Hormonal & HPTA

Hormone replacement for hypogonadal men; widely used off-label for performance and body composition.

Alpha-MSH's Anti-Inflammatory Fragment — And It May Work Completely Differently Than Everyone Thinks

Six Human Clinical Trials. 900+ Participants. Safety Indistinguishable From Placebo. Primary Fat Loss Endpoint Failed. WADA Banned. FDA Rejected for Compounding. The Community Uses It Anyway at Doses That Never Worked in the Trials.

NOT a Peptide — An Oral Small Molecule Drug in Active Phase 1b/2 Clinical Development. Formerly O-304 (Betagenon). Now ATX-304 (Amplifier Therapeutics / Cambrian Bio). Pan-AMPK Activator + Mitochondrial Uncoupler. Exercise Mimetic. Phase 2a Human Data: Significant Fasting Glucose Reduction in T2D. Multiple Strong Animal Studies: Fat Loss, MASLD, Cardiovascular, Kidney Protection. The Most Clinically Advanced Novel Compound in This Book.

The Mitochondrial Uncoupler That Doesn't Kill You. DNP Kills People in 2026. BAM15 Was Designed to Solve That. Fat Loss Without Hyperthermia. Without Reduced Food Intake. Without Lean Mass Loss. Without Toxicity Markers. In Mice. Nature Communications 2020. Zero Human Trials. The Most Mechanistically Elegant Fat Loss Compound in This Book — and the Most Preclinical.

GlaxoSmithKline Halted Their Own Drug in 2007 Because It Caused Cancer in Every Animal Species They Tested. The Community Is Still Using It. The Drug Worked. That Is the Entire Problem.

The Most Prescribed GH Secretagogue Combination in Clinical Practice — and the One Decision That Changes Everything: DAC or No DAC.

The Pure Active Isomer in Clomid. The Drug That Raised Testosterone as Well as TRT While Preserving Fertility — and Still Failed FDA Approval. The Zuclomiphene Problem: Why the Racemic Mixture Causes Side Effects Pure Enclomiphene Shouldn't. The NDA That Died in 2021. How It Differs from TRT, HCG, and Gonadorelin for Male Hypogonadism. The 2025 Meta-Analysis: +273 ng/dL Testosterone vs Placebo.

NOTE: This chapter covers GHK as a free tripeptide — its endogenous biology, copper-carrier function, and primary topical cosmetic applications. The systemic, injectable, and regenerative applications of the copper-chelated complex are covered in the GHK-Cu chapter, which should be read alongside or before this chapter. Plasma Levels: 200 ng/mL at Age 20, Declining to 80 ng/mL by Age 60. The Connectivity Map and 4,000 Genes. Loren Pickart (1938–2023). The Copper Switch.

The Most Potent Injectable GHRP. Japan-Approved as a Diagnostic Agent. WADA S2 Banned. The Cortisol Problem That Cuts Against What You're Using It For. The Compound the Community Has Mostly Moved Past — and Why Understanding It Anyway Matters.

The Nobel Prize Decapeptide (Schally and Guillemin, 1977). The Compound That Is Stimulatory When Pulsatile and Suppressive When Continuous — From the Same Receptor. The Most Pharmacologically Nuanced Chapter in This Book. Why the FDA's March 2020 HCG Compounding Ban Changed TRT Practice Overnight. Gonadorelin vs HCG: The Fertility Preservation Head-to-Head. Why FSH Matters for Spermatogenesis. The Pulsatile Dosing Problem in Practice.

The Compound Every Secretagogue in This Book Targets. 191 Amino Acids. FDA-Approved for GH Deficiency, HIV Wasting, Short Bowel Syndrome. July 2025: Skytrofa Once-Weekly Now Approved for Adults. The Pulsatile vs Continuous GH Exposure Distinction. IGF-1 as the Surrogate Marker. The Fake HGH Crisis. WADA S2 Absolute Ban. Why Secretagogues (Sermorelin, Ipamorelin, MK-677) Are Different. The Active Malignancy Hard Stop. The Cancer-IGF-1 Question That Never Goes Away.

FDA-Approved for Fertility and Male Hypogonadism. The Most Important Hormone in Post-Cycle Therapy. The Active Ingredient in the Simeons 500-Calorie Diet — a Fraud With Its Own FDA Warning. WADA S2 Banned. A Tumor Marker. Three Completely Different Identities in One Glycoprotein.

