Responsiveness to a physiological regimen of GnRH therapy and relation to genotype in women with isolated hypogonadotropic hypogonadism.

Détails

ID Serval
serval:BIB_44E23B2760A4
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Responsiveness to a physiological regimen of GnRH therapy and relation to genotype in women with isolated hypogonadotropic hypogonadism.
Périodique
Journal of Clinical Endocrinology and Metabolism
Auteur⸱e⸱s
Abel B.S., Shaw N.D., Brown J.M., Adams J.M., Alati T., Martin K.A., Pitteloud N., Seminara S.B., Plummer L., Pignatelli D., Crowley W.F., Welt C.K., Hall J.E.
ISSN
1945-7197 (Electronic)
ISSN-L
0021-972X
Statut éditorial
Publié
Date de publication
2013
Volume
98
Numéro
2
Pages
E206-E216
Langue
anglais
Notes
Publication types: Clinical Trial ; Journal Article ; Research Support, N.I.H., ExtramuralPublication Status: ppublish
Résumé
CONTEXT: Isolated hypogonadotropic hypogonadism (IHH) is caused by defective GnRH secretion or action resulting in absent or incomplete pubertal development and infertility. Most women with IHH ovulate with physiological GnRH replacement, implicating GnRH deficiency as the etiology. However, a subset does not respond normally, suggesting the presence of defects at the pituitary or ovary.
OBJECTIVES: The objective of the study was to unmask pituitary or ovarian defects in IHH women using a physiological regimen of GnRH replacement, relating these responses to genes known to cause IHH.
DESIGN, SETTING, AND SUBJECTS: This study is a retrospective analysis of 37 IHH women treated with iv pulsatile GnRH (75 ng/kg per bolus).
MAIN OUTCOME MEASURES: Serum gonadotropin and sex steroid levels were measured, and 14 genes implicated in IHH were sequenced.
RESULTS: During their first cycle of GnRH replacement, normal cycles were recreated in 60% (22 of 37) of IHH women. Thirty percent of women (12 of 37) demonstrated an attenuated gonadotropin response, indicating pituitary resistance, and 10% (3 of 37) exhibited an exaggerated FSH response, consistent with ovarian resistance. Mutations in CHD7, FGFR1, KAL1, TAC3, and TACR3 were documented in IHH women with normal cycles, whereas mutations were identified in GNRHR, PROKR2, and FGFR1 in those with pituitary resistance. Women with ovarian resistance were mutation negative.
CONCLUSIONS: Although physiological replacement with GnRH recreates normal menstrual cycle dynamics in most IHH women, hypogonadotropic responses in the first week of treatment identify a subset of women with pituitary dysfunction, only some of whom have mutations in GNRHR. IHH women with hypergonadotropic responses to GnRH replacement, consistent with an additional ovarian defect, did not have mutations in genes known to cause IHH, similar to our findings in a subset of IHH men with evidence of an additional testicular defect.
Mots-clé
Adolescent, Adult, Female, Genotype, Gonadotropin-Releasing Hormone/administration & dosage, Gonadotropin-Releasing Hormone/therapeutic use, Hormone Replacement Therapy/methods, Humans, Hypogonadism/drug therapy, Hypogonadism/genetics, Middle Aged, Mutation, Pituitary Gland/physiopathology, Retrospective Studies, Treatment Outcome
Pubmed
Web of science
Open Access
Oui
Création de la notice
12/04/2013 17:56
Dernière modification de la notice
20/08/2019 13:49
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