VGF

* Exogenous: Lifitegrast (LFA-1 antagonist)

See also
Receptor/signaling modulators
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