Chronic subcutaneous kisspeptin-10 stimulates gonadotropin secretion for 12 days in healthy men

Daily intermittent subcutaneous kisspeptin-10 infusions sustained gonadotropin and testosterone secretion in healthy men for 12 days, whereas a 5-day continuous infusion raised testosterone but not gonadotropins. Acute infusions produced dose-dependent rises in LH, FSH, and testosterone, and kisspeptin receptor responsiveness remained detectable after 12 days. These findings provide a basis for chronic kisspeptin dosing protocols for reproductive disorders.

Randomized controlled trial — Randomized, single-blinded, placebo-controlled study. Population: Healthy men across three substudies; 12 men served as controls. Sample size: 15 healthy men overall (substudy n=7, n=4, and n=7; 12 controls). Follow-up: 8 h acute; 5 days continuous; 12 days intermittent (8 h/day). Interventions: subcutaneous kisspeptin-10 infusion (1.25-10.0 nmol/kg/h for 8 h); continuous subcutaneous kisspeptin-10 infusion (180 nmol/h for 5 days); daily 8 h subcutaneous kisspeptin-10 infusion (150 nmol/h for 12 days); kisspeptin-10 bolus (1 nmol/kg).

Acute subcutaneous kisspeptin-10 infusions at 1.25-10.0 nmol/kg/h dose-dependently increased LH, FSH, and testosterone versus vehicle (P<.0001). After 5 days of continuous kisspeptin-10 at 180 nmol/h, testosterone remained elevated but gonadotropins were similar to vehicle. Daily 8 h infusions at 150 nmol/h over 12 days sustained gonadotropin increases: mean LH increase was -0.16 ± 0.19 with vehicle versus +1.68 ± 0.25 on day 1 and +1.14 ± 0.33 on day 12 (P=.003 versus vehicle). A 1 nmol/kg kisspeptin-10 bolus given after the 12-day period still produced gonadotropin rises, indicating kisspeptin receptor function was preserved.

This paper provides kisspeptin researchers with evidence that intermittent subcutaneous kisspeptin-10 can maintain gonadotropin and testosterone secretion over 12 days while preserving kisspeptin receptor responsiveness, which is relevant for chronic dosing protocols. It does not establish clinical efficacy, long-term safety, or optimal dosing for treating reproductive disorders.

Key findings

Acute 8 h subcutaneous kisspeptin-10 infusions at 1.25-10.0 nmol/kg/h dose-dependently increased LH, FSH, and testosterone versus vehicle (P<.0001).
After 5 days of continuous kisspeptin-10 at 180 nmol/h, testosterone remained elevated but gonadotropin concentrations were similar to vehicle.
Daily 8 h subcutaneous infusions at 150 nmol/h for 12 days sustained gonadotropin increases, with mean LH change of -0.16 ± 0.19 on vehicle versus +1.68 ± 0.25 on day 1 and +1.14 ± 0.33 on day 12 (P=.003 versus vehicle).
A 1 nmol/kg kisspeptin-10 bolus after 12 days still produced gonadotropin rises, indicating kisspeptin receptor function was preserved.

Limitations

Small sample and small substudy groups (n=4-7).
Single-blinded, short-term design in healthy men, with no follow-up beyond 12 days.
Results in healthy men may not generalize to patients with reproductive disorders.

The record

Journal: European journal of endocrinology 195(2): 206-216
Published: 2026-08-04
PMID: 42549827 — DOI: 10.1093/ejendo/lvag134
MeSH terms: Humans, Testosterone, Gonadotropins, Follicle Stimulating Hormone, Luteinizing Hormone, Injections, Subcutaneous, Single-Blind Method, Dose-Response Relationship, Drug, Adult, Male, Infusions, Subcutaneous, Young Adult, Kisspeptins, Hypothalamic-Pituitary-Gonadal Axis
Funding: Medical Research Council; NIHR/Imperial Biomedical Research Centre; National Institute for Health Research (NIHR); NIHR/Wellcome Trust Imperial Clinical Research Facility
Author countries: United Kingdom

Peptide profiles: Kisspeptin.

All indexed evidence: Kisspeptin trials & papers.