Kisspeptin-10 Dosing for Gonadotropin Stimulation in Males
The typical effective dosage of kisspeptin-10 for stimulating gonadotropin release in male patients ranges from 300 mcg to 1000 mcg (0.3-1.0 mcg/kg) administered as an intravenous bolus, with maximal LH stimulation occurring at approximately 1000 mcg/kg (1.0 mcg/kg). 1, 2
Bolus Dosing Parameters
Minimal effective dose: As low as 300 mcg/kg (0.3 mcg/kg) produces robust LH and FSH elevation in healthy men 1, 2
Optimal single bolus dose: 1000 mcg/kg (1.0 mcg/kg) achieves maximal gonadotropin stimulation, increasing mean LH from baseline 4.1 IU/L to 12.4 IU/L at 30 minutes 2
Supramaximal dosing caveat: Doses of 3000 mcg/kg (3.0 mcg/kg) paradoxically elicit reduced LH responses compared to 1000 mcg/kg, suggesting receptor desensitization at higher doses 2
Dose-response relationship: Serum LH levels are approximately 3-fold lower with kisspeptin-10 compared to equivalent doses of GnRH, though kisspeptin may provide more physiological stimulation 1
Continuous Infusion Dosing
High-dose infusion: 4000 mcg/kg/hour (4.0 mcg/kg/h) for 22.5 hours increases mean LH from 5.4 IU/L to 20.8 IU/L and elevates testosterone from 16.6 nmol/L to 24.0 nmol/L 2
Moderate-dose infusion: 1500 mcg/kg/hour (1.5 mcg/kg/h) increases LH pulse frequency from 0.7 to 1.0 pulses/hour and increases LH secretory burst mass from 3.9 IU/L to 12.8 IU/L 2
Repeated bolus protocol: Four boluses of kisspeptin-10 at 75-minute intervals maintain consistent LH secretory responses without tachyphylaxis in animal models 3
Alternative Intranasal Delivery
Intranasal kisspeptin-54: 12,800 mcg/kg (12.8 nmol/kg) administered intranasally produces clinically significant LH increases of 4.4 IU/L above baseline in healthy men (mean difference 3.1 IU/L vs placebo, P=0.002) 4
Non-invasive advantage: Intranasal delivery offers the first non-invasive method to robustly stimulate gonadotropins, with kisspeptin-54 remaining stable for 60 days at 4°C and demonstrating no adverse events 4
Clinical Context and Limitations
Comparison to GnRH: Direct pituitary stimulation with GnRH produces approximately 2-3 fold higher gonadotropin levels than kisspeptin at equivalent doses, though kisspeptin stimulates the reproductive axis more physiologically through hypothalamic GnRH neuron activation 1
Kisspeptin-54 vs kisspeptin-10: Both isoforms produce similar gonadotropin responses when administered intravenously at equivalent doses in humans, though kisspeptin-54 shows slightly greater magnitude and duration of effect 1
Therapeutic potential: Kisspeptin analogues represent emerging therapeutic agents for regulating LH and testosterone secretion, particularly in hypogonadotropic hypogonadism where preservation of fertility is desired 2
Important Caveats
Sexual dimorphism: Kisspeptin-10 demonstrates markedly different responses between men and women, with women during the follicular phase showing no gonadotropin response to doses up to 10,000 mcg/kg (10 nmol/kg), while men respond robustly at 300 mcg/kg 5
Receptor desensitization: The reduced response at 3000 mcg/kg compared to 1000 mcg/kg suggests that higher doses do not necessarily produce greater effects and may cause receptor downregulation 2
Route-dependent efficacy: Intravenous administration produces more consistent and predictable responses than subcutaneous routes in current research, though intranasal delivery shows promise for clinical application 4, 5