TESTOSTERONE REPLACEMENT THERAPY -A RECIPE FOR SUCCESS- --John Crisler, DO --John Crisler, DO...

TESTOSTERONE TESTOSTERONE REPLACEMENT REPLACEMENT

THERAPYTHERAPY-A RECIPE FOR SUCCESS--A RECIPE FOR SUCCESS-

--John Crisler, DO--John Crisler, DO Lansing, MI USALansing, MI USA

MSU-COMMSU-COM www.AllThingsMale.comwww.AllThingsMale.com

““Everything You Always Wanted to Everything You Always Wanted to Know About TRT But Didn’t Have Know About TRT But Didn’t Have

Time to Ask”Time to Ask”

WHAT IS TESTOSTERONE WHAT IS TESTOSTERONE REPLACEMENT THERAPY?REPLACEMENT THERAPY?

TRT: Restoration of TRT: Restoration of Testosterone to HEALTHY Testosterone to HEALTHY

physiological levels.physiological levels.

TRT is NOT:TRT is NOT:

Total T>normal rangeTotal T>normal range SteroidsSteroids ViagraViagra

SCREENING FOR SCREENING FOR HYPOGONADISMHYPOGONADISM

WHAT ARE THE SYMPTOMS WHAT ARE THE SYMPTOMS OF LOW TESTOSTERONE?OF LOW TESTOSTERONE?

TAT SyndromeTAT Syndrome FatigueFatigue USTA SyndromeUSTA Syndrome Loss of muscle massLoss of muscle mass Fat gainFat gain Poor recoveryPoor recovery

Pain/InflammationPain/Inflammation IrritabilityIrritability DepressionDepression Decreased memoryDecreased memory Loss of LibidoLoss of Libido Erectile DysfunctionErectile Dysfunction

ADAM QuestionnaireADAM Questionnaire

1. Do you have a decrease in sex drive? 1. Do you have a decrease in sex drive?

2. Do you have a lack of energy? 2. Do you have a lack of energy?

3. Do you have a decrease in strength and/or 3. Do you have a decrease in strength and/or endurance? endurance?

4. Have you lost height? 4. Have you lost height?

5. Have you noticed a decreased enjoyment of 5. Have you noticed a decreased enjoyment of life? life?

ADAM Questionnaire (con’t)ADAM Questionnaire (con’t)

6.6. Are you sad and/or grumpy? Are you sad and/or grumpy?

7.7. Are your erections less strong? Are your erections less strong?

8.8. Has it been more difficult to maintain Has it been more difficult to maintain your erection throughout sexual intercourse? your erection throughout sexual intercourse?

9.9. Are you falling asleep after dinner? Are you falling asleep after dinner?

10. Has your work performance deteriorated 10. Has your work performance deteriorated recently? recently?

INITIAL LAB WORKINITIAL LAB WORK

INITIAL HYPOGONADISM PANELINITIAL HYPOGONADISM PANEL

Total TestosteroneTotal Testosterone Bioavailable/Free TBioavailable/Free T SHBGSHBG DHT (?)DHT (?) LH/FSHLH/FSH DHEA-SDHEA-S EstradiolEstradiol Total Estrogens (urine)Total Estrogens (urine) ProlactinProlactin

CortisolCortisol Thyroid Panel (TSH, Thyroid Panel (TSH,

FT4, FT3)FT4, FT3) Comp Metabolic Comp Metabolic

PanelPanel CBCCBC Lipid PanelLipid Panel PSA (if over 40)PSA (if over 40) ProgesteroneProgesterone

MEASURES OF TESTOSTERONEMEASURES OF TESTOSTERONE

Total Testosterone—all that is producedTotal Testosterone—all that is produced (300-1000ng/dL)(300-1000ng/dL)

Free Testosterone—all that is unbound (2-4%)Free Testosterone—all that is unbound (2-4%) (80-300pg/dL)(80-300pg/dL) --Equilibrium Dialysis, NOT RIA!--Equilibrium Dialysis, NOT RIA!

