Trt androgen therapy

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Lecture by Prof.Intisar Taibah Universty
Androgen |Therapy replacement

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Trt androgen therapy

  1. 1. TESTOSTERONEREPLACEMENT THERAPY INTESSAR SULTAN 52802 8068 MD, MRCP PROF. OF MEDICINE, TAIBAH U CONSULTANT ENDOCRINOLOGIST KFH, MADINAH, 2010
  2. 2. TRT: Restoration of Testosterone to HEALTHY physiological levels: Sexualfunction, mood and bone and muscle mass.
  3. 3. Natural androgens OH OH H H H H H HO O H TESTOSTERONE DIHYDROTESTOSTERONE
  4. 4. TestesTestes & adipose tissues
  5. 5. Estrogen action in males1. Pubertal growth2. Fusion of epiphysis3. Maintenance of bone density4. Gonadotropins regulation
  6. 6. INDICATIONS HypogonadismNot osteoporosis or chronicillness or refractory anemia Or to build muscles
  7. 7. Prevalence of Testosterone Deficiency
  8. 8. ANDROPAUSEThe correct term is viropause • The end of virility • Testosterone deficiency increases with age • Clinical effects of this physiological abnormality is difficult • More gradual than menopause, hot flushes are rare. • Symptoms and signs have only been associated with frank hypogonadism (T < 200 ng/dl) (350- 1200 ng/dl).
  9. 9. • Current data do not support testosterone supplementation in healthy, asymptomatic older men with normal or low–normal testosterone levels.• Treatment may be beneficial in older men with clear hypoandrogenic symptoms, especially reduced libido, erectile dysfunction and decreased muscle strength, if testosterone concentration is consistently low, and the patient selection, counselling and follow–up are adequate.
  10. 10. DIAGNOSIS
  11. 11. SYMPTOMS SYSTEMIC DZ NOT SD• Fatigue • Pain/Inflammation• Loss of muscle • Irritability mass • Depression• Fat gain • Decreased memory• Poor recovery • Loss of Libido • Erectile Dysfunction
  12. 12. Androgen Deficiency in Aging Males (ADAM) score1. Do you have a decrease in sex drive?2. Do you have a lack of energy?3. Do you have a decrease in strength and/or endurance?4. Have you lost height?5. Have you noticed a decreased enjoyment of life?
  13. 13. ADAM Questionnaire (con’t)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?
  14. 14. ADAM• Positive: if pt answers yes: – To any of the questions pertaining to sexual disorders or – To at least three of the other questions.• Negative in all other cases• Sensitive but not specific test
  15. 15. INITIALHYPOGONADISM PANEL
  16. 16. 1. Total Testosterone2. Bioavailable/Free T3. SHBG4. LH/FSH5. DHEA-S6. Estradiol7. Prolactin
  17. 17. 10. Cortisol11. Thyroid Panel12. CBC13. Lipid Panel14. PSA (if over 40)
  18. 18. Measures of testosterone • Total Testosterone— 300 -1000 ng/dl sample in the morning on plain tubes. • Free Testosterone — 2-4% (80-300 pg/dL) Equilibrium Dialysis • Bioavailable Testosterone—Gold StandardSHBG ―Free and Loosely/Weakly Bound‖ 40-60% (120-600 ng/dL)
  19. 19. SHBG• Obesity (lowering SHBG): – Lower total testosterone – Normal free or bioavailable testosterone• Aging (increasing SHBG): – Higher total – Lower bioavailable testosterone.
