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

Cordeddu, Lina; Bergvall, Monika; Sand, Elin LU ; Roth, Bodil LU ; Papadaki, Evangelia; Li, Ling; D'Amato, Mauro and Ohlsson, Bodil LU (2015) In Scandinavian Journal of Gastroenterology 50(3). p.291-299
Abstract
Background. Sporadic cases of abdominal pain and dysmotility has been described after treatment with gonadotropin-releasing hormone (GnRH) analogs. The aim of the present study was to scrutinize for patients with severe gastrointestinal complaints after treatment with GnRH analogs, to describe the expression of antibodies against progonadoliberin-2, GnRH1, GnRH receptor (GnRHR), luteinizing hormone (LH), and LH receptor in serum in these patients, and to search for possible triggers and genetic factors behind the development of this dysmotility. Methods. Patients suffering from prolonged gastrointestinal complaints after treatment with GnRH analogs at the Department of Gastroenterology, Skane University Hospital, were included. GnRHR and... (More)
Background. Sporadic cases of abdominal pain and dysmotility has been described after treatment with gonadotropin-releasing hormone (GnRH) analogs. The aim of the present study was to scrutinize for patients with severe gastrointestinal complaints after treatment with GnRH analogs, to describe the expression of antibodies against progonadoliberin-2, GnRH1, GnRH receptor (GnRHR), luteinizing hormone (LH), and LH receptor in serum in these patients, and to search for possible triggers and genetic factors behind the development of this dysmotility. Methods. Patients suffering from prolonged gastrointestinal complaints after treatment with GnRH analogs at the Department of Gastroenterology, Skane University Hospital, were included. GnRHR and LH receptor (LHCGR) genes were exome-sequenced. Serum was analyzed by enzyme-linked immune sorbent assays for the presence of antibodies. Healthy blood donors and women treated with GnRH analogs because of in vitro fertilization (IVF) were used as controls. Results. Seven patients with severe gastrointestinal complaints after GnRH treatment were identified, of whom six suffered from endometriosis. Several variants were found within the 11 exons of LHCGR. The minor allele G, at the single nucleotide polymorphism rs6755901, was detected in homozygosity in two patients (28.5%) who had developed chronic intestinal pseudo-obstruction and in 5.5% of the IVF controls. Three patients expressed IgM antibodies against progonadoliberin-2 and three against GnRH1 (42.9%) when cut off was set to a titer >97.5th percentile in blood donors. Conclusion. 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
chronic intestinal pseudo-obstruction, enteric dysmotility, gonadotropin-releasing hormone, in vitro fertilization, luteinizing, hormone, progonadoliberin-2
in
Scandinavian Journal of Gastroenterology
volume
50
issue
3
pages
291 - 299
publisher
Taylor & Francis
external identifiers
  • wos:000349399400005
  • scopus:84922700476
ISSN
1502-7708
DOI
10.3109/00365521.2014.958098
language
English
LU publication?
yes
id
db48522e-11f0-4429-8018-4f84e090561c (old id 5172996)
date added to LUP
2015-03-25 12:10:33
date last changed
2017-08-13 03:57:31
@article{db48522e-11f0-4429-8018-4f84e090561c,
  abstract     = {Background. Sporadic cases of abdominal pain and dysmotility has been described after treatment with gonadotropin-releasing hormone (GnRH) analogs. The aim of the present study was to scrutinize for patients with severe gastrointestinal complaints after treatment with GnRH analogs, to describe the expression of antibodies against progonadoliberin-2, GnRH1, GnRH receptor (GnRHR), luteinizing hormone (LH), and LH receptor in serum in these patients, and to search for possible triggers and genetic factors behind the development of this dysmotility. Methods. Patients suffering from prolonged gastrointestinal complaints after treatment with GnRH analogs at the Department of Gastroenterology, Skane University Hospital, were included. GnRHR and LH receptor (LHCGR) genes were exome-sequenced. Serum was analyzed by enzyme-linked immune sorbent assays for the presence of antibodies. Healthy blood donors and women treated with GnRH analogs because of in vitro fertilization (IVF) were used as controls. Results. Seven patients with severe gastrointestinal complaints after GnRH treatment were identified, of whom six suffered from endometriosis. Several variants were found within the 11 exons of LHCGR. The minor allele G, at the single nucleotide polymorphism rs6755901, was detected in homozygosity in two patients (28.5%) who had developed chronic intestinal pseudo-obstruction and in 5.5% of the IVF controls. Three patients expressed IgM antibodies against progonadoliberin-2 and three against GnRH1 (42.9%) when cut off was set to a titer >97.5th percentile in blood donors. Conclusion. 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.},
  author       = {Cordeddu, Lina and Bergvall, Monika and Sand, Elin and Roth, Bodil and Papadaki, Evangelia and Li, Ling and D'Amato, Mauro and Ohlsson, Bodil},
  issn         = {1502-7708},
  keyword      = {chronic intestinal pseudo-obstruction,enteric dysmotility,gonadotropin-releasing hormone,in vitro fertilization,luteinizing,hormone,progonadoliberin-2},
  language     = {eng},
  number       = {3},
  pages        = {291--299},
  publisher    = {Taylor & Francis},
  series       = {Scandinavian Journal of Gastroenterology},
  title        = {Severe gastrointestinal dysmotility developed after treatment with gonadotropin-releasing hormone analogs},
  url          = {http://dx.doi.org/10.3109/00365521.2014.958098},
  volume       = {50},
  year         = {2015},
}