Assessing Sex Steroid Influence on Kisspeptin Responsiveness in Idiopathic Hypogonadotropic Hypogonadism

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. 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. 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.