Bioavailable Testosterone—Gold StandardBioavailable Testosterone—Gold Standard “ “Free and Loosely/Weakly Bound”Free and Loosely/Weakly Bound” 40-60% (120-600ng/dL)40-60% (120-600ng/dL)

““Laboratory reference values Laboratory reference values for testosterone vary widely, for testosterone vary widely, and are established without and are established without

clinical considerations.” clinical considerations.”

LazarouLazarou S S, et al. Harvard Medical , et al. Harvard Medical School, Division of Urology, Beth School, Division of Urology, Beth Israel Deaconess Medical CenterIsrael Deaconess Medical Center

T SAMPLE PREPARATIONT SAMPLE PREPARATION(SERUM)(SERUM)

Refrigerated, no additive serum preferredRefrigerated, no additive serum preferred (Plain, Red Top)(Plain, Red Top)

Heparanized serum less acceptableHeparanized serum less acceptable (green-top)(green-top)

NO Serum Separator Tubes (SST)NO Serum Separator Tubes (SST)

IMPORTANT ABOUT ESTROGEN IMPORTANT ABOUT ESTROGEN TESTINGTESTING

Total Estrogens is NOT a valid assay for Total Estrogens is NOT a valid assay for adult malesadult males

--cross reactivity w/ progesterone--cross reactivity w/ progesterone Estradiol MUST be by “ultrasensitive” Estradiol MUST be by “ultrasensitive”

method, LC/MS assay--ALL OTHERS method, LC/MS assay--ALL OTHERS NOT VALIDNOT VALID

Gold standard is 24 hour urine, esp w/ Gold standard is 24 hour urine, esp w/ TD’s (TransDermals)TD’s (TransDermals)

Be extra mindful of SHBG levelBe extra mindful of SHBG level

Sample MatrixesSample Matrixes BLOODBLOOD --most common--most common --Total, Free, Bioavailable--Total, Free, Bioavailable --”snap shot” only--”snap shot” only --limited value given TD’s, hormone conversions, etc. --limited value given TD’s, hormone conversions, etc. URINEURINE --best of all, esp. w/ TD’s--best of all, esp. w/ TD’s --”free” levels provided--”free” levels provided --limited assays --limited assays --expanded hormone assay types, incl. metabolites--expanded hormone assay types, incl. metabolites --use only 24 hour collections—no spots--use only 24 hour collections—no spots --be careful of contamination--be careful of contamination --better to assess intracellular 5-AR activity--better to assess intracellular 5-AR activity

Many times T on bloods Many times T on bloods (especially for morning draw) (especially for morning draw)

will be well within normal will be well within normal range. But when you collect a range. But when you collect a

24 hour urine, T will be 24 hour urine, T will be deficient. Thus a spurt of T in deficient. Thus a spurt of T in

the morning, then very little the the morning, then very little the rest of the day.rest of the day.

COMMON SENSECOMMON SENSE

IN ORDER TO TEST THE IN ORDER TO TEST THE LEVEL OF A DRUG, YOU LEVEL OF A DRUG, YOU

MUST TAKE THE DRUG, ON MUST TAKE THE DRUG, ON SCHEDULE!!!SCHEDULE!!!

COMMON SENSECOMMON SENSE

HAVE PATIENT DRAW AT HAVE PATIENT DRAW AT SAME TIME OF DAY EACH SAME TIME OF DAY EACH TIME, ESPECIALLY WITH TIME, ESPECIALLY WITH

TRANSDERMALS (b/c PK’s)TRANSDERMALS (b/c PK’s)

COMMON SENSECOMMON SENSE

1. NEVER SMOKE IN BED1. NEVER SMOKE IN BED

2. ALWAYS WEAR PAJAMAS 2. ALWAYS WEAR PAJAMAS

DHTDHT

Most responsible for All Things MaleMost responsible for All Things Male 5-AR’d from T5-AR’d from T Unfairly deemed “evil hormone”Unfairly deemed “evil hormone” NOT responsible for prostate morbidityNOT responsible for prostate morbidity 25-75ng/dL25-75ng/dL Serum assay valid?Serum assay valid? Metabolite ratios on 24 hour urines bestMetabolite ratios on 24 hour urines best Avoid finasterideAvoid finasteride

