Assessing Sex Steroid Influence on Kisspeptin Responsiveness in Idiopathic Hypogonadotropic Hypogonadism.

Abstract

ContextIndividuals with idiopathic hypogonadotropic hypogonadism (IHH), even those with evidence of some hypothalamic reproductive endocrine activity, fail to complete puberty and fail to respond to physiologic doses of kisspeptin.ObjectiveThis case series examined whether treatment with sex steroids could stimulate kisspeptin responsiveness in patients with IHH.DesignThis was a case series.SettingThis study was conducted at an academic medical center.ParticipantsSeven patients with IHH were studied.Intervention(s)Participants, both on and off sex steroid therapy, underwent frequent blood sampling to measure LH at baseline, in response to kisspeptin and GnRH.Main Outcome Measure(s)The main outcome measure was LH responses to kisspeptin on and off sex steroids.ResultsAll participants responded to exogenous GnRH, but no participant responded to exogenous kisspeptin. Sex steroid treatment did not modify responsiveness to kisspeptin.ConclusionsThe functional impairment of the GnRH neuronal network in patients with IHH, as evidenced by their inability to respond to a physiologic dose of kisspeptin, is observed in both sex steroid– deficient and sex steroid–replete states. In this case series, a normalized sex steroid milieu does not appear capable of overcoming the kisspeptin resistance of these patients.