Goserelin acetate (Zoladex, AstraZeneca) is an injectable gonadotropin releasing hormone superagonist (GnRH agonist), also known as a luteinizing hormone releasing hormone (LHRH) agonist. Structurally, it is a decapeptide. Goserelin acetate is used to suppress production of the sex hormones (testosterone and estrogen), particularly in the treatment of breast and prostate cancer.
Goserelin acetate stimulates the production of the sex hormones testosterone and estrogen in a non-pulsatile (non-physiological) manner. This causes the disruption of the endogenous hormonal feedback systems, resulting in the down-regulation of testosterone and estrogen production.
Zoladex was approved by the U.S. Food and Drug Administration in 1989 for treatment of prostate cancer.
Goserelin is a synthetic analogue of a naturally occurring luteinising-hormone releasing hormone (LHRH). Bioavailability is almost complete. Goserelin is poorly protein bound and has a serum elimination half-life of two to four hours in patients with normal renal function. The half-life increases with patients with impaired renal function. There is no significant change in pharmacokinetics in subjects with hepatic failure. After administration, peak serum concentrations are reached in about two hours. It rapidly binds to the LHRH receptor cells in the pituitary gland thus leading to an initial increase in production of luteinizing hormone and thus leading to an initial increase in the production of corresponding sex hormones. This initial flare may be treated by co-prescribing/co-administering Casodex (Bicalutamide) or similar medication. Eventually, after a period of about 14–21 days, production of LH is greatly reduced due to receptor downregulation, and sex hormones are generally reduced to castrate levels.
Goserelin Acetate is used to treat hormone-sensitive cancers of the breast (in pre- and peri- menopausal women) and prostate, and some benign gynaecological disorders (endometriosis, uterine fibroids and endometrial thinning). In addition, goserelin is used in assisted reproduction and in the treatment of precocious puberty. It may also be used in the treatment of male-to-female transsexuals and is favoured above other anti-androgens in some countries, such as the UK. It is available as a 1-month depot and a long-acting 3-month depot.
Goserelin Acetate may cause a temporary increase in bone pain and symptoms of prostatic cancer during the first few weeks of treatment. This is known as the tumour flare effect, and is the result of an initial increase in luteinizing hormone production, before the receptors are desensitised and hormonal production is inhibited. The symptoms will disappear, with hormonal inhibition. It is therefore advisable to co-treat with an antiandrogen during the first 2–3 weeks of Gosrelin treatment, particularly in patients with pre-existing bone symptoms. Goserelin may cause bone pain, hot flushes, headache, stomach upset, depression, difficulty urinating (isolated cases), weight gain, swelling and tenderness of breasts (infrequent), decreased erections and reduced sexual desire. Bone pain can be managed symptomatically, and erectile dysfunction can be treated by Levitra (Vardenafil) or other similar oral therapies.