EstradiolEstradiol Major player amongst estrogensMajor player amongst estrogens Total Estrogens is NOT valid assay for malesTotal Estrogens is NOT valid assay for males MUST be monitored during TRTMUST be monitored during TRT Masks benefits of TRTMasks benefits of TRT Adjunctive cause of serious illnessAdjunctive cause of serious illness Numerous benefits for health, so…Numerous benefits for health, so… Must not be driven too lowMust not be driven too low (10-50pg/mL) maintain mid-range ( w/ mid-range (10-50pg/mL) maintain mid-range ( w/ mid-range

SHBG)SHBG) May rise over timeMay rise over time TD’s elevate E more than IMTD’s elevate E more than IM

Luteinizing Hormone (LH)Luteinizing Hormone (LH)

Produced by pituitaryProduced by pituitary Stimulates T productionStimulates T production Pulsatile productionPulsatile production Short half-lifeShort half-life Acute phase reactantAcute phase reactant Must be careful in its interpretationMust be careful in its interpretation Possible Gn-secreting tumorPossible Gn-secreting tumor

Follicle Stimulating Hormone Follicle Stimulating Hormone (FSH)(FSH)

Produced by pituitaryProduced by pituitary SpermatogenesisSpermatogenesis 180-240 minute half-life180-240 minute half-life Inhibited largely by estrogenInhibited largely by estrogen Better measure of gonadotrophin output?Better measure of gonadotrophin output? Possible FSH-secreting tumorPossible FSH-secreting tumor

ProlactinProlactin

Significant cause of hypogonadismSignificant cause of hypogonadism May signal tumor presenceMay signal tumor presence Health benefitsHealth benefits Must be maintained within normal rangeMust be maintained within normal range Ref Range (3.0-18.0 ng/mL)Ref Range (3.0-18.0 ng/mL) >300= tumor>300= tumor Elevated by eating, sex (<30)Elevated by eating, sex (<30)

HYPERPROLACTINEMIAHYPERPROLACTINEMIACAUSESCAUSES

Pituitary tumorPituitary tumor Stalk compressionStalk compression Primary Primary

hypothyroidismhypothyroidism Chronic renal failureChronic renal failure CirrhosisCirrhosis

OpiatesOpiates Tri-cyclicsTri-cyclics D2 antagonistsD2 antagonists MetoclopramideMetoclopramide VerapamilVerapamil Chest wall traumaChest wall trauma

CortisolCortisol ““Stress hormone”Stress hormone” Cause of secondary hypogonadismCause of secondary hypogonadism Healthful benefitsHealthful benefits Must be maintained within normal rangeMust be maintained within normal range If elevated: Tx’d with Phosphatidylserine If elevated: Tx’d with Phosphatidylserine

(PS) (300mg po QD)(PS) (300mg po QD) If depressed: Tx’d with Hydrocortisone POIf depressed: Tx’d with Hydrocortisone PO

““Progesterone puts plaque inProgesterone puts plaque in the arteries, and wrinkles in the arteries, and wrinkles in

the penis”the penis”

--Dr. John Crisler--Dr. John Crisler

T/E ratioT/E ratio Measure of system performanceMeasure of system performance --ratio does have importance, but…--ratio does have importance, but… --absolute values of hormones are important--absolute values of hormones are important --cannot elevate E without consequence as long--cannot elevate E without consequence as long as T is proportionately highas T is proportionately high

Used to explain pathophysiologyUsed to explain pathophysiology --low T--low T higher proportionate E higher proportionate E morbiditymorbidity NOT to be used as treatment goalNOT to be used as treatment goal

LABS (con’t)LABS (con’t)

Thyroid Panel (TSH, FT4, FT3)Thyroid Panel (TSH, FT4, FT3)

CBC ( anemia mimics CBC ( anemia mimics ↓T )↓T )

Comprehensive Metabolic PanelComprehensive Metabolic Panel

Lipid ProfileLipid Profile

PSA (if over 40)PSA (if over 40)

