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TESTOSTERONE REPLACEMENT THERAPY -A RECIPE FOR SUCCESS- --John Crisler, DO --John Crisler, DO Lansing, MI USA Lansing, MI USA MSU-COM MSU-COM www.AllThingsMale.com.

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Presentation on theme: "TESTOSTERONE REPLACEMENT THERAPY -A RECIPE FOR SUCCESS- --John Crisler, DO --John Crisler, DO Lansing, MI USA Lansing, MI USA MSU-COM MSU-COM www.AllThingsMale.com."— Presentation transcript:

1 TESTOSTERONE REPLACEMENT THERAPY -A RECIPE FOR SUCCESS- --John Crisler, DO --John Crisler, DO Lansing, MI USA Lansing, MI USA MSU-COM MSU-COM

2 Everything You Always Wanted to Know About TRT But Didnt Have Time to Ask

3 WHAT IS TESTOSTERONE REPLACEMENT THERAPY?

4 TRT: Restoration of Testosterone to HEALTHY physiological levels.

5 TRT is NOT: Total T>normal range Total T>normal range Steroids Steroids Viagra Viagra

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8 SCREENING FOR HYPOGONADISM

9 WHAT ARE THE SYMPTOMS OF LOW TESTOSTERONE? TAT Syndrome TAT Syndrome Fatigue Fatigue USTA Syndrome USTA Syndrome Loss of muscle mass Loss of muscle mass Fat gain Fat gain Poor recovery Poor recovery Pain/Inflammation Pain/Inflammation Irritability Irritability Depression Depression Decreased memory Decreased memory Loss of Libido Loss of Libido Erectile Dysfunction Erectile Dysfunction

10 ADAM 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 endurance? 3. Do you have a decrease in strength and/or endurance? 4. Have you lost height? 4. Have you lost height? 5. Have you noticed a decreased enjoyment of life? 5. Have you noticed a decreased enjoyment of life?

11 ADAM Questionnaire (cont) 6.Are you sad and/or grumpy? 7.Are your erections less strong? 8.Has it been more difficult to maintain your erection throughout sexual intercourse? 9.Are you falling asleep after dinner? 10. Has your work performance deteriorated recently?

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13 INITIAL LAB WORK

14 INITIAL HYPOGONADISM PANEL Total Testosterone Total Testosterone Bioavailable/Free T Bioavailable/Free T SHBG SHBG DHT (?) DHT (?) LH/FSH LH/FSH DHEA-S DHEA-S Estradiol Estradiol Total Estrogens (urine) Total Estrogens (urine) Prolactin Prolactin Cortisol Cortisol Thyroid Panel (TSH, FT4, FT3) Thyroid Panel (TSH, FT4, FT3) Comp Metabolic Panel Comp Metabolic Panel CBC CBC Lipid Panel Lipid Panel PSA (if over 40) PSA (if over 40) Progesterone Progesterone

15 MEASURES OF TESTOSTERONE Total Testosteroneall that is produced Total Testosteroneall that is produced ( ng/dL) ( ng/dL) Free Testosteroneall that is unbound (2-4%) Free Testosteroneall that is unbound (2-4%) (80-300pg/dL) (80-300pg/dL) --Equilibrium Dialysis, NOT RIA! --Equilibrium Dialysis, NOT RIA! Bioavailable TestosteroneGold Standard Bioavailable TestosteroneGold Standard Free and Loosely/Weakly Bound Free and Loosely/Weakly Bound 40-60% ( ng/dL) 40-60% ( ng/dL)

16 Laboratory reference values for testosterone vary widely, and are established without clinical considerations. Lazarou SLazarou S, et al. Harvard Medical School, Division of Urology, Beth Israel Deaconess Medical Center Lazarou S

17 T SAMPLE PREPARATION (SERUM) Refrigerated, no additive serum preferred Refrigerated, no additive serum preferred (Plain, Red Top) (Plain, Red Top) Heparanized serum less acceptable Heparanized serum less acceptable (green-top) (green-top) NO Serum Separator Tubes (SST) NO Serum Separator Tubes (SST)

