Gonadotropin preparations

Type of medication

Gonadotropin preparations

Drug class
Class identifiers
Synonyms| Gonadotropins; LH; FSH; hCG
Use| Infertility, hypogonadism
ATC code| G03GA
Biological target| Gonadotropin receptors (LHCGR, FSHR)
Chemical class| Glycoproteins
Legal status
In Wikidata

Gonadotropin preparations are drugs that mimic the physiological effects of gonadotropins, used therapeutically mainly as fertility medication for ovarian hyperstimulation and ovulation induction.[1] For example, the so-called menotropins consist of LH and FSH extracted from human urine from menopausal women.[2] There are also recombinant variants.[medical citation needed]

## FSH and LH preparations

[edit]

hMG (human Menopausal Gonadotrophins), FSH and LH prepared from human urine collected from postmenopausal women. First extracted in 1953.[3] 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.

Common side effects of preparations containing FSH and LH are:[4]

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

## FSH preparations

[edit]

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.[5]

### Urinary preparations

[edit]

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.

Brands

Fertinex (≤ 0.1 IU LH/1000 IU FSH)

### Recombinant preparations

[edit]

Follitropin alfa

Generic

Follitropin alfa injection

Brands

Gonal-f[6][7]
Cinnal-f
Fertilex
Ovaleap[8][9]
Bemfola[10]

Generic

Follitropin alfa / lutropin alfa combination

Brands

Pergoveris[11]

Follitropin beta

Generic

follitropin beta injection

Brands

Follistim AQ[12]
Puregon[13]

Follitropin delta

Generic

follitropin delta injection

Brands

Rekovelle[14][15]

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.[16][17] However, a more recent study showed there 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.[18]

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).[19] Further, the ogliosaccharide side chains are very similar, but not completely identical to that of natural hFSH.[20] However, these small differences do not affect the bioactivity compared to natural hFSH.[medical citation needed]

Gonal-f was approved for medical use in the European Union in October 1995.[6]

Puregon was approved for medical use in the European Union in February 1996.[13]

Rekovelle was approved for medical use in the European Union in December 2016.[14]

#### Biosimilars

[edit]

See also: Biosimilars

Ovaleap was approved for medical use in the European Union in September 2013.[8] It was approved for medical use in Australia in March 2021.[9]

Bemfola was approved for medical use in the European Union in March 2014.[10]

### Side effects of FSH preparations

[edit]

Side effects of FSH preparations include:[21][medical citation needed]

* 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 analogues

[edit]

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.[22][23]

## LH (Luteinizing hormone) preparations

[edit]

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|

Prepared from recombinant DNA.

Generic

lutropin alfa for injection
Brands

Luveris

## hCG preparations

[edit]

Human chorionic gonadotropin (hCG) can be recovered from the urine of pregnant women or be produced from recombinant DNA. It acts similarly to LH, but the larger supply makes it less costly; it also has a longer half-life. In veterinary medicine, equine chorionic gonadotropin (eCG) extracted from pregnant mare serum is used instead on a variety of mammals, sometimes eliciting an immune response in non-horse species.[24]

In Women: Used to induce final maturation of follicle and subsequent ovulation.[medical citation needed] Also used for luteal phase support.[medical citation needed]

In men: Used to treat select cases of Hypogonadotropic Hypogonadism in adult males.[25] In off-label use, some urologists prescribe hCG in low doses in combination with testosterone replacement to preserve fertility.[26]

In male children: Also used to treat prepubertal cryptorchidism not due to anatomical obstruction. Therapy is usually administered between ages 4 and 9.[25]

### Urinary preparations

[edit]

This section does not cite any sources. Please help improve this section by adding citations to reliable sources. Unsourced material may be challenged and removed. (December 2022) (Learn how and when to remove this message)

|

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]

This section does not cite any sources. Please help improve this section by adding citations to reliable sources. Unsourced material may be challenged and removed. (December 2022) (Learn how and when to remove this message)

|

Generic

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

Ovidrel

## References

[edit]

