Abstract
Background: The management of youth presenting with delayed puberty is challenging because it can be difficult to predict which children will eventually progress through puberty and which children will not. We have previously shown that exogenous administration of the neuropeptide kisspeptin, which stimulates GnRH release, can be used to probe the integrity of the reproductive endocrine axis. We hypothesized that responses to kisspeptin could predict outcomes for individuals with pubertal delay. Methods: We conducted a longitudinal study of 16 children (3 girls and 13 boys) with delayed or stalled puberty who had undergone stimulation testing with kisspeptin and GnRH. Participants were followed with serial physical examinations and laboratory studies every six months for evidence of progression through puberty. Inhibin B was measured in boys. A subset of participants underwent exome sequencing. Results: “Kisspeptin responders” who had responded to kisspeptin with a rise in LH of 0.8 mIU/mL or greater all subsequently progressed through puberty (n = 8). In contrast, “kisspeptin nonresponders” who had exhibited LH responses to kisspeptin ≤0.4 mIU/mL all reached age 18 years without developing physical signs of puberty (n = 8). Thus, responses to kisspeptin accurately predicted later pubertal outcomes (p = 0.0002), with sensitivity and specificity of 100% (95% CI 74-100%). Moreover, the kisspeptin-stimulation test outperformed overnight LH measurements, GnRH-stimulated LH, inhibin B, and genetic testing in predicting pubertal outcomes. Conclusion: The kisspeptin-stimulation test can be used to reveal future reproductive endocrine potential in prepubertal children and is a promising novel tool for predicting pubertal outcomes for children with delayed puberty. Trial registration: ClinicalTrials.gov NCT01438034
Influences of the stress endocrine system on the reproductive endocrine axis in sheep (Ovis aries)