Although spontaneous activation of the hypothalamic–pituitary–gonadal axis resulting in improved reproductive endocrine function is a hallmark of reversal of idiopathic hypogonadotropic hypogonadism (IHH), clinical features that can confidently predict reversal have yet to be identified. A new study now suggests that dynamic changes in the sensitivity of the gonadotropin-releasing hormone (GnRH) neuronal network to kisspeptin are responsible for this reversal. Six men with IHH and evidence of reversal (testicular volume growth after age 18 years without exogenous gonadotropins or GnRH therapy) at enrolment participated in the study. Upon administration of intravenous boluses of kisspeptin (0.24–2.20 nmol/kg), patients with sustained reversal of IHH (n = 4) had robust GnRH-induced pulsatile luteinizing hormone secretion, whereas those who had relapsed back to the hypogonadotropic state (n = 2) did not.
Lippincott, M. F. et al. Kisspeptin responsiveness signals emergence of reproductive endocrine activity: implications for human puberty. J. Clin. Endocrinol. Metab. http://dx.doi.org/10.1210/jc.2016-1545 (2016)
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Holmes, D. Acquisition of kisspeptin responsiveness is key to reversal of hypogonadotropic hypogonadism. Nat Rev Endocrinol 12, 436 (2016). https://doi.org/10.1038/nrendo.2016.95