18 IMPORTANT ABOUT ESTROGEN TESTING Total Estrogens is NOT a valid assay for adult males Total Estrogens is NOT a valid assay for adult males --cross reactivity w/ progesterone --cross reactivity w/ progesterone Estradiol MUST be by ultrasensitive method, LC/MS assay--ALL OTHERS NOT VALID Estradiol MUST be by ultrasensitive method, LC/MS assay--ALL OTHERS NOT VALID Gold standard is 24 hour urine, esp w/ TDs (TransDermals) Gold standard is 24 hour urine, esp w/ TDs (TransDermals) Be extra mindful of SHBG level Be extra mindful of SHBG level

19 Sample Matrixes BLOOD BLOOD --most common --most common --Total, Free, Bioavailable --Total, Free, Bioavailable --snap shot only --snap shot only --limited value given TDs, hormone conversions, etc. --limited value given TDs, hormone conversions, etc. URINE URINE --best of all, esp. w/ TDs --best of all, esp. w/ TDs --free levels provided --free levels provided --limited assays --limited assays --expanded hormone assay types, incl. metabolites --use only 24 hour collectionsno spots --use only 24 hour collectionsno spots --be careful of contamination --be careful of contamination --better to assess intracellular 5-AR activity --better to assess intracellular 5-AR activity

20 Many times T on bloods (especially for morning draw) will be well within normal range. But when you collect a 24 hour urine, T will be deficient. Thus a spurt of T in the morning, then very little the rest of the day.

21 COMMON SENSE IN ORDER TO TEST THE LEVEL OF A DRUG, YOU MUST TAKE THE DRUG, ON SCHEDULE!!!

22 COMMON SENSE HAVE PATIENT DRAW AT SAME TIME OF DAY EACH TIME, ESPECIALLY WITH TRANSDERMALS (b/c PKs)

23 COMMON SENSE 1. NEVER SMOKE IN BED 2. ALWAYS WEAR PAJAMAS

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25 DHT Most responsible for All Things Male Most responsible for All Things Male 5-ARd from T 5-ARd from T Unfairly deemed evil hormone Unfairly deemed evil hormone NOT responsible for prostate morbidity NOT responsible for prostate morbidity 25-75ng/dL 25-75ng/dL Serum assay valid? Serum assay valid? Metabolite ratios on 24 hour urines best Metabolite ratios on 24 hour urines best Avoid finasteride Avoid finasteride

26 Estradiol Major player amongst estrogens Major player amongst estrogens Total Estrogens is NOT valid assay for males Total Estrogens is NOT valid assay for males MUST be monitored during TRT MUST be monitored during TRT Masks benefits of TRT Masks benefits of TRT Adjunctive cause of serious illness Adjunctive cause of serious illness Numerous benefits for health, so… Numerous benefits for health, so… Must not be driven too low Must not be driven too low (10-50pg/mL) maintain mid-range ( w/ mid-range SHBG) (10-50pg/mL) maintain mid-range ( w/ mid-range SHBG) May rise over time May rise over time TDs elevate E more than IM TDs elevate E more than IM

27 Luteinizing Hormone (LH) Produced by pituitary Produced by pituitary Stimulates T production Stimulates T production Pulsatile production Pulsatile production Short half-life Short half-life Acute phase reactant Acute phase reactant Must be careful in its interpretation Must be careful in its interpretation Possible Gn-secreting tumor Possible Gn-secreting tumor

28 Follicle Stimulating Hormone (FSH) Produced by pituitary Produced by pituitary Spermatogenesis Spermatogenesis minute half-life minute half-life Inhibited largely by estrogen Inhibited largely by estrogen Better measure of gonadotrophin output? Better measure of gonadotrophin output? Possible FSH-secreting tumor Possible FSH-secreting tumor

29 Prolactin Significant cause of hypogonadism Significant cause of hypogonadism May signal tumor presence May signal tumor presence Health benefits Health benefits Must be maintained within normal range Must be maintained within normal range Ref Range ( ng/mL) Ref Range ( ng/mL) >300= tumor >300= tumor Elevated by eating, sex (<30) Elevated by eating, sex (<30)

30 HYPERPROLACTINEMIA CAUSES Pituitary tumor Pituitary tumor Stalk compression Stalk compression Primary hypothyroidism Primary hypothyroidism Chronic renal failure Chronic renal failure Cirrhosis Cirrhosis Opiates Opiates Tri-cyclics Tri-cyclics D2 antagonists D2 antagonists Metoclopramide Metoclopramide Verapamil Verapamil Chest wall trauma Chest wall trauma