  20. 20. ―Laboratory reference values for testosterone vary widely, and are established without clinical considerations.‖Lazarou S, et al. Harvard Medical School, Division of Urology, Beth Israel Deaconess Medical Center
  21. 21. LH/FSH• LH: primary VS secondary• FSH: reflect spermatogenesis
  22. 22. DHT: ―Evil hormone‖• 5-AR’d from T so Avoid AROMATASE INHIBITORS before testing.• 25-75 ng/dL• Serum assay valid?• Metabolite ratios on 24 hour urines
  23. 23. ESTROGEN TESTING• Total Estrogens is NOT a valid assay for adult males --cross reactivity w/ progesterone• Estradiol MUST be by ―ultrasensitive‖ method -ALL OTHERS NOT VALID• Gold standard is 24 hour urine
  24. 24. CONTRAINDICATIONS TO TRT: • Prostate CA • Breast CA • Untreated prolactinoma
  25. 25. RELATIVECONTRAINDICATIONS:• PSA >4.0 or accelerated >0.75• Hb/Hc> 18/55• Sleep Apnea• Cardiac, Hepatic, Renal Dz
  26. 26. POTENTIAL RISKS1. Bladder outlet symptoms due to increase in prostate volume2. Stimulation of growth in previously undiagnosed prostate cancer3. Edema in patients with preexisting dz4. Gynecomastia & Weight gain5. Erythrocytosis (monitor H/H)6. Precipitation or worsening of sleep apnea7. Acne8. Decreased sperm production9. CVD??: Adverse lipid: LDL, HDL
  27. 27. DRUG INTERACTIONS:• Diabetic Medications• Propranolol• Oxyphenbutazone
  28. 28. TESTOSTERONEDELIVERY SYSTEMS
  29. 29. TESTOSTERONE DELIVERY SYSTEMS• Trans-dermal: consistent, ? adequate T level, no First-pass effect through the liver 1. Gels 2. Patches 3. Pellets 4. Buccal• IM• Orals: xxxxx
  30. 30. Testosterone Gels• Gel is clear, colorless mixture with• an alcohol and water base that• dries quickly after rubbing .• Applied daily to abdomen, upper arms or shoulders AM after bathingProducts :-AndroGel® 5-10 g per day-Testim™ 5-10 g per day (50 mg testosterone)
  31. 31. Testosterone GelsAdvantages :Once-a-day dosingNormalizes testosterone in 24 hrsConvenient application sitesMore potent & Less skin irritation than patchesDisadvantages :Potential for transfer to partner ?? pregnant orchildMore expensive than other forms of therapyMay elevate ESTROGENS
  32. 32. Testosterone Patches:Androderm®5 mg per day Use different sites 7 days interval to use same site Advantage: •Applied to various areas of the skin as scrotum •Once-a-day dosing mimics natural cycle •No risk of accidental transfer Disadvantage •Less potency than gels •2/3’s--Contact Dermatitis •Higher cost
  33. 33. Mean Steady-State Testosterone Concentrations in Patients Receiving AndroGel® Day 90Swerdloff RS, Wang C, Cunningham G, et al. JCEM. 2000;85:4500-4510.
  34. 34. Buccal TestosteroneDose: mucoadhesive table (30 mg) bidAdvantages :Consistent T levelDisadvantages :Local irritationGingivitisBitter tasteBID use
  35. 35. Testosterone pellets: Testopel•Pellets are slowly released pure T crystals: 100 mg•Local anesthetic , 6-10 pellets are introduced by a needleinto the fat of the buttock.•Advantages : Infrequent dosing, every 3-6 months Slow rise in T that is maintained over long period Safe•Disadvantages : Requires surgical procedure Pain and discomfort Inability to adjust dose easily
  36. 36. Testosterone Injections• Testosterone propionate in oil• Testosterone enanthate in oil (Delatestryl)• Testosterone cypionate in oil (Depotest)
  37. 37. Testosterone Injection• Infrequent dosing, /2-4 wks• Dramatic physical feeling immediately after the injection• The least cost• Ease of dose titration• The ―Gold Standard‖ NO MORE!• Used mainly for men with serious causes as trauma or cancer.
  38. 38. Disadvantages of testosterone IM:• Initial levels of testosterone are very high, may have harmful effects.• The "roller coaster effect" dosing irregularities: mood changes, both at the peak and trough of the dosing cycle.
  39. 39. Injection doses• Testosterone Cypionate IM in oil (Depotest): 100 mg QW --double dose ―front load‖• Glutes: 22 ga 1 ½‖• Thighs: 25 ga 1‖
  40. 40. ORAL PREPARATIONS• Alkylated to be absorbed and be active.• First-pass effect through the liver• Poor serum T levels• Liver toxicity: cholestasis• Not recommended for replacement therapy in long-term situations.
