William Llewellyn’s ANABOLICS · Preface ANABOLICS is a reference manual of drug compounds used...

W i l l i a m L l e w e l l y n ’ s

ANABOL ICS ,10th ed.

SoftcoverISBN-13: 978-0-9828280-0-7

ISBN-10: 0-9828280-0-4

HardcoverISBN-13: 978-0-9828280-1-4

ISBN-10: 0-9828280-1-2

DISCLAIMER: This information was gathered from sources including, but not limited to medical journals,pharmaceutical reports, laboratory reports, textbooks, as well as interviews with medical experts, athletes, andsteroid distributors. Neither the author nor publisher assumes any liability for the information presented. Thisbook is intended to provide a compendium of information for the reader. None of the information is meant to beapplied and is for entertainment purposes only. It is not intended to provide nor replace medical advice. Readersare advised that the substances described in this reference book are to be used only under a physician’s care andmay be prohibited in certain jurisdictions.Readers should consult with appropriate medical authorities before usingany drug, and proper legal authorities on the status of substances described herein. Neither the publisher norauthor advocate readers engage in any illegal activities.

Copyright © 2011 and published by Molecular Nutrition, LLC in Jupiter, FL 33458. All rightsreserved. None of the content in this publication may be reproduced, stored in a retrieval system,resold, redistributed, or transmitted in any form or by any means (digital, electronic, mechanical,

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W I L L I A M L L E W E L L Y N ’ S

ANABOLICSE

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ion

10th

Preface

ANABOLICS is a reference manual of drug compounds used to enhance body composition, strength, and/or athleticperformance. This book includes an extensive review of the history, global availability, and application ofanabolic/androgenic steroids, as well as related performance-enhancing drugs such as human growth hormone, insulin,anti-estrogens, diuretics, reductase inhibitors, and fat loss agents. The core focus of ANABOLICS is to provide a nonbiasedand comprehensive review of the current science surrounding these drugs, as well as their medical and non-medical use.The effort of this book is always to help readers understand the potential risks of these drugs, in addition to their benefits.ANABOLICS is not intended to promote steroid or other drug use, but is designed to help readers, may they be physicians,patients, or illicit users, better understand these drugs, and make well-informed decisions about them.

Regular readers will notice the latest edition includes updates and new additions in the following sections:

Anabolic Overview (Part I):

Part I was extensively updated in the 9th Edition of ANABOLICS, though the 10th Edition has seen some minor edits, andthe addition of a section on AAS-linked tendon injury.

Practical Application (Part II):

A new chapter of Counterfeit Steroid Detection has been added. It discloses techniques for identifying deviant productswith a handheld microscope.

The Harm Reduction section has been modified, along with a follow-up chapter on Sterilizing Injectable AAS preparations.

The Post-Cycle Therapy section has been updated to include a modified PCT program, and Start of PCT timing calculations.

An Off-Cycle Therapy (OCT) section has been added, which discusses ways to better retain muscle mass between cycles,and make follow up programs more productive.

A chapter on Obtaining AAS has been added, which covers the popular ways these medications are obtained. This sectionincludes advice about reducing risks.

Drug Profiles (Part III):

Updates concerning drug manufacture and global availability have been made in most of the commonAnabolic/Androgenic Steroid Profiles.

New or extensively re-written profiles have been added for Catapres (clonidine), Geref (sermorelin), Glucophage(metformin), and BP Stabil.

Steroid Availability Tables (Appendix A):

Global steroid manufacturing status has been extensively updated. Many dozens of new steroid preparations have beenadded, and numerous out of commerce steroids have been removed.

Photographic Database (Appendix B):

The photographic database has been extensively expanded, and includes approximately 3,000 pictures ofanabolic/androgenic steroids and other drugs. Legitimate pharmaceuticals are labeled and grouped by their country ofmanufacture. The following terms are used to identify the origin of individual drug products.

Real (or no specification other than country): These legitimate pharmaceutical products are distributed in pharmacies or veterinary clinics in the labeled country of origin. Real drugs offer the greatest assurance of productpurity and safety, although production standards may vary by country or market (veterinary/human).

Counterfeit (CF): This is an illicit duplicate of a real drug product and/or manufacturer. These items are of unknown quality and safety, and often contain substitute or no steroid ingredients.

Export (EX): These are drugs made by registered pharmaceutical companies, but are not licensed for sale in their

Wil l iam L lewel lyn ’s ANABOLICS, 10th ed.

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country of origin. They must be exported. Export products should be made in legitimate pharmaceutical manufacturing facilities, but depending on the region may not be made under the same close government supervision as locally distributed products.

Underground (UG): These products are made from unlicensed illegal manufacturers specifically for sale on the black market. Due to the completely unregulated nature of these drugs, they offer little assurance of quality, andare generally not recommended.

Fake: This is an illicitly manufactured drug that purports to be a real pharmaceutical, but bears no relation to an actual product. Fake is a distinction that suggests all forms of the photographed steroid should be considered illegitimate.

NLM: Indicates a drug that is No Longer Manufactured.This distinction is important because when NLM drugs arestill found in active black market commerce they usually turn out to be illegitimate.

New Service (HRT-Rx):

As longtime advocates of the legitimate medical use of anabolic/androgenic steroids, we have launched HRT-Rx, a nationalreferral service to help patients find progressive HRT/Anti-Aging physicians. Network doctors are the type that regularlywork with testosterone medications, and understand the value of hormone replacement and optimization therapies. Youcan find a physician near you at www.HRT-Rx.com. Note that most offices require you are at least 30 years of age to makean appointment.

New Service (HRT-Labs):

We have also partnered with a laboratory that can run extensive blood tests including hormone levels, liver/kidneyenzymes, and general health markers. The service is available in all 50 states and can be accessed at www.HRT-Labs.com.


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TABLE OF CONTENTS

PART I: ANABOLIC OVERVIEWAn Introduction to Testosterone ......................................................................... 5Direct and Indirect Anabolic Effects .................................................................. 7Free vs. Bound Testosterone ................................................................................. 10Estrogen Aromatization ......................................................................................... 12 DHT Conversion ......................................................................................................... 14Brief History of Anabolic/Androgenic Steroids ............................................. 15Synthetic AAS Development ................................................................................ 16Synthetic AAS Chemistry ....................................................................................... 21Steroid Nomenclature ............................................................................................. 26Clinical Applications ................................................................................................ 27Side Effects .................................................................................................................. 33 UpdatedAcute Steroid Safety: Studies with Real-World Dosages ............................ 55The Endocrinology of Muscle Growth .............................................................. 57

PART II: PRACTICAL APPLICATIONSteroid Cycles ............................................................................................................. 65 Sample Steroid Cycles ............................................................................................. 69PCT: Post Cycle Therapy .......................................................................................... 84 UpdatedOCT: Off Cycle Therapy ........................................................................................... 89 * NEW *Injection Protocols ................................................................................................... 92Steroid Frequently Asked Questions ................................................................. 95Understanding Blood Tests ................................................................................... 97Harm Reduction/Safer Use Guidelines ............................................................. 112 UpdatedSterilizing Injectable AAS ....................................................................................... 115 * NEW *Counterfeit Steroids ................................................................................................. 117Counterfeit Steroid Identification ....................................................................... 121 UpdatedCountry Specifics ...................................................................................................... 128Underground Steroids ............................................................................................ 130Designer Steroids ..................................................................................................... 135Anabolic Steroid Possesion and the Law ......................................................... 137Acquiring AAS (Best Practices) ............................................................................ 140 * NEW *

PART III: DRUG PROFILESANABOLIC/ANDROGENIC STEROIDS (Listed by Common Brand)

1-Testosterone (dihydroboldenone) .................................................................. 14920 AET-1 (testosterone buciclate) ....................................................................... 152Agovirin Depot (testosterone isobutyrate) ..................................................... 155 B-109Anabol 4-19 (norclostebol acetate) ................................................................... 158Anabolicum Vister (quinbolone) ......................................................................... 160Anadrol®- 50 (oxymetholone) .............................................................................. 163 B-1 UpdatedAnadur® (nandrolone hexyloxyphenylpropionate) ..................................... 168Anatrofin (stenbolone acetate) ........................................................................... 171


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Anavar (oxandrolone) .............................................................................................. 173 B-7 UpdatedAndractim® (dihydrotestosterone) ..................................................................... 177 B-11 UpdatedAndriol® (testosterone undecanoate) ............................................................... 180 B-11 UpdatedAndroderm® (testosterone) .................................................................................. 183 B-13AndroGel® (testosterone) ...................................................................................... 186 B-14 UpdatedAndromar Retard (testosterone cyclohexylpropionate) ............................ 189Andronaq (testosterone suspension) ................................................................ 192 B-107 UpdatedBolfortan (testosterone nicotinate) ................................................................... 196Cheque Drops® (mibolerone) .............................................................................. 199 B-15Danocrine® (danazol) .............................................................................................. 202Deca-Durabolin® (nandrolone decanoate) ..................................................... 204 B-15 UpdatedDelatestryl®(testosterone enanthate) ............................................................... 208 B-86 UpdatedDepo®-Testosterone (testosterone cypionate) .............................................. 212 B-79 UpdatedDeposterona (testosterone blend) ..................................................................... 217 B-30Dianabol®(methandrostenolone, methandienone) .................................... 220 B-31 UpdatedDimethyltrienolone (dimethyltrienolone) ....................................................... 224Dinandrol (nandrolone blend) ............................................................................. 227 B-39Drive® (boldenone/methylandrostenediol blend) ...................................... 230 B-40Durabolin® (nandrolone phenylpropionate) ................................................. 232 B-41 UpdatedDynabol® (nandrolone cypionate) ..................................................................... 235 B-43Dynabolon®(nandrolone undecanoate) .......................................................... 238 B-43Emdabol (thiomesterone) ..................................................................................... 241Equilon 100 (boldenone blend) .......................................................................... 244 B-43Equipoise® (boldenone undecylenate) ............................................................ 247 B-43Equitest 200 (testosterone blend) ...................................................................... 250 B-51Ermalone (mestanolone) ....................................................................................... 253Esiclene® (formebolone, formyldienolone) ..................................................... 256Estandron (testosterone/estrogen blend) ....................................................... 259 B-52Fherbolico (nandrolone cyclohexylpropionate) ........................................... 262 B-69Finajet (trenbolone acetate) ................................................................................. 265 B-111 UpdatedGenabol (norbolethone) ........................................................................................ 269Halodrol (chlorodehydromethylandrostenediol) ......................................... 272Halotestin® (fluoxymesterone) ............................................................................ 275 B-52 UpdatedHavoc (methepitiostane) ....................................................................................... 279Hydroxytest (hydroxytestosterone) ................................................................... 282Laurabolin® (nandrolone laurate) ...................................................................... 285 B-53Libriol (nandrolone/methandriol blend) ......................................................... 288 B-53Madol (desoxymethyltestosterone) ................................................................... 290Masteron® (drostanolone propionate) ............................................................. 293 B-54 UpdatedMegagrisevit-Mono® (clostebol acetate) ......................................................... 296MENT (methylnortestosterone acetate) ........................................................... 299Metandren (methyltestosterone) ....................................................................... 303 B-56 UpdatedMethandriol (methylandrostenediol) ................................................................ 306 B-56 UpdatedMethosarb (calusterone) ........................................................................................ 309Methyl-1-testosterone (methyldihydroboldenone) ..................................... 311Methyl-D (methyldienolone) ................................................................................ 314Metribolone (methyltrienolone) ......................................................................... 317Miotolan® (furazabol) .............................................................................................. 320MOHN (methylhydroxynandrolone) .................................................................. 323Myagen (bolasterone) ............................................................................................. 326Nandrabolin (nandrolone/methandriol blend) ............................................. 329Nebido (testosterone undecanoate) ................................................................. 331 B-57 Updated


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Neo-Ponden (androisoxazol) ................................................................................ 334Neodrol (dihydrotestosterone) ............................................................................ 337Neotest 250 (testosterone decanoate) ............................................................. 339Nilevar® (norethandrolone) .................................................................................. 342 B-57Omnadren® 250 (testosterone blend) .............................................................. 345 B-57Orabolin® (ethylestrenol) ....................................................................................... 348 B-58 UpdatedOral Turinabol (4-chlorodehydromethyltestosterone) ................................ 351 B-59 UpdatedOranabol (oxymesterone) ...................................................................................... 354Oreton (testosterone propionate) ...................................................................... 357 B-100 UpdatedOrgasteron (normethandrolone) ........................................................................ 362Parabolan® (trenbolone hexahydrobenzylcarbonate) ................................ 365 B-59 UpdatedPerandren (testosterone phenylacetate) ......................................................... 368Primobolan® (methenolone acetate) ................................................................ 371 B-65 UpdatedPrimobolan® Depot (methenolone enanthate) ............................................ 374 B-60 UpdatedPromagnon (chloromethylandrostenediol) .................................................... 377Prostanozol (demethylstanozolol tetrahydropyranyl) ................................ 379Proviron® (mesterolone) ........................................................................................ 381 B-66 UpdatedRoxilon (dimethazine) ............................................................................................. 384Roxilon Inject (bolazine caproate) ...................................................................... 386Spectriol (testosterone/nandrolone/methandriol blend) ......................... 388 B-69Sten (testosterone cypionate & propionate) .................................................. 390 B-69Steranabol Ritardo (oxabolone cypionate) ..................................................... 393Sterandryl Retard (testosterone hexahydrobenzoate) ............................... 395Striant® (testosterone) ............................................................................................ 398Superdrol (methyldrostanolone) ........................................................................ 401Sustanon® 100 (testosterone blend) ................................................................. 404 UpdatedSustanon® 250 (testosterone blend) ................................................................. 407 B-69 UpdatedSynovex® (testosterone propionate & estradiol) .......................................... 411 B-78Testoderm® (testosterone) .................................................................................... 414Testolent (testosterone phenylpropionate) .................................................... 417 B-79Testopel® (testosterone) ........................................................................................ 420Testoviron® (testosterone propionate/enanthate blend) .......................... 423 B-110 UpdatedTHG (tetrahydrogestrinone) ..................................................................................427Thioderon (mepitiostane) ...................................................................................... 430Trenabol® (trenbolone enanthate) ..................................................................... 432 B-115Tribolin (nandrolone/methandriol blend) ....................................................... 434 B-116Triolandren (testosterone blend) ........................................................................ 436Winstrol® (stanozolol) ............................................................................................. 439 B-117 Updated

ANABOLIC/ANDROGENIC STEROIDS (Listed by Generic Name)

androisoxazol (Neo-Ponden) ................................................................................ 334bolasterone (Myagen) ............................................................................................. 326bolazine caproate (Roxilon Inject) ...................................................................... 386boldenone blend (Equilon 100) .......................................................................... 244 B-43boldenone undecylenate (Equipoise®) ............................................................ 247 B-43 Updatedboldenone/methylandrostenediol blend (Drive®) ....................................... 230 B-40calusterone (Methosarb) ........................................................................................ 309chlorodehydromethylandrostenediol (Halodrol) ..........................................2724-chlorodehydromethyltestosterone (Oral Turinabol) ................................ 351 B-59 Updatedchloromethylandrostenediol (Promagnon) .................................................... 377clostebol acetate (Megagrisevit-Mono®) ......................................................... 296


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danazol (Danocrine®) .............................................................................................. 202demethylstanozolol tetrahydropyranyl (Prostanozol) ................................ 379desoxymethyltestosterone (Madol) ................................................................... 290dihydroboldenone (1-Testosterone) ................................................................. 149dihydrotestosterone (Andractim®) ..................................................................... 177 B-11 Updateddihydrotestosterone (Neodrol) ............................................................................ 337dimethazine (Roxilon) ............................................................................................. 384dimethyltrienolone (Dimethyltrienolone) ....................................................... 224drostanolone propionate (Masteron®) ............................................................. 293 B-54 Updatedethylestrenol (Orabolin®) ....................................................................................... 348 B-58 Updatedfluoxymesterone (Halotestin®) ............................................................................ 275 B-52 Updatedformebolone, formyldienolone (Esiclene®) ..................................................... 256furazabol (Miotolan®) .............................................................................................. 320hydroxytestosterone (Hydroxytest) ................................................................... 282mepitiostane (Thioderon) ..................................................................................... 430mestanolone (Ermalone) ....................................................................................... 253mesterolone (Proviron®) ........................................................................................ 381 B-66 Updatedmethandrostenolone, methandienone (Dianabol®) ................................... 220 B-31 Updatedmethenolone acetate (Primobolan®) ................................................................ 371 B-65 Updatedmethenolone enanthate (Primobolan® Depot) ............................................ 374 B-60 Updatedmethepitiostane (Havoc) ...................................................................................... 279methylandrostenediol (Methandriol) ............................................................... 306 B-56Methyldienolone (Methyl-D) ................................................................................ 314methyldihydroboldenone (Methyl-1-testosterone) .................................... 311methyldrostanolone (Superdrol) ........................................................................ 401methylhydroxynandrolone (MOHN) ................................................................. 323methylnortestosterone acetate (MENT) .......................................................... 299methyltestosterone (Metandren) ...................................................................... 303 B-56 Updatedmethyltrienolone (Metribolone) ........................................................................ 317mibolerone (Cheque Drops®) .............................................................................. 199 B-15nandrolone blend (Dinandrol) ............................................................................. 227 B-39nandrolone cyclohexylpropionate (Fherbolico) ........................................... 262 B-69nandrolone cypionate (Dynabol®) ..................................................................... 235 B-43nandrolone decanoate (Deca-Durabolin®) ..................................................... 204 B-15 Updatednandrolone hexyloxyphenylpropionate (Anadur®) ..................................... 168nandrolone laurate (Laurabolin®) ...................................................................... 285 B-53nandrolone phenylpropionate (Durabolin®) ................................................. 232 B-41 Updatednandrolone undecanoate (Dynabolon®) ......................................................... 238 B-43nandrolone/methandriol blend (Libriol) ......................................................... 288 B-53nandrolone/methandriol blend (Tribolin) ...................................................... 434 B-116nandrolone/methandriol blend (Nandrabolin) ............................................. 329norbolethone (Genabol) ........................................................................................ 269norclostebol acetate (Anabol 4-19) ................................................................... 158norethandrolone (Nilevar®) .................................................................................. 342 B-57normethandrolone (Orgasteron) ........................................................................ 362oxabolone cypionate (Steranabol Ritardo) ..................................................... 393oxandrolone (Anavar) ............................................................................................. 173 B-7 Updatedoxymesterone (Oranabol) ...................................................................................... 354oxymetholone (Anadrol®- 50) .............................................................................. 163 B-1 Updatedquinbolone (Anabolicum Vister) ......................................................................... 160stanozolol (Winstrol®) ............................................................................................. 439 B-117 Updatedstenbolone acetate (Anatrofin) ........................................................................... 171


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testosterone (Androderm®) .................................................................................. 183 B-13 Updatedtestosterone (AndroGel®) ...................................................................................... 186 B-14testosterone (Striant®) ............................................................................................ 398testosterone (Testoderm®) .................................................................................... 414testosterone (Testopel®) ........................................................................................ 420testosterone blend (Deposterona) ..................................................................... 217 B-30testosterone blend (Equitest 200) ...................................................................... 250 B-51testosterone blend (Omnadren® 250) .............................................................. 345 B-57testosterone blend (Sustanon® 100) ................................................................. 404 Updatedtestosterone blend (Sustanon® 250) ................................................................. 407 B-69 Updatedtestosterone blend (Triolandren) ........................................................................ 436testosterone buciclate (20 AET-1) ....................................................................... 152testosterone cyclohexylpropionate (Andromar Retard) ............................ 189testosterone cypionate & propionate (Sten) .................................................. 390 B-69testosterone cypionate (Depo®-Testosterone) .............................................. 212 B-79 Updatedtestosterone decanoate (Neotest 250) ............................................................. 339testosterone enanthate (Delatestryl®) .............................................................. 208 B-86 Updatedtestosterone hexahydrobenzoate (Sterandryl Retard) ............................... 395testosterone isobutyrate (Agovirin Depot) ..................................................... 155 B-109testosterone nicotinate (Bolfortan) .................................................................... 196testosterone phenylacetate (Perandren) ......................................................... 368testosterone phenylpropionate (Testolent) ................................................... 417 B-79testosterone propionate & estradiol (Synovex®) ...........................................411 B-78testosterone propionate (Oreton) ...................................................................... 357 B-100 Updatedtestosterone propionate/enanthate blend (Testoviron®) ......................... 423 B-110 Updatedtestosterone suspension (Andronaq) ................................................................ 192 B-107 Updatedtestosterone undecanoate (Andriol®) ............................................................... 180 B-11 Updatedtestosterone undecanoate (Nebido) ................................................................. 331 B-57 Updatedtestosterone/estrogen blend (Estandron) ....................................................... 259 B-52testosterone/nandrolone/methandriol blend (Spectriol) ......................... 388 B-69tetrahydrogestrinone (THG) ................................................................................ 427thiomesterone (Emdabol) ...................................................................................... 241trenbolone acetate (Finajet) ................................................................................. 265 B-111 Updatedtrenbolone enanthate (Trenabol) .................................................................... 432 B-115 Updatedtrenbolone hexahydrobenzylcarbonate (Parabolan®) ............................... 365 B-59 Updated

ANABOLIC AGENTS (NON-STEROID)