31 Cortisol Stress hormone Stress hormone Cause of secondary hypogonadism Cause of secondary hypogonadism Healthful benefits Healthful benefits Must be maintained within normal range Must be maintained within normal range If elevated: Txd with Phosphatidylserine (PS) (300mg po QD) If elevated: Txd with Phosphatidylserine (PS) (300mg po QD) If depressed: Txd with Hydrocortisone PO If depressed: Txd with Hydrocortisone PO

32 Progesterone puts plaque in the arteries, and wrinkles in the penis --Dr. John Crisler --Dr. John Crisler

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35 T/E ratio Measure of system performance Measure 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 high as T is proportionately high Used to explain pathophysiology Used to explain pathophysiology --low T higher proportionate E morbidity --low T higher proportionate E morbidity NOT to be used as treatment goal NOT to be used as treatment goal

36 LABS (cont) Thyroid Panel (TSH, FT4, FT3) Thyroid Panel (TSH, FT4, FT3) CBC ( anemia mimics T ) CBC ( anemia mimics T ) Comprehensive Metabolic Panel Comprehensive Metabolic Panel Lipid Profile Lipid Profile PSA (if over 40) PSA (if over 40)

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38 TESTOSTERONE DELIVERY SYSTEMS Gels and Creams Gels and Creams Patches Patches Implantable Pellets Implantable Pellets IM IM Orals Orals

39 Gels and Creams Ease of application Ease of application May be more convenientOR NOT May be more convenientOR NOT Stable across week, not day Stable across week, not day Pulsing [T] may be beneficial Pulsing [T] may be beneficial Quickly attains stable serum levels Quickly attains stable serum levels Boosts DHT Boosts DHT May elevate estrogens May elevate estrogens Risk of accidental transferal Risk of accidental transferal Be mindful of application method Be mindful of application method Avoid antecubital fossalooks like AAS use Avoid antecubital fossalooks like AAS use EXTREMELY variable absorption… EXTREMELY variable absorption… Especially with hypothyroidism Especially with hypothyroidism

40 Gels and Creams (cont) Big House products Big House products Solvay Pharmaceuticals Androgel Solvay Pharmaceuticals Androgel Auxilium Pharmaceuticals Testim Auxilium 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

41 Gels and Creams (cont) Compounded gels/creams Compounded gels/creams --various bases --various bases --1%, 5%, 10, 20% --1%, 5%, 10, 20% --higher conc. < E, DHT conversion --higher conc. < E, DHT conversion --soy, yam-based Ts --soy, yam-based Ts --ALL T gels/creams are bio-identical --ALL T gels/creams are bio-identical --creams slow absorption --creams slow absorption --can compound anti-Es into product --can compound anti-Es into product --MUCH less expensive --MUCH less expensive --syringe applicators great --syringe applicators great --pumps coming onto market --pumps coming onto market

42 T GEL APPLICATION Jars with measuring spoons Jars with measuring spoons Plastic capped syringes Plastic capped syringes Metered Dose Pumps Metered Dose Pumps 1% apply to outer arms, shoulders, flanks 1% apply to outer arms, shoulders, flanks 5%, 10% applied to forearms 5%, 10% applied to forearms NO scrotal application! NO scrotal application!

43 Testosterone Patches ConvenientMAYBE! ConvenientMAYBE! No risk of accidental transfer No risk of accidental transfer Stable serum androgen levels Stable serum androgen levels Little DHT, E boost Little DHT, E boost Scrotal patches available (WHEW!) Scrotal patches available (WHEW!) 2/3s--Contact Dermatitis 2/3s--Contact Dermatitis

44 Testosterone Injection ConvenientMAYBE! ConvenientMAYBE! MUST be injected weekly MUST be injected weekly Stable across day, not week Stable across day, not week Ease of dose titration Ease of dose titration Injection risks Injection risks The Gold Standard NO MORE! The Gold Standard NO MORE!