  41. 41. FOLLOW-UP LABS• Total T• Bio T• SHBG• Estradiol : (especially with transdermal) maintain in mid range• LH/FSH (especially with transdermal)• CBC• Lipid profile• PSA (if over 40)
  42. 42. Initial F/U at 2 weeks with TD• Stable serum T levels quickly attained• TD should be applied at same time / day• Always ask pt. when they apply• Split dose?• Allow at least 2 hours s/p application prior to draw• 2-4 hours is best with T gels
  43. 43. Initial F/U at 6 weeks with IM• Takes that long to equilibrate• Cypionate, Enanthate esters peak at 48-72 hours s/p IM injection• T1/2 = 5-8 days• No lab draw on injection day
  44. 44. FOLLOW-UP LABS (con’t)• Once dose is titrated: --q 6 months or yearly --Include PSA --Perform Digital Rectal Exam (DRE)
  45. 45. FU: test Estradiol• Total Estrogens is NOT valid assay• MUST be monitored during TRT• Beneficial on lipids and bone BUT Masks benefits of TRT• Maintain mid-range (10-50 pg/Ml)• May rise over time• TD’s elevate E more than IM
  46. 46. Testicular atrophy nightmare!!!!!!!!
  47. 47. • Small doses of HCG are regularly added to traditional TRT• Restore the testicles to previous form and function.• Stabilizes serum levels• Rebalance expression of other hormones• Increased sense of well-being and libido.
  48. 48. CRISLER HCG PROTOCOL modified• -IM: start at 250IU SC two days immediately previous to IM shot. -TD: start at 200IU SC every 3rd day--Never > 500 IU/week (4000 for fertility): aromatization, elevates estrogens, progesterone: gynecomastia Leydig cell desensitization to LH: 1ry hypogonadism
  49. 49. HCG as sole TRT• Treatment of choice for hypogonadotrophic hypogonadism• But it just does not bring the same subjective benefits as pure testosterone delivery systems do—even with similar serum androgen levels
  50. 50. Do we have other • adjunctive for TRT!!!!!!
  51. 51. Tamoxifen: SERM’s• --Elevates T, but… --Does not bring subjective benefits of TRT• --Cannot assay estrogens on SERM- class drugs!• -- Tx for gynocomastia of recent onset as 3 ms trial before surgery
  52. 52. Clomiphene: SERM’s• -- Racemic mixture (antagonist AND agonist) -- May bring untoward visual effects -- May bring untoward emotional effects
  53. 53. Raloxifen : SERM’s• --Great estrogen antagonism --MUCH more expensive
  54. 54. DHEA• -- Effect??• --25mg BID --100mg QD can elevate E1
  55. 55. Aromatase Inhibitor• Testolactone 450 mg/d• Anastrozole 1mg/d• For gynecomastia ?????• AI’s as sole TRT is RARE• Allow 4-5 weeks prior to f/u labs
  56. 56. 5 alpha reductase inhibitor• Men on testosterone replacement should block the conversion of testosterone to dihydrotestosterone (DHT) which affects prostate hypertrophy and possibly cancer development.• Proscar®
  57. 57. ANABOLIC STEROIDS OH OH CH3 C CH H H O N H H H H OO H OXANDROLONE (OXANDRIN) DANAZOL (DANOCRINE) Also classified as 17-alpha alkylated androgens
  58. 58. Longlist ofSEs
  59. 59. DANAZOLE• Non aromatizable androgen• 300 -600 mg/d• Used in gynecomastia ??• Weight gain• Acne
  60. 60. Androgenic steroids Abuse Young Athletes
  61. 61. Superphysiologic doses• Suppress LH/FSH• Inhibits spermatogenesis• Testicular atrophy• Lower HDL• Testosterone / epitestosterone < 6
  62. 62. Symptoms• Gynecomastia• Acne• Small testicular volume
  63. 63. WHAT IS THE FUTURE OF TRT?• Elevating T to healthy, happy levels• Estrogen metabolism• Actions at the androgen, estrogen receptors• Restoring endocrine pathways

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