Arachidonic acid (eicosa-5,8,11,14-enoic acid) ............................................. 447 UpdatedKynoselen® .................................................................................................................. 450 C-11Lutalyse® (diniprost) ................................................................................................ 452

ANTI-ACNE

Accutane (isotretinoin) ........................................................................................... 457

ANTI-ESTROGENS

Arimidex® (anastrozole) ......................................................................................... 461 C-1Aromasin® (exemestane) ....................................................................................... 463Clomid® (clomiphene citrate) .............................................................................. 465 C-3Cytadren® (aminoglutethimide) ......................................................................... 467 C-4Evista (raloxifene) ...................................................................................................... 470Fareston® (toremifene citrate) ............................................................................. 472

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Faslodex® (fulvestrant) ........................................................................................... 474Femara® (letrozole) .................................................................................................. 476 C-4Fertodur® (cyclofenil) .............................................................................................. 478 C-3Lentaron® (formestane) ......................................................................................... 480 C-11 Nolvadex® (tamoxifen citrate) ............................................................................. 482 C-12Teslac® (testolactone) ............................................................................................. 484

ANTI-PROLACTIN

Dostinex® (cabergoline) ......................................................................................... 489Parlodel® (bromocriptine mesylate) .................................................................. 491 C-13

APPETITE STIMULANTS

Periactin (cyproheptadine hydrochloride) ...................................................... 495

CARDIOVASCULAR SUPPORT

Lipid StabilTM ............................................................................................................... 499Lovaza® (omega-3 ethyl esters) ........................................................................... 500

DIURETICS

Aldactone® (spironolactone) ................................................................................ 503 C-1Dyrenium® (triamterene) ....................................................................................... 505Hydrodiuril® (hydrochlorthiazide) ...................................................................... 507Lasix® (furosemide) .................................................................................................. 509 C-11

ENDURANCE/ERYTHROPOIETIC DRUGS

Aranesp® (darbepoetin alfa) ................................................................................. 513Epogen® (epoetin alfa) ........................................................................................... 515 C-4Provigil® (modafinil) ................................................................................................ 517

FAT LOSS AGENTS – SYMPATHOMIMETICS

Adipex-P (phentermine hydrochloride) ........................................................... 521Albuterol (albuterol sulfate) ................................................................................. 522Clenasma (clenbuterol hydrochloride) ............................................................. 524 C-2Ephedrine (ephedrine hydrochloride) .............................................................. 527Meridia® (sibutramine hydrochloride monohydrate) ................................. 529 C-11Zaditen® (ketotifen fumarate) .............................................................................. 531 C-14

FAT LOSS AGENTS – THYROID

Cytomel® (liothyronine sodium) ......................................................................... 535 C-4Synthroid® (levothyroxine sodium) ................................................................... 537 C-13

FAT LOSS AGENTS – OTHER

DNP (2,4-dinitrophenol) ......................................................................................... 541Lipostabil N (phosphatidylcholine/sodium deoxycholate) ...................... 543 C-11

GROWTH HORMONES & RELATED

Geref®(sermorelin acetate) ....................................................................................547 * NEW *Human Growth Hormone (somatropin) .......................................................... 550 C-5 UpdatedIncrelex® (mecasermin) .......................................................................................... 553Protropin® (somatrem) ............................................................................................555 C-5


HYPOGLYCEMICS

Glucophage ................................................................................................................. 559 * NEW *Insulin ............................................................................................................................ 561 C-10

HYPOTENSIVES

BP StabilTM .....................................................................................................................571 * NEW *Catapres ........................................................................................................................572 * NEW *

LIVER DETOXIFICATION

Essentiale forte N ...................................................................................................... 577LIV-52® .......................................................................................................................... 578Liver StabilTM ............................................................................................................... 579

REDUCTASE INHIBITORS

Avodart® (dutasteride) ........................................................................................... 583 C-1 Proscar® (finasteride) .............................................................................................. 585 C-13

TANNING AGENTS

Oxsoralen (methoxsalen) ....................................................................................... 589Trisoralen® (trioxsalen) ........................................................................................... 591

TESTOSTERONE STIMULATING DRUGS

HCG (human chorionic gonadotropin) ............................................................ 595 C-8

BIBLIOGRAPHY

GLOSSARY

APPENDIX

DRUG AVAILABILITY TABLES: COUNTRY A-1 Updated

STEROID PHOTO LIBRARY B-1 Updated

DRUG PHOTO LIBRARY (NON-STEROID) C-1


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Anabolic/androgenic steroids are approved for sale byprescription in virtually every pharmaceutical marketaround the world. Having been applied for many decadesto treat a variety of diseased states, today these drugshave a number of well-established medical uses. Theyhave been used to treat most patient populations,including men and women of almost all ages, rangingfrom children to the elderly. In many instancesanabolic/androgenic steroids have proven to be lifesaving medications, which is a fact easily overlooked withall of the discussion about steroid abuse. This sectiondetails some of the most common and accepted medicalapplications for anabolic/androgenic steroids.

Androgen Replacement Therapy/Hypogonadism

The most widely used medical application foranabolic/androgenic steroids in the world is that ofandrogen replacement therapy. Also referred to asHormone Replacement Therapy (HRT) or TestosteroneReplacement Therapy (TRT), this therapy involves thesupplementation of the primary male hormonetestosterone to alleviate symptoms of low hormone levels(clinically referred to as hypogonadism). Patients may beadolescent males suffering from childhoodhypogonadism or a specific disorder that causesandrogenic hormone disruption, although most of thetreated population consists of adult men over the age of30. In most cases hormone levels have declined in thesemen as a result of the normal aging process.

The most common complaints associated with lowtestosterone in adult men include reduced libido, erectiledysfunction, loss of energy, decreased strength and/orendurance, reduced ability to play sports, moodfluctuations, reduced height (bone loss), reduced workperformance, memory loss, and muscle loss.50 Whenassociated with aging, these symptoms are collectivelyplaced under the label of “andropause”. In a clinical settingthis disorder is referred to as late-onset hypogonadism.Blood testosterone levels below 350ng/dL are usuallyregarded as clinically significant, although somephysicians will use a level as low as 200ng/dL as thethreshold for normal. Hypogonadism is, unfortunately, stillwidely under-diagnosed. Most physicians will also notrecommend treatment for low testosterone unless apatient is complaining about symptoms (symptomaticandrogen deficiency).

Androgen replacement therapy effectively alleviates most

symptoms of low testosterone levels. To begin with,raising testosterone levels above 350ng/dL (the very lowend of the normal range) will often restore normal sexualfunction and libido in men with dysfunctions related tohormone insufficiency. With regard to bone mineraldensity, hormone replacement therapy is alsodocumented to have a significant positive effect. Forexample, studies administering 250 mg of testosteroneenanthate every 21 days showed a 5% increase in bonemineral density after six months.51 Over time this mayprevent some loss of height and bone strength withaging, and may also reduce the risk of fracture. Hormonereplacement therapy also increases red blood cellconcentrations (oxygen carrying capacity), improvingenergy and sense of well-being.Therapy also supports theretention of lean body mass, and improves musclestrength and endurance.

Unlike steroid abuse, hormone replacement therapy mayhave benefits with regard to cardiovascular disease risk.For example, studies tend to show hormone replacementas having a positive effect on serum lipids. This includes areduction in LDL and total cholesterol levels, combinedwith no significant change in HDL (good) cholesterollevels.52 53 Testosterone supplementation also reducesmidsection obesity, and improves insulin sensitivity andglycemic control.54 These are important factors inmetabolic syndrome, which may also be involved in theprogression of atherosclerosis. Additionally, testosteronereplacement therapy has been shown to improve theprofile of inflammatory markers TNF·, IL-1‚, and IL-10.55 Thereduced inflammation may help protect arterial wallsfrom degeneration by plaque and scar tissue. The medicalconsensus today appears to be that replacement therapyin otherwise healthy men generally does not have anegative effect on cardiovascular disease risk, and mayactually decrease certain risk factors for the disease insome patients.

There are some concerns with initiating testosteronereplacement therapy when the individual is in poorhealth. One study examined the safety of HRT in menaged 65 and older with limited mobility and varioushealth conditions such as obesity, hypertension, diabetes,or hyperlipidemia.56 Each subject took a transdermaltestosterone gel (10g/100mg) or placebo gel daily for sixmonths. During the course of treatment, a total of 23 menin the testosterone group had cardiovascular-relatedadverse events. This was compared to only 9 in theplacebo group. Another study with middle-aged


27

Clinical Applications

hypogonadal men found that testosterone replacementtherapy (testosterone enanthate 250mg/2 weeks)reduced vascular reactivity, an important factor inatherosclerosis.57 These studies suggest that care shouldbe taken when considering HRT in men with heartdisease, strong contributing factors to heart disease, orother chronic health conditions.

There are other areas of concern with elderly patients. Tobegin with, testosterone administration may increaseprostate volume and PSA values.58 59 While this does notappear to be of clinical significance with normal healthypatients, benign prostate hypertrophy and prostatecancer can be stimulated by testosterone. Men withprostate cancer, high PSA values, or breast cancer aregenerally not prescribed testosterone. Androgensupplementation has also been linked to sleep apnea,which can interfere with the most restful (REM) phase ofsleep.60 The studies have produced conflicting data,however, and the potential relationship remains thesubject of much debate.61 Lastly, testosteronereplacement therapy has demonstrated negative,positive, and neutral effects on cognitive functioning inelderly men.62 63 64 Studies do suggest that the dose candictate the level of response, with the most positiveeffects noted when the androgen level reaches the mid-to upper-range of normal, not supraphysiological.65

Elderly patients with preexisting deficits in cognitivefunction should have their cognitive performance andblood hormone levels monitored closely during hormonereplacement therapy.

Common Treatment Protocols:

Transdermal: Transdermal application is the mostcommonly prescribed method for supplementingtestosterone in the United States and Canada, and isgenerally the first course of therapy initiated withandrogen replacement therapy patients. This method ofdrug delivery offers a number of advantages to thepatient when compared to injection. Since thetransdermal application is painless, patient complianceand comfort is increased in comparison. Transdermalapplication also provides stable day-to-day hormonelevels, and does not produce the broad fluctuationsusually noticed with injectable testosterone esters. Themost common protocol among hormone replacementdoctors is to prescribe a dosage of 2.5-10 mg oftestosterone per day (approximate absorbed dose). This isapplied as a rub-on gel or adhesive transdermal patchthat is replaced daily. Note that due to metabolism in theskin, transdermal application of testosterone tends toincrease serum dihydrotestosterone (DHT) levels moreprofoundly than testosterone injection. This mayexacerbate androgenic side effects during therapy in

some patients, causing some to seek out injectable formsof testosterone as an alternative.

Injection: Testosterone enanthate and testosteronecypionate are the most widely prescribed injectabletestosterone drugs in the United States and Canada. Inmany other markets the blended ester products Sustanon100 and Sustanon 250 are also commonly prescribed.Injection of one of these testosterone ester products willprovide the patient supplemental androgen levels forapproximately 2 to 3 weeks after each application. Themost common protocol among hormone replacementdoctors is to administer 200 mg of testosterone enanthateor cypionate once every 2 to 3 weeks. It is important toremember that testosterone esters will deliver varyinglevels of testosterone to the body on a day-to-day basisthroughout each application window. Levels will behighest the first several days after injection, and will slowlydecline to baseline over the following weeks. Physiciansare usually encouraged to monitor their patients closelyto ensure androgen supplementation is sustaininghormone levels within the normal range (and alleviatingsymptoms of hypogonadism) throughout the entiretherapeutic period. The longer acting injectabletestosterone preparation Nebido (testosteroneundecanoate) is undergoing review in the U.S., and hasalready been approved in other markets. This drugrequires only 4 to 5 injections per year for most patients.

Oral: Testosterone undecanoate (Andriol) is the onlyprescription medication that delivers testosterone via anoral capsule. This medication is not approved for sale inthe United States, but is a prescription drug in Canada andmany other markets around the world. Patient complianceand comfort are high with this form of therapy, as thereare no special routines or requirements aside from takinga few capsules each day with meals. Oral testosteroneundecanoate is usually given at an initial dosage of 120 to160 mg per day, which equates to three to four 40 mgcapsules. This dosage may be reduced in subsequentweeks to 120 mg per day. The capsules are given in twodivided doses per day, which are usually taken withbreakfast and dinner. While this form of therapy is highlyconvenient, serum hormone levels can fluctuate greatlyon a day-to-day basis.The amount of fat consumption hasa particularly strong impact on hormone bioavailability,and meals providing at least 20 grams of fat arerecommended when taking the capsules for maximumabsorption. Note that as with transdermal testosterone,oral testosterone undecanoate tends to increase serumdihydrotestosterone (DHT) levels more profoundly thantestosterone injections.


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Angioedema, Hereditary

Anabolic steroids are commonly prescribed for thetreatment of hereditary angioedema, a rare andpotentially life-threatening disorder of the immunesystem. Hereditary angioedema is caused by geneticmutations of blood clotting factors, characterized by adecrease in the level or functioning of the protein C1esterase inhibitor. This protein controls C1, which is a“complement system”protein that plays an important rolein the control of inflammation. Symptoms of hereditaryangioedema include an intermittent but rapid swelling ofthe hands, arms, legs, lips, eyes, tongue, or throat. Swellingmay also be noticed in the digestive tract, resulting inabdominal cramping, nausea, or vomiting. In the mostserious cases, the patient may notice a swelling of thethroat and a blockage of the airway passages, resulting inasphyxiation and sydden death. Many attacks occurwithout a specific trigger, although stress, trauma, surgery,and dental work are commonly associated withangioedema attacks.

Oral c-17 alpha alkylated anabolic/androgenic steroidshave been shown to be a useful form of preventivetherapy, stabilizing complement system protein levels andreducing the frequency and severity of angioedemaattacks.66 They are usually administered in a low dose,which is to be taken for long-term support of this disorder.The anabolic steroids that have been most commonlyused in the United States for this purpose are stanozololand danocrine, although historically many other agentshave also been prescribed including oxandrolone,methyltestosterone, oxymetholone, fluoxymesterone, andmethandrostenolone. The amount of steroid needed canvary depending on the individual, and is usuallymaintained at the lowest therapeutically effective dosagein an effort to offset undesirable side effects. FDAapproved prescribing guidelines for stanozololrecommended an initial dosage of 2 mg three times daily(6 mg per day). This would be slowly adjusted downwardto a maintenance level after a positive response wasnoted, usually to 2 mg given once every 1 to 2 days.

Anemia

As a class of drugs, anabolic/androgenic steroids stimulatethe synthesis of erythropoietin in the kidneys, a hormonethat supports the manufacture of new red blood cells. Bydoing this, the administration of steroids tends to increasethe red cell count and hematocrit level, making them oftangible therapeutic value for treating certain forms ofanemia (a disease characterized by insufficient red bloodcell production). Forms of anemia likely to respond tosteroid therapy include anemias caused by renalinsufficiency, sickle cell anemia, refractory anemias

including aplastic anemia, myelofibrosis, myelosclerosis,agnogenic myeloid metaplasia, and anemias caused bymalignancy or myelotoxic drugs.The level of response willvary depending on the patient, type of therapy, and formof anemia, but in many cases the management of anormal hematocrit level can be achieved.

In the United States, both oxymetholone (Anadrol 50) andnandrolone decanoate (Deca-Durabolin) are approved bythe FDA for the treatment of severe anemia. Theguidelines for using oxymetholone with both male andfemale anemic patients (children and adults) recommenda dosage of 1-2 mg/kg/per day. This would equate to adaily dosage of 75-150 mg for an individual weighingabout 160 lbs. Doses as high as 5 mg/kg/day aresometimes necessary to achieve the desired therapeuticresponse. The guidelines for nandrolone decanoaterecommend a dosage of 50-100 mg per week for womenand 100-200 mg per week for men. Children (2 to 13 yearsof age) are recommended a dosage of 25- 50 mg every 3to 4 weeks.

In recent years, the advent of recombinant erythropoietinas a prescription drug has changed the face of anemiatreatment considerably. While anabolic/androgenicsteroids still offer therapeutic value here, and are stillmarketed and sold to treat anemic patients, they arepresently regarded as adjunct or fallback medications foruse only when therapy with an erythropoietin alone hasfailed to achieve a desired response. The hematocritincrease from anabolic/androgenic steroids is generallyless predictable and positive than the newererythropoietins, and these drugs also tend to producevery noticeable side effects when given in the levelsnecessary to stimulate erythropoiesis, especially inwomen and children. In many instances the risks totherapy strongly outweigh the benefits ofanabolic/androgenic steroids, given that there are newerand directly targeted medications available with muchlower side effect potential.

Breast Cancer

Anabolic/androgenic steroids are sometimes prescribedto treat beast cancer in postmenopausal women orpremenopausal women who have had their ovariesremoved. These drugs are of value when the cancer ishormone responsive, which means that its growth can beaffected (positively or negatively) by hormonalmanipulation. Androgens and estrogens have opposingactions on hormone-responsive tumors, with estrogenssupporting the growth of breast cancer tissue andandrogens inhibiting it67. The supplementation of ananabolic/androgenic steroid can shift the androgen toestrogen balance in a direction that favors a reduction in


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tumor size, a therapy that has elicited a successfulresponse in a fair number of patients. The masculinizingside effects of steroid therapy can be very pronounced inwomen, however, so therapy is usually initiated with greatcaution. An oral androgen such as fluoxymesterone isusually preferred to a slower acting injectable steroid suchas nandrolone decanoate as well, as it can be abruptlyhalted if undesirable side effects become too apparent.Both primarily anabolic agents, however, have beenwidely prescribed for this purpose.

In recent years the development of newer and moretargeted anti-estrogenic drugs such as selective estrogenreceptor modulators (SERMs) and aromatase inhibitingdrugs have almost completely eliminated the use ofanabolic/androgenic steroids for breast cancer treatment.Medicative treatment for breast cancer today usuallyconsists of a SERM like Nolvadex (tamoxifen), which maybe used with a strong aromatase inhibitor such asArimidex (anastrozole) or Femara (exemestane).Anabolic/androgenic steroids are still made available inthe United States and many other nations for treatingbreast cancer, and are sometimes still applied. They arevery much regarded as adjunct or fallback medications,however, for use only when therapy with anti-estrogenicdrugs alone has failed to achieve a desired response.

Decreased Fibrinolytic Activity

Anabolic steroids may be prescribed to treat conditionsassociated with decreased fibrinolytic activity. Fibrinolysisis the process in which a blood clot is broken down andmetabolized by the body. It represents a counter to bloodcoagulation, with the two systems working together tomaintain the hemostatic balance. Disorders of thefibrinolytic system are rare, although can be very seriousin nature when they do occur. Decreased fibrinolyticactivity can result in a shift in blood clotting factors thatgreatly favor coagulation (hypercoagulability), increasingthe risk of a serious cardiovascular event such asthromboembolism, heart attack, or stroke. Oral C-17 alphaalkylated anabolic steroids are recognized to increasefibrinolytic activity, and as a result have been beneficial inmany patients suffering from decreased fibrinolyticactivity linked to Antithrombin III deficiency or fibrinogenexcess.68 69 Stanozolol has been most commonly used inthe United States for this treatment, although similartherapeutic benefits can be seen with many otheranabolic steroids. The maintenance dose is tailored to theindividual, and is determined with close monitoring ofboth side effects and changes to blood coagulationparameters. Esterified injectables and oral non-alkylatedsteroids do not produce the same fibrinolytic response.70

Infertility (Male)

In a small percentage of cases, anabolic/androgenicsteroids may be prescribed for the treatment of maleinfertility. When the cause of infertility is low spermconcentration due to Leydig-cell secretion deficiencies, anandrogen might be able to alleviate the condition. In suchcases the steroid may increase the sperm count, spermquality and the fructose concentration,71 72 which canincrease the chance of conception. The oral androgenmesterolone (Proviron) is most commonly prescribed forthis purpose, although has not been granted FDAapproval for sale in the United States. Note thatanabolic/androgenic steroids usually reduce male fertility,so the potential for these agents to successfully treat malefertility is limited.

Growth Failure

Anabolic steroids may be prescribed to treat growthfailure in children, both with and without growthhormone deficiency. These agents have been shown tohave positive effects on both muscle and bone mass.When they are administered before the ends of the longbones (epiphysis) have fused and further linear growthhas been halted, their anabolic effects on bone maysupport an increase in height.73 This can occur boththrough direct anabolic action of the steroid on bonecells, and indirectly via the stimulation of growthhormone and IGF-1 release.74 An anabolic steroid that isnon-aromatizable and non-estrogenic is typically used forthis purpose, as estrogen is known to cause anacceleration of growth arrest. Anabolic steroid therapymust always be used with caution in pediatric patients,however. In addition to the possibility of common adverseeffects, even non-aromatizable steroids may acceleratethe rate of epiphysis closure.75

In the United States, oxandrolone is the anabolic steroidmost widely prescribed for the treatment of growthfailure. It is usually given as a supportive medication, usedto augment the anabolic effects of human growthhormone therapy.The drug is typically taken for periods of6-12 months at a time, in an effort to accelerate thegrowth rate without substantially affecting the rate ofepiphysis fusion. A dosage of 2.5 mg per day is often usedfor this purpose, although this may be adjusted upwardsor downwards depending on the patient’s sex, age,bodyweight, and sensitivity to adverse effects. When usedunder optimal conditions, the result may be anenhancement of the growth rate and an increase in totalheight compared to not initiating therapy.This benefit hasbeen difficult to achieve consistently in clinical studies,however. A number of trials with oxandrolone have failedto produce a statistically significant effect on total height,


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While anabolic/androgenic steroids (AAS) are generallyregarded as therapeutic drugs with high safety, their usecan also be associated with a number of adverse cosmetic,physical, and psychological effects. Many of these sideeffects are often apparent during therapeutic-useconditions, although their incidence tends to increaseprofoundly as the dosages reach supratherapeutic ranges.Virtually everyone that abuses anabolic/androgenicsteroids for physique- or performance-enhancingpurposes notices some form of adverse effects from theiruse. According to one study, the exact frequency oftangible side effects in a group of steroid abusers was96.4%. This shows very clearly that it is far more rare toabuse these drugs and not notice side effects than it is toendure them.90 In addition to the side effects thatanabolic/androgenic steroids can have on various internalsystems, there are others which may not be immediatelyapparent to the user. The following is a summary of thebiological systems and reactions effected by AAS use.