Designed as a Research Tool to Bypass IGFBP Regulation. ~100-Fold Reduced Binding-Protein Affinity. 20-30 Hour Half-Life vs IGF-1's 10-15 Minutes. The Most Potent IGF-1 Analog Available. No Controlled Human Trial for Body Composition. No Tumor Selectivity. WADA S2 Banned. A Compound Whose Full Cancer Risk Is Genuinely Unknown.

The Drug That Reversed Brain Aging in Mice. Discovered by Phenotypic Screen. Target Unknown for 7 Years. ATP Synthase: The Unexpected Bridge Between Alzheimer's and Aging. BDNF Induction. AMPK/mTOR via a Completely Novel Entry Point. Phase 1 Human Safety Trial Completed (NCT03838185). The Compound That Is Structurally Related to Curcumin But Pharmacologically Nothing Like It.

40+ Years of Russian Research. 500+ Publications. One Institution. The Most Concentrated Single-Lab Provenance of Any Compound Class in This Book. Vladimir Khavinson (1946-2024) and the St. Petersburg Institute of Bioregulation and Gerontology. The Epigenetic Chromatin Mechanism. The Cytomax vs Cytogen Distinction. The 6-to-8-Year Mortality Study. The 2025 Independent Replication That Changed the Evidence Conversation. 14 Organ-Specific Bioregulators — Their Sequences, Targets, Evidence, and Protocols.

Named After Hershey's Kisses. Discovered as a Metastasis Suppressor Gene. Repurposed as the Master Upstream Regulator of the Entire HPG Axis. The Most Potent Known Activator of GnRH Neurons. Human Clinical Trials in Hypogonadotropic Hypogonadism, Hypothalamic Amenorrhea, IVF Triggering, and Hypoactive Sexual Desire Disorder. Limbic Brain Activation Proven by fMRI. No FDA Approval. The Most Pharmacologically Compelling Compound in PCT That No One Has Properly Studied for PCT.

NOT a Peptide — An Amino Acid Quaternary Ammonium Compound. The Most Commercially Overstated Compound in This Book. Genuine Grade B Evidence for Neuropathy (ALCAR), Peripheral Artery Disease (PLCAR), Muscle Recovery (LCLT), Male Infertility (L-Carnitine), and Post-MI Cardiac Outcomes. The TMAO Safety Question. Why Using the Wrong Form Explains Half the Negative Trials. FDA-Approved for Dialysis-Related Carnitine Deficiency.

The Most Phase-1-Tested SARM in History. The Problem: Phase 1 Used 0.1-1 mg. The Community Uses 5-20 mg. +1.21 kg Lean Mass at 1 mg in 21 Days. Phase 2 Hip Fracture Trial Positive. HPTA Suppression Dose-Dependent and Documented in Clinical Data. The Dose Gap Between Clinical Trials and Community Use Is the Central Risk Issue. Multiple Elite Athlete Doping Violations Including Canelo Álvarez. WADA S1.2.

NOT a Single Molecule — A Compounded Formulation That Varies by Pharmacy. The Most Commercially Prominent Injectable in Weight Loss Clinics. Zero RCTs for the Combination as a Weight Loss Intervention. Strong Component-Level Evidence for Inositol in PCOS/Insulin Resistance (Oral). Legitimate Bioavailability Advantage for B12 Injection in Deficiency Only. The Injection That Is More Psychologically Than Pharmacologically Distinctive.

The Only Oral Compound in This Book That Reliably Raises GH and IGF-1. GHSR-1a Agonist: Not a SARM. The Merck Story: Six Indications, No NDA, Program Discontinued. IGF-1 Goes Up. Fat-Free Mass Goes Up. Strength Doesn't Follow. Glucose Does Go Up. Appetite Definitely Goes Up. The CHF Signal in Elderly Patients. FDA October 2024 PCAC: No Compounding. WADA S2. The Water Weight Trap. Why Sleep Quality Is the Most Reliable Benefit. The Community's Most Misunderstood Compound.

Tuftsin → Selank → N-Acetyl Selank Amidate: Three Generations of Molecular Engineering. Russian-Approved Anxiolytic Without Sedation, Without Tolerance, Without Dependence. Comparable to Benzodiazepines for GAD With Psychostimulant Properties They Lack. BDNF Upregulation. Enkephalin Stabilization. The Evidence Is for Selank. NASA Is the More Stable Delivery Format Whose Equivalent Efficacy Is Chemically Logical but Clinically Unproven.

