Context: Individuals 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.
Objective: This case series examined whether treatment with sex steroids could stimulate kisspeptin responsiveness in patients with IHH.
Design: This was a case series.
Setting: This study was conducted at an academic medical center.
Participants: Seven patients with IHH were studied.
Interventions: 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 measures: The main outcome measure was LH responses to kisspeptin on and off sex steroids.
Results: All participants responded to exogenous GnRH, but no participant responded to exogenous kisspeptin. Sex steroid treatment did not modify responsiveness to kisspeptin.
Conclusions: The 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.
Keywords: hypogonadotropic hypogonadism; kisspeptin; sex steroids.