Cardiovascular SystemThe use of anabolic/androgenic steroids insupratherapeutic (and often therapeutic) doses can havea number of adverse effects on the cardiovascular system.This may be noticed in several areas including unfavorablealterations in serum cholesterol, a thickening ofventricular walls, increased blood pressure, and changesin vascular reactivity. In an acute sense these drugs areadmittedly very safe. The risk of an otherwise healthyperson suffering a heart attack from an isolated steroidcycle is extremely remote. The risk of stroke is alsoextremely low. When these drugs are abused for longperiods, however, their adverse effects on thecardiovascular system are given time to accumulate. Anincreased chance of early death due to heart attack orstroke is, likewise, a valid risk with long-term steroid abuse.In order to better understand this risk, we must lookspecifically at how anabolic/androgenic steroids affectthe cardiovascular system in several key ways.

Cholesterol/Lipids

Anabolic/androgenic steroids use can adversely affectboth HDL (good) and LDL (bad) cholesterol values. Theratio of HDL to LDL cholesterol fractions provides a roughsnapshot of the ongoing disposition of plaque in thearteries, either favoring atherogenic or anti-atherogenicactions. The general pattern seen during steroid use is alowering of HDL concentrations, which is often combined

with stable or increased LDL levels.Triglyceride levels mayalso increase.The shift can be unfavorable in all directions.Note that in some cases, the total cholesterol count willnot change significantly. The total cholesterol level can,therefore, give a false representation of uncompromisedlipid health. Almost invariably the underlying HDL/LDLratio will decrease.While this ratio should return to normalfollowing the cessation of steroid intake, plaque depositsin the arteries are more permanent. If unfavorable shifts inlipids are exacerbated by the long-term use of steroidalcompounds, significant damage to the cardiovascularsystem can result.

Anabolic/androgenic steroids are most consistent in theirlowering of HDL levels. This adverse effect is mediatedthrough the androgenic stimulation of hepatic lipase, aliver enzyme responsible for the breakdown of HDL(good) cholesterol.91 With more hepatic lipase activity inthe body, the favorable (anti-atherogenic) HDL cholesterolparticles are cleared from circulation more quickly, andtheir levels drop. This is an effect that seems to be verypronounced at even modest supratherapeutic dosagelevels. For example, studies with testosterone cypionatenoted a 21% drop in HDL cholesterol with a dosage of 300mg per week.92 Increasing this dosage to 600 mg did nothave any significant additional effect, suggesting that thedosage threshold for strong HDL suppression is fairly low.

Oral steroids, especially c-17 alpha alkylated compounds,are particularly potent at stimulating hepatic lipase andsuppressing HDL levels. This is due to first passconcentration and metabolism in the liver. A drug like


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Steroid Side Effects

Over time, plaque deposits may begin to narrow and clogarteries.

stanozolol may, therefore, be milder than testosteronewith regard to androgenic side effects, but not when itcomes to cardiovascular strain. A study comparing theeffects of a weekly injection of 200 mg testosteroneenanthate to only a 6 mg daily oral dose of stanozololdemonstrates the strong difference between these twotypes of drugs very well.93 After only six weeks, 6 mg ofstanozolol was shown to reduce HDL and HDL-2cholesterol levels by an average of 33 and 71%respectively. HDL levels (mainly the HDL-3 subfraction)were reduced by only 9% in the testosterone group. LDLcholesterol levels also rose 29% with stanozolol, whilethey dropped 16% with testosterone. Esterified injectablesteroids are generally less stressful to the cardiovascularsystem than oral agents.

It is also important to note that estrogens can have afavorable impact on cholesterol profiles. Thearomatization of testosterone to estradiol may, therefore,prevent a more dramatic change in serum cholesterol. Astudy examined this effect by comparing the lipidchanges caused by 280 mg of testosterone enanthate perweek, with and without the aromatase inhibitortestolactone.94 Methyltestosterone was also tested in athird group, at a dose of 20 mg daily, to judge thecomparative effect of an oral alkylated steroid. The groupusing only testosterone enanthate in this study showed asmall but not significant decrease in HDL cholesterolvalues over the course of the 12-week investigation. Afteronly four weeks, however, the group using testosteroneplus the aromatase inhibitor displayed an HDL reductionof an average of 25%. The group takingmethyltestosterone experienced the strongest HDLreduction in the study, which dropped 35% after fourweeks. This group also noticed an unfavorable rise in LDLcholesterol levels.

The potential positive effect of estrogen on cholesterolvalues also makes the issue of estrogen maintenancesomething to consider when it comes to health risks. Tobegin with, one may want to consider whether or notestrogen maintenance drugs are actually necessary in anygiven circumstance. Are side effects apparent, or is theiruse a preventative step and perhaps unnecessary? Themaintenance drug of choice can also have a measurableimpact on cholesterol outcomes. For example, theestrogen receptor antagonist tamoxifen citrate does notseem to exhibit anti-estrogenic effects on cholesterolvalues, and in fact tends to increase HDL levels in somepatients. Many individuals decide to use tamoxifen tocombat estrogenic side effects instead of an aromataseinhibitor for this reason, particularly when they are usingsteroids for longer periods of time, and are concernedabout their cumulative cardiovascular side effects.

Enlarged Heart

The human heart is a muscle. It possesses functionalandrogen receptors, and is growth-responsive to malesteroid hormones. This fact partly accounts for menhaving a larger heart mass on average than women.95

Physical activity can also have a strong effect on thegrowth of the heart. Resistance exercise (anaerobic) tendsto increase heart size by a thickening of the ventricularwall, usually without an equal expansion of the internalcavity. This is known as concentric remodeling. Endurance(aerobic) athletes, on the other hand, tend to increaseheart size via expansion of the internal cavity, withoutsignificant thickening of the ventricles (eccentricremodeling). Even with concentric or eccentricremodeling, diastolic function usually remains normal inthe athletic heart.The heart muscle is also dynamic. Whenregular training is removed from a conditioned athlete,the wall thickening and cavity expansion tend to reduce.

Anabolic steroid abusers are at risk for thickening of theleft and right ventricular walls,96 known as ventricularhypertrophy. Hypertrophy of the left ventricle (the mainpumping chamber) in particular is extensivelydocumented in anabolic/androgenic steroid abusers.97

While left ventricular hypertrophy is, again, also found innatural power athletes, substance-abusing athletes tendto have a much more profound wall thickening. They alsotend to develop pathological issues related to thisthickening, including impaired diastolic function, andultimately reduced heart efficiency.98 The level ofimpairment is closely associated with the dose andduration of steroid abuse. A left ventricle wall exceeding13mm in thickness is rare naturally, and may be indicativeof steroid-abuse or other causes.99 It may further suggestthat pathological left ventricular hypertrophy hasdeveloped. Additional testing of such patients isrecommended.

Left ventricular hypertrophy (LVH) is an independentpredictor of mortality in overweight individuals with highblood pressure.100 It has also been linked to atrialfibrillation, ventricular arrhythmia, and sudden collapseand death.101 While LVH in non-steroid-using athletestends to be without clinical significance, pathologicalincreases in QT dispersion are noticed in steroid abuserswith LVH.102 These changes tend to be similar to theincreases in QT dispersion noted in hypertensive patientswith LVH.103 Among other things, this could leave a steroidabusing individual more susceptible to a serious adverseevent, including arrhythmia or heart attack. Isolatedmedical case studies of longtime steroid abusers supportan association between LVH and related pathologiesincluding ventricular tachycardia (arrhythmia originatingin the left ventricle), left ventricular hypokinesis


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(weakened contraction of the left ventricle), anddecreased ejection fraction (reduced pumping volumeand efficiency).104

Heart mass can increase or decrease in relation to thecurrent state of anabolic/steroid use, the average dosage,and duration of intake. Likewise, the heart usually beginsto reduce in size once anabolic/androgenic steroids areno longer being used. This effect is similar to the way theheart will reduce in size once an athlete no longer followsa rigorous training schedule.105 Even with this effect,however, some changes in heart muscle size and functioncaused by the drugs may persist. Studies examining theeffects of steroid use and withdrawal on left ventricularhypertrophy noted that athletic subjects who abstainedfrom steroid abuse for at least several years still had aslightly greater degree of concentric left ventricularhypertrophy compared to non-steroid-using athleticcontrols.106 The disposition of pathological left ventricularhypertrophy following long-term steroid abuse and thenabstinence remains the subject of investigation anddebate.

Heart Muscle Damage

Anabolic/androgenic steroid abuse is suspected ofproducing direct damage to the heart muscle in somecases. Studies exposing heart cell cultures to AAS havereported reduced contractile activity, increased cellfragility, and reduced cellular (mitochondrial) activity,providing some support for a possible direct toxic effectto the heart muscle.107 108 Furthermore, a number of casereports have found such pathologies as myocardialfibrosis (scar tissue buildup in the heart), myocardialinflammation (inflammation of heart tissue), cardiacsteatosis (accumulation of triglycerides inside heart cells),and myocardial necrosis (death of heart tissue) in long-term steroid abusers.109 110 111 112 A direct link betweendrug abuse and cardiac pathologies is assumed in thesecases, but cannot be proven given the slow nature inwhich these cardiac pathologies develop, and theinfluence many other factors (such as diet, exercise,lifestyle, and genetics) can have on them. Individualsremain cautioned about the possibility of cardiac muscledamage with long-term steroid abuse.

Blood Pressure

Anabolic/androgenic steroids may elevate bloodpressure. Studies of bodybuilders taking these drugs insupratherapeutic doses have demonstrated increases inboth systolic and diastolic blood pressure readings.113

Another study measured the average blood pressurereading in a group of steroid users to be 140/85, whichwas compared to 125/80 in weight lifting controls not

taking steroids.114 Hypertension, or consistently highblood pressure at or above 140/90 for either systolic ordiastolic measures, has been reported in steroid users,115

although in most cases the elevations are more modest.Increased blood pressure may be caused by a number offactors, including increased water retention, increasedvascular stiffness, and increased hematocrit. Aromatizingor highly estrogenic steroids tend to cause the greatestinfluences over blood pressure, although elevationscannot be excluded with non-estrogenicanabolic/androgenic steroids. Blood pressure tends tonormalize once anabolic/androgenic steroids have beendiscontinued.

Hematological (Blood Clotting)

Anabolic/androgenic steroids can cause a number ofchanges in the hematological system that affect bloodclotting. This effect can be very variable, however. Thetherapeutic use of these drugs is known to increaseplasmin, antithrombin III, and protein S levels, stimulatefibrinolysis (clot breakdown), and suppress clottingfactors II, V, VII, and X.116 117 These changes all work toreduce clotting ability. Prescribing guidelines foranabolic/androgenic steroids warn of potential increasesin prothrombin time, a measure of how long it takes for ablood clot to form.118 If prothrombin time increases toogreatly, healing may be impaired. The effects ofanabolic/androgenic steroids on prothrombin time aregenerally of no clinical significance to healthy individualsusing these drugs in therapeutic dosages. Patients takinganticoagulants (blood thinners), however, could beadversely affected by their use.

Conversely, anabolic/androgenic steroid abuse has beenlinked to increases in blood clotting ability. These drugscan elevate levels of thrombin119 and C-reactiveprotein,120 as well as thromboxane A2 receptor density,121

which can support platelet aggregation and theformation of blood clots. Studies of steroid users havedemonstrated statistically significant increases in plateletaggregation values in some subjects.122 There are also agrowing number of case reports where (sometimes fatal)blood clots, embolisms, and stokes have occurred insteroid abusers.123 124 125 126 127 Although it has beendifficult to conclusively link these events directly tosteroid abuse, the adverse effects of anabolic steroids oncomponents of the blood coagulation system are wellunderstood. These serious adverse effects are nowregarded as recognized risks of steroid abuse amongmany that study these drugs.

In therapeutic levels, the anti-thrombic effects ofanabolic/androgenic steroids seem to dominatephysiology, and decreases in blood clotting ability may be


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noted. At a certain supratherapeutic dosage point,however, the pro-thrombic changes appear to overtakethe anti-thrombic changes, and physiology begins tofavor fast and abnormally thick clot formation(hypercoagulability). The exact dosage threshold orconditions required to increase blood clotting has notbeen determined, and some studies with steroid userstaking supraphysiological doses fail to demonstrateincreased coagulability.128 Individuals remain warned ofthe potential increases in thrombic risk withanabolic/androgenic steroid abuse. Blood clottingtendency should return to the pretreated state after thediscontinuance of anabolic/androgenic steroids.

Hematological (Polycythemia)

Anabolic/androgenic steroids stimulate erythropoiesis(red blood cell production). One potential adverse effectof this is polycythemia, or the overproduction of red bloodcells. Polycythemia can be reflected in the hematocritlevel, or the percentage of blood volume that is made upof red cells. As the hematocrit rises, so too does theviscosity of the blood. If the blood becomes too thick, itsability to circulate becomes impaired. This can greatlyincrease the risk of serious thrombic event includingembolism and stroke. A high hematocrit level is also anindependent risk factor for heart disease.129 The normalhematocrit level in men is 40.7 to 50.3%, and in women itis 36.1 to 44.3% (numbers may vary very slightlydepending on the source). For the sake of scale, while ahematocrit of 50% may be normal, a hematocrit of 60% orabove is considered critical (life threatening).

Anabolic/steroid administration tends to raise thehematocrit level by several percentage points, sometimesmore. As a result, many steroid-using bodybuilders willhave hematocrit levels that are above the normal range.For example, one study measured the average hematocritin a group of steroid abusing competitive bodybuilders tobe 55.7%.130 This level is considered clinically high, andwould increase blood viscosity enough to raise the risk ofserious cardiovascular event. Although not likely to be anisolated cause, high hematocrit is believed to have been acontributing factor in the deaths of a number of steroidabusers, usually paired with high blood pressure,homocysteine, and/or atherosclerosis. The averagehematocrit level in bodybuilders not takinganabolic/androgenic steroids was 45.6%, well within thenormal range for healthy adult men.

Many physicians that specialize in hormone replacementtherapy consider a hematocrit level of 55% to be anabsolute cutoff point. At or above this point, andanabolic/androgenic steroid therapy cannot becontinued safely. Drug intake would be ceased at this

point until the hematocrit issues have been corrected.Minor elevations in hematocrit may be addressed withphlebotomy. For this, 1 pint of blood may be removedperiodically during steroid intake, often every twomonths. Proper hydration is also important, asdehydration can temporarily cause the hematocrit level toelevate, giving a false positive for polycythemia. The dailyintake of aspirin is also commonly advised if thehematocrit is above normal, as this will reduce plateletaggregation, or the tendency for platelets to sticktogether and form clots. Individuals remain cautioned ofthe potential cardiovascular danger of high hematocritlevels associated with anabolic/androgenic steroid use.

Homocysteine

Anabolic/androgenic steroids may elevate homocysteinelevels. Homocysteine is an intermediary amino acidproduced as a byproduct of methionine metabolism. Highlevels of homocysteine have been linked to elevations inthe risk for cardiovascular disease.131 It is believed to playa direct role in the disease, increasing oxidative stress,including the oxidation of LDL cholesterol, andaccelerating atherosclerosis.132 Elevated levels ofhomocysteine may also induce vascular cell damage,support platelet aggregation, and increase the likelihoodof thrombic event.133 134 135 The normal range forhomocysteine levels in men aged 30 to 59 years is 6.3-11.2umol/L. For women of the same age the average is4.5-7.9umol/L. Increased risk of heart attack, stroke, orother thrombic event are noted with even modestelevations in homocysteine. According to one study, ahomocysteine level exceeding 15umol/L in patients withheart disease is associated with a 24.7% increasedlikelihood of death within five years.136

Androgens stimulate elevations in homocysteine,137 andmen have an approximately 25% higher level on averagethan women.138 Anabolic/androgenic steroid abuse hasbeen associated with hyperhomocysteinaemia, orconsistent clinically high homocysteine levels.139 Onestudy found that the average homocysteineconcentration in a group of 10 men that had been self-administering anabolic/androgenic steroids (in a cyclicpattern) for 20 years was 13.2 umol/L.140 Three of thesemen died of a heart attack during the investigation, andhad homocysteine levels between 15umol/L and18umol/L. The average homocysteine level inbodybuilders who had never taken steroids was8.7umol/L, while it was 10.4umol/L in previous steroidusers (3 months abstinence). One study did show thatadministering 200 mg of testosterone enanthate (withand without an aromatase inhibitor) for three weeks failedto produce a significant elevation in homocysteine.141 It isunknown if the moderate dosage, drug type (esterified


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injectable vs. c17-aa), or short duration of intake werefactors in the differing outcome from other studies.Individuals remain warned of the potential for elevationsin the homocysteine level with steroid abuse.

Vascular Reactivity

The endothelium is a layer of cells that line the entirecirculatory system. These cells are found on the inside ofall blood vessels, and help increase or decrease blood flowand pressure by relaxing or constricting the vessels(referred to as vasodilation and vasoconstriction,respectively).These cells also help regulate the passage ofmaterials in and out of blood vessels, and are involved in anumber of important vascular processes including bloodclotting and new blood vessel formation. Having a moreflexible (reactive) endothelium is generally considereddesirable for health, and, likewise, the endothelium isoften compromised in individuals with cardiovasculardisease. Patients with endothelial dysfunction tend tonotice greater vasoconstriction, restricted blood flow,higher blood pressure, local inflammation, and reducedcirculatory capacity.142 This may place them at greater riskfor heart attack, stroke, or thrombosis (blood clot).

Endothelial cells are androgen responsive, which maypartly account for men exhibiting less vascular reactivitythan women.143 Similarly, anabolic/androgenic steroid usehas been shown to impair endothelial activity and

vascular reactivity. Studies at the University of Innsbruck inAustria compared the level of endothelial dilation in 20steroid users to a group of control athletes.144 Thoseindividuals using anabolic steroids noticed slight butmeasurably impaired vascular dilation and endothelialfunction. Additional studies at the University of Wales inCardiff comparing vascular dilation in active, previous, andnon- steroid users, also demonstrated anabolic steroids tocause a decline in endothelial-independentvasodilation.145 These effects leave the steroid user withmore relative “stiffness” in the vascular system, whichcould increase the chance of an adverse cardiovascularevent. In both studies, vascular reactivity improved afterthe discontinuance of anabolic/androgenic steroids.

Proving an Association

Direct links between steroid abuse and individual cases ofstroke and heart attack have been difficult to prove.Thereare a number of things that have made this difficult. Forone, cardiovascular disease is very common in men. It alsousually takes decades to develop. This makes individualcontributing factors (which include many things such asdiet, lifestyle, health status, and genetic variables)extremely difficult to isolate. Data concerning the long-term use of steroids in physique- or performance-enhancing doses is also very limited. It would be unethicalto conduct a controlled study where participants weregiven abusive doses of steroids for many years, so the data


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Anabolic/androgenic steroid abuse can produce changes in a number of areas of cardiovascular health that can work togetherto increase the risk of heart attack, stroke, or embolism.

The road to anabolic insight must include a biologicalunderstanding of what muscle growth actually entails.Often simplified by the term “protein synthesis”, musclegrowth is actually a highly complex process involvingmuch more than just building proteins from amino acids.Muscle hypertrophy, the correct scientific term for the waywe adult humans build skeletal muscle, actually requiresthe fusion of new cells (called satellite cells) with existingmuscle fibers. Since this discovery of satellite cells in 1961,a great deal of research into the mechanisms of musclehypertrophy has been undertaken. Scientists have cometo understand that unlike normal muscle cells, thesesatellite cells can be regenerated throughout adult life.Furthermore, they serve not as functional units of theirown, but provide some of the necessary components torepair and rebuild damaged muscle cells. These satellitecells are normally dormant, and sit resting in smallindentations on the outer surface of the muscle fibers,waiting for something to trigger them into activation.

