Kisspeptin
Kisspeptin-54 / Kisspeptin-10
Kisspeptin is a neuropeptide encoded by the KISS1 gene that plays a critical role in regulating the hypothalamic-pituitary-gonadal (HPG) axis. It stimulates gonadotropin-releasing hormone (GnRH) secretion by binding to the GPR54/Kiss1R receptor, making it essential for reproductive function, puberty onset, and fertility. Originally discovered as a metastasis suppressor in certain cancers, kisspeptin has emerged as a promising therapeutic target for reproductive disorders including infertility, hypothalamic amenorrhea, and hypoactive sexual desire disorder.
Kisspeptin Dosing Guide
Primary Benefits
- Stimulates natural gonadotropin-releasing hormone (GnRH) production
- Increases luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels
- Effective alternative to hCG for IVF ovulation induction with 23% pregnancy rate
- Improves reproductive function in hypothalamic amenorrhea
- Modulates sexual brain processing in hypoactive sexual desire disorder
How It Works
Kisspeptin exerts its effects by binding with high affinity to the G-protein coupled receptor GPR54 (also known as Kiss1R), which is predominantly expressed on GnRH neurons in the hypothalamus. Upon binding, it activates the Gq/11 signaling pathway, leading to increased intracellular calcium levels and phospholipase C activation. This cascade stimulates GnRH neurons to release GnRH into the hypothalamic-pituitary portal system, which subsequently binds to GnRH receptors on gonadotroph cells in the anterior pituitary. The result is pulsatile release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which regulate gonadal steroidogenesis and gametogenesis. The kisspeptin/Kiss1R system serves as the master regulator of reproductive function and is essential for pubertal development and maintenance of fertility.
Quick Reference
Typical Dosage Range
Kisspeptin dosing protocols vary significantly based on the specific clinical application and desired outcome. For IVF ovulation induction, single subcutaneous doses of kisspeptin-54 range from 1.6 nmol/kg (minimal effective dose) to 12.8 nmol/kg (optimal efficacy dose), administered 36 hours after final gonadotropin injection. For hypothalamic amenorrhea treatment, the established protocol uses 6.4 nmol/kg subcutaneously twice weekly for 8 weeks, with monitoring of LH and FSH levels. In research settings for male subjects, kisspeptin-10 doses from 0.03-3.0 μg/kg intravenously have been used to assess HPG axis responsiveness. For hypoactive sexual desire disorder studies, continuous intravenous infusion at 1 nmol/kg/h for 75 minutes has been employed. Chronic administration requires careful monitoring due to potential receptor desensitization and tachyphylaxis, necessitating dose holidays or pulsatile protocols to maintain efficacy.
Administration Methods
Kisspeptin administration requires careful attention to route, timing, and preparation to ensure optimal bioavailability and efficacy. For subcutaneous injection (most common clinical route), kisspeptin-54 is reconstituted in sterile saline or water for injection at concentrations of 1-2 mg/mL, administered via 25-27 gauge needle into the abdominal subcutaneous tissue. Injection sites should be rotated to prevent local irritation. For intravenous administration, kisspeptin is diluted in normal saline and given as either bolus injection (over 1-2 minutes) or continuous infusion (typically 75 minutes for research protocols). The peptide should be protected from light and used within 24 hours of reconstitution. Pre-medication with antihistamines is not routinely required but may be considered in patients with known allergies. Monitoring of vital signs is recommended during initial administration, particularly with intravenous routes.
What It's Used For
Kisspeptin-10 is a master reproductive hormone regulator that stimulates the hypothalamic-pituitary-gonadal (HPG) axis. It acts upstream to trigger natural hormone cascades, making it essential for fertility and hormonal balance.
Male Fertility Enhancement
Increases LH and FSH to boost testosterone and sperm production naturally
Female Fertility Support
Helps trigger ovulation and regulates menstrual cycles in women with hormonal imbalances
TRT Support
Prevents testicular atrophy and maintains fertility during TRT by preserving natural hormone signaling
Sexual Enhancement
Enhances libido and sexual brain processing in both men and women
IVF & Assisted Reproduction
Safer alternative to hCG for triggering egg maturation with lower risk of ovarian hyperstimulation
How Much to Take
For Fertility
100-200 mcg every 3 days
Pulse dosing prevents receptor desensitization and maintains natural hormone rhythms
For TRT Support
50-100 mcg twice weekly
Maintains testicular function and natural hormone production during testosterone therapy
For Libido Enhancement
50 mcg every 3 days
Lower doses for sexual enhancement, effects occur within 2-4 hours of injection
Frequency
Every 2-3 days for pulse dosing. Avoid daily dosing to prevent receptor desensitization.
