Products
GnRH analogs are commercially available in many countries in the form of injectables, implants, and nasal sprays, among others. The first agent to be approved was goserelin (Zoladex) in 1990.
Structure and properties
GnRH analogs are synthetically produced derivatives of gonadotropin-releasing hormone (GnRH, LHRH) produced in the hypothalamus. GnRH is a decapeptide and has the following structure: GnRH: Pyr-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly For example, in triptorelin at position 6, the amino acid glycine is replaced by D-tryptophan: Pyr-His-Trp-Ser-Tyr-D-Trp-Leu-Arg-Pro-Gly. Pyr stands for pyroglutamic acid, a non-proteinogenic amino acid.
Effects
GnRH analogs (ATC L02AE) cause reduced release of the gonadotropins LH and FSH from the pituitary gland with longer-term treatment of approximately four weeks. The effects are due to down-regulation of the receptors. This reduces the formation of estrogens and androgens (testosterone) and the concentrations decrease. In contrast, with short-term or one-time treatment, LH and FSH secretion is promoted and hormone levels increase.
Agents
- Gonadorelin (Lutrelef) – equivalent to GnRH, not a derivative.
- Goserelin (Zoladex)
- Histrelin (Vantas)
- Leuprorelin (Eligard)
- Nafarelin (Synrelina)
- Triptorelin (Pamorelin)
Not commercially available in many countries:
- Buserelin (Suprefact)
Veterinary drugs:
- Deslorelin (Suprelorin)
- Lecirelin (Dalmarelin)
- Peforelin (Maprelin)
Indications
- Prostate cancer
- Breast cancer
- Endometriosis
- Uterine fibroid
- Endometrial ablatio
- In reproductive medicine
- Hypothalamic amenorrhea
- Central hypogonadism in males, e.g. Kallmann syndrome, to induce puberty.
Contraindications
GnRH analogs are contraindicated in hypersensitivity, in unexplained vaginal bleeding, in hormone-independent tumors, and during pregnancy and lactation. For complete precautions, see the drug label.
Interactions
Drug-drug interactions are possible with agents that affect the same hormonal systems.
Adverse effects
Adverse effects occur as a result of estrogen or androgen withdrawal. In women, postmenopausal symptoms such as hot flashes, sweating, and vaginal dryness are common. Other common side effects include headache, mood changes, depression, decrease in libido, erectile dysfunction, and local reactions at the injection site.
