Intranasal kisspeptin administration rapidly stimulates gonadotropin release in humans.

Summary

In a randomized, double-blind, crossover, placebo-controlled study, intranasal kisspeptin-54 rapidly increased serum LH in healthy men, healthy women, and patients with hypothalamic amenorrhea without adverse events. Pharmaceutical testing confirmed nasal delivery and stability, and rodent studies implicated an olfactory GnRH pathway.

Key Findings

• Intranasal kisspeptin-54 (12.8 nmol/kg) significantly increased serum LH across healthy men (+4.4 IU/L; mean difference 3.1 IU/L, P=0.002), healthy women (+1.4 IU/L; mean difference 1.0 IU/L, P=0.004), and hypothalamic amenorrhea patients (+4.4 IU/L; mean difference 4.3 IU/L, P<0.001).
• No side effects or adverse events were observed; nasal spray formulation remained stable up to 60 days at 4 °C.
• Rodent studies showed LH stimulation and fluorescently tagged kisspeptin accumulation in olfactory epithelium with kisspeptin receptors in olfactory bulb GnRH neurons, supporting a mechanistic pathway.

Clinical Implications

Intranasal kisspeptin may provide a patient-friendly alternative to injectable therapies for conditions like hypothalamic amenorrhea and could be integrated into diagnostic stimulation testing for GnRH/LH axis assessment.

Limitations

• Sample size and duration are not detailed in the abstract; long-term efficacy and safety remain to be established.
• Generalizability to broader reproductive disorders and dosing optimization require further trials.

Future Directions

Conduct larger, longer RCTs to evaluate reproductive outcomes (ovulation, pregnancy rates) and compare intranasal kisspeptin with established therapies; refine dosing and delivery for outpatient use.