Timing
Morning injections align with natural hormone rhythms. For sexual enhancement, inject 2-3 hours prior.
Adjustment
Start with lower doses and monitor hormone response. Adjust based on lab results and symptoms.
How Long to Use It
Recommended Cycle Length
Use for 4-6 weeks, followed by a break of 2-4 weeks. Maximum duration: avoid continuous use beyond 8 weeks without breaks.
First results: Hormone changes within 24-48 hours. Sexual and fertility benefits typically seen after 2-3 weeks of consistent use.
Critical Timing Guidelines
- Never use daily for extended periods - causes receptor desensitization
- Take regular breaks to maintain effectiveness and reset sensitivity
- Women should time based on menstrual cycle - most effective during preovulatory phase
- If effects diminish, take a 2-4 week break to restore responsiveness
Need-to-Know Information
How It Works
Binds to KISS1R receptors in the hypothalamus and stimulates GnRH neurons to release gonadotropin-releasing hormone. This triggers a natural cascade of LH and FSH from the pituitary, maintaining the body's natural feedback loops unlike direct hormone replacement.
Key Benefits
- Natural Stimulation: Works with your body's existing systems, not against them
- No Cortisol/Prolactin Effects: Unlike older peptides, doesn't affect stress hormones
- Preserves Fertility: Ideal for men on TRT who want to maintain fertility
- Gender-Specific Response: Effects vary based on menstrual cycle phase in women
Who Should Avoid It
- Pregnant or breastfeeding women
- Those with hormone-sensitive cancers
- People with active pituitary tumors
- Women during follicular phase (less responsive)
Possible Side Effects
- Injection site irritation
- Temporary flushing or warmth
- Mild headache
- Potential hormone fluctuations if overdosed
Storage & Injection
Mixing Instructions
Use bacteriostatic water to reconstitute the peptide.
Example: Add 2 mL of bacteriostatic water to a 5 mg vial. For a 100 mcg dose, draw 0.04 mL (4 units on insulin syringe).
Storage Requirements
Store mixed vials in the fridge at 2-8°C (36-46°F).
Use within 30 days after reconstitution. Protect from light and avoid shaking.
Injection Sites
- Belly fat (most common)
- Upper thigh
- Buttocks area
Method
Subcutaneous (under the skin). Clean site with alcohol, pinch skin, insert at 45-degree angle.
Tips
Inject slowly, rotate sites, time injections based on your protocol (not daily).
Example Schedule
Weekly Dosing Schedules
Male Fertility Protocol
Monday: 200 mcg injection
Thursday: 200 mcg injection
Continue for 4-6 weeks, then 2-week break
Female Fertility Protocol
Day 10-12: 100 mcg injection
Day 13-14: 150 mcg injection
Monitor ovulation and adjust timing
TRT Support Protocol
Tuesday: 100 mcg injection
Friday: 100 mcg injection
Continue throughout TRT cycle
Missed Dose Guidelines
If you miss a dose, take it as soon as you remember, but maintain the 2-3 day spacing between injections. Do not double dose to make up for missed injections. Since kisspeptin works on pulse dosing, missing one injection won't significantly impact your overall progress.
Extra Tips for Best Results
Timing is Everything
Pulse dosing (every 2-3 days) is more effective than daily dosing. Prevents receptor downregulation and maintains sensitivity.
Monitor Hormone Levels
Test LH, FSH, and testosterone/estrogen before starting. Retest after 4 weeks to assess response and adjust dosing.
For Male Fertility
Combine with lifestyle changes: reduce heat exposure to testicles, maintain healthy weight, exercise regularly, consider zinc and vitamin D supplementation.
For Female Fertility
Most effective during preovulatory phase (days 10-14). Less responsive during follicular phase. Track ovulation with basal body temperature.
Expected Timeline
24-48 Hours
Initial hormone changes detectable in blood work
Week 2-3
Sexual and fertility benefits become noticeable
Week 4-6
Peak fertility and hormone optimization effects
Important Reminders
- Research compound only - Not FDA-approved for human therapeutic use
- Avoid receptor fatigue - Never use daily for extended periods without breaks
- Monitor hormone levels - Regular blood work is essential for safe use
- Gender-specific timing - Women should coordinate with menstrual cycle phases
- Consider medical supervision - Especially important for fertility applications
Medical Disclaimer
Kisspeptin is in Phase 2 clinical trials for reproductive applications. This information is for educational purposes only and should not be construed as medical advice. Any clinical use should occur only under medical supervision in approved research or clinical settings.