trt androgen therapy
DESCRIPTION
Lecture by Prof.Intisar Taibah Universty Androgen |Therapy replacementTRANSCRIPT
INTESSAR SULTAN
52802
8068
MD, MRCP
PROF. OF MEDICINE, TAIBAH U
CONSULTANT ENDOCRINOLOGIST
KFH, MADINAH, 2010
TESTOSTERONE REPLACEMENT
THERAPY
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الرحيم الرحمن الله بسم
TRT: Restoration of Testosterone to HEALTHY physiological levels: Sexual function, mood and bone and
muscle mass.
Natural androgens
O
OH
HH
H
TESTOSTERONE
O
OH
HH
H
H
DIHYDROTESTOSTERONE
Testes & adipose tissues
Testes
Estrogen action in males
1. Pubertal growth
2. Fusion of epiphysis
3. Maintenance of bone density
4. Gonadotropins regulation
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Hypogonadism
Not osteoporosis or chronic illness or refractory anemia
Or to build muscles
INDICATIONS
Prevalence of Testosterone Deficiency
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).
• 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. 14
DIAGNOSIS
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SYMPTOMSSYSTEMIC DZ NOT SD
• Fatigue• Loss of muscle
mass• Fat gain• Poor recovery
• Pain/Inflammation• Irritability• Depression• Decreased
memory• Loss of Libido• Erectile
Dysfunction
Androgen Deficiency in Aging Males (ADAM) score
1. 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?
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?
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
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INITIAL HYPOGONADISM
PANEL
1. Total Testosterone2. Bioavailable/Free T3. SHBG4. LH/FSH5. DHEA-S6. Estradiol7. Prolactin
10. Cortisol
11. Thyroid Panel
12. CBC
13. Lipid Panel
14. PSA (if over 40)
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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
Standard “Free and Loosely/Weakly Bound” 40-60% (120-600 ng/dