Goserelin

Mechanism (as reported)

Research reported that goserelin acts as a GnRH/LHRH agonist and that its mechanism centers on sustained GnRH receptor desensitization leading to pituitary downregulation and subsequent suppression of ovarian steroid production (estradiol and progesterone described as reduced to postmenopausal levels). (PMID: 42226753; also consistent with endocrine response description in PMID: 10926349)

Key findings (each cites a source)

• A pharmacokinetic study described goserelin as a synthetic decapeptide analogue of luteinising hormone-releasing hormone (LHRH) and reported that depot formulations determine serum profile shapes through release from a biodegradable lactide-glycolide copolymer matrix. (PMID: 10926349) [PMID 10926349]
• In that pharmacokinetic study, serum goserelin after administration as an aqueous solution was reported to be rapidly absorbed and eliminated, with mean elimination half-life (t1/2beta) values reported for males and females. (PMID: 10926349) [PMID 10926349]
• That pharmacokinetic study reported no clinically relevant accumulation with multiple administration of 1-month or 3-month depot formulations. (PMID: 10926349) [PMID 10926349]
• That pharmacokinetic study reported extensive metabolism prior to excretion and described that pharmacokinetics were unaffected by hepatic impairment, while mean t1/2beta increased in patients with severe renal impairment. (PMID: 10926349) [PMID 10926349]
• The same pharmacokinetic study reported an endocrine pattern after depot administration: an initial increase in luteinising hormone (LH) and increases in serum testosterone or oestradiol, followed by decreases in LH and suppression of testosterone/oestradiol to within castrate/menopausal ranges, with continued suppression during ongoing depot treatment. (PMID: 10926349) [PMID 10926349]
• A multicenter, prospective observational real-world study in hormone treatment-naïve Chinese prostate cancer patients reported effectiveness outcomes using changes in serum testosterone and prostate-specific antigen (PSA) and reported attainment of chemical castration in a high proportion of evaluable patients. (PMID: 38318809) [PMID 38318809]
• In that prostate cancer real-world study, treatment-emergent adverse events (TEAEs) and severe TEAEs were reported with specified proportions. (PMID: 38318809) [PMID 38318809]
• A U.S. real-world evidence study using electronic medical records analyzed 3-month goserelin 10.8 mg versus monthly goserelin 3.6 mg in premenopausal breast cancer and reported that goserelin 10.8 mg was non-inferior to 3.6 mg based on observed 12-month real-world event-free survival (rwEFS) rates. (PMID: 40050524) [PMID 40050524]
• A review article stated that the mechanism of goserelin centers on sustained GnRH receptor desensitization leading to pituitary downregulation and ovarian suppression, with reduction of estradiol and progesterone to postmenopausal levels. (PMID: 42226753) [PMID 42226753]
• A review reported a range of gynecological conditions and discussed an expanded set of roles for goserelin, including endometriosis and uterine fibroids, and described additional research in conditions such as adenomyosis and different types of female cancers. (PMID: 42226753) [PMID 42226753]