TESTOSTERONE DELIVERY TESTOSTERONE DELIVERY SYSTEMSSYSTEMS

Gels and CreamsGels and Creams

PatchesPatches

Implantable PelletsImplantable Pellets

IMIM

OralsOrals

Gels and CreamsGels and Creams Ease of applicationEase of application May be more convenient—OR NOTMay be more convenient—OR NOT Stable across week, not dayStable across week, not day ““Pulsing” [T] may be beneficialPulsing” [T] may be beneficial Quickly attains stable serum levelsQuickly attains stable serum levels Boosts DHTBoosts DHT May elevate estrogensMay elevate estrogens Risk of accidental transferalRisk of accidental transferal Be mindful of application methodBe mindful of application method Avoid antecubital fossa—looks like AAS useAvoid antecubital fossa—looks like AAS use EXTREMELY variable absorption…EXTREMELY variable absorption… Especially with hypothyroidismEspecially with hypothyroidism

Gels and Creams (con’t)Gels and Creams (con’t)

““Big House” productsBig House” products

Solvay Pharmaceuticals’ AndrogelSolvay Pharmaceuticals’ Androgel

Auxilium Pharmaceuticals’ TestimAuxilium Pharmaceuticals’ Testim

--MUCH more expensive--MUCH more expensive

--support physician education (“The Cause”)--support physician education (“The Cause”)

--covered by insurance--covered by insurance

--vouchers/sample--vouchers/sample

--1%--1%

--be mindful of application technique--be mindful of application technique

Gels and Creams (con’t)Gels and Creams (con’t) Compounded gels/creamsCompounded gels/creams --various bases--various bases --1%, 5%, 10, 20%--1%, 5%, 10, 20% --higher conc. --higher conc. < E, DHT conversion < E, DHT conversion --soy, yam-based T’s--soy, yam-based T’s --ALL T gels/creams are ”bio-identical”--ALL T gels/creams are ”bio-identical” --creams slow absorption--creams slow absorption --can compound anti-E’s into product--can compound anti-E’s into product --MUCH less expensive--MUCH less expensive --syringe applicators great--syringe applicators great --pumps coming onto market--pumps coming onto market

T GEL APPLICATIONT GEL APPLICATION

Jars with measuring spoonsJars with measuring spoons Plastic capped syringes Plastic capped syringes Metered Dose PumpsMetered Dose Pumps 1% apply to outer arms, shoulders, flanks1% apply to outer arms, shoulders, flanks 5%, 10% applied to forearms5%, 10% applied to forearms NO scrotal application!NO scrotal application!

Testosterone PatchesTestosterone Patches

Convenient—MAYBE!Convenient—MAYBE! No risk of accidental transferNo risk of accidental transfer Stable serum androgen levelsStable serum androgen levels Little DHT, E boostLittle DHT, E boost Scrotal patches available (WHEW!)Scrotal patches available (WHEW!) 2/3’s--Contact Dermatitis2/3’s--Contact Dermatitis

Testosterone InjectionTestosterone Injection

Convenient—MAYBE!Convenient—MAYBE! MUST be injected weeklyMUST be injected weekly Stable across day, not weekStable across day, not week Ease of dose titrationEase of dose titration Injection risksInjection risks The “Gold Standard” NO MORE!The “Gold Standard” NO MORE!

NEEDLE SIZESNEEDLE SIZES

Glutes: 22ga 1 ½” Glutes: 22ga 1 ½” Thighs: 25ga 1”Thighs: 25ga 1”

OTHER MEDICATIONS:OTHER MEDICATIONS: HCGHCG --LH analog--LH analog --traditional treatment-of-choice for 2--traditional treatment-of-choice for 2ndnd low T low T --not just “fertility drug”--not just “fertility drug” --best use is adjunctive to TRT--best use is adjunctive to TRT --does not produce subjective benefits of T delivery--does not produce subjective benefits of T delivery SERM’sSERM’s --elevates T, but…--elevates T, but… --does not bring subjective benefits of TRT--does not bring subjective benefits of TRT --for testing, purposes of HPTA intactness--for testing, purposes of HPTA intactness --HPTA recovery “PCT” (AAS Post Cycle Therapy)--HPTA recovery “PCT” (AAS Post Cycle Therapy) --”rescue” Tx for gynocomastia (Tamoxifen)--”rescue” Tx for gynocomastia (Tamoxifen) --possible issues with respect to brain function--possible issues with respect to brain function