45 NEEDLE SIZES Glutes: 22ga 1 ½ Glutes: 22ga 1 ½ Thighs: 25ga 1 Thighs: 25ga 1

46 OTHER MEDICATIONS: HCG HCG --LH analog --LH analog --traditional treatment-of-choice for 2 nd low T --traditional treatment-of-choice for 2 nd 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 SERMs SERMs --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

47 SERMs (cont) Clomiphene Clomiphene --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 Tamoxifen Tamoxifen --pure estrogen antagonism --pure estrogen antagonism --great for nipple issues --great for nipple issues -- progesterone receptor [conc] -- progesterone receptor [conc] Raloxifen Raloxifen --great estrogen antagonism --great estrogen antagonism --MUCH more expensive --MUCH more expensive Others (more to come) Others (more to come)

48 CONTRAINDICATIONS TO TRT: Prostate CA Prostate CA Breast CA Breast CA Untreated prolactinoma Untreated prolactinoma

49 RELATIVE CONTRAINDICATIONS: PSA >4.0 or accel>0.75 PSA >4.0 or accel>0.75 H/H> 18/55 H/H> 18/55 Sleep Apnea Sleep Apnea Cardiac, Hepatic, Renal Dz Cardiac, Hepatic, Renal Dz

50 POTENTIAL RISKS (listed) Increased risk of bladder outlet symptoms due to increase in prostate volume Increased risk of bladder outlet symptoms due to increase in prostate volume Edema in patients with preexisting cardiac, renal, or hepatic disease Edema in patients with preexisting cardiac, renal, or hepatic disease Gynecomastia Gynecomastia Erythrocytosis (monitor H/H) Erythrocytosis (monitor H/H) Precipitation or worsening of sleep apnea Precipitation or worsening of sleep apnea Acne Acne Decreased sperm production Decreased sperm production Stimulation of growth in previously undiagnosed prostate cancer Stimulation of growth in previously undiagnosed prostate cancer

51 DRUG INTERACTIONS: Diabetic Medications Diabetic Medications Propranolol Propranolol Oxyphenbutazone Oxyphenbutazone

52 The Meat and Potatoes of TRT

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54 INITIAL DOSAGES Transdermal gels/creams Transdermal gels/creams 50mgs total QD 50mgs total QD 5mgs (delivered) 5mgs (delivered) Testosterone Cypionate IM: Testosterone Cypionate IM: 100mg QW 100mg 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)?

55 FOLLOW-UP LABS Total T Total T Bio T Bio T LH/FSH (especially with transdermal) LH/FSH (especially with transdermal) FSHto back up LH interpretation of HPTA status FSHto back up LH interpretation of HPTA status SHBG SHBG Estradiol Estradiol CBC CBC Comp. Metabolic Panel Comp. Metabolic Panel PSA (if over 40) PSA (if over 40)

56 FOLLOW UP LABS (cont) 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 IM Initial F/U at 6 weeks with IM --takes that long to equilibrate --takes that long to equilibrate --interpret by PKs of T ester (48-72 hour peak) --interpret by PKs 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 estrogen control s/p HPTA-suppression F/U at 4-6 weeks S/P dosage change or estrogen control s/p HPTA-suppression

57 FOLLOW-UP LABS (cont) 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)

58 TIMING OF LABS FOR IM Cypionate, Enanthate esters peak at hours s/p IM injection Cypionate, Enanthate esters peak at hours s/p IM injection Decline thereafter Decline thereafter T1/2=5-8 days T1/2=5-8 days No lab draw on injection day No lab draw on injection day --no urines first three days --no urines first three days Use these facts to interpret labs Use these facts to interpret labs

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60 TIMING OF LABS FOR TDs Apply at same time each day Apply 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 draw Allow at least 2 hours prior to draw 2-4 hours is best with T gels 2-4 hours is best with T gels Above no consequence with 24 hour urines Above no consequence with 24 hour urines Absorption is slowed, lost with T creams Absorption is slowed, lost with T creams

61 ESTROGEN ISSUES Do not Tx until post F/U labs Do not Tx until post F/U labs --E2 may actually DROP with TRT --E2 may actually DROP with TRT --insight into bodys response --insight into bodys response Maintain E2 at mid-range Maintain E2 at mid-range --with mid-range SHBG --with mid-range SHBG

62 Detriments of Elevated Estrogen Suppresses HPTA Suppresses HPTA Elevates SHBG Elevates SHBG Impotence Impotence Infertility Infertility Psychological morbidities Psychological morbidities Vasospasm Vasospasm Increases clotting factors Increases clotting factors Water retention Water retention Prostate morbidity Prostate morbidity Cancers Cancers Female fat distribution Female fat distribution Fx on thyroid function Fx on thyroid function Wimpy Factor Wimpy Factor

