What is the recommended dosage protocol for kisspeptin-10 (a peptide) in micrograms (mcg) for female patients?

Kisspeptin-10 Dosage Protocol for Female Patients

For acute gonadotropin stimulation in women, administer kisspeptin-10 as an intravenous bolus at 0.24-10 mcg/kg (240-10,000 mcg for a 70 kg woman), with the response varying significantly by menstrual cycle phase. 1, 2

Dosing by Clinical Context

Acute Gonadotropin Stimulation

Intravenous Bolus Administration:

• Standard dose: 0.24 mcg/kg (approximately 17 mcg for a 70 kg woman) effectively stimulates LH pulses in preovulatory and luteal phase women 2
• Higher dose: 0.3 mcg/kg (approximately 21 mcg for a 70 kg woman) stimulates LH secretion in follicular phase women, though response is inconsistent 3
• Maximum tested dose: 10 mcg/kg (700 mcg for a 70 kg woman) produces robust LH and FSH elevation in preovulatory phase women 1

Subcutaneous Bolus Administration:

• Dose: 6.4 mcg/kg (approximately 448 mcg for a 70 kg woman) produces potent LH increases (mean maximal increment 24.0 IU/L) and FSH increases (mean maximal increment 9.1 IU/L) in women with hypothalamic amenorrhea 4
• Maximum tested dose: 32 mcg/kg (2,240 mcg for a 70 kg woman) failed to stimulate gonadotropins in follicular phase women 1

Intravenous Infusion:

• Dose: 720 pmol/kg/min (0.72 mcg/kg/min) failed to stimulate gonadotropins in follicular phase women 1

Critical Cycle-Dependent Considerations

The response to kisspeptin-10 demonstrates profound sexual dimorphism and menstrual cycle variation that must guide clinical application:

• Preovulatory phase: Most responsive period; 10 mcg/kg IV bolus reliably elevates LH and FSH 1
• Luteal phase: Consistent LH pulse generation occurs immediately after 0.24 mcg/kg IV bolus 2
• Early follicular phase: Only 50% of women respond to 0.24 mcg/kg IV bolus; increasing to 0.72 mcg/kg does not improve response rate 2
• Hypothalamic amenorrhea: Highly responsive to 6.4 mcg/kg subcutaneous injection 4

Chronic Administration Protocols

Twice-daily subcutaneous injections at 6.4 mcg/kg for women with hypothalamic amenorrhea produce initial robust responses but result in tachyphylaxis by day 14:

• Day 1: LH increases by 24.0 ± 3.5 IU/L and FSH by 9.1 ± 2.5 IU/L 4
• Day 14: LH increases only by 2.5 ± 2.2 IU/L (P < 0.05) and FSH by 0.5 ± 0.5 IU/L (P < 0.05) 4
• GnRH responsiveness remains intact despite kisspeptin desensitization 4

Sex Steroid Modulation Effects

Endogenous and exogenous sex steroids profoundly alter kisspeptin responsiveness:

• Post-menopausal women (low endogenous steroids): Enhanced response with LH ΔAUC of 5.3 ± 0.9 IU/L·h and FSH ΔAUC of 2.6 ± 0.8 IU/L·h after 0.3 mcg/kg IV 3
• Combined oral contraceptive users: Suppressed response with LH ΔAUC of only 0.9 ± 0.4 IU/L·h (P = 0.13, not significant) after 0.3 mcg/kg IV 3
• Progestogen implant users: Preserved response with LH ΔAUC of 2.6 ± 0.8 IU/L·h (P < 0.05) after 0.3 mcg/kg IV 3

Practical Dosing Algorithm

For diagnostic or acute therapeutic use:

1. Determine menstrual cycle phase or hormonal status (amenorrhea, post-menopausal, contraceptive use) 1, 2, 3
2. Preovulatory/luteal phase or hypothalamic amenorrhea: Use 0.24-10 mcg/kg IV bolus or 6.4 mcg/kg subcutaneous 1, 4, 2
3. Early follicular phase: Expect inconsistent response; consider higher doses (up to 10 mcg/kg IV) or alternative timing 1, 2
4. Post-menopausal: Use lower doses (0.3 mcg/kg IV) due to enhanced sensitivity 3
5. Contraceptive users: Combined estrogen-progestogen suppresses response; progestogen-only preserves partial response 3

Critical Pitfalls to Avoid

• Do not use chronic kisspeptin administration for sustained gonadotropin stimulation, as tachyphylaxis develops within 2 weeks despite preserved GnRH responsiveness 4
• Do not assume consistent responses across the menstrual cycle; early follicular phase women show markedly reduced responsiveness compared to preovulatory or luteal phases 1, 2
• Do not extrapolate male dosing to females; men respond to doses as low as 0.3 mcg/kg (21 mcg for a 70 kg man), whereas women require cycle-dependent dosing 1, 5
• Do not administer to women on combined oral contraceptives expecting robust responses, as estrogen-progestogen combinations suppress kisspeptin responsiveness 3