Using Kisspeptin to Predict Pubertal Outcomes for Youth With Pubertal Delay

J Clin Endocrinol Metab. 2020 Aug 1;105(8):e2717-e2725. doi: 10.1210/clinem/dgaa162.


Context: The management of youth with delayed puberty is hampered by difficulty in predicting who will eventually progress through puberty and who will fail to attain adult reproductive endocrine function. The neuropeptide kisspeptin, which stimulates gonadotropin-releasing hormone (GnRH) release, can be used to probe the integrity of the reproductive endocrine axis.

Objective: We sought to determine whether responses to kisspeptin can predict outcomes for individuals with pubertal delay.

Design, setting, and participants: We conducted a longitudinal cohort study in an academic medical center of 16 children (3 girls and 13 boys) with delayed or stalled puberty.

Intervention and outcome measures: Children who had undergone kisspeptin- and GnRH-stimulation tests were followed every 6 months for clinical evidence of progression through puberty. Inhibin B was measured in boys. A subset of participants underwent exome sequencing.

Results: All participants who had responded to kisspeptin with a rise in luteinizing hormone (LH) of 0.8 mIU/mL or greater subsequently progressed through puberty (n = 8). In contrast, all participants who had exhibited LH responses to kisspeptin ≤ 0.4 mIU/mL reached age 18 years without developing physical signs of puberty (n = 8). Thus, responses to kisspeptin accurately predicted later pubertal outcomes (P = .0002). Moreover, the kisspeptin-stimulation test outperformed GnRH-stimulated LH, inhibin B, and genetic testing in predicting pubertal outcomes.

Conclusion: The kisspeptin-stimulation can assess future reproductive endocrine potential in prepubertal children and is a promising novel tool for predicting pubertal outcomes for children with delayed puberty.

Trial registration: NCT01438034.

Keywords: Delayed puberty; constitutional delay; hypogonadotropic hypogonadism; kisspeptin.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Diagnostic Techniques, Endocrine*
  • Exome Sequencing
  • Female
  • Follicle Stimulating Hormone / blood
  • Follow-Up Studies
  • Genetic Testing / methods
  • Gonadotropin-Releasing Hormone / administration & dosage
  • Humans
  • Inhibins / blood
  • Kisspeptins / administration & dosage*
  • Longitudinal Studies
  • Luteinizing Hormone / blood*
  • Male
  • Predictive Value of Tests
  • Prospective Studies
  • Puberty, Delayed / blood
  • Puberty, Delayed / diagnosis*
  • Puberty, Delayed / genetics
  • Reference Values


  • KISS1 protein, human
  • Kisspeptins
  • inhibin B
  • Gonadotropin-Releasing Hormone
  • Inhibins
  • Luteinizing Hormone
  • Follicle Stimulating Hormone

Associated data