Gonadotropin preparations are drugs that mimic the physiological effects of gonadotropins, used therapeutically mainly as fertility medication for ovarian hyperstimulation and ovulation induction. For example, the so-called menotropins consist of LH and FSH extracted from human urine from menopausal women. There are also recombinant variants.
FSH and LH preparations
hMG (human Menopausal Gonadotrophins), FSH and LH prepared from human urine collected from postmenopausal women. First extracted in 1953. 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: Mild bloating Pain, swelling, or irritation injection site Rash at injection site or other part of body Stomach pain or pelvic pain
FSH preparations
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.
Urinary preparations
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
Follitropin alfa
Generic
Follitropin alfa injection
Brands
Gonal-f
Cinnal-f
Fertilex
Ovaleap
Bemfola
Follitropin beta
Generic
follitropin beta injection
Brands
Follistim AQ
Puregon
Follitropin delta
Generic
follitropin delta injection
Brands
Rekovelle
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. 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.
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.
Gonal-f was approved for medical use in the European Union in October 1995.
Puregon was approved for medical use in the European Union in February 1996.
Rekovelle was approved for medical use in the European Union in December 2016.
Biosimilars
Ovaleap was approved for medical use in the European Union in September 2013. It was approved for medical use in Australia in March 2021.
Bemfola was approved for medical use in the European Union in March 2014.
Side effects of FSH preparations
Side effects of FSH preparations include: 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
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.
LH (Luteinizing hormone) preparations
Prepared from recombinant DNA.