SERM’s (con’t)SERM’s (con’t) ClomipheneClomiphene --racemic mixture (antagonist AND agonist)--racemic mixture (antagonist AND agonist) --enclomiphene+zuclomiphene--enclomiphene+zuclomiphene --may bring untoward visual effects--may bring untoward visual effects --may bring untoward emotional effects--may bring untoward emotional effects TamoxifenTamoxifen --pure estrogen antagonism--pure estrogen antagonism --great for “nipple issues”--great for “nipple issues” ----↑ progesterone receptor [conc]↑ progesterone receptor [conc] RaloxifenRaloxifen --great estrogen antagonism--great estrogen antagonism --MUCH more expensive--MUCH more expensive Others (more to come)Others (more to come)

CONTRAINDICATIONS TO CONTRAINDICATIONS TO TRT:TRT:

Prostate CAProstate CA Breast CABreast CA Untreated prolactinomaUntreated prolactinoma

RELATIVE RELATIVE CONTRAINDICATIONS:CONTRAINDICATIONS:

PSA >4.0 or accel>0.75PSA >4.0 or accel>0.75 H/H> 18/55H/H> 18/55 Sleep ApneaSleep Apnea Cardiac, Hepatic, Renal DzCardiac, Hepatic, Renal Dz

POTENTIAL RISKS (listed)POTENTIAL RISKS (listed) Increased risk of bladder outlet symptoms due Increased risk of bladder outlet symptoms due

to increase in prostate volumeto increase in prostate volume Edema in patients with preexisting cardiac, Edema in patients with preexisting cardiac,

renal, or hepatic diseaserenal, or hepatic disease GynecomastiaGynecomastia Erythrocytosis (monitor H/H)Erythrocytosis (monitor H/H) Precipitation or worsening of sleep apneaPrecipitation or worsening of sleep apnea AcneAcne Decreased sperm productionDecreased sperm production Stimulation of growth in previously Stimulation of growth in previously

undiagnosed prostate cancerundiagnosed prostate cancer

DRUG INTERACTIONS:DRUG INTERACTIONS:

Diabetic MedicationsDiabetic Medications PropranololPropranolol OxyphenbutazoneOxyphenbutazone

The Meat and Potatoes of TRTThe Meat and Potatoes of TRT

INITIAL DOSAGESINITIAL DOSAGES Transdermal gels/creams Transdermal gels/creams 50mgs total QD50mgs total QD 5mgs (delivered)5mgs (delivered)

Testosterone Cypionate IM:Testosterone Cypionate IM: 100mg QW100mg QW --double dose “front load”--double dose “front load” --split weekly dose for those with--split weekly dose for those with anxiety issues (not initially)?anxiety issues (not initially)?

FOLLOW-UP LABSFOLLOW-UP LABS

Total TTotal T Bio TBio T LH/FSH (especially with transdermal)LH/FSH (especially with transdermal) FSH—to back up LH interpretation of HPTA statusFSH—to back up LH interpretation of HPTA status SHBGSHBG Estradiol Estradiol CBCCBC Comp. Metabolic PanelComp. Metabolic Panel PSA (if over 40)PSA (if over 40)

FOLLOW UP LABS (con’t)FOLLOW UP LABS (con’t) Initial F/U at 2 weeks with TD (transdermal)Initial F/U at 2 weeks with TD (transdermal) --stable serum T levels quickly attained--stable serum T levels quickly attained --logistical consideration of 30-day dose--logistical consideration of 30-day dose

Initial F/U at 6 weeks with IMInitial F/U at 6 weeks with IM --takes that long to equilibrate--takes that long to equilibrate --interpret by PK’s of T ester (48-72 hour peak)--interpret by PK’s of T ester (48-72 hour peak) --cypionate/enanthate t1/2 5-8 days--cypionate/enanthate t1/2 5-8 days

