Severe gastrointestinal dysmotility developed after treatment with gonadotropin-releasing hormone analogs

Abstract

A high prevalence of endometriosis, polymorphism in the LHCGR and GnRH1 and progonadoliberin-2 antibodies in serum was found among the patients with severe dysmotility after treatment with GnRH analogs.

Gonadotropin-Releasing Hormone and Its Physiological and Pathophysiological Roles in Relation to the Structure and Function of the Gastrointestinal Tract

“…Future research should focus on explaining the interaction between GnRH and LH receptors in the bowel wall and the mechanisms underlying GnRH-induced neurodegeneration. Intermittent stimulation with GnRH in vivo is harmful to the gastrointestinal tract [8,9,10,46,50,51], whereas continuous GnRH treatment has the opposite effect [26,27,28,29]. These contradictory results may be due to very different hormonal effects in response to the hyperstimulation of FSH and LH secretion after intermittent GnRH stimulation and the downregulation of hormonal levels after continuous GnRH stimulation [1,2,6,50].…”

“…The high prevalence of LH receptor polymorphism in patients who develop severe dysmotility after GnRH treatment further points to a central role of the LH receptor in gastrointestinal function [46]. Future research should focus on explaining the interaction between GnRH and LH receptors in the bowel wall and the mechanisms underlying GnRH-induced neurodegeneration.…”

“…Severe gastrointestinal dysmotility has been described in some women after treatment with GnRH analogs [8,9,46]. Histopathological examinations of these patients have revealed a reduction in the total number of enteric neurons and a reduced percentage of GnRH-expressing enteric neurons, along with the presence of serum IgM antibodies against GnRH1 and/or progonadoliberin-2 [8,9,46].…”

“…Antibody development does not appear to be obligatory after GnRH treatment, but it does appear to occur more frequently in patients who develop complications in relation to the treatment [48,49]. Although no specific pathophysiological mechanisms have been confirmed, polymorphisms of the LH receptor gene and concomitant endometriosis have been suggested as triggering factors for developing gastrointestinal dysmotility in response to GnRH analogs [46]. …”

“…Histopathological examinations of these patients have revealed a reduction in the total number of enteric neurons and a reduced percentage of GnRH-expressing enteric neurons, along with the presence of serum IgM antibodies against GnRH1 and/or progonadoliberin-2 [8,9,46]. In a previous study, LH receptor-containing neurons were downregulated in the single patient examined for LH receptor expression, but no antibodies against LH or the LH receptor were found in any patients [46]. …”