Injury or trauma will provide the stimulus necessary toactivate satellite cells. Once activated, they will begin todivide, multiply, and form into myoblasts (myoblasts areessentially donor cells that express myogenic genes). Thisstage of hypertrophy is often referred to as satellite cellproliferation. The myoblasts will then fuse with existingmuscle fibers, donating their nuclei. This stage of theprocess is usually called differentiation. Skeletal musclecells are multinucleated, which means they possess manynuclei. Increasing the number of nuclei allows the cell toregulate more cytoplasm, which allows more actin andmyosin, the two dominant contractile proteins in skeletalmuscle, to be produced. This increases the overall cell sizeand protein content of the muscle cell. Incidentally, thenumber of nuclei in relation to cross-sectional area alsohelps to determine the fiber type of the cell, namely slowtwitch (aerobic) or fast twitch (anaerobic)332 333. It isimportant to note that we are not increasing muscle cellnumber with muscle hypertrophy. We are only increasingcell size and protein content, even though we are usingsatellite cells to help accomplish this. It is possible formyoblasts to fuse together and actually form new musclefibers.This is called muscle hyperplasia, and equates to thelegitimate growth of new muscle tissue. This is, however,not the primary mechanism of muscle growth in adult life.

The Anabolic ChainNow that we know what muscle hypertrophy is reallyabout, let's look at anabolic stimulus and ongoing

regulation. The following is a rundown of the chain ofhormones and growth factors that mediate musclegrowth, from the initiation of damage, to final recovery,repair, and growth. For the sake of organization, I havepresented them in what I consider to be three logicalphases of action. These are not scientifically accepteddefinitions. Additionally, we could continue to go deeperand deeper into each of the various compounds,messengers, binding proteins, and receptors involved inthis intricate and amazing biological activity. I believe theincluded text will demonstrate the process of muscleanabolism in a very tangible way, however, without toomuch unnecessary information. Each of the key areas ofthis section can be further researched for more detail ifyou are interested. For one so inclined, the medicalreferences in the endnotes would be an excellent place tostart.

TriggerWe all understand that weight training is fundamental togrowing muscle tissue. To date, no “sit on your ass and gethuge and ripped”pill has been invented.The reason is thata number of changes take place in your local muscletissues during intense training that are vital to the growthprocess. Without these early changes, growth is difficult ifnot impossible to stimulate. So for our purposes, we willstart here. Training is the “trigger” in the anabolic process.More specifically, it is the localized cellular damage thatweight training produces that will first set us down theroad of anabolism.The body will respond by repairing thisdamage, and in the process will try to adapt by makingitself stronger. Muscle growth is always a circular process,with a step back (damage) being necessary to take anysteps forward.

Phase I: Initial Response The Initial Response phase covers those changes inmuscle chemistry that begin immediately, during training,which will lay the groundwork for later repair and growth.In many regards, the Initial Response Phase will controlthe potential magnitude of other signals to follow. In theanabolic process, this phase is categorized by the releaseof arachidonic acid from muscle cells, and the formation ofactive messengers including prostaglandins, cytokines,leukotrienes, and prostacyclins. This begins with thebreakdown of the outer phospholipid layer of musclecells, which is initiated by the cellular disruption ofdamaging exercise.334 Phospholipases are released in


57

The Endocrinology of Muscle Growth

response to this trauma, which causes some of thephospholipids stored in the outer layer of the muscle cellsto be released. The eccentric part of the exercisemovement is of particular importance here, which is the“negative” part of the lift, where the muscle is stretchedunder resistance.

The amount of arachidonic acid, which is the centralbioactive lipid in the anabolic process, liberated willlargely control what occurs during this phase. Arachidonicacid is converted locally and immediately via enzymes toa number of active anabolic end products, the mostnotable of which (in terms of muscle growth) areprostaglandins, which are produced via interaction withcyclooxygenase enzymes. These prostaglandins (PGE2and PGF2alpha mainly) will control much of the nextphase, identified here as the Localized Tissue Primingphase. Additionally, the prostaglandin PGE2 will work toincrease local nitric oxide levels, which is also an activemolecule in the anabolic process. It has such actions as

dilating blood vessels (to increase the flow of nutrientsand hormones to the muscles) and increasing theproduction of HGF (hepatocyte growth factor) for satellitecell activation. Arachidonic acid contributes toinflammation and pain signaling as well, and its releaseplays an integral role in the soreness that follows aproductive bout of training.

Training intensity and the relative density of arachidonicacid in the phospholipid layer (arachidonic acidavailability is ultimately the rate-limiting step in theformation of anabolic prostaglandins) will dictate howmuch of this potent lipid can be liberated during exercise.The amount of arachidonic acid stored in skeletal muscletissue is also in a state of constant flux.A number of factorsare involved with its regulation, the most notable of whichare dietary intake and daily utilization. Regular resistancetraining depletes arachidonic acid stores, replacing it withother, more abundant, fatty acids.337 With less arachidonicacid available, the responsiveness of the prostaglandin


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Resting Myofiber

Quiescent Satellite Cell

Myonuclei Satellite Cell Activation and Proliferation

Migration to Injured FiberRegenerated Myofiber

with Added Nuclei

Self-Renewal

MYOTRAUMA

Fusion to DamagedMyofiber (Hypertrophy)

Fusion to Produce NewMyofibers (Hyperplasia)

MUSCLE HYPERTROPHY AND THE 4 STAGES OF THE SATELLITE CELL CYCLE

During the Activation stage, dormant satellite cells are stimulated to enter the cell cycle. Proliferation marks the formation ofnew myoblasts (active donor cells). These myoblasts will fuse with existing damaged muscle fibers during the Differentiationphase. This allows for greater protein synthesis and the expansion of cell size. Quiescence marks the return to a dormantstate, where the inactive satellite cells will again rest on the outer layer of the fibers. Myostatin, a known inhibitor of musclegrowth, is believed to be a key regulator in this stage.335 336

system to regular exercise starts to diminish.338 Have youever wondered why you were so sore when you first starttraining, or after you took a long break? Or why those earlyworkouts tended to be so much more productive than laterones, where you struggle to notice even moderate soreness?Much of this is directly tied to your arachidonic acidstores. The more arachidonic acid you have, the easier it isto liberate during training, and vice versa.Thankfully, levelscan be augmented with dietary intervention (for moreinformation, see the arachidonic acid profile).

Phase II: Localized Tissue PrimingPhase II is characterized by a localized increase in growthfactor expression and tissue sensitivity to anabolichormones. Those who have always wondered whyanabolic drugs do not work without training will find agood explanation right here. Simply put, your musclesneed to be primed for the actions of these drugs first. Oneway the body accomplishes this is to increase the densityof certain receptors in those specific muscles (fibers really)where it needs to initiate repair. This includes, amongothers, androgen, IGF-1, MGF, and insulin receptors.Stretch-induced muscle damage and the Phase I responseare both principle triggers here. Receptor densityregulation is important because it prevents anabolichormones from stimulating tissue growth in areas of thebody that do not require it. Receptor density can,therefore, be as strong a regulating force on thepharmacological activity of anabolic drugs as the serumlevels of the drugs themselves.

To put it in perspective, we need to remember that thereare two separate components that interact before anymessage is sent to a muscle cell telling it to increasegrowth. We have a hormone or growth factor on onehand, such as testosterone, IGF-1, MGF, or insulin, and itscorresponding receptor on the other. Injecting exogenousanabolic drugs facilitates greater receptor binding andanabolic signaling by providing more messengerhormones/growth factors (obviously). The morehormones or growth factors you have around the cell, themore binding and activation of receptor sites will takeplace. We cannot forget, however, that having morereceptor sites (instead of more hormones) can alsofacilitate the process too. More receptors mean theexisting hormones or growth factors will find them faster.Faster binding means the anabolic message is sent morequickly, and once completed that the anabolic messengerwill be more likely to find another receptor site (to sendanother message) before it is broken down by enzymes. Itis all about how much signal can be sent in a given timeperiod, and both sides of the equation are equallyimportant in determining this.

While on one hand we have an increase in tissuesensitivity to anabolic hormones and growth factors, alsovital during the Localized Tissue Priming phase is anincrease in the localized expression of certain vital growthfactors themselves.This includes IGF-1, MGF, FGF, HGF,TNF,IL-1, and IL-6. These compounds will be released, and willwork together on the existing damaged muscle fibers andsatellite cells, in a sort of grand symphony of muscleanabolism, with each playing its own vital role in the


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Muscle DamageFocus on eccentric movement

PhospholipaseCatabolizes outer phospholipid layer

Arachidonic Acid ReleaseThe body’s core anabolic lipid

Prostaglandin FormationAnd other active end products

of arachidonic acid

Note: Inhibition of the cyclooxygenase-2 enzyme withanti-inflammatory drugs like ibuprofen,acetaminophen, or aspirin, prevents the formation ofactive prostaglandins. The anabolic cascade is stalledwithout sufficient prostaglandin formation (Am JPhysiol Endocrinol Metab 282:E551-6), interferingwith the normal increase in protein synthesis ratesafter exercise. It is often advised to use such drugsonly when necessary if muscle growth is a key focus.

process. In many cases, the actions of one compound willsupport the other, either by enhancing its levels,suppressing restricting binding proteins, or supporting itssignaling via intertwined mechanisms. A detailedroadmap to all such interactions would go well beyondthe scope of this book, and in fact are as of yet not evenfully understood to science. A general overview of what isgoing on with each compound itself, however, is providedin our review of Phase III.

Phase III: RepairYour local muscle tissues are primed during Phases I andII. During Phase III, the hormones and growth factors go towork to finish the job. We categorize this phase as one ofongoing anabolic action, action mediated by thecombined effects of many anabolic hormones and growthfactors including androgens, insulin, IGF-1, IGF-2, MGF, FGF,HGF, TNF, IL-1, and IL-6. This is the time when repair andhypertrophy are physically taking place in your muscles,and each compound will play an intricate role in theprocess. We must not forget, however, that everythingleading up to this point (the actions in Phase I & II) has stillbeen determining how strong the growth response will be,via modifying receptor densities and hormone/growthfactor expression. We will follow the individual actions ofthe anabolic components very closely here. During thethird phase, tissue repair and growth will be finalized withthe help of the following hormones and growth factors.

Hepatocyte Growth Factor (HGF): HGF is a heparin-binding growth factor that resides on the outer surface ofuninjured cells. Upon injury, it migrates to satellite cellswhere it triggers their activation and entry into the cellcycle.339 HGF expression is regulated via nitric oxiderelease,340 which is stimulated upon injury to also aid inthe flow of nutrients and hormones to the area. PGE2plays a pivotal role in nitric oxide synthesis and HGFrelease.341

Androgens: Androgens (the hormones thatanabolic/androgenic steroids mimic) are strongsupporters of protein synthesis rates in skeletal muscletissue. They are also known to stimulate local IGF-1expression, so the effects of these hormones extend to thesatellite cell cycle (perhaps explaining why they are suchstrong stimulators of muscle growth). It is also of note thatarachidonic acid increases androgen receptor density inskeletal muscle tissue.This helps to further piece togetherthe biochemical links between the Phase I and Phase IIresponse.

Insulin-Like Growth Factor I (IGF-I): IGF-I is an insulin-like hormone with marked anabolic effects. Owing to itsname, it also has some insulin-like effects as well. IGF-I

increases protein synthesis, and supports the proliferationand differentiation of satellite cells. The prostaglandinPGF2alpha is known to strongly up-regulate local IGF-Ireceptor expression.342 343 PGE2 is also believed to play arole in increasing local IGF-1 synthesis.344

Insulin-Like Growth Factor II (IGF-II): IGF-II is a secondinsulin-like growth factor that plays a role in theproliferation of satellite cells. Unlike IGF-I, IGF-II expressiondoes not appear to drastically increase in response totraining.345

Mechano-Growth Factor (MGF): Mechano-GrowthFactor is a recently discovered variant of Insulin-LikeGrowth Factor I. This growth factor is produced during analternate splicing sequence of the IGF protein, and plays astrong role in the support of myoblast proliferation. MGFexpression, like many of the growth factors discussedhere, is strongly up-regulated in muscle tissue in responseto stretch stimulus.346

Fibroblast Growth Factor (FGF): FGF is actually a familyof growth factors, with nine different isoforms (FGF-1through FGF-9). The full role that FGF plays in musclehypertrophy in adulthood is not fully understood,however, it is believed to be a strong proliferator ofsatellite cells, serving to expand their population.347 FGF'smay also play a role in cell differentiation. As with manygrowth factors, FGF expression up-regulation isproportional to the degree of tissue damage.348 FGF-2 andFGF-4 seem to be the most prolific representatives of thisfamily in mature muscle tissue.

Insulin: In addition to having some ability to increaseprotein synthesis and inhibit protein breakdown, insulin isthe body's chief nutrient transport hormone. The actionsof insulin allow cells to transport glucose and amino acidsthrough the plasma membrane. Insulin receptorexpression is strongly up-regulated after traumaticexercise, so as to provide more immediate nutrition to theaffected area. This up-regulation has been closely linkedto the prostaglandin PGE2.349 350

Cytokines (IL-1, IL-6, TNF): Cytokines are a group ofimmunomodulatory compounds, though in the contextof this section we are loosely referring to them as growthfactors. The IL cytokines are called interleukins, and TNF isshort for Tumor Necrosis Factor. Among other things,cytokines are known to stimulate the migration oflymphocytes, neutrophils, monocytes, and other healingcells to a site of tissue damage, to aid in cell repair. Theyhelp in a number of other ways too, such as aiding in theremoval of damaged cells and regulating certaininflammatory responses, including the production ofsome prostaglandins. Prostaglandins are known to playimportant roles in the expression of all three of the


60

cytokines mentioned here,351 352 however, they may notbe the sole stimulus. Other pathways of arachidonic acidmetabolism may also be involved.

Prostaglandins: Although these are the key initialreactionary chemicals, prostaglandins continue to play arole throughout the muscle building process (includingPhase III). This includes their support of hormone receptorproliferation, the enhancement of protein synthesis rates,and an intensification of the anabolic signaling of IGF-1 via ashared pathway (PI3K).353

Estrogens: Although not specifically highlighted in thisoutline, estrogens also play a minor role in the anabolicprocess. This includes helping to increase androgenreceptor density in certain tissues (though perhaps notskeletal muscle), stimulating the GH/IGF-1 axis, andenhancing glucose utilization for tissue growth and repair.

Bringing it All TogetherSo that, in a very loose nutshell, is what is going on insideyour body from the time you pick up a weight to the timeyour muscles are repaired, stronger, and ready for more. Ifthe above seems confusing to you, it should. The fact is,the whole process of muscle growth has been

confounding scientists for decades, and undoubtedly willfor decades more. We still have a great way to go beforebeing able to explain fully how it is that musclehypertrophy occurs in humans. But as you can see, wehave traveled a great distance as well. During the mid-1960s, scientists were only first learning that we growmuscle with the help of satellite cells. More than fortyyears later we have identified, and are experimentingwith, dozens of growth factors that were unheard of backthen. It is a new world today, and despite not having all theanswers, we know enough to enhance humanperformance in many exciting new ways. But please don'tmistake the intention of this section. It is not here to giveyou a functional roadmap of the entire anabolic process,or to guide you in the ultimate polydrug program. It ishere simply to open your mind to the true complexity ofanabolism. When we start to see muscle growth from itsvarious angles and intricacies, we begin to see our ownpotential opportunities for successful exploitation. Howmany of these opportunities you act upon will depend onyour own goals and interests. But no matter how much orhow little you actually apply this information, I hope youfeel better equipped by having it.


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Skeletal muscle growth is a complex process that involves a variety of signaling compounds.

Anabolic/androgenic steroids are not medically approvedto promote excessive muscle mass gains (bodybuilding)or improve athletic performance. Aside from earlyexperimentation on athletes by a handful of sportsphysicians, an extensive effort to study the physique- andperformance-enhancing properties of these drugs,specifically with an eye on developing strategies for usingthem to maximize benefits and minimize adverse effects,has not been undertaken by the medical community.Because of this, illicit users have been left to develop theirown protocols for administering these drugs. The resulthas been a large variety of different approaches to usingthese agents, some safer or more effective than others.While it would not be possible to comprehensivelyevaluate all known approaches, this section will discusssome of the most fundamental and time-proven methodsfor using AAS.

Steroid SelectionWhen first considering what steroid(s) to use, one willnotice there are many different medications that fallunder the category of anabolic/androgenic steroids. Thishas been the result of many years of development, wherespecific patients and needs are addressed with drugs thathave specific characteristics. For example, some drugs areconsidered milder (less androgenic), and produce fewerside effects in women and children. Others are moreandrogenic, which makes them better at supportingsexual functioning in men. Some are injectablemedications, and others made for oral administration.There are limits to this diversity, however. All AAS drugsactivate the same cellular receptor, and as such sharesimilar protein anabolizing properties. In other words,while different AAS drugs may have some differingproperties, if your objective is to gain muscle mass andstrength, this could be accomplished with virtually anyone of the commercially available agents.

While all AAS drugs may be capable of improving musclemass, strength, and performance, it would not be correctto say there are no advantages to choosing one agentover another for a particular purpose. Mostfundamentally, the quantity and quality of muscle gainedmay be different from one agent to another. In a generalsense, AAS that are also estrogenic tend to be moreeffective at promoting increases in total muscle size.Thesesteroids also tend to produce visible water (andsometimes fat) retention, however, and are generallyfavored when raw size is more important than muscle

definition. Drugs with low or no significant estrogenicitytend to produce less dramatic size gains in comparison,but the quality is higher, with greater visible muscularityand definition. In reviewing the most popular AAS drugs,we can separate them into these two main categories asfollows.

Mass (Bulking):Methandrostenolone – Oral

Oxymetholone – Oral

Testosterone (cypionate, enanthate) – Injectable

Lean Mass:Boldenone undecylenate – Injectable

Methenolone enanthate – Injectable

Nandrolone decanoate – Injectable

Oxandrolone – Oral

Stanozolol – Oral

The early stages of AAS use usually involve cycles with asingle anabolic/androgenic steroid. Building muscle massis the most common goal, and usually entails the use ofone of the more androgenic substances such astestosterone, methandrostenolone, or oxymetholone.Those looking for lean mass often find favor in suchanabolic staples as nandrolone decanoate, oxandrolone,or stanozolol. First time users rarely welcome injectinganabolic/androgenic steroids, and will usually choose anoral compound for the sake of convenience.Methandrostenolone is the most common choice formass building, and is almost universally regarded ashighly effective and only moderately problematic (interms of estrogenic or androgenic side effects). Stanozololis the oral anabolic steroid most often preferred forimproving lean mass or athletic performance.

The potential for adverse reactions should also beconsidered when choosing a steroid to use, especially ifAAS use is to be regularly repeated. For example, the listedoral medications present greater strain on the


65

Steroid Cycles

cardiovascular system, and are also liver toxic. For thesereasons, the injectable medications listed are actuallypreferred for safety (testosterone most of all). Potentialcosmetic side effects may also be taken into account. Forexample, men with a strong sensitivity to gynecomastiasometimes prefer non-estrogenic drugs such asmethenolone, stanozolol, or oxandrolone. Individualsworried about hair loss, on the other hand, may isolatetheir use to predominantly anabolic drugs, such asnandrolone, methenolone, and oxandrolone. A detailedreview of personal goals, health status, and potential sideeffects of each drug is advised before committing to anyAAS regimen.

DosageThe dosage used is important in determining the level ofbenefit received. Anabolic/androgenic steroids tend to bemost efficient at promoting muscle gains when taken at amoderately supratherapeutic dosage level. Below this(therapeutic), potential anabolic benefits are oftencounterbalanced, at least to some extent, by thesuppression of endogenous testosterone. At very highdoses (excessive supratherapeutic), smaller incrementalgains are noticed (diminishing returns). In the case oftestosterone enanthate or cypionate, for example, adosage of 100 mg per week is considered therapeutic, andis generally insufficient for noticing strong anabolicbenefits. When the dosage is in the 200-600 mg per weekrange, however, the drug is highly efficient at supportingmuscle growth (moderate supratherapeutic). Above thisrange, a greater level of muscle gain may be noticed, butthe amount will be small in comparison to the dosageincrease. Below are some commonly recommendeddosages for the steroids listed earlier.

- Boldenone undecylenate: 200-400 mg/wk

- Methandrostenolone: 10-30 mg/day

- Methenolone enanthate: 200-400 mg/wk

- Nandrolone decanoate: 200-400 mg/wk

- Oxandrolone: 10-30 mg/day

- Oxymetholone: 50-100 mg/day

- Stanozolol: 10-30 mg/day

- Testosterone (cypionate, enanthate): 200-600 mg/wk

There are additional considerations other than the costeffectiveness of a particular dosage. To begin with, highdoses of anabolic/androgenic steroids tend to producestronger negative cosmetic, psychological, and physicalside effects. In light of diminishing returns, the tradeoffbetween results and adverse reactions becomes less andless favorable. Gains made on lower doses also tend to bebetter retained after steroid discontinuance than thoseresulting from excessive intake. It is generally not realisticto expect that rapid double-digit weight gains induced bymassive dosing will remain long after a cycle is over.Slower steadier gains are advised. It is also very importantto remember that higher doses aren’t always what areneeded to achieve greater gains. An individual morefocused on his or her training and diet will often makebetter gains on lower dosages of AAS than a lessdedicated individual taking higher doses. With thisunderstanding, AAS should only be considered when allother variables of training and diet have been addressed,and always limited to the minimum dosage necessary toachieve the next realistic training/performance goal.