1. ^ "Gonadotropins", LiverTox: Clinical and Research Information on Drug-Induced Liver Injury, Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases, 2012, PMID 31644163, archived from the original on 2023-09-26, retrieved 2023-12-11
2. ^ Menotropins at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
3. ^ Ghumman, Surveen, 2006. Step by Step Ovulation Induction. Anshan Ltd, Kent, United Kingdom. ISBN 1-904798-96-9. Page 44.
4. ^ "Follicle Stimulating Hormone and Luteinizing Hormone (Intramuscular Route, Subcutaneous Route)". Mayo Clinic. Archived from the original on 2013-12-10.
5. ^ Dickey RP, Thornton M, Nichols J, Marshall DC, Fein SH, Nardi RV (June 2002). "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. 77 (6): 1202–1208\. doi:10.1016/s0015-0282(02)03131-x. PMID 12057729.
6. ^ a b "Gonal-f EPAR". European Medicines Agency (EMA). 17 September 2018. Archived from the original on 1 July 2020. Retrieved 2 April 2020.
7. ^ "Gonal-f- follitropin alfa kit". DailyMed. Archived from the original on 1 April 2021. Retrieved 22 March 2021.
8. ^ a b "Ovaleap EPAR". European Medicines Agency (EMA). 17 September 2018. Archived from the original on 23 September 2020. Retrieved 2 April 2020.
9. ^ a b "AusPAR: Follitropin alfa". Therapeutic Goods Administration (TGA). 19 May 2021. Archived from the original on 20 May 2021. Retrieved 12 June 2021.
10. ^ a b "Bemfola EPAR". European Medicines Agency (EMA). 17 September 2018. Archived from the original on 28 October 2020. Retrieved 2 April 2020.
11. ^ "Pergoveris EPAR". European Medicines Agency (EMA). 25 June 2007. Retrieved 12 October 2024.
12. ^ "Follistim AQ- follitropin injection, solution". DailyMed. Archived from the original on 30 March 2021. Retrieved 22 March 2021.
13. ^ a b "Puregon EPAR". European Medicines Agency (EMA). 17 September 2018. Archived from the original on 8 March 2021. Retrieved 22 March 2021.
14. ^ a b "Rekovelle EPAR". European Medicines Agency (EMA). 17 September 2018. Archived from the original on 1 July 2020. Retrieved 22 March 2021.
15. ^ "Prescription medicines and biologicals: TGA annual summary 2017". Therapeutic Goods Administration (TGA). 21 June 2022. Archived from the original on 31 March 2024. Retrieved 31 March 2024.
16. ^ Brinsden P, Akagbosu F, Gibbons LM, Lancaster S, Gourdon D, Engrand P, Loumaye E (January 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\. doi:10.1016/s0015-0282(99)00450-1. PMID 10632423.
17. ^ Williams RS, Vensel T, Sistrom CL, Kipersztok S, Rhoton-Vlasak A, Drury K (August 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\. doi:10.1067/s0002-9378(03)00728-2. PMID 14520188.
18. ^ Orvieto R, Nahum R, Rabinson J, Ashkenazi J, Anteby EY, Meltcer S (April 2009). "Follitropin-alpha (Gonal-F) versus follitropin-beta (Puregon) in controlled ovarian hyperstimulation for in vitro fertilization: is there any difference?". Fertility and Sterility. 91 (4 Suppl): 1522–1525\. doi:10.1016/j.fertnstert.2008.08.112. PMID 18851846.
19. ^ Smitz J, Wolfenson C, Chappel S, Ruman J (June 2016). "Follicle-Stimulating Hormone: A Review of Form and Function in the Treatment of Infertility". Reproductive Sciences. 23 (6): 706–716\. doi:10.1177/1933719115607992. PMID 26446000. S2CID 6023362.
20. ^ Belorkar SA, Gupta AK (December 2016). "Oligosaccharides: a boon from nature's desk". AMB Express. 6 (1): 82. doi:10.1186/s13568-016-0253-5. PMC 5047869. PMID 27699701.
21. ^ "Pharmacy FAQ". from Regional Fertility Program, Cambrian Wellness Centre. Archived from the original on 2013-12-02.
22. ^ Koper NP, Boostanfar R, Devroey P, Fauser BC, IJzerman-Boon PC, Mannaerts BM (2008). "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: S75. doi:10.1016/j.fertnstert.2008.07.864.
23. ^ Devroey P, Boostanfar R, Koper NP, Mannaerts BM, Ijzerman-Boon PC, Fauser BC (December 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. 24 (12): 3063–3072\. doi:10.1093/humrep/dep291. PMC 2777786. PMID 19684043.
24. ^ Hervé V, Roy F, Bertin J, Guillou F, Maurel MC (January 2004). "Antiequine chorionic gonadotropin (eCG) antibodies generated in goats treated with eCG for the induction of ovulation modulate the luteinizing hormone and follicle-stimulating hormone bioactivities of eCG differently". Endocrinology. 145 (1): 294–303\. doi:10.1210/en.2003-0595. PMID 14525910.
25. ^ a b "Pregnyl - FDA prescribing information, side effects and uses". Drugs.com. Archived from the original on 2018-07-24. Retrieved 2018-07-23.
26. ^ Hsieh TC, Pastuszak AW, Hwang K, Lipshultz LI (February 2013). "Concomitant intramuscular human chorionic gonadotropin preserves spermatogenesis in men undergoing testosterone replacement therapy". The Journal of Urology. 189 (2): 647–650\. doi:10.1016/j.juro.2012.09.043. PMID 23260550. Archived from the original on March 20, 2020. Retrieved March 20, 2020.