ACTH Fragment Without the Cortisol Effect. Russia's Premier Nootropic-Neuroprotective Peptide. Approved for Stroke, Encephalopathy, Optic Nerve Atrophy, Cognitive Disorders. BDNF Upregulation 50-300% in Hippocampus and Frontal Cortex. Default Mode Network Changes by fMRI. 71% vs 41% Memory Test Accuracy in Fatigued Volunteers. Half-Life Extended from 3-5 Minutes (Semax) to 4-6 Hours (MASA) by N-Acetyl and Amidate Modifications.

The Most Legitimate Longevity Target in This Book. The Most Commercially Weaponized. The Man Promoting NMN Has Financial Ties to NMN. The Man Criticizing Him Has Financial Ties to NR. The Clinical Evidence Is Real and More Modest Than Either Side Tells You.

The Most Clinically Studied SARM. The Phase 3 Trials That Nearly Got It Approved. Why the FDA Said No — and Why It Matters. The Most Modest HPTA Suppression Profile in the SARM Class. The Lowest Hepatotoxicity Signal. The Closest Any SARM Has Come to an FDA Indication. Why Phase 3 Failure Doesn't Mean the Compound Doesn't Work. Jonas Brodin and the NHL Doping Case.

The First Peptide Ever Synthesized (Nobel Prize 1955). FDA-Approved for Obstetric Use Since the 1950s. The 'Love Hormone' That Science Has Substantially Complicated. Intranasal Bioavailability ~2%. Trust Enhancement Replication Failures. Autism Trials: Mixed to Null. Context-Dependent Effects That Can Go Either Direction. And an OTC Nasal Spray Industry Built on Evidence That Doesn't Support What It Claims.

The 7-Amino-Acid Antidepressant That Works in 4 Days Instead of 4 Weeks. TREK-1: The Potassium Channel That Keeps You Depressed. IC50 of 0.12 nM — 333x More Potent Than Its Parent Spadin. Duration Extended to 23 Hours vs 7 Hours. Hippocampal Neurogenesis in 4 Days. The Same One French Research Group Since 2010. Zero Human Trials. A Novel Mechanism That Bypasses the Serotonin Transporter Entirely.

The Only FDA-Approved Peptide in This Book — Approved for Women, Used Primarily by Men, for Different Reasons, With Different Evidence.

The Selectivity Claim That Doesn't Hold Up in the Only Published Human Trial. Phase 1 Breast Cancer Study: 59% Elevated AST, 45% Elevated ALT. Six or More Published DILI Case Reports — Including Near-Transplant Cholestatic Hepatitis. HPTA Suppression: As Real as Testosterone. WADA S1.2 Absolute Ban. FDA Warnings. The 53% Problem: Only Half of SARM Products Contain What They Claim. Why 'Fewer Side Effects Than Steroids' Doesn't Mean Safe.

The ITP Mouse Data: Lifespan Extended at Multiple Labs, Doses, and Start Ages. The PEARL Trial (April 2025): First 48-Week Placebo-Controlled Human Longevity Trial Published. The Bioavailability Finding That Changes Everything: Compounded Rapamycin Is ~3x Less Bioavailable Than Commercial. Intermittent vs Continuous Dosing: The Pharmacological Divide Between Transplant Medicine and Longevity Use. The Immunosuppression Risk That Needs Honest Framing. The Drug Interaction Profile That Makes This the Most Dangerous Compound in This Book to Stack. Why the Community Uses ~6 mg Weekly. What Happens When You Stop.

The Drug That Extended Rat Lifespan in 1988 and Still Fascinates the Longevity Community. Irreversible MAO-B Inhibitor. Dopamine Preservation. BDNF Upregulation. The DATATOP Trial: Symptomatic Effect, Not Neuroprotection — The Distinction That Matters. The Amphetamine Metabolites: L-Enantiomers Only — What That Means Clinically. Low-Dose Community Protocols (1-5 mg Every Few Days). Why High-Dose Loses MAO-B Selectivity and What Happens Then. Selegiline vs Rasagiline. The Cheese Reaction: When It Applies and When It Doesn't.