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64 ESTROGEN ELEVATORS Age Age Obesity Obesity ETOH over- consumption (incl HOPS in beer!) ETOH over- consumption (incl HOPS in beer!) Liver Dz Liver Dz Zinc deficiency (50mg Zn/2mg Cu QD) Zinc deficiency (50mg Zn/2mg Cu QD) Vitamin C deficiency Vitamin C deficiency Excessive DHEA supplementation (100mg QD) Excessive DHEA supplementation (100mg QD) Androstenedione supplementation Androstenedione supplementation Xenoestrogens (incl Vinyl IV bags!) Xenoestrogens (incl Vinyl IV bags!) --Lavender, Tea Tree Oil --Lavender, Tea Tree Oil Liver Detoxification issues Liver Detoxification issues Soy Soy Flax seed Flax seed Foods Foods

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66 ANASTROZOLE Aromatase (Estrogen synthase) Inhibitor Aromatase (Estrogen synthase) Inhibitor Competitive Inhibitor Competitive Inhibitor #1 use of this med in world: Male TRT #1 use of this med in world: Male TRT other AIs available other AIs available concerns with Endocrine pathway disruption (as with finasteride) concerns with Endocrine pathway disruption (as with finasteride) Some c/o H/As Some c/o H/As AIs as sole TRT is RARE AIs as sole TRT is RARE

67 ANASTROZOLE DOSING 0.25mg QOD, 0.5mg Q2-3D 0.25mg QOD, 0.5mg Q2-3D 2 day t1/2, never >Q3D 2 day t1/2, never >Q3D Frontload (double initial dose) Frontload (double initial dose) Titrate from there Titrate from there Allow 4-5 weeks prior to f/u labs Allow 4-5 weeks prior to f/u labs

68 CRISLER HCG PROTOCOL 250IU twice per week SC (starting dose) 250IU twice per week SC (starting dose) NEVER more than 500IU QD NEVER 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!

69 CRISLER HCG PROTOCOL (cont) Evens out serum androgen levels by t1/2 of cypionate ester Evens out serum androgen levels by t1/2 of cypionate ester Prevents testicular atrophy Prevents testicular atrophy Stimulates all three CHOL pathways Stimulates all three CHOL pathways Abundant boost in libido/sense of well being Abundant boost in libido/sense of well being

70 RESTORING PATHWAYS HCG HCG --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 DHEA DHEA --25mg BID --25mg BID --100mg QD can elevate E mg QD can elevate E1 --oral SR>TD>standard oral preparation --oral SR>TD>standard oral preparation Pregnenolone Pregnenolone --50mg TD QD in a cream --50mg TD QD in a cream

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72 Rescue from Nipple Issues Burning, itching, swelling, FREAKING Burning, itching, swelling, FREAKING Occurs with mere changes in hormone levels, even within physiological range, so… Occurs with mere changes in hormone levels, 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 taper 40mg QD tamoxifen until gone, then taper --cut dose ½ Q5D --cut dose ½ Q5D Prefer tamoxifen over clomiphene Prefer tamoxifen over clomiphene Cannot assay estrogens on SERM-class drugs! Cannot assay estrogens on SERM-class drugs! Hold GhRT (magnifies E fx) Hold GhRT (magnifies E fx) Gyno may be caused by progesterones Gyno may be caused by progesterones

73 NO TRT CYCLING Historically borrowed from AAS use. Historically borrowed from AAS use. No evidence of benefit No evidence of benefit Does not do what is claimed Does not do what is claimed Leaves substantial periods of letdown Leaves substantial periods of letdown The body thrives on regularity The body thrives on regularity

74 WHAT IS THE FUTURE OF TRT? Elevating T to healthy, happy levels Elevating T to healthy, happy levels Estrogen metabolism Estrogen metabolism Actions at the androgen, estrogen receptors Actions at the androgen, estrogen receptors Restoring endocrine pathways Restoring endocrine pathways

75 THE GOAL? The ultimate goal of TRT medicine is to optimize health and happiness in our patients, which means producing an environment where we have elevated testosterone to sufficient levels, with the body responding as if it is unaware of the exogenous manipulations. The ultimate goal of TRT medicine is to optimize health and happiness in our patients, which means producing an environment where we have elevated testosterone to sufficient levels, with the body responding as if it is unaware of the exogenous manipulations. --John Crisler, DO --John Crisler, DO

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