F/U at 4-6 weeks S/P dosage change or F/U at 4-6 weeks S/P dosage change or estrogen control s/p HPTA-suppressionestrogen control s/p HPTA-suppression

FOLLOW-UP LABS (con’t)FOLLOW-UP LABS (con’t)

Once dose is titrated:Once dose is titrated:

--q 6 months or yearly--q 6 months or yearly

--Include PSA--Include PSA

--Perform Digital Rectal Exam (DRE)--Perform Digital Rectal Exam (DRE)

TIMING OF LABS FOR IMTIMING OF LABS FOR IM

Cypionate, Enanthate esters peak at 48-Cypionate, Enanthate esters peak at 48-72 hours s/p IM injection72 hours s/p IM injection

Decline thereafterDecline thereafter T1/2=5-8 daysT1/2=5-8 days No lab draw on injection dayNo lab draw on injection day

--no urines first three days--no urines first three days Use these facts to interpret labsUse these facts to interpret labs

Mean SteadyMean Steady--State Testosterone Concentrations State Testosterone Concentrations in Patients Receiving in Patients Receiving AndroGelAndroGel®®

Day 90Day 90

Swerdloff RS, Wang C, Cunningham G, et al. JCEM. 2000;85:4500-4510.

TIMING OF LABS FOR TD’sTIMING OF LABS FOR TD’s

Apply at same time each dayApply at same time each day Always ask pt. when they apply (lifestyle)Always ask pt. when they apply (lifestyle) Split dose?Split dose? Consider TD carrier!Consider TD carrier! Allow at least 2 hours prior to drawAllow at least 2 hours prior to draw 2-4 hours is best with T gels2-4 hours is best with T gels Above no consequence with 24 hour Above no consequence with 24 hour

urinesurines Absorption is slowed, lost with T creamsAbsorption is slowed, lost with T creams

ESTROGEN ISSUESESTROGEN ISSUES

Do not Tx until post F/U labsDo not Tx until post F/U labs

--E2 may actually DROP with TRT--E2 may actually DROP with TRT

--insight into body’s response--insight into body’s response

Maintain E2 at mid-rangeMaintain E2 at mid-range

--with mid-range SHBG--with mid-range SHBG

Detriments of Detriments of ElevatedElevated EstrogenEstrogen

Suppresses HPTASuppresses HPTA Elevates SHBGElevates SHBG ImpotenceImpotence InfertilityInfertility Psychological Psychological

morbiditiesmorbidities VasospasmVasospasm

Increases clotting Increases clotting factorsfactors

Water retentionWater retention Prostate morbidityProstate morbidity CancersCancers Female fat distributionFemale fat distribution Fx on thyroid functionFx on thyroid function ↑ “↑ “Wimpy Factor”Wimpy Factor”

ESTROGEN ELEVATORSESTROGEN ELEVATORS

AgeAge ObesityObesity ETOH over-ETOH over-

consumption (incl consumption (incl HOPS in beer!)HOPS in beer!)

Liver DzLiver Dz Zinc deficiency (50mg Zinc deficiency (50mg

Zn/2mg Cu QD)Zn/2mg Cu QD) Vitamin C deficiencyVitamin C deficiency Excessive DHEA Excessive DHEA

supplementation supplementation (100mg QD)(100mg QD)

Androstenedione Androstenedione supplementationsupplementation

Xenoestrogens (incl Xenoestrogens (incl Vinyl IV bags!)Vinyl IV bags!)

--Lavender, Tea Tree --Lavender, Tea Tree OilOil

Liver Detoxification Liver Detoxification issuesissues

SoySoy Flax seedFlax seed FoodsFoods

ANASTROZOLEANASTROZOLE

Aromatase (“Estrogen synthase”) InhibitorAromatase (“Estrogen synthase”) Inhibitor Competitive InhibitorCompetitive Inhibitor #1 use of this med in world: Male TRT#1 use of this med in world: Male TRT other AI’s availableother AI’s available concerns with Endocrine pathway concerns with Endocrine pathway

disruption (as with finasteride)disruption (as with finasteride) Some c/o H/A’sSome c/o H/A’s AI’s as sole TRT is RAREAI’s as sole TRT is RARE