The Only FDA-Approved Drug in This Book. The Most Prescribed Drug in Human History. STEP Program: -14.9% Body Weight at 68 Weeks. SELECT Trial: 20% Reduction in Major Cardiovascular Events. Grade A Evidence Across the Broadest Human Trial Program of Any Compound in This Book. The Weight Rebound Question: 2/3 of Weight Returns Within 1 Year of Stopping in Controlled Trials. The Compounded Semaglutide Regulatory Crisis. What the Real-World Data Actually Shows About Discontinuation.

Genuinely FDA-Approved for 18 Years. Withdrawn for Commercial Reasons, Not Safety. The Gateway Anti-Aging Peptide for a Decade of Compounding Medicine. Put on Category 2 in 2023. Apparently Returned to Category 1 Before the Broader 2026 Reclassification. The Cleanest Safety Profile of Any GH Secretagogue. The Somatostatin Feedback Ceiling That Makes It Physiologically Impossible to Overdose.

Not a Peptide. 70% Endurance Gain in Mice. Zero Human Trials. WADA Banned Before Anyone Had Studied It in a Human.

Ketamine Without the Dissociation. Oral Once-Daily. AMPA Receptor Positive Allosteric Modulation: The Glutamate Pathway to Antidepressant Effect. Phase 2 SAVITRI (Psych Congress September 2025): Statistically Significant Improvements in Depression Severity. No Body Sway. No Subjective Drug Effects. No Dissociation. No Abuse Liability. Takeda Licensed to Neurocrine Biosciences. Phase 3 Development Horizon 2026-2027.

The Only FDA-Approved GHRH Analog. Two Phase 3 RCTs in HIV Lipodystrophy — 15-18% Visceral Fat Reduction. A Lancet HIV NAFLD Trial Showing 37% Liver Fat Reduction and Fibrosis Prevention. A Cognitive Function Trial in Older Adults. And a Prescribing Label That Explicitly Says It Is Not a Weight Loss Drug.

The Most Referenced Compound in This Book Given Its Own Chapter. FDA-Approved for Confirmed Hypogonadism. Schedule III Controlled Substance. WADA S1 Absolute Ban. TRAVERSE Trial (NEJM 2023): TRT Does Not Increase Cardiovascular Events in Hypogonadal Men. The TTrials: Sexual Function, Bone Density, Anemia All Improved. The Central Paradox: The Compound That Is Appropriate Medical Treatment at One Baseline Testosterone Level Is Misuse at Another. Aromatization, Estradiol Management, HPTA Suppression, Testicular Atrophy, Fertility, and the Full Monitoring Protocol.

Approved in 37+ Countries. The Most Extensively Studied Thymic Peptide in Clinical Medicine. 30+ RCTs. 11,000+ Subjects. HBeAg Seroconversion RR 2.31. A Positive Sepsis Trial in 2013 Followed by a Definitive Negative Phase 3 in 2025. The US Regulatory Rollercoaster: Category 2 (2023) → Nomination Withdrawn (2024) → Pending PCAC Review (2026). Immunomodulator, Not Immunostimulant — A Critical Distinction.

The Only Thymic Hormone That Requires a Metal Cofactor. Biologically Inactive Without Zinc. The Most Important Clinical Point: Zinc Deficiency Causes Functional Thymulin Deficiency — And Zinc Supplementation Restores It. One Human Interventional Study from 1982. Extensive Animal Evidence. The Chapter That Is Also a Zinc Education.

The Most Efficacious Approved Obesity Drug in Human History. SURMOUNT-1: -22.5% at 72 Weeks. SURMOUNT-5 Head-to-Head vs Semaglutide (NEJM 2025): 20.2% vs 13.7% — 47% Greater Relative Weight Loss. GI Discontinuation Lower Than Semaglutide. The GIP Receptor Rehabilitation Story. The Weight Rebound Data. SURMOUNT-4: >25% Regain in Most Within 1 Year of Stopping. Compounded Tirzepatide FDA Status After December 2024 Shortage Removal. SURPASS-CVOT: The CV Question Semaglutide Already Answered.

The Most Physiologically Broad Compound in This Book. 28 Amino Acids. Every System in the Body. VPAC1 and VPAC2. The 90-Second Half-Life Problem That Blocked IV Use. How Intranasal Administration Changed Everything. Dr. Shoemaker's CIRS Protocol: 300+ Physicians, 90%+ Symptom Reduction. The Long-COVID Connection. Aviptadil COVID ARDS Trials. The Mast Cell / MCAS Intersection. Why the Community Uses It and What the Evidence Actually Shows.