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Dosage vs. Weight Increase

Wei

ghtI

ncre

ase

-/+

Dosage - / +

Figure 1. Anabolic/androgenic steroids tend to be most effective in moderately supratherapeutic doses. The anabolic benefitsdiminish in relation to the amount of drug given at both the high and low ends of the dosage range.

Duration (Cycling)The administration of anabolic/androgenic steroids at agiven dosage will typically produce noticeable increasesin muscle size and strength for approximately 6-8 weeks.After this point, the rate of new muscle gain typicallyslows significantly. A plateau may be reached soon after,where all forward momentum has ceased. To continuemaking significant progress beyond this point can entailescalating dosages, which is likely to coincide with agreater incidence of adverse reactions and diminishinganabolic returns. Even without dosage escalation,negative health changes are already likely to be apparent,and should be corrected fairly quickly. The practice ofextended or continuous steroid administration isdiscouraged for these reasons. It is generallyrecommended to use AAS drugs for no longer than 8weeks at a time (10-12 weeks at the maximum), followedby an equal or longer period of abstinence before anothersteroid regimen is initiated. This pattern of rotatingbetween “on” and “off” periods is referred to as cycling.

Off-Cycle (Recovery, Bridging, andTapering)The period immediately following steroid cession caninvolve a state of hypogonadism (low androgen levels),and as a result protein catabolism. In an effort to minimizemuscle loss, the objective here is usually on restoringnatural testosterone production, maintaining an optimallevel of muscle stimulation, and remaining dedicated toproper nutrition. A hormonal recovery program is usuallyinitiated, which may involve the use of HCG, tamoxifen,and clomiphene (see PCT: Post Cycle Therapy). Asubstantial off-cycle period is also advised, involvingabstinence from anabolic/androgenic steroids for at least

8-12 weeks. Some AAS abusers have difficulties withcomplete drug abstinence, and will initiate “bridging”routines between full-dose cycles. This may involve theperiodic low-dose administration of an injectable steroid,such as 200 mg of testosterone enanthate ormethenolone enanthate every 2-3 weeks. Such practice isdiscouraged, however, as it can interfere with hormonalrecovery, and prevent a return to metabolic homeostasis.

When concluding a cycle, some steroid users also follow apractice of first slowly reducing their dosages (tapering).This tapering may proceed for a 3-4 week period, and willinvolve an even stepping down of the dose each weekuntil the point of drug discontinuance. It is unknown,however, if such tapering offers any tangible value. Thispractice has never been evaluated in a clinical setting, andis not widely recommended with steroid medications as itis with some other drugs such as thyroid hormones orantidepressants. Virtually every high-dose AASadministration study can also be found to end at themaximum dosage, with no time allotted to tapering. Oneflaw in the logic of using a tapering program is that theyare ostensibly designed to aid hormone recovery.Recovery is not possible, however, whilesupraphysiological levels of androgens are present, andsuch levels are usually found during all weeks of a normal(nonmedical) steroid taper. Individuals remain cautionedthat dosage tapering is not a proven way to reduce post-cycle muscle catabolism.

StackingAs individuals become more experienced withanabolic/androgenic steroid use they may beginexperimenting with the use of more than one steroid at atime. This practice is referred to as stacking. Stacking is


67

Duration vs. Weight Increase

Wei

ghtG

ain

-/+

Week of Intake - / +

1 2 3 4 5 6 7 8 9 10 11 12

Figure 2. Anabolic/androgenic steroids tend to be most effective at a given dosage for approximately 6-8 weeks. After thispoint, the rate of new muscle gain will slow, and soon after will usually hit a full plateau.

most common with advanced bodybuilders who find thatat a certain level of physical development they beginhitting plateaus that are difficult to break with a previoussingle-agent approach. In many cases, however, it maysimply be the greater cumulative steroid dosage that isnecessary for the resumed progress. Stacking usuallyinvolves the combination of a more androgenic steroidwith one or more primarily anabolic agents. On theanabolic side, common steroids of choice includeboldenone, methenolone, nandrolone, oxandrolone, andstanozolol. Testosterone, oxymetholone, ormethandrostenolone will serves as the androgenic baseof most stacks.

The reasons for stacking androgenic and anabolic steroidstogether in this manner are two fold. On the one hand,high doses of testosterone, oxymetholone, ormethandrostenolone are prone to producing strongandrogenic and estrogenic side effects. Stacking firstbecame very popular during the 1960s, a time wheneffective estrogen maintenance drugs were not widelyavailable. An anabolic-androgen stack allowed the use ofa higher total steroid dosage than would be tolerable witha single androgen. Anabolic-androgen pairing alsoappears to offer efficacy advantages over the use ofprimarily anabolic agents alone, even when they are takenin higher doses. This conflicts with the originalexpectations for “anabolic” steroids, which were

specifically designed to emphasize muscle-buildingproperties, but is repeatedly noticed by users. The reasonthe basic androgenic steroids are more anabolicallyproductive is not fully understood, but is believed toinvolve the interplay of estrogenic hormones, androgenicstimulation in the central nervous system, and potentiallyother unidentified synergisms necessary for optimalmuscle growth.

Today, the availability of drugs that can reduce estrogenicactivity makes the continued use of single agent cyclesbased on a strong androgen like testosterone enanthateor cypionate much more viable than it was decades ago.Side effects like gynecomastia and water retention cannow be effectively minimized with anti-estrogens oraromatase inhibitors, even when taking higher doses.Individuals should be aware that stacking is, likewise, nota necessary practice. It is likely to remain commonlyapplicable in competitive bodybuilding circles, however,or when an individual is sure they have progressed as faras they possibly can with a single-agent approach.Otherwise, for many athletes and recreationalbodybuilders, the periodic use of a single steroid will bemore than sufficient to maintain optimal levels of musclemass and performance, and it may never be necessary todeviate from this approach.


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The following cycles are presented as examples of common steroid administration protocols. These programs have notbeen evaluated in a clinical setting for safety and efficacy, and are provided for informational purposes only. These are notrecommendations for anabolic/androgenic steroid use. As with any supplemental drug program, it is important to examineyour own individual health status, health risks, and performance goals before deciding to engage in anyanabolic/androgenic steroid use. For those who have made the decision, it is important to emphasize again that therecommended approach to AAS use is to limit drug intake to the lowest levels necessary to achieve the next rational goal.More aggressive cycles should not be attempted unless one is sure they cannot achieve the results needed on a moremoderate program. Note that given the difficulty in predicting androgenic threshold and dosages for female users, thebelow cycles are examples of programs for men only.

Single Agent Cycles

Products: 100 tablets 5 mg Methandrostenolone

All Weeks: Liver Support: Liver Stabil, Liv-52, or Essentiale Forte (label recommended dosage).

Cholesterol Support: Lipid Stabil (3 caps/day) and Fish Oil (4 g/day).

Estrogen Support: tamoxifen (10-20 mg/day).

Comments: This is a very common first cycle for building muscle mass, and utilizes a single standard bottle ofmethandrostenolone. This cycle is likely to produce very noticeable muscle growth in a first-timesteroid user, often in excess of 8-10lbs of weight gain. This is usually not accompanied by significantvisible side effects such as gynecomastia and water retention. Although this is considered a beginner’scycle, methandrostenolone is a c-17 alpha alkylated oral steroid, and presents significant cardiovascularand liver toxicity. The repeated use of such drugs should be limited.


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Dianabol Cycle #1 (Mass)

Week Methandrostenolone

1

2

3

4 15 mg/day

5 20 mg/day

10 mg/day

10 mg/day

15 mg/day

Sample Steroid Cycles

Stack Cycles

Products: 10 mL 200 mg/mL nandrolone decanoate

100 tablets 5 mg methandrostenolone


Cholesterol Support: Lipid Stabil (3 caps/day) and Fish Oil (4g/day).


Comments: This is an extremely old and widely repeated steroid combination, based on the predominantly anabolic steroid nandrolone decanoate. Methandrostenolone serves as the androgenic component of this stack, and is added during week 3, which is a time that side effects of reduced androgenicity (with the exclusive use of nandrolone decanoate) are commonly noticed, such as loss of libido and sexual dysfunction. The doses used in this cycle are not high by most bodybuilding standards, but are sufficient to impart a noticeable increase in muscle size and strength.


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Week Nandrolone Methandrostenolone

1

2

3

4

200 mg

200 mg

10 mg/day200 mg

10 mg/day200 mg

10 mg/day300 mg

15 mg/day300 mg

15 mg/day300 mg

15 mg/day300 mg

5

6

7

8

Deca/Dianabol Cycle #1 (Mass)

Products: 20 mL 200 mg/mL nandrolone decanoate

200 tablets 5 mg methandrostenolone




Comments: A more popular manifestation of the Deca/Dianabol Cycle, with more commonly accepted dosages for a moderately experienced steroid user. Incidences of side effects are expected to be higher at these dosages, although overall this stack is likely to be less problematic than a combination of testosterone and oxymetholone.


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Week Nandrolone Methandrostenolone

1

2

10 mg/day

10 mg/day

20 mg/day

20 mg/day

20 mg/day

20 mg/day

20 mg/day

20 mg/day

3

4

5

6

7

8

9

10 400 mg

400 mg

400 mg

400 mg

400 mg

400 mg

400 mg

400 mg

400 mg

400 mg

Deca/Dianabol Cycle #2 (Mass)

Products: 20 mL 200 mg/mL testosterone (enanthate or cypionate)

100 tablets 50 mg oxymetholone




Comments: A combination of testosterone and oxymetholone is generally regarded as the most potent 2-drug stack for gaining raw muscle mass. Both drugs will present significant estrogenicity, and will be likely to induce gynecomastia quickly unless an estrogen maintenance drug such as tamoxifen is used.Inexperienced steroid users have been known to gain over 25-30 pounds on a cycle such as this. Water retention will be very high with this stack, however, and a rapid loss of water weight (possibly up to 10 pounds or more) is expected soon after the cycle is discontinued.


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Week Testosterone Oxymetholone

1

2

50 mg/day

50 mg/day

100 mg/day

100 mg/day

100 mg/day

100 mg/day

100 mg/day

100 mg/day

3

4

5

6

7

8

9

10 200 mg

500 mg

500 mg

500 mg

500 mg

400 mg

400 mg

400 mg

400 mg

200 mg

Testosterone/Anadrol Cycle (Mass)

Harm reduction is a concept among healthcare workersthat seeks to reduce the negative health consequences ofdrug abuse. The principles of harm reduction call for anacceptance of the fact that, good or bad, illicit drugs existin today’s society. Instead of ignoring drug users, harmreduction practitioners actively work with them topromote safer use strategies and decrease the healthdamage of drug abuse. The effort of harm reduction isalways helping, not judging, the individual. Althoughpreviously focused exclusively on narcotic drugs of abuse,

harm reduction principles can (and should) also bedeveloped for steroid users, a group that rarely has thebenefit of full physician oversight in its drug programs. Inan effort to further this goal, ANABOLICS has outlined thefollowing principles of steroid harm reduction. If followed,these principles should measurably reduce the negativehealth impact of steroid use, making it a safer (althoughnot completely safe) practice.

1. Avoid Counterfeit and UndergroundSteroids. Anabolic steroids produced by illicitmanufacturers are often of low quality, and maypresent additional health risks to the userbeyond what are presented by the steroidsthemselves. Even if they contain actual steroids inproperly labeled doses, underground drugs maycontain toxic heavy metals, use dirty rawmaterials, or even carry bacterial, viral, and otherforms of contamination. Pharmaceutical drugpurity is assured to the public only by anextremely costly, tedious, and methodical processof quality assurance and government oversight.There is little financial and even logisticalincentive for most underground drug makers toproduce their drugs at such high levels of purity.Counterfeit and underground drugs are notconsidered equal substitutes for realpharmaceutical products, and should be avoided.

2. Avoid Toxic Oral Steroids. Aside from Andriol,Primobolan, and Proviron, every oral steroiddiscussed in this reference book is a c-17 alphaalkylated compound and should be avoidedwhenever possible.While there may be a numberof clinical reasons to prescribe such a drug, whenused in the higher doses necessary for musclegrowth these agents tend to have significantnegative impacts on certain health markers.Theirmost notable effect is to increase the ratio of LDL(bad) to HDL (good) cholesterol in the body,which favors increased plaque deposition in the

arteries. Over time this may increase the risk ofheart disease. C-17 alpha alkylated steroids arealso the drugs exclusively associated with strongliver stress and (rarely) liver cancer. If injection canbe tolerated, and moderate physique orperformance improvement is the goal, all of thesame results can be achieved without oralsteroids. Note that injectable forms of otherwiseoral steroids (such as stanozolol andmethandrostenolone) should also be avoided, asthey provide a similar level of hepatic andcardiovascular strain regardless of the differingroute of administration.

3. Think of Testosterone First. Of all theanabolic/androgenic steroids produced,testosterone esters like cypionate, enanthate, andSustanon tend to have the lowest negativeimpact on health when taken in muscle buildingand performance-enhancing doses. Testosteronedrugs provide a hormone identical to thatalready produced in the body, presenting thesame spectrum of physical and physiologicaleffects. In addition to being one of the mostefficient muscle-builders available, testosteronegenerally has a positive (not negative) effect onlibido, supports a positive mood, andsupplements necessary estrogen so thatcholesterol levels are less negatively shifted. Theexclusive use of testosterone drugs for body orperformance enhancement is advised if possible.


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Harm Reduction / Safer Use Guidelines

Principles of Anabolic Steroid Harm Reduction

4. Limit Yourself to the “Safest” Drugs. If theexclusive use of an injectable testosterone is notfeasible, limiting use to the safest group ofsteroids is advised. Of the injectable class, thefollowing drugs have the lowest cardiovascularstrain and are recommended: Deca-Durabolin(nandrolone decanoate), Durabolin (nandrolonephenylpropionate), Equipoise (boldenoneundecylenate), and Primobolan Depot(methenolone enanthate). If an oral steroid isdesired, only Andriol, Primobolan, or Provironshould be used. These drugs are not c-17 alphaalkylated, and can all provide additional steroidactivity without the same level of cardiovascularand hepatic strain seen with other common oralsteroids including Anadrol (oxymetholone),Anavar (oxandrolone), Dianabol(methandrostenolone), and Winstrol (stanozolol).

5. Use Health Support Supplements.Anabolic/androgenic steroid users can help lowerthe negative health impact of steroid use with theconsumption of natural health supportsupplements. To begin with, the negativecardiovascular effects of these drugs can be offset(at least to some degree) with cholesterolsupplements. Fish oil is recommended as a base,which should be stacked with a number of otherclinically studied cholesterol support ingredientsincluding green tea, garlic powder, resveratrol,phytosterols, niacin, and policosinol. The blendedproduct Lipid Stabil (Molecular Nutrition)includes these ingredients and is recommended.Cholesterol support supplements should betaken at all times during anabolic steroid therapy.Next, those taking oral steroids should bereducing liver strain with a liver supportsupplement. Recommended products includeLiver Stabil (Molecular Nutrition), Liv-52(Himalaya Drug Company), and Essentiale Forte(Aventis). One of these products should be takenat all times during therapy with hepatotoxicagents

6. Always Cycle Steroids. A steroid cycle usuallyconsists of 6 to 12 weeks of drug use followed byan equal period of time or more abstaining fromall anabolic/androgenic steroids. This practice isadvised for a number of reasons. For one, as yousupplement male steroid hormones your bodywill reduce the production of its owntestosterone. Cycling helps reduce the risk of

developing long-term fertility and hormonalissues, which are sometimes caused by theuninterrupted use of steroids for many months oryears. Cycling also lets your general markers ofhealth (such as cholesterol levels, hematocrit, andblood pressure) return to their normal stateperiodically, reducing the impact temporarychanges may have over time. Those individualswho use anabolic/androgenic steroids for longperiods of time without interruption run a greaterrisk that these negative changes in healthmarkers will result in long-term health issues.

7. Use Reasonable Dosages. High doses ofsteroids are not necessary to achieve significantmuscle growth, especially if moderate physiqueor performance enhancement is desired. Adosage limit of 400 mg per week on injectables isadvised. In the case of testosterone cypionate,400 mg per week equates to at least 4 to 5 timesthe level of hormone naturally produced in ahealthy male body. This level of use will producedramatic muscle gain if combined with propertraining and diet. In fact, during the 1970s and 80sthe dosage range of 200-400 mg per week wasconsidered “standard”for the bodybuilding use oftestosterone, nandrolone, boldenone, ormethenolone. There is actually little real need forextreme doses of 750-1,000 mg or more ofsteroid per week, or to supplement an injectablebase with additional orals. High doses mayproduce a faster rate of gain, but are generally notcost effective for the extra muscle they provide.Additionally, high doses of steroids greatlyincrease cardiovascular strain and the incidenceof other side effects.

8. Avoid Aromatase Inhibitors. Aromatase-inhibiting drugs counter estrogenic side effectsby preventing the production of estrogen in thebody. While an effective practice, they alsodeprive the body of a hormone that is importantto cardiovascular health. In particular, estrogensupports the production of good (HDL)cholesterol, which means that aromataseinhibitors may inadvertently increase thecardiovascular strain of a steroid cycle. Ifestrogenic side effects are apparent and areduction or elimination of the offendingsteroid(s) is not considered an option, the SERM(Selective Estrogen Receptor Modulator) drugNolvadex could be used instead. This drug offers


113

partial estrogenic action in the liver, which mayallow it to counter estrogenic side effects withoutthe same negative shift in cholesterol.

9. Get Regular Blood Tests. Comprehensiveblood testing including an examination ofhormones, cholesterol, blood cell concentrations,and enzymes is the most useful tool for assessingthe negative health impact of steroid use.Changes in cholesterol, for example, can helpquantify for the user what effect a particular drugregimen is having on their cardiovascular health.The individual then has the opportunity to betterassess long-term risk if this cycle is to berepeated. At a minimum, blood testing should beconducted before a cycle is initiated, 3 to 4 weeksinto a cycle, and a couple of months after a cycle.This allows for 1) a baseline for later comparison;2) a snapshot of the on-cycle health impact; and3) an opportunity to assess if natural homeostasishas been restored post-cycle.

10. Use Proper Injection Procedures. Carefulattention to correct injection procedures canhelp eliminate some of the complicationsassociated with nonmedical steroid use. Steroidsare given via deep intramuscular injections. Themost common site of application is the upperouter quadrant of the gluteus muscle, althoughthe drugs are also commonly injected to theupper outer thigh and shoulder. Site injections (insmaller muscle groups like the biceps, triceps, orcalf muscles) for cosmetic purposes arediscouraged, as they are technically more difficultto navigate and more prone to complications.Comfortable injection volumes should also beused, generally no more than 3 mL perapplication. Each injection site should be rotatedso that the same muscle is not injected morethan once every two weeks. A general focusshould be made on cleanliness, including the useof alcohol pads on the vials and skin beforeinjection, and the proper disposal of all needlesand empty vials/ampules after use.

11. Sterilize. Though never advised, should thechoice be made to use an injectable steroid ofunderground origin, an effort should be made tosterilize the solution before use. This will reducethe likelihood of illness or infection due tomicroorganism.

12. Watch Your Diet. Anabolic/androgenicsteroids can allow an individual significantlymore latitude with their diet than normal. Thecaloric demand typically increases due to theeffects of these drugs on muscle mass andmetabolism, allowing more calories to beconsumed each day without adding fat mass. It isimportant not to let this latitude affect yourhealth in a negative way. Remember, the use ofsteroids at physique- and performance-enhancing doses is expected to cause anunfavorable shift in cholesterol levels and othercardiovascular health markers, favoring a higherrisk of cardiovascular disease. Simultaneouslyfeeding your body greater amounts of saturatedfats, cholesterol, and simple carbohydrates canmake the impact of these drugs even worse. Dietslow in saturated fats, cholesterol, and simplesugars are recommended, and are known toreduce cardiovascular disease risk. Note, however,that diet alone is not effective at countering thenegative cardiovascular effects of steroid use, butdietary restrictions can reduce these risks.

13. Always Consider Reward AND Risk. It canbe easy to ignore the potential health impact ofsteroid use when the positive benefits are sorapid and the negative consequences so remote.At the end of the day, however, it is veryimportant to remember that the use of steroids indoses sufficient to support short term musclegain are virtually always going to have somenegative impact on your body. Your cholesterolwill shift in an unfavorable direction, your bloodpressure may go up a little bit, and you may everso slightly thicken the ventricles in your heart.Your hormones are out of balance when you takesteroids, which will invariably cause other thingsto go out of balance. Steroid use is rarelydangerous over a short term period. Thesehormonal drugs are acutely very safe. As usecontinues over the years, however, these short-term periods accumulate, and total on-cycle timemay become very long. Always remember toconsider the risks as well as the rewards of eachcycle. Choosing your drug program carefully andkeeping the negative effects of steroid use incheck over the short term is the best way toreduce long term risks.


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This section pertains to methods for differentiatingbetween legitimate pharmaceutical products andillegitimate copies (counterfeits). Before we begin, I needto remind you that counterfeiting anabolic steroids is avery lucrative business these days. Counterfeiters areinvesting a lot of money in printing and packagingequipment so that you’ll have a hard time picking outtheir products. Furthermore, there are now many large“commercial scale” counterfeiting operations, with thecapacity to manufacture all product formats includingampules, logo imprinted pills, and push-through tabletstrips. Given this high level of sophistication, steroidspurchased on the black market need to be inspected withgreat care. The mistakes made by counterfeiters are oftenminor, and noticed in the fine (not obvious) detail.

