Donnez, Jacques
Cacciottola, Luciana
[UCL]
Squifflet, Jean-Luc
Dolmans, Marie-Madeleine
[UCL]
Estrogens play a critical role in the pathogenesis of endometriosis and it is logical to assume that lowering estradiol levels with oral gonadotropin-releasing hormone (GnRH) antagonists may prove effective, especially in women who fail to respond to progestogens. Indeed, due to progesterone resistance, oral contraceptives and progestogens work well in two-thirds of women suffering from endometriosis, but are ineffective in 33% of women. Oral GnRH antagonists have therefore been evaluated for management of premenopausal women with endometriosis-associated pelvic pain. The first publication on these drugs reported the efficacy of elagolix. The present paper is a narrative review of linzagolix, which is an orally administered GnRH receptor antagonist with low pharmacokinetic/pharmacodynamic variability. It binds to and blocks the GnRH receptor in the pituitary gland, resulting in a dosedependent drop in luteinizing hormone (LH) and follicle-stimulating hormone (FSH) production. This reduction in LH and FSH levels in turn leads to a dose-dependent decline in estrogen. Phase 2 and 3 trials are reviewed and discussed here. There is a place for GnRH antagonists in the management of symptomatic endometriosis, and linzagolix with or without add-back therapy (ABT) is one option that can be used at low doses, avoiding the need for ABT, which is contraindicated in some patients.
Bibliographic reference |
Donnez, Jacques ; Cacciottola, Luciana ; Squifflet, Jean-Luc ; Dolmans, Marie-Madeleine. Profile of Linzagolix in the Management of Endometriosis, Including Design, Development and Potential Place in Therapy: A Narrative Review. In: Drug Design, Development and Therapy, Vol. Volume 17, p. 369-380 (2023) |
Permanent URL |
http://hdl.handle.net/2078.1/272311 |