ANASTROZOLE DOSINGANASTROZOLE DOSING

0.25mg QOD, 0.5mg Q2-3D0.25mg QOD, 0.5mg Q2-3D 2 day t1/2, never >Q3D2 day t1/2, never >Q3D ““Frontload” (double initial dose)Frontload” (double initial dose) Titrate from thereTitrate from there Allow 4-5 weeks prior to f/u labsAllow 4-5 weeks prior to f/u labs

CRISLER HCG PROTOCOLCRISLER HCG PROTOCOL

250IU twice per week SC (starting dose)250IU twice per week SC (starting dose) NEVER more than 500IU QDNEVER more than 500IU QD

(or elevates estrogens, progesterone)(or elevates estrogens, progesterone) Transdermal T patients:Transdermal T patients:

--every third day--every third day Test cyp IM patients:Test cyp IM patients:

--T-2/T-1 prior to IM injection--T-2/T-1 prior to IM injection

--Fri/Sat c/ Sun IM is nice!--Fri/Sat c/ Sun IM is nice!

CRISLER HCG PROTOCOL (con’t)CRISLER HCG PROTOCOL (con’t)

Evens out serum androgen levels by t1/2 Evens out serum androgen levels by t1/2 of cypionate esterof cypionate ester

Prevents testicular atrophyPrevents testicular atrophy Stimulates all three CHOL pathwaysStimulates all three CHOL pathways Abundant boost in libido/sense of well Abundant boost in libido/sense of well

beingbeing

RESTORING PATHWAYSRESTORING PATHWAYS HCGHCG --IM: start at 250IU SC Days5/6--IM: start at 250IU SC Days5/6 --TD: start at 200IU SC QOD--TD: start at 200IU SC QOD --never more than 500IU --never more than 500IU DHEADHEA --25mg BID--25mg BID --100mg QD can elevate E1--100mg QD can elevate E1 --oral SR>TD>standard oral preparation--oral SR>TD>standard oral preparation PregnenolonePregnenolone --50mg TD QD in a cream--50mg TD QD in a cream

Rescue from “Nipple Issues”Rescue from “Nipple Issues”

Burning, itching, swelling, FREAKINGBurning, itching, swelling, FREAKING Occurs with mere changes in hormone levels, Occurs with mere changes in hormone levels,

even within physiological range, so…even within physiological range, so… DO NOT treat in first month (get F/U labs)DO NOT treat in first month (get F/U labs) 40mg QD tamoxifen until gone, then taper40mg QD tamoxifen until gone, then taper --cut dose ½ Q5D--cut dose ½ Q5D Prefer tamoxifen over clomiphenePrefer tamoxifen over clomiphene Cannot assay estrogens on SERM-class Cannot assay estrogens on SERM-class

drugs!drugs! Hold GhRT (magnifies E fx)Hold GhRT (magnifies E fx) Gyno may be caused by progesteronesGyno may be caused by progesterones

NO TRT “CYCLING”NO TRT “CYCLING”

Historically “borrowed” from AAS use.Historically “borrowed” from AAS use. No evidence of benefitNo evidence of benefit Does not do what is claimedDoes not do what is claimed Leaves substantial periods of letdownLeaves substantial periods of letdown The body thrives on regularityThe body thrives on regularity

WHAT IS THE FUTURE OF TRT?WHAT IS THE FUTURE OF TRT?

Elevating T to healthy, happy levelsElevating T to healthy, happy levels Estrogen metabolismEstrogen metabolism Actions at the androgen, estrogen Actions at the androgen, estrogen

receptorsreceptors Restoring endocrine pathwaysRestoring endocrine pathways

THE GOAL?THE GOAL?

“ “The ultimate goal of TRT medicine is to The ultimate goal of TRT medicine is to optimize health and happiness in our optimize health and happiness in our patients, which means producing an patients, which means producing an environment where we have elevated environment where we have elevated testosterone to sufficient levels, with the testosterone to sufficient levels, with the body responding as if it is unaware of the body responding as if it is unaware of the exogenous manipulations.”exogenous manipulations.”

--John Crisler, DO--John Crisler, DO