Step #1: Eliminate the ObviousWhen counterfeit steroids first appeared decades ago,they were often very easy to spot. The manufacturersoperated on a small scale, and made small-scale mistakes.For example, the printing might be sloppy, or thecontainers thin and flimsy. They might have lacked theequipment to put the product in a box, or even affix anexpiration date and lot number to it. No legitimatepharmaceutical would be sold like this. Much has changedover the years, however. Few counterfeiters still make thebasic mistakes that were once common. Don’t expectidentifying these products to be easy. Still, that is not tosay that obvious counterfeits aren’t available. Indeed, theycan be found on the black market from time to time. Thisfirst set of instructions, therefore, seeks to eliminate onlythe most obvious fakes. For the rest, we will need a moredetailed analysis.

1. Sloppy Printing. Drug manufacturing is not a smallscale endeavor. Sizable pharmaceutical companies controlthe global drug trade, and make products that aretypically very professional in appearance. You should notexpect to see things like runny inks, sloppy lines, ormisaligned images on real drug packaging. Sometimescounterfeiters still use cheap (small-scale) printing andreproduction methods, which make labels and boxes thatstand out as sloppy. Don’t ever use a product if it justdoesn't “look right” to you. You are probablysubconsciously picking up on minor deviations.

2. Cheap Packaging. Virtually all legitimate steroidproducts come in boxes. Inside the box you should find adrug information sheet. Some counterfeiters will skip

these steps entirely. Real ampules, vials, and tablets aresometimes smuggled loose, but let someone else take therisk. The box for a pharmaceutical product should bestructurally sound, closing tightly and evenly. Somecounterfeiters seal their own boxes by hand, and they maybe uneven or poorly glued. Real boxes should be printed(ink directly on cardboard). Some counterfeiters coverplain white boxes with stickers. If the vial, ampule, or bottlehas a label, machines should have put it on straight.Counterfeiters often apply labels by hand, so many will becrooked. Some counterfeiters use ampules, but blanklaboratory samples. These are filled by hand and sealedover a flame. They are a bit larger than the averageampule, and somewhat unusual in appearance. A goodrule of thumb is to avoid any steroid that does not comein a professional looking package.

3. Multi-dose Containers. In the United States, we areused to our injectable medications coming in multi-dosevials (these have a rubber top to let needles pass throughmore than once), and our pills loose in bottles. Most othercountries, however, do not allow this type of packaging forhuman medicines.They consider it unsterile, and permit itonly for animal drugs. Instead, they require each dosageunit to be separate. This usually means break open glassampules for injectable medications, and push throughblisters for pills and capsules. Since you are unlikely to findreal American products on the black market, it may bebest to avoid all multi-dose containers when it comes tohuman pharmaceuticals. Most are going to be counterfeit.When you find veterinary drugs in multi-dose containers,extra care should be taken to examine them closely, sincethese products are more easily counterfeited.


121

Counterfeit Steroid Identification

The ampule [right] is alaboratory blank, meant to besealed by hand over a flame. It islarger and more unusual inappearance than mosttraditional ampules.

Step #2: Examine Lot Number/ExpirationA more formal analysis should always begin with the lotnumber/expiration date. Pharmaceutical companies havetheir boxes and labels manufactured in bulk, usually at anoffsite printing facility. They are not serialized; lotnumbers/expiration dates have not yet been applied tothem. This information is added with a mechanicalstamping machine or computer/inkjet printer at the timethe drug is packaged. Counterfeiters often don’t wait, andsimply print the lot number/expiration date with the restof the boxes and labels. This means less work, lessequipment, and less cost. Knowing this, examining the lotnumber/expiration date information can be a good wayto spot counterfeits. You need to look at the lot/dateinformation very closely, preferably with a handheldmicroscope with 100-200X magnification.

The photographs below show what it looks like when thelot number and expiration date are added after the initialbox/label printing, as well as counterfeit products withoutthis feature. The characters on a real pharmaceuticalproduct should stand out from the rest of the printing,which will consist of tiny dots blended together to createa solid image (see Step #3 for more information on theink). When the lot/expiration information is added with amechanical stamp, the ink will be much more solid undermagnification (note that it may appear blotchy underdeep magnification). Depending on the equipment, it mayalso have left a physical indent you can feel when rubbingyour thumb over the information. When the dates wereadded by computer, we usually see large dots that arevisible to the naked eye. Be careful to look at thecharacters closely. Counterfeiters will try to make theinformation look like it was added by machine orcomputer, even though it was printed. If you see that tinydots make up the characters under 200X magnification, itis not legitimate stamp or computer printing.


122

The above is a crude copy of an American testosteroneproduct, which uses the same label on the box and vial. Acounterfeit as simple as this is rare to find today.

Another example of an obvious counterfeit. This box iscrude in design and uses a brand name that has been offthe market since the 1980s.

Example #1. A real box of Proviron. Under magnification wecan see that the lot number and expiration date werestamped on mechanically.

Normal

20X

200X


123

20X

200X

Example #2. Another example of mechanical stamping ofthe lot number and expiration date.

Normal

20X

200X

Example #3. Real testosterone cypionate from Watson (U.S.)The above lot/expiration date were added by computerprinter. Under magnification we see the large dots are solidink.

Normal

20X

200X

Example #4. Another real product (Proviron) withinformation applied post-printing with a computer printer.

Normal

20X

200X

Example #5. (Counterfeit). At first glance the slight run onthe ink appears to be the result of mechanical stamping.Under magnification, however, we see this is simulated.

Description:

Oxandrolone is an oral anabolic steroid derived fromdihydrotestosterone. It was designed to have a very strongseparation of anabolic and androgenic effect, and nosignificant estrogenic or progestational activity.Oxandrolone is noted for being quite mild as far as oralsteroids are concerned, well tailored for the promotion ofstrength and quality muscle tissue gains withoutsignificant side effects. Milligram for milligram it displays asmuch as six times the anabolic activity of testosterone inassays, with significantly less androgenicity.421 This drug isa favorite of dieting bodybuilders and competitive athletesin speed/anaerobic performance sports, where itstendency for pure tissue gain (without fat or waterretention) fits well with the desired goals.

History:

Oxandrolone was first described in 1962.422 It wasdeveloped into a medicine several years later bypharmaceutical giant G.D. Searle & Co. (now Pfizer), whichsold it in the United States and the Netherlands under theAnavar trade name. Searle also sold/licensed the drugunder different trade names including Lonavar (Argentina,Australia), Lipidex (Brazil), Antitriol (Spain), Anatrophill(France), and Protivar. Oxandrolone was designed to be anextremely mild oral anabolic, one that could even be usedsafely by women and children. In this regard Searle seemsto have succeeded, as Anavar has shown a high degree oftherapeutic success and tolerability in men, women, andchildren alike. During its early years, Anavar had beenoffered for a number of therapeutic applications, includingthe promotion of lean tissue growth during catabolicillness, the promotion of lean tissue growth followingsurgery, trauma, infection, or prolonged corticosteroidadministration, or the support of bone density in patientswith osteoporosis.

By the 1980’s, the FDA had slightly refined the approvedapplications of oxandrolone to include the promotion of

weight gain following surgery, chronic infection, trauma, orweight loss without definite pathophysiologic reason. Inspite of its ongoing track record of safety, Searle decided tovoluntarily discontinue the sale of Anavar on July 1, 1989.Lagging sales and growing public concern about theathletic use of anabolic steroids appeared to be at the rootof this decision. With the Anavar brand off the market,oxandrolone had completely vanished from U.S.pharmacies. Soon after, oxandrolone products ininternational markets (often sold by or under license fromSearle) began to disappear as well, as the leading globalmanufacturer of the drug continued its withdrawal fromthe anabolic steroid business. For several years during theearly 1990’s, it looked as if Anavar might be on its way outof commerce for good.

It would be approximately six years before oxandrolonetablets would be back on the U.S. market. The productreturned to pharmacy shelves in December 1995, this timeunder the Oxandrin name by Bio-Technology GeneralCorp. (BTG). BTG would continue selling it for the FDAapproved uses involving lean mass preservation, but hadalso been granted orphan-drug status for the treatment ofAIDS wasting, alcoholic hepatitis, Turner's syndrome ingirls, and constitutional delay of growth and puberty inboys. Orphan drug status gave BTG a 7-year monopoly onthe drug for these new uses, allowing them to protect avery high selling price. Many patients were outraged tolearn that the drug would cost them (at wholesale price)between $3.75 and $30 per day, which was many timesmore costly than Anavar had been just several years back.The release of a 10 mg tablet from BTG several years laterdid little to reduce the relative cost of the drug.

Oxandrin® continues to be sold in the U.S., but is nowunder the Savient label (formerly known as BTG). It iscurrently approved by the FDA for “adjunctive therapy topromote weight gain after weight loss following extensivesurgery, chronic infections, or severe trauma and in somepatients who without definite pathophysiologic reasons


OH

O

O

Oxandrolone

Androgenic 24

Anabolic 322-630

Standard Methyltestosterone (oral)

Chemical Names 17b-hydroxy-17a-methyl-2-oxa-5a-androstane-3-one

Estrogenic Activity none

Progestational Activity none

Anavar (oxandrolone)

173

fail to gain or to maintain normal weight, to offset theprotein catabolism associated with prolongedadministration of corticosteroids, and for the relief of thebone pain frequently accompanying osteoporosis.”Generic versions of the drug are now available in the U.S. ,which has reduced the price of oxandrolone therapy.Outside of the U.S., oxandrolone remains available,although not widely.

How Supplied:

Oxandrolone is available in select human drug markets.Composition and dosage may vary by country andmanufacturer. The original Anavar brand contained 2.5mg of steroid per tablet. Oxandrin contains 2.5 mg or 10mg per tablet. Other modern brands commonly contain2.5 mg, 5 mg, or 10 mg of steroid per tablet.

Structural Characteristics:

Oxandrolone is a modified form of dihydrotestosterone. Itdiffers by: 1) the addition of a methyl group at carbon 17-alpha to protect the hormone during oral administrationand 2) the substitution of carbon-2 in the A-ring with anoxygen atom. Oxandrolone is the only commerciallyavailable steroid with such a substitution to its basic ringstructure, an alteration that considerably increases theanabolic strength of the steroid (partly by making itresistant to metabolism by 3-hydroxysteroiddehydrogenase in skeletal muscle tissue).

Side Effects (Estrogenic):

Oxandrolone is not aromatized by the body, and is notmeasurably estrogenic. Oxandrolone also offers no relatedprogestational activity.423 An anti-estrogen is notnecessary when using this steroid, as gynecomastiashould not be a concern even among sensitiveindividuals. Since estrogen is the usual culprit with waterretention, oxandrolone instead produces a lean, qualitylook to the physique with no fear of excess subcutaneousfluid retention. This makes it a favorable steroid to useduring cutting cycles, when water and fat retention aremajor concerns. Oxandrolone is also very popular amongathletes in strength/speed sports such as sprinting,swimming, and gymnastics. In such disciplines one usuallydoes not want to carry around excess water weight, andmay find the raw muscle-growth brought about byoxandrolone to be quite favorable over the lower qualitymass gains of aromatizable agents.

Side Effects (Androgenic):

Although classified as an anabolic steroid, androgenic sideeffects are still possible with this substance. This mayinclude bouts of oily skin, acne, and body/facial hairgrowth. Anabolic/androgenic steroids may also aggravate

male pattern hair loss.Women are warned of the potentialvirilizing effects of anabolic/androgenic steroids. Thesemay include a deepening of the voice, menstrualirregularities, changes in skin texture, facial hair growth,and clitoral enlargement. Oxandrolone is a steroid withlow androgenic activity relative to its tissue-buildingactions, making the threshold for strong androgenic sideeffects comparably higher than with more androgenicagents such as testosterone, methandrostenolone, orfluoxymesterone.

The low androgenic activity of oxandrolone is due in partto it being a derivative of dihydrotestosterone.This createsa less androgenic steroid because the agent lacks thecapacity to interact with the 5-alpha reductase enzymeand convert to a more potent “di-hydro”form.This is unliketestosterone, which is several times more active inandrogen responsive target tissues such as the scalp, skin,and prostate (where 5-alpha reductase is present in highamounts) due to its conversion to DHT. In essence,oxandrolone has a more balanced level of potencybetween muscle and androgenic target tissues. This is asimilar situation as is noted with Primobolan and Winstrol,which are also derived from dihydrotestosterone and notknown to be very androgenic substances.

Side Effects (Hepatotoxicity):

Oxandrolone is a c17-alpha alkylated compound. Thisalteration protects the drug from deactivation by the liver,allowing a very high percentage of the drug entry into thebloodstream following oral administration. C17-alphaalkylated anabolic/androgenic steroids can behepatotoxic. Prolonged or high exposure may result inliver damage. In rare instances life-threateningdysfunction may develop. It is advisable to visit aphysician periodically during each cycle to monitor liverfunction and overall health. Intake of c17-alpha alkylatedsteroids is commonly limited to 6-8 weeks, in an effort toavoid escalating liver strain.

Oxandrolone appears to offer less hepatic stress thanother c-17 alpha alkylated steroids. The manufactureridentifies oxandrolone as a steroid that is not extensivelymetabolized by the liver like other 17-alpha alkylatedorals, which may be a factor in its reduced hepatotoxicity.This is evidenced by the fact that more than a third of thecompound is still intact when excreted in the urine.424

Another study comparing the effects of oxandrolone toother alkylated agents including methyltestosterone,norethandrolone, fluoxymesterone, and methandrioldemonstrated that oxandrolone causes the lowestsulfobromophthalein (BSP; a marker of liver stress)retention of the agents tested.425 20 mg of oxandroloneproduced 72% less BSP retention than an equal dosage offluoxymesterone, which is a considerable difference being


174

that they are both 17-alpha alkylated.

A more recent study looked at escalating doses (20 mg, 40mg, and 80 mg) of oxandrolone in 262 HIV+ men.The drugwas administered for a period of 12 weeks. The grouptaking 20 mg of oxandrolone per day showed nostatistically significant trends of hepatotoxicity in liverenzyme (AST/ALT; aminotransferase and alanineaminotransferase) values. Those men taking 40 mgnoticed a mean increase of approximately 30-50% in liverenzyme values, while the group of men taking 80 mgnoticed an approximate 50-100% increase. Approximately10-11% of the patients in the 40 mg group noticed WorldHealth Organization grade III and IV toxicity according toAST and ALT values. This figure jumped to 15% in the 80mg group. While serious hepatotoxicity cannot beexcluded with oxandrolone, these studies do suggest thatit is measurably safer than other alkylated agents.

The use of a liver detoxification supplement such as LiverStabil, Liv-52, or Essentiale Forte is advised while takingany hepatotoxic anabolic/androgenic steroids.

Side Effects (Cardiovascular):

Anabolic/androgenic steroids can have deleterious effectson serum cholesterol. This includes a tendency to reduceHDL (good) cholesterol values and increase LDL (bad)cholesterol values, which may shift the HDL to LDLbalance in a direction that favors greater risk ofarteriosclerosis. The relative impact of ananabolic/androgenic steroid on serum lipids is dependanton the dose, route of administration (oral vs. injectable),type of steroid (aromatizable or non-aromatizable), andlevel of resistance to hepatic metabolism. Oxandrolonehas a strong effect on the hepatic management ofcholesterol due to its structural resistance to liverbreakdown, non-aromatizable nature, and route ofadministration. In the previously cited study in HIV+males, 20 mg of oxandrolone daily for 12 weeks caused amean serum HDL reduction of 30%. HDL values weresuppressed 33% in the 40 mg group, and 50% in the 80mg group. This was accompanied by a statisticallysignificant increase in LDL values (approximately 30-33%)in the 40 mg and 80 mg groups, further increasingatherogenic risk. Anabolic/androgenic steroids may alsoadversely effect blood pressure and triglycerides, reduceendothelial relaxation, and support left ventricularhypertrophy, all potentially increasing the risk ofcardiovascular disease and myocardial infarction.

At one time oxandrolone was looked at as a possible drugfor those suffering from disorders of high cholesterol ortriglycerides. Early studies showed it to be capable oflowering total cholesterol and triglyceride values incertain types of hyperlipidemic patients, which was

thought to signify potential for this drug as a lipid-lowering agent.426 With further investigation it was found,however, that any lowering of total cholesterol values wasaccompanied by a redistribution in the ratio of good(HDL) to bad (LDL) cholesterol that favored greateratherogenic risk.427 428 This negates any positive effect thisdrug might have on triglycerides or total cholesterol, andactually makes it a potential danger in terms of cardiacrisk, especially when taken for prolonged periods of time.Today we understand that as a group,anabolic/androgenic steroids tend to produceunfavorable changes in lipid profiles, and are really notuseful in disorders of lipid metabolism. As an oral c17alpha alkylated steroid, oxandrolone is even more risky touse in this regard than an esterified injectable such as atestosterone or nandrolone.

To help reduce cardiovascular strain it is advised tomaintain an active cardiovascular exercise program andminimize the intake of saturated fats, cholesterol, andsimple carbohydrates at all times during active AASadministration. Supplementing with fish oils (4 grams perday) and a natural cholesterol/antioxidant formula such asLipid Stabil or a product with comparable ingredients isalso recommended.

Side Effects (Testosterone Suppression):

All anabolic/androgenic steroids when taken in dosessufficient to promote muscle gain are expected tosuppress endogenous testosterone production.Oxandrolone is no exception. In the above-cited study onHIV+ males, twelve weeks of 20 mg or 40 mg per daycaused an approximate 45% reduction in serumtestosterone levels.The group taking 80 mg noticed a 66%decrease in testosterone. Similar trends of decrease werenoticed in LH production, with the 20 mg and 40 mgdoses causing a 25-30% reduction, and the 80 mg groupnoticing a decline of more than 50%. Additionally, studieson boys with constitutionally delayed puberty havedemonstrated significant suppression of endogenous LHand testosterone with as little as 2.5 mg per day.429

Without the intervention of testosterone stimulatingsubstances, testosterone levels should return to normalwithin 1-4 months of drug secession. Note that prolongedhypogonadotrophic hypogonadism can developsecondary to steroid abuse, necessitating medicalintervention.

The above side effects are not inclusive. For more detaileddiscussion of potential side effects, see the Steroid Side Effectssection of this book.


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Administration (General):

Studies have shown that taking an oral anabolic steroidwith food may decrease its bioavailability.430 This iscaused by the fat-soluble nature of steroid hormones,which can allow some of the drug to dissolve withundigested dietary fat, reducing its absorption from thegastrointestinal tract. For maximum utilization, this steroidshould be taken on an empty stomach.

Administration (Men):

The original prescribing guidelines for Anavar called for adaily dosage of between 2.5 mg and 20 mg per day (5-10mg being most common). This was usually recommendedfor a period of two to four weeks, but occasionally it wastaken for as long as three months. The dosing guidelinesrecommended with the current U.S. production form ofthe drug (Oxandrin, Savient Pharmaceuticals) also call forbetween 2.5 and 20 mg of drug per day, taken inintermittent cycles of 2 to 4 weeks. The usual dosage forphysique- or performance-enhancing purposes is in therange of 15-25 mg per day, taken for 6 to 8 weeks. Theseprotocols are not far removed from those of normaltherapeutic situations.

Oxandrolone is often combined with other steroids for amore dramatic result. For example, while bulking onemight opt to add in 200-400 mg of a testosterone ester(cypionate, enanthate, or propionate) per week. The resultshould be a considerable gain in new muscle mass, with amore comfortable level of water and fat retention than iftaking a higher dose of testosterone alone. For dietingphases, one might alternately combine oxandrolone witha non-aromatizing steroid such as 150 mg per week of atrenbolone ester or 200-300 mg of Primobolan®(methenolone enanthate). Such stacks are highly favoredfor increasing definition and muscularity. An in-between(lean mass gain) might be to add in 200-400 mg of a lowestrogenic compound like Deca-Durabolin® (nandrolonedecanoate) or Equipoise® (boldenone undecylenate).

Administration (Women):

The original prescribing guidelines for Anavar did notoffer separate dosing recommendations for women,although it was indicated that women who werepregnant, or may become pregnant, should not use thedrug. The current guidelines for Oxandrin also do notmake special dosing recommendations for women.Women who fear the masculinizing effects of manysteroids would be quite comfortable using this drug, asthese properties are very rarely seen with low doses. Forphysique- or performance-enhancing purposes, a dailydosage of 5-10 mg should illicit considerable growthwithout the noticeable androgenic side effects of other

drugs. This would be taken for no longer than 4-6 weeks.Eager females may wish to add another mild anabolicsuch as Winstrol®, Primobolan® or Durabolin®. Whencombined with such anabolics, the user should noticefaster, more pronounced muscle-building effects, but itmay also increase the likelihood of seeing androgenic sideeffects (or hepatotoxicity in the case of Winstrol).

Availability:

Pharmaceutical preparations containing oxandrolone arefairly limited.The drug is unavailable in Europe, and with ahandful of exceptions in the west, its production isincreasingly being shifted to less regulated markets inAsia. In reviewing some of the remaining products andchanges on the global pharmaceutical market, we havemade the following observations.

Various forms of generic oxandrolone are now available inthe U.S. in both 2.5 mg and 10 mg dosages, frommanufacturers such as Par Pharm, Sandoz, Upsher Smith,and Watson.