* v
* t
* e

Merck Serono

Products|

* Avelumab
* Bisoprolol
* Cetuximab
* Cladribine
* Efalizumab
* Gonadotropin preparations
* Human chorionic gonadotropin
* Interferon beta-1a
* Levothyroxine
* Luteinizing hormone
* Metformin
* Mitoxantrone
* Saizen
* Serostim
* Tegafur/uracil

Related|

* Merck Group
* Serono

* v
* t
* e

GnRHTooltip Gonadotropin-releasing hormone and gonadotropins

GnRH modulators
(incl. analogues)|

| Agonists|

* Peptide: Azagly-nafarelin
* Buserelin
* Deslorelin
* Fertirelin
* Gonadorelin
* Goserelin
* Histrelin
* Lecirelin
* Leuprorelin (leuprolide)
* Nafarelin
* Peforelin
* Triptorelin

|

Antagonists|

* Peptide: Abarelix
* Cetrorelix
* Degarelix
* Ganirelix

* Non-peptide: Elagolix
* Linzagolix†
* Relugolix (+estradiol/norethisterone acetate)

Gonadotropins|

| Preparations|

* Follicle-stimulating hormone
* Human chorionic gonadotropin
* Luteinizing hormone
* Menotropin
* Urofollitropin

|

Others
(indirect)|

| Progonadotropins|

* Sex steroid antagonists (via disinhibition of the HPG axis): Antiandrogens (e.g., flutamide, bicalutamide, enzalutamide)
* Antiestrogens/SERMsTooltip Selective estrogen receptor modulators (e.g., tamoxifen, clomifene, enclomifene)
* Aromatase inhibitors (e.g., anastrozole)
* GnRH agonists (e.g., GnRHTooltip gonadotropin-releasing hormone)

|

Antigonadotropins|

* Sex steroid agonists (via negative feedback on the HPG axis): Androgens/anabolic steroids (e.g., testosterone, nandrolone esters, oxandrolone)
* D2 receptor antagonists (prolactin releasers) (incl., domperidone, metoclopramide, risperidone, haloperidol, chlorpromazine, sulpiride)
* Estrogens (incl., bifluranol, estradiol, estradiol esters, ethinylestradiol, diethylstilbestrol, paroxypropione)
* Progestogens (incl. progestins, e.g., chlormadinone acetate, cyproterone acetate, hydroxyprogesterone caproate, gestonorone caproate, medroxyprogesterone acetate, megestrol acetate)

* Others (mixed or unknown mechanism of action): Danazol
* Gestrinone
* Metallibure

* #WHO-EM
* ‡Withdrawn from market
* Clinical trials:
* †Phase III
* §Never to phase III

See also
GnRH and gonadotropin receptor modulators
Androgens and antiandrogens
Estrogens and antiestrogens
Progestogens and antiprogestogens

* v
* t
* e

GnRHTooltip Gonadotropin-releasing hormone receptor and gonadotropin receptor modulators

GnRHTooltip Gonadotropin-releasing hormone receptor|

* Agonists: Peptides: Alarelin
* Avorelin
* Azagly-nafarelin
* Buserelin
* Deslorelin
* Fertirelin
* GnRH
* Gonadorelin
* Goserelin
* Histrelin
* Leuprorelin (leuprolide)
* Lutrelin
* Nafarelin
* Peforelin
* Salmon GnRH
* Triptorelin
* Zoptarelin
* Zoptarelin doxorubicin

* Antagonists: Peptides: Abarelix
* Acyline
* Azaline B
* Cetrorelix
* Degarelix
* Detirelix
* Ganirelix
* Iturelix (antide)
* LXT-101
* Ornirelix (ornitide)
* Ozarelix
* Prazarelix
* Ramorelix
* Teverelix (antarelix); Non-peptides: Elagolix
* Linzagolix
* Merigolix
* Opigolix
* Relugolix
* Sufugolix

Gonadotropin|

| LH/hCGTooltip Luteinizing hormone/choriogonadotropin receptor|

* Agonists: Peptides: Choriogonadotropin alfa
* Human chorionic gonadotropin
* Luteinizing hormone
* Lutropin alfa
* Menotropin (human menopausal gonadotropin)

|

FSHTooltip Follicle-stimulating hormone receptor|

* Agonists: Peptides: Corifollitropin alfa
* Follicle-stimulating hormone
* Follitropin alfa
* Follitropin beta
* Follitropin epsilon
* Menotropin (human menopausal gonadotropin)
* Urofollitropin
* Varfollitropin alfa

* NAMs: Non-peptides: ADX-61623

*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[GnRH]: Gonadotropin-releasing hormone receptor
*[HPG]: hypothalamic–pituitary–gonadal
*[SERMs]: Selective estrogen receptor modulators
*[LH/hCG]: Luteinizing hormone/choriogonadotropin receptor
*[FSH]: Follicle-stimulating hormone receptor
*[NAMs]: negative allosteric modulators