Leuprolide vs PE-22-28
Side-by-side comparison of key properties, dosing, and research.
Sexual Health & Libido
LeuprolideCognitive Enhancement
PE-22-28- Summary
- Leuprolide is a synthetic GnRH superagonist that, with continuous administration, paradoxically suppresses LH and FSH through receptor desensitization — the opposite effect of pulsatile GnRH. Used medically for prostate cancer, endometriosis, and precocious puberty. In men's health, short-duration use for PCT and testosterone suppression rebound.
- PE-22-28 is a synthetic analog of spadin derived from sortilin, designed to block TREK-1 potassium channels with rapid-onset antidepressant and neurogenic effects. It shows fast-acting depression relief (within 24 hours) and promotes hippocampal neurogenesis.
- Half-Life
- ~3 hours (SC/IM), but depot formulations last 1–12 months
- Relatively short; CNS effects may persist due to neurogenic mechanisms
- Admin Route
- SubQ, IM
- SubQ, Intranasal
- Research
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- Typical Dose
- 7.5 mg monthly, 22.5 mg 3-monthly, or 45 mg 6-monthly
- 200–400 mcg
- Frequency
- Per depot schedule
- Once daily
- Key Benefits
- Medical: reduces testosterone in prostate cancer
- Medical: suppresses estrogen in endometriosis and uterine fibroids
- Medical: delays precocious puberty
- Research: testosterone rebound effect after short course
- Transgender care: hormone suppression in adolescents
- Research: hormonal re-sensitization protocols
- Rapid-onset antidepressant effects (within 24 hours)
- Promotes hippocampal neurogenesis
- Improves cognitive performance and memory
- Reduces anxiety and depressive behavior
- Novel mechanism — does not act on serotonin/dopamine/GABA receptors directly
- May help treatment-resistant depression
- Neuroprotective effects
- Side Effects
- Hot flashes (with testosterone suppression)
- Decreased libido and erectile dysfunction
- Initial testosterone flare (first 1–2 weeks)
- Bone density loss with long-term use
- +3 more
- Generally well tolerated in animal models
- Limited human data available
- Possible mild headache or transient mood changes at initiation
- Injection site reactions (SC)
- Stacks With
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