Brand name Oxandrin is still available in the U.S. under theSavient brand name. It comes in bottles of 60 (10 mg)tablets or 100 (2.5 mg) tablets each.

The generic Italian product Oxandrolone (SPA) is nolonger available. It was previously being made for exportsales only. There are no remaining oxandrolone productsavailable on the Italian market.

Atlantis (Mexico) produces an oxandrolone product calledXtendrol. It carries 2.5 mg of steroid per tablet, and comesin a box of 30 tablets each.

Asia Pharma makes the product Oxanabolic in Malaysia. Itcomes in strips of 10 tablets each, 10 strips per box. Eachproduct should carry a unique product ID code that canbe verified with the company for authenticity. Thisproduct is presently export only, but the manufacturerclaims to be in the process of seeking Thai FDA approval.

Balkan Pharmaceuticals (Moldova) makes the productOxandrolon. It is prepared in 10 mg tablets, with 20 tabletscontained in each foil and plastic strip.


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Description:

Testosterone cypionate is a slow-acting injectable ester ofthe primary male androgen testosterone. Testosterone isalso the principle anabolic hormone in men, and is thebasis of comparison by which all otheranabolic/androgenic steroids are judged. As with alltestosterone injectables, testosterone cypionate is highlyfavored by athletes for its ability to promote strongincreases in muscle mass and strength. It is interesting tonote that while a large number of other steroidalcompounds have been made available since testosteroneinjectables, they are still considered to be the dominantbulking agents among bodybuilders. There is littleargument that these are among the most powerful massdrugs available, testosterone cypionate included.

History:

Testosterone cypionate first appeared on the U.S. drugmarket during the mid-1950’s under the brand name ofDepo-Testosterone cyclopentylpropionate (soon abridgedto simply Depo-Testosterone). It was developed by thepharmaceutical giant Upjohn, and is still sold to this day bythe same company under the same trade name (althoughnow they are called Pharmacia & Upjohn). This is a drugwith limited global availability, and has historically been(largely) identified as an American item. It is not surprisingthat American athletes have long favored this form oftestosterone over testosterone enanthate, the dominantslow-acting ester of testosterone on the global market.Thispreference, however, is likely rooted in history andavailability, not actual therapeutic advantages.

Testosterone cypionate and testosterone enanthateprovide extremely comparable patterns of testosteronerelease. Not only are physical advantages not possible inone over the other, but actual differences inpharmacokinetic patterns are hard to notice (these twodrugs are for all intents and purposes functionallyinterchangeable).The only key difference between the two

seems to be in the area of patient comfort. Cypionic acid isless irritating at the site of injection than enanthoic acid(enanthate) for a small percentage of patients. This makestestosterone cypionate a more favorable choice for thosewith recurring issues of injection-site pain withtestosterone enanthate. This difference likely hadsomething to do with the early development of thistestosterone ester as a commercial drug product.

The main use of testosterone cypionate in clinical medicinehas historically been the treatment of low androgen levelsin males, although many other applications have existedfor this drug as well. During the 1960’s, for example, thedrug’s prescribing recommendations called for such usesas supporting bone structure maturity, treatingmenorrhagia (heavy menstrual bleeding) and excessivelactation in females, and increasing muscle mass andcombating osteoporosis in the elderly. It was also beingrecommended for increasing male fertility, wherebyinduced testosterone/spermatogenesis suppression(caused by administering 200 mg of testosteronecypionate per week for 6 to 10 weeks) was potentiallyfollowed by a period of rebound spermatogenesis (due totemporarily higher than normal gonadotropin levels).

By the 1970’s, the FDA had been granted much strongercontrol over the prescription drug market, and the broaduses in which testosterone cypionate was first indicatedwere now being refined. For example, “testosteronerebound therapy” as a way to increase male fertility wasproving to be unreliable, especially in the face of newermore effective medications, and was soon eliminated fromprescribing guidelines.So too was the recommendation forits use to treat things like excessive menstrual bleedingand lactation. In general, testosterone therapy was beingpulled back to focus mainly on male androgen deficiency,and less on other applications, especially when involvingpopulations more susceptible to androgenic side effects,such as women and the elderly.


Testosterone

Androgenic 100

Anabolic 100

Standard Standard

Chemical Names 4-androsten-3-one-17beta-ol17beta-hydroxy-androst-4-en-3-one

Estrogenic Activity moderate

Progestational Activity low

Depo®-Testosterone (testosterone cypionate)

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Today, testosterone cypionate remains readily availableon the U.S. prescription drug market, where it is FDA-approved for hormone replacement therapy in men withconditions associated with a deficiency of endogenoustestosterone, and as a secondary treatment for inoperablemetastatic breast cancer in women (although it is notwidely used for this purpose anymore). Testosteronecypionate is currently available outside of the UnitedStates, but not widely. Known international sources for thedrug include Canada, Australia, Spain, Brazil, and SouthAfrica.

How Supplied:

Testosterone cypionate is available in select human andveterinary drug markets. Composition and dosage mayvary by country and manufacturer, but usually contain 50mg/ml, 100 mg/ml, 125 mg/ml, or 200 mg/ml of steroiddissolved in oil.

Structural Characteristics:

Testosterone cypionate is a modified form of testosterone,where a carboxylic acid ester (cyclopentylpropionic acid)has been attached to the 17-beta hydroxyl group.Esterified forms of testosterone are less polar than freetestosterone, and are absorbed more slowly from the areaof injection. Once in the bloodstream, the ester is removedto yield free (active) testosterone. Esterified forms oftestosterone are designed to prolong the window oftherapeutic effect following administration, allowing for aless frequent injection schedule compared to injections offree (unesterified) steroid. The half-life of testosteronecypionate is approximately 8 days after injection.

Figure 1. Pharmacokinetics of 200 mg testosteronecypionate injection. Source: Comparison oftestosterone, dihydrotestosterone, luteinizinghormone, and follicle-stimulating hormone in serumafter injection of testosterone enanthate ortestosterone cypionate. Schulte-Beerbuhl M,Nieschlag E. Fertility and Sterility 33 (1980):201-3.

Side Effects (Estrogenic):

Testosterone is readily aromatized in the body to estradiol(estrogen). The aromatase (estrogen synthetase) enzymeis responsible for this metabolism of testosterone.Elevated estrogen levels can cause side effects such asincreased water retention, body fat gain, andgynecomastia. Testosterone is considered a moderatelyestrogenic steroid. An anti-estrogen such as clomiphenecitrate or tamoxifen citrate may be necessary to preventestrogenic side effects. One may alternately use anaromatase inhibitor like Arimidex® (anastrozole), whichmore efficiently controls estrogen by preventing itssynthesis. Aromatase inhibitors can be quite expensive incomparison to anti-estrogens, however, and may alsohave negative effects on blood lipids.

Estrogenic side effects will occur in a dose-dependantmanner, with higher doses (above normal therapeuticlevels) of testosterone cypionate more likely to require theconcurrent use of an anti-estrogen or aromatase inhibitor.Since water retention and loss of muscle definition arecommon with higher doses of testosterone cypionate, thisdrug is usually considered a poor choice for dieting orcutting phases of training. Its moderate estrogenicitymakes it more ideal for bulking phases, where the addedwater retention will support raw strength and muscle size,and help foster a stronger anabolic environment.

Side Effects (Androgenic):

Testosterone is the primary male androgen, responsiblefor maintaining secondary male sexual characteristics.Elevated levels of testosterone are likely to produceandrogenic side effects including oily skin, acne, andbody/facial hair growth. Men with a geneticpredisposition for hair loss (androgenetic alopecia) maynotice accelerated male pattern balding.Those concernedabout hair loss may find a more comfortable option innandrolone decanoate, which is a comparably lessandrogenic steroid. Women are warned of the potentialvirilizing effects of anabolic/androgenic steroids,especially with a strong androgen such as testosterone.These may include deepening of the voice, menstrualirregularities, changes in skin texture, facial hair growth,and clitoral enlargement.

In androgen-responsive target tissues such as the skin,scalp, and prostate, the high relative androgenicity oftestosterone is dependant on its reduction todihydrotestosterone (DHT). The 5-alpha reductaseenzyme is responsible for this metabolism oftestosterone. The concurrent use of a 5-alpha reductaseinhibitor such as finasteride or dutasteride will interferewith site-specific potentiation of testosterone action,lowering the tendency of testosterone drugs to produceandrogenic side effects. It is important to remember that


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Pharmacokinetics of TestosteroneCypionate Injection

Day

Test

oste

rone

(ng/

ml)

0

1 0

2 0

3 0

4 0

5 0

0 5 10 15 2 0 2 5

anabolic and androgenic effects are both mediated viathe cytosolic androgen receptor. Complete separation oftestosterone’s anabolic and androgenic properties is notpossible, even with total 5-alpha reductase inhibition.

Side Effects (Hepatotoxicity):

Testosterone does not have hepatotoxic effects; livertoxicity is unlikely. One study examined the potential forhepatotoxicity with high doses of testosterone byadministering 400 mg of the hormone per day (2,800 mgper week) to a group of male subjects. The steroid wastaken orally so that higher peak concentrations would bereached in hepatic tissues compared to intramuscularinjections. The hormone was given daily for 20 days, andproduced no significant changes in liver enzyme valuesincluding serum albumin, bilirubin, alanine-amino-transferase, and alkaline phosphatases.478

Side Effects (Cardiovascular):

Anabolic/androgenic steroids can have deleterious effectson serum cholesterol. This includes a tendency to reduceHDL (good) cholesterol values and increase LDL (bad)cholesterol values, which may shift the HDL to LDLbalance in a direction that favors greater risk ofarteriosclerosis. The relative impact of ananabolic/androgenic steroid on serum lipids is dependanton the dose, route of administration (oral vs. injectable),type of steroid (aromatizable or non-aromatizable), andlevel of resistance to hepatic metabolism.Anabolic/androgenic steroids may also adversely affectblood pressure and triglycerides, reduce endothelialrelaxation, and support left ventricular hypertrophy, allpotentially increasing the risk of cardiovascular diseaseand myocardial infarction.

Testosterone tends to have a much less dramatic impacton cardiovascular risk factors than synthetic steroids. Thisis due in part to its openness to metabolism by the liver,which allows it to have less effect on the hepaticmanagement of cholesterol. The aromatization oftestosterone to estradiol also helps to mitigate thenegative effects of androgens on serum lipids. In onestudy, 280 mg per week of testosterone ester (enanthate)had a slight but not statistically significant effect on HDLcholesterol after 12 weeks, but when taken with anaromatase inhibitor a strong (25%) decrease was seen.479

Studies using 300 mg of testosterone ester (enanthate)per week for 20 weeks without an aromatase inhibitordemonstrated only a 13% decrease in HDL cholesterol,while at 600 mg the reduction reached 21%.480 Thenegative impact of aromatase inhibition should be takeninto consideration before such drug is added totestosterone therapy.

Due to the positive influence of estrogen on serum lipids,tamoxifen citrate or clomiphene citrate are preferred toaromatase inhibitors for those concerned withcardiovascular health, as they offer a partial estrogeniceffect in the liver. This allows them to potentially improvelipid profiles and offset some of the negative effects ofandrogens. With doses of 600 mg or less per week, theimpact on lipid profile tends to be noticeable but notdramatic, making an anti-estrogen (for cardioprotectivepurposes) perhaps unnecessary. Doses of 600 mg or lessper week have also failed to produce statisticallysignificant changes in LDL/VLDL cholesterol, triglycerides,apolipoprotein B/C-III, C-reactive protein, and insulinsensitivity, all indicating a relatively weak impact oncardiovascular risk factors.481 When used in moderatedoses, injectable testosterone esters are usuallyconsidered to be the safest of all anabolic/androgenicsteroids.

To help reduce cardiovascular strain it is advised tomaintain an active cardiovascular exercise program andminimize the intake of saturated fats, cholesterol, andsimple carbohydrates at all times during active AASadministration. Supplementing with fish oils (4 grams perday) and a natural cholesterol/antioxidant formula such asLipid Stabil or a product with comparable ingredients isalso recommended.

Side Effects (Testosterone Suppression):

All anabolic/androgenic steroids when taken in dosessufficient to promote muscle gain are expected tosuppress endogenous testosterone production.Testosterone is the primary male androgen, and offersstrong negative feedback on endogenous testosteroneproduction.Testosterone-based drugs will, likewise, have astrong effect on the hypothalamic regulation of naturalsteroid hormones. Without the intervention oftestosterone-stimulating substances, testosterone levelsshould return to normal within 1-4 months of drugsecession. Note that prolonged hypogonadotrophichypogonadism can develop secondary to steroid abuse,necessitating medical intervention.

As with all anabolic/androgenic steroids, it is unlikely thatone will retain every pound of new bodyweight after acycle is concluded. This is especially true whenwithdrawing from a strong (aromatizing) androgen liketestosterone cypionate, as much of the new weight gain islikely to be in the form of water retention, quicklyeliminated after drug discontinuance. An imbalance ofanabolic and catabolic hormones during the post-cyclerecovery period may further create an environment that isunfavorable for the retention of muscle tissue. Properancillary drug therapy is usually recommended to helprestore hormonal balance more quickly, ultimately


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helping the user retain more muscle tissue.

Another way to lessen the post-cycle “crash” is to firstreplace testosterone cypionate with a milder anabolicsuch as nandrolone decanoate or methenoloneenanthate. The new steroid would be administered alonefor one to two more months, at a dosage of 200-400 mgper week. In this “stepping down” procedure the user isattempting to eliminate the watery bulk of a testosterone-based drug while simultaneously preserving the solidmuscularity underneath. This practice can prove to beeffective, even if mainly for psychological reasons (somemay view it as simply dividing the crash into water andhormonal stages). Testosterone-stimulating drugs are stilltypically used at the conclusion of therapy, asendogenous testosterone production will not reboundduring the administration of nandrolone decanoate ormethenolone enanthate.

The above side effects are not inclusive. For more detaileddiscussion of potential side effects, see the Steroid Side Effectssection of this book.

Administration (Men):

To treat androgen insufficiency, the prescribing guidelinesfor testosterone cypionate call for a dosage of 50-400 mgevery two to four weeks. Although active in the body for alonger time, testosterone cypionate is usually injected ona weekly basis for physique- or performance-enhancingpurposes. The usual dosage is in the range of 200-600 mgper week, taken in cycles 6 to 12 weeks in length.This levelis sufficient for most users to notice exceptional gains inmuscle size and strength.

Testosterone is usually incorporated into bulking phasesof training, when added water retention will be of littleconsequence, the user more concerned with raw massthan definition. Some do incorporate the drug intocutting cycles as well, but typically in lower doses (100-200 mg per week) and/or when accompanied by anaromatase inhibitor to keep estrogen levels under control.Testosterone cypionate is a very effective anabolic drug,and is often used alone with great benefit. Some, however,find a need to stack it with other anabolic/androgenicsteroids for a stronger effect, in which case an additional200-400 mg per week of boldenone undecylenate,methenolone enanthate, or nandrolone decanoateshould provide substantial results with no significanthepatotoxicity. Testosterone is ultimately very versatile,and can be combined with many otheranabolic/androgenic steroids to tailor the desired effect.

While large doses are generally not advised, somebodybuilders have been known to use excessively highdosages of this drug (1,000 mg per week or more). This

was much more common before the 1990’s, whencypionate vials were usually very cheap and easy to find. A“more is better” attitude is easy to justify when payingonly $20 for a 10cc vial (today the typical price for a singleinjection). At dosages of 800-1000 mg per week or more,water retention will likely account for more of theadditional weight gain than new muscle tissue. Thepractice of “megadosing” is inefficient (not to mentionpotentially dangerous), especially when we take intoaccount the typical high cost of steroids today.

Administration (Women):

Testosterone cypionate is rarely used with women inclinical medicine. When applied, it is most often used as asecondary medication during inoperable breast cancer,when other therapies have failed to produce a desirableeffect and suppression of ovarian function is necessary.Testosterone cypionate is not recommended for womenfor physique- or performance-enhancing purposes due toits strong androgenic nature, tendency to producevirilizing side effects, and slow-acting characteristics(making blood levels difficult to control).

Availability:

Testosterone cypionate remains widely available as aprescription drug product. Its production is largelyassociated with American companies, although recentlyhas been expanding into loosely regulated Asian marketsthat still cater to demand by bodybuilders and athletes. Inreviewing some of the products and changes in the globalpharmaceutical market, we have made the followingobservations.

Brand name testosterone cypionate (Depot-Testosterone)remains available in the United Stated from Prizer.This is ahigh-profile target of counterfeiters. All legitimate boxeswill carry a “Jh” symbol hidden on one of the top insideflaps. It will appear when placed under UV light.

Many generic forms of the drug are also produced in theU.S. market by manufacturers such as Watson, Sandoz,Paddock, Synerx, and Bedford. All come packaged inmultiple-dose vials. Due to strict controls these productsare rarely diverted for illicit sale. There are also severalpharmacies custom-compounding testosteronecypionate for doctors that specialize in androgenreplacement therapy.

Cypionax is available in Thailand by T.P. Drug Laboratories.It comes in 2 mL ampules containing 100 mg/mL ofsteroid.

Cypiobolic from Asia Pharma (Malaysia) is now approvedfor sale through pharmacies in Thailand. Each box shouldcarry a scratch-off security sticker, which will display a


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code that can be validated on the company website.

Testex Prolongatum remains available in Spain. Thissteroid is produced by Laboratorios Q Pharma. It ispackaged in 2 mL dark glass ampules with grey silkscreenlettering. It comes in two doses, containing a total of 100mg or 250 mg of steroid. Testex has always been a high-profile item for counterfeiters.

Found in Chile is a high-dose cypionate product calledciclo-6. The product is manufactured by the firm DragPharma, and contains 300 mg/ml of steroid in a 2 mLampule (600 mg of cypionate in total).

Balkan Pharmaceuticals (Moldova) makes the productTestosterona C. It is prepared in both 1 mL ampules andmulti-dose vials.


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Description:

Insulin is peptide hormone produced in the Islets ofLangerhans in the pancreas.The release of this hormone inthe human body is most closely tied to blood glucoselevels, although a number of other factors includingpancreatic and gastrointestinal hormones, amino acids,fatty acids, and ketone bodies are also involved. The mainbiological role of insulin is to promote the intracellularutilization and storage of amino acids, glucose, and fattyacids, while simultaneously inhibiting the breakdown ofglycogen, protein, and fat. It is most notably identified withthe control of blood sugar levels, and insulin medicationsare typically prescribed to people with diabetes, ametabolic disorder characterized by hyperglycemia (highblood sugar).While insulin targets many different organs inthe body, this hormone is both anabolic and anti-catabolicto skeletal muscle tissue,926 927 928 a fact that explains theinclusion of pharmaceutical insulin in the realm of athleticsand bodybuilding.

The use of insulin to improve performance and bodycomposition can be a little tricky because this hormonecan also promote nutrient storage in fat cells.This, however,is an activity of insulin that can be somewhat managed bythe user. Athletes have found that a strict regimen ofintense weight training and a diet without excess caloricand fat intake can enable insulin to show a much higheraffinity for protein and glucose storage in muscle (asopposed to fatty acid storage in adipose) cells. This isespecially true in the post-exercise enhanced-absorptivestate, where insulin sensitivity in skeletal muscle has beenshown to increase significantly over baseline (rested)levels.929 When used during the post-training window, thehormone is, likewise, capable of producing rapid andnoticeable muscle gains. The muscles often begin to lookfuller (and even sometimes more defined) very soon afterinitiating insulin therapy, and the overall results of therapyare often described as dramatic.

The fact that insulin use cannot be detected by urinalysishas ensured it a place in the drug regimens of manyathletes and professional bodybuilders. Note that there hasbeen some progress in drug detection, especially with theanalogs, but to date regular insulin is still considered a”safe” drug. Insulin is often used in combination with other“contest safe” drugs like human growth hormone, thyroidmedications, and low dose testosterone injections, andtogether can have a dramatic effect on the user’s physiqueand performance without fear of a positive urinalysisresult.Those who do not have to worry about drug testing,however, often find that insulin combined with

anabolic/androgenic steroids can be a very synergisticcombination. This is because the two actively support ananabolic state through different mechanisms. Insulinstrongly enhances the transport of nutrients into musclecells and inhibits protein breakdown, and the anabolicsteroids (among other things) strongly increase the rate ofprotein synthesis.

As mentioned, the usual medical purpose for insulin is totreat different forms of diabetes. More specifically, thehuman body may not be producing enough insulin (Type-I diabetes), or may not recognize insulin well at the cell sitealthough some level is present in the blood (Type-IIdiabetes). Type-I diabetics are, therefore, required to injectinsulin on a regular basis, as they are left without asufficient level of this hormone. Along with medication, theindividual will need to constantly monitor blood glucoselevels and regulate their sugar intake. Together withlifestyle modifications such as regular exercise anddeveloping a balanced diet, insulin dependent individualscan live a healthy and full life. When left untreated,however, diabetes can be a fatal disease.

History:

Insulin first became available as a medicine during the1920s. Credit for the discovery is most appropriately givento Canadian physician Fred Banting and Canadianphysiologist Charles Best, who worked together toproduce the first insulin preparations, and the world’s firsteffective treatment of diabetes. Their work stemmed froman idea initially proposed by Banting, who as a youngdoctor theorized that an active extract could be made fromanimal pancreases to regulate blood sugar in humanpatients. He needed help to try and actualize his idea, andhe sought out world-renowned physiologist J.J.R. Macleodat the University of Toronto. Macleod, initially less thanimpressed with the unusual concept (but likely impressedwith Banting’s conviction and tenacity), assigned a coupleof graduate students to assist him in his work. A coin flipdetermined who would work with Banting, and he waseventually paired with graduate student Best. Togetherthey made medical history.

The first insulin preparations they produced were made ofcrude pancreatic extracts taken from dogs. At one pointthe supply of laboratory animals was exhausted, anddesperate to continue their research, the pair actuallybegan taking stray dogs to supplement their pancreassupply. Shortly after, the two found that they could workwith the pancreases of slaughtered cows and pigs, makingtheir work much easier (and ethically acceptable). Theysuccessfully treated their first diabetic patient with insulin


Insulin (rDNA Origin)

561

in January 1922. By August of that year, they had beensuccessful in treating a group of clinical patients, including15-year-old Elizabeth Hughes, daughter of formerpresidential candidate Charles Evans Hughes. Elizabethwas diagnosed with diabetes in 1918, and her dramaticfight for life with the disease gained national attention.Elizabeth would be saved by insulin on the doorstep ofstarvation, as severe calorie restriction was the onlyremedy known to slow the disease at the time. Bantingand Macleod swiftly won the Nobel Prize for theirdiscovery, which was presented to them approximately ayear later in 1923. Shortly after, dispute over credit arose,and ultimately Banting shared his prize with Best, andMacleod shared his prize with J. B. Collip, a chemist thatassisted in the extraction and purification process.

After initially declining the assistance in the hopes thatthey could work out production issues on their own,Banting and his team worked with Eli Lilly & Co. to developthe first mass-produced insulin medicines using theiranimal extraction techniques. Their production successwas extreme and rapid, and the drug becamecommercially available on a wide scale in 1923, the sameyear Banting and Macleod won the Nobel prize.That sameyear, Nordisk Insulinlaboratorium was founded by Danishscientist Augusta Krogh, who desperately wanted to bringback an insulin manufacturing technique to Denmark totreat his wife, who was ill with diabetes.This Denmark firmeventually became Novo Nordisk, the world’s secondleading producer of insulin next to Eli Lilly & Co.

The early insulin medications were fairly impure bytoday’s standards. They typically contained 40 units ofanimal insulin per milliliter, in contrast to today’s acceptedstandard concentration of 100 units. The large dosesneeded with these early low-concentration drugs werenot very comfortable for patients, and injection-sitereactions were not uncommon. They also containedsignificant protein impurities that would sometimes causeallergic reactions in users. Despite these faults, the drugssaved the lives of countless individuals who beforehandwere faced with a sure death sentence following adiagnosis of diabetes. Eli Lilly and Novo Nordisk improvedthe purity of their products in the coming years, but nomajor improvements in insulin technology developeduntil the mid-1930s, when the first longer-acting insulinpreparations began to surface.

The first longer-acting drug made use of protamine andzinc to delay the action of insulin in the body, extendingthe activity curve and reducing the number of dailyinjections required for many patients. Dubbed ProtamineZinc Insulin (PZI), the preparation would have an effectlasting as long as 24-36 hours. Neutral ProtamineHagedorn (NPH) Insulin, also known as Isophane insulin,

followed, reaching market by 1950. This preparation wasvery similar to PZI insulin except that it could be mixedwith regular insulin without disturbing the release curveof the respective insulins. In other words, a regular insulindrug could be mixed in the same syringe with NPH insulin,providing a biphasic release pattern characterized by anearly peak effect due to the regular insulin, and anextended action brought on by the NPH.

In 1951 the Lente insulins began to surface, whichincluded semilente, lente, and ultra-lente preparations.The amount of zinc used in each varied, producingpreparations with distinct and long-actingpharmacokinetics. Unlike previous Insulins, this was alsoachieved without the use of protamine. Many physicianswere soon able to successfully switch their patients fromNPH insulin over to a single morning dose of Lente insulin,often heralding the release of the new drugs as a bigadvance in insulin medications (though some would stillrequire an evening dose with a Lente insulin to maintainfull control over blood glucose levels during the 24-hourperiod). Up to this point the insulin drugs made by thelarge pharmaceutical companies worked very well. Nosubstantial step forward in the development of newinsulin delivery technologies would come for another 23years.

In 1974, chromatographic purification techniques allowedthe manufacture of animal insulin with extremely lowimpurity levels (less than 1 pmol/l of protein impurities).Novo was the first to release a drug made with thistechnology, which it called monocomponent (MC) Insulin.Eli Lilly also released a version called “Single Peak” Insulin,likely referring to the single protein peak noticed uponchemical analysis. This advance, though significant, wouldbe short lived. In 1975, Ciba-Geigy produced the firstsynthetic insulin preparation (CGP 12831). And just threeyears later, scientists at Genentech were able to produceinsulin using modified E. coli bacteria, the first syntheticinsulin with an identical amino acid sequence as humaninsulin (although the animal insulins work fine in humanstheir structures are slightly different). The U.S. Food andDrug administration approved the first such medicines in1982, with the acceptance of Humulin R (Regular) andHumulin NPH from Eli Lilly & Co. The name Humulin is acontraction of the words “human” and “insulin”, of course.Novo would follow with semi-synthetic insulins ActrapidHM and Monotard HM.

The FDA has approved a variety of other insulin drugcombinations over the years, including various biphasicinsulin blends that use differing amounts of rapid andlonger-acting insulins. More recently, we have also seenthe FDA approval of Eli Lilly’s rapid-acting insulin analogHumalog. Several other analogs are also now available


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including Lantus and Apidra from Aventis, and Levemirand Novorapid from Novo Nordisk. A number ofadditional analogs are also under investigation at thistime. With the large variety of different insulinmedications approved and sold in the U.S. and othernations, it is important to understand that “insulin”represents an extremely broad class of medicines. As aclass, these drugs are likely to continue to expand as newagents are developed and successfully tested. Today, it isestimated that 55 million people use some form ofinjectable insulin on a regular basis to manage theirdiabetes, making this an extremely important andlucrative area of human medicine.

How Supplied:

Pharmaceutical insulin comes from one of two basicorigins, animal or synthetic.With animal source insulin, thehormone is extracted from the pancreas of either pigs orcows (or both) and prepared for medical use. Thesepreparations are further divided into the categories“standard” and “purified”, dependent on the level of purityand non-insulin content of the solution. With suchproducts there is always the slight possibility of pancreaticcontaminants making their way into the prepared drug.Specifically called biosynthetic, synthetic insulin isproduced by a recombinant DNA procedure similar to theprocess used to manufacture human growth hormone.The result is a polypeptide hormone consisting of one 21-amino acid “A-chain” coupled by two disulfide bonds withone 30-amino acid “B-chain”. The biosynthetic process willproduce a drug free of the pancreatic proteincontaminants possible with animal insulin, and that isstructurally and biologically identical to humanpancreatic insulin. With the innate (remote) risk ofcontamination involved with animal insulin, coupled withthe fact that the structure is (very slightly) different fromhuman insulin, synthetic human insulin drugs dominatethe market today. Biosynthetic human insulin/insulinanalogs are also the most common insulins of use amongathletes, and the main focus of this profile.

There are a variety of synthetic insulins available, witheach possessing unique properties relating to speed ofonset, peak and duration of activity, and concentration ofdose. This therapeutic variety may allow physicians totailor a treatment program for insulin-dependantdiabetics that allows for the least amount of dailyinjections and the greatest level of patient comfort. It isimportant that one should be aware of the individualactivity of any insulin drug before attempting its use. Dueto the differences between preparations, it is alsomedically advised that extreme care be taken whenever aphysician attempts to switch an insulin-dependantdiabetic patient from one form of insulin medication to

another.

Below is a list showing the distinctions between popularforms of biosynthetic insulin.

Short-acting Insulins:

Humalog® (Insulin Lispro): Humalog® is a short-actinganalog of human insulin, specifically the Lys(B28) Pro(B29)analog of insulin created when the amino acids atpositions 28 and 29 are reversed. It is consideredequipotent to regular soluble insulin on a unit-to-unitbasis, but with more rapid activity.930 The onset of drugaction following subcutaneous administration isapproximately 15 minutes, and its peak effect is reached in30 to 90 minutes. It has a total duration of action between3 and 5 hours. Insulin lispro is usually used as asupplement to a longer acting insulin product, providinga fast-acting medication that can be taken before orimmediately after meals to mimic the body’s naturalinsulin response. Many athletes believe that its shortwindow of effect makes it an ideal insulin medication forphysique- or performance-enhancing purposes, as mostof its action can be concentrated in the post-trainingenhanced-nutrient-uptake window.

Novolog® (Insulin Aspart): Novolog is a short-acting analogof human insulin created when the amino acid proline atposition B28 is replaced with aspartic acid. The onset ofdrug action following subcutaneous administration isapproximately 15 minutes, and its peak effect is reached in1-3 hours. It has a total duration of action between 3 and5 hours. Insulin lispro is usually used as a supplement to alonger acting insulin product, providing a fast-actingmedication that can be taken before or immediately aftermeals to mimic the body’s natural insulin response. Manyathletes believe that its short window of effect makes it anideal insulin medication for physique- or performance-enhancing purposes, as most of its action can beconcentrated in the post-training enhanced-nutrient-uptake window.

Humulin®-R “Regular” (insulin Inj): Identical to humaninsulin. Also sold as Humulin-S® (Soluble) in somemarkets, this product consists of zinc-insulin crystalsdissolved in clear fluid.There is nothing added to slow the


563

release of this product, so it is generically referred to assoluble human Insulin. This drug works rapidly and has ashort duration of effect.The onset of drug action followingsubcutaneous administration is 20-30 minutes, and itspeak effect is reached in 1-3 hours. It has a total durationof action between 5 and 8 hours. Together with Humalog,these two forms of insulin are the most popular (almostexclusive) choices among athletes and bodybuilders forphysique- or performance-enhancement purposes.

Intermediate- and Long-acting Insulins:

Humulin®-N, NPH (insulin isophane): A crystallinesuspension of insulin with protamine and zinc to delay itsrelease and extend its action. Insulin isophane isconsidered intermediate length insulin. The onset of drugaction following subcutaneous administration isapproximately 1-2 hours, and its peak effect is reached in4-10 hours. It has a total duration of activity lasting morethan 14 hours. This type of insulin is not commonly usedfor physique- or performance-enhancement purposes.

Humulin®-L, Lente (medium zinc suspension): A crystallinesuspension of insulin with zinc to delay its release andextend its action. Humulin-L is considered anintermediate length insulin. The onset of drug actionfollowing subcutaneous administration is approximately1-3 hours, and its peak effect is reached in 6-14 hours. Ithas a total duration of activity lasting more than 20 hours.This type of insulin is not commonly used for physique- orperformance-enhancement purposes.

Humulin®-U, Ultralente (prolonged zinc suspension): Acrystalline suspension of insulin with zinc to delay itsrelease and extend its action. Humulin-U is considered along-acting insulin. The onset of drug action followingsubcutaneous administration is approximately 6 hours,and its peak effect is reached in 14-18 hours. It has a totalduration of activity lasting 18-24 hours.This type of insulinis not commonly used for physique- or performance-enhancement purposes.

Lantus (insulin glargine): A long-acting analog of humaninsulin. Insulin glargine is created when the amino acidasparagine at position A21 is replaced by glycine, and twoarginines are added to the C-terminus of the insulin Bchain. The onset of drug action following subcutaneousadministration is approximately 1-2 hours, and the drug isconsidered to have no significant peak (it is designed tohave a very stable release pattern throughout theduration of activity). Insulin glargine lasts between 20-24hours in the body following subcutaneous injection. Thistype of insulin is not commonly used for physique- orperformance-enhancement purposes.


564

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Biphasic Insulins:

Humulin® Mixtures: These are mixtures of regular solubleinsulin for a fast onset of action, and a long- orintermetiate-acting insulin for a prolonged effect. Theseare labeled by the mixture percentage, commonly 10/90,20/80, 30/70, 40/60, and 50/50. Mixtures using Humalog asthe rapid-acting insulin are also available.

Warning: Concentrated Insulin

The most common forms of insulin come in aconcentration of 100 IU of hormone per milliliter. Theseare identified as “U-100” preparations in the U.S. and manyother regions. In addition to this, however, there are alsoconcentrated forms of insulin available for patients thatrequire higher doses and a more economical orcomfortable option to U-100 preparations. In the U.S.,products containing as much as 5 times the normalconcentration, or 500 IU per milliliter, are also sold. Theseare identified as “U-500” preparations, and are available byprescription only. It can be extremely dangerous or lifethreatening to replace a U-100 insulin product with a U-500 product without making the necessary dosingadjustments to compensate for the greater drugconcentration. Given the general difficulty in accuratelymeasuring athletic doses (2-15 IU) with a drug of suchhigh concentration, U-100 preparations are used almostexclusively for physique- and performance-enhancingpurposes.

Side Effects (Hypoglycemia):

Hypoglycemia is the primary danger with the use ofinsulin. This is a dangerous condition that occurs whenblood glucose levels fall too low. It is a common andpotentially fatal reaction experienced at some time oranother by most medical and nonmedical insulin users, soit needs to be taken seriously. It is, therefore, critical tounderstand the warning signs of hypoglycemia. Thefollowing is a list of symptoms that may indicate mild tomoderate hypoglycemia: hunger, drowsiness, blurredvision, depressive mood, dizziness, sweating, palpitation,tremor, restlessness, tingling in the hands, feet, lips, ortongue, lightheadedness, inability to concentrate,headache, sleep disturbances, anxiety, slurred speech,irritability, abnormal behavior, unsteady movement, andpersonality changes. If any of these warning signs shouldoccur, one should immediately consume a food or drinkcontaining simple sugars such as a candy bar orcarbohydrate drink.This will hopefully raise blood glucoselevels sufficiently enough to ward off mild to moderatehypoglycemia. There is always a possibility of severehypoglycemia, which is very serious and requiresimmediate emergency medical attention. Symptoms ofthis include disorientation, seizure, unconsciousness, and

death. Note that in some cases the symptoms ofhypoglycemia are mistaken for drunkenness.

It is also very important to note that you may notice atendency to get sleepy after injecting insulin. This is anearly symptom of hypoglycemia, and a clear sign the usershould be consuming more carbohydrates. One shouldabsolutely avoid the temptation to go to sleep at thispoint, as the insulin may take its peak effect during rest,and blood glucose levels could be left to dropsignificantly. Unaware of this condition during sleep, theathlete may be at a high risk for going into a state ofsevere hypoglycemia. The serious dangers of such a statehave already been discussed, and unfortunatelyconsuming more carbohydrates during sleep will not bean option. Those experimenting with insulin would,therefore, be wise to always stay awake for the duration ofthe drug’s effect, and also avoid using insulin in the earlyevening to ensure the drug will not be inadvertentlyactive when retiring for the night. It is also important tomake sure others are aware of your use of the drug so thatthey may inform emergency medical technicians shouldyou lose consciousness or the ability to inform others ofyour condition due to hypoglycemia.This information canspare valuable (perhaps life saving) time in helpingmedical professionals establish a diagnosis and providesupportive treatment.

Side Effects (Lipodystrophy):

The subcutaneous administration of insulin may cause alocalized increase in adipose tissue at the site of injection.This may be compounded by the repeated administrationof insulin at the same site of injection.

Side Effects (Allergy to Insulin):

In a small percentage of users, the administration ofinsulin may cause a localized allergy. This may includeirritation, swelling, itching, and/or redness at the site ofinjection. This often subsides as therapy continues. Insome instances it may be due to an allergy to aningredient, or in the case of animal insulin, a proteincontaminant. Less common, but potentially more serious,is a systemic allergic reaction to insulin administration.This may include a rash on the whole body, wheezing,shortness of breath, fast pulse, sweating, and/or areduction in blood pressure. In rare instances this may belife threatening. Any adverse reaction should be reportedto a medical authority.

Administration (General):

Given that there are varying forms of insulin available formedical use with differing pharmacokinetic patterns, aswell as products with different drug concentrations, it isextremely important that the user be familiar with the


565

dosage and actions of any specific insulin preparationthey intend to use so that peak-effect, total time of effect,total dosage, and carbohydrate intake can be closelymonitored. Rapid-acting insulin preparations (Novolog,Humalog, and Humulin-R) are the most popular choicesfor physique- or performance-enhancing purposes, andthe subject of the dosing information presented in thisbook. It is also important to stress that before oneconsiders using insulin they should also become veryfamiliar with using a glucometer. This is a medical devicethat can give you a quick and accurate reading of yourblood glucose level. This device can be indispensable inhelping one manage and optimize theirinsulin/carbohydrate intake.

Administration (Short-acting Insulin):

Short acting forms of insulin (Novolog, Humalog,Humulin-R) are designed for subcutaneous injection.Following subcutaneous injection, the injection siteshould be left alone and not rubbed, to prevent the drugfrom releasing into circulation too quickly. It is alsoadvised to rotate subcutaneous injection sites regularly toavoid the localized buildup of subcutaneous fat that maydevelop due to the lipogenic properties of this hormone(see Adverse Reactions: Lipodystrophy). The medicaldosage will vary depending on the individualrequirements of the patient. Furthermore, changes in suchthings as diet, activity level, or work/sleep schedule mayaffect the required insulin dose. Although notrecommended medically, it is possible to administer someshort-acting insulins via intramuscular injection. This,however, may create more variability (and potential risk)with regard to drug dissipation and hypoglycemic effect.

Insulin dosages can vary slightly among athletes, and areoften dependent upon factors like body weight, insulinsensitivity, activity level, diet, and the use of other drugs.Most users choose to administer insulin immediately aftera workout, which is the most opportunistic time of the dayto use this drug. Among bodybuilders, dosages of regularinsulin (Humulin-R) used are usually in the range of 1IUper 15-20 pounds of lean bodyweight; 10IU is perhaps themost common dosage. This amount may be adjusteddownward slightly for users of the more rapid-actingHumalog and Novolog preparations, which provide ahigher and faster peak effect. First-time cautious usersusually ignore bodyweight guidelines, and instead start ata low dosage with the intention of gradually working upto a normal dosage. For example, on the first day of insulintherapy one may begin with a dose as low as 2 IU. Eachconsecutive post-workout application this dosage mightbe increased by 1IU, until the user determines acomfortable range. Many feel this is safer and much moretailored to the individual than simply calculating and

injecting a dose, as some find they tolerate slightly moreor less insulin than weight guidelines would dictate.Athletes using growth hormone in particular often haveslightly higher insulin requirements, as HGH therapy isshown to both lower secretion of, and induce cellularresistance to, insulin.

One must also remember that it is very important toconsume carbohydrates for several hours followinginsulin use. One should generally follow the rule-of-thumbof ingesting at least 10-15 grams of simple carbohydratesper IU of insulin injected (with a minimum immediateintake of 100 grams regardless of dose).This is timed 10 to30 minutes after subcutaneous injection of Humulin-R, orimmediately after using Novolog or Humalog.The use of acarbohydrate replacement drink is often used as a fastcarbohydrate source. Properly cautious insulin users willalways have a source for simple sugars on-hand in case anunexpected drop in glucose levels is noticed. Manyathletes will also take creatine monohydrate with theircarbohydrate drink, since the insulin may help force morecreatine into the muscles. 30-60 minutes after injectinginsulin, one should also eat a good meal and consume aprotein shake. The carbohydrate drink and meal/proteinshake are absolutely necessary, as without them bloodsugar levels may drop dangerously low and the athletemay enter a state of hypoglycemia (see AdverseReactions: Hypoglycemia). Carbohydrates and proteins arecontinually provided in sufficient amounts to meetglucose requirements throughout the entire window ofinsulin effect.

Administration (Intermediate-acting, Long-acting,and Biphasic Insulins):

Intermediate-acting, long-acting, and biphasic insulins aredesigned for subcutaneous injection. Intramuscularinjection will cause the drug to be released too rapidly,potentially resulting in hypoglycemia. Followingsubcutaneous injection, the injection site should be leftalone and not rubbed, to prevent the drug from releasinginto circulation too quickly. It is also advised to rotatesubcutaneous injection sites regularly to avoid thelocalized buildup of subcutaneous fat due to thelipogenic properties of this hormone (see AdverseReactions: Lipodystrophy). The medical dosage will varydepending on the individual requirements of the patient.Furthermore, changes in such things as diet, activity level,or work/sleep schedule may affect the required insulindose. Intermediate-acting, long-acting, and biphasicinsulins are not widely used for physique- orperformance-enhancing purposes due to their longeracting nature, which makes them poorly suited forconcentrating the nutrient partitioning effect of insulinduring the short post-workout enhanced-nutrient-uptake


566

window.

Availability:

U-100 insulins may be dispensed from pharmacies in theUnited States without a prescription. This is so that aninsulin-dependent diabetic will have easy access to thislife-saving medication. Concentrated (U-500) insulin issold by prescription only. In most regions of the world,high medical use of the drug leads to easy access and lowprices on the black market.


567

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William Llewellyn’s ANABOLICS · Preface ANABOLICS is a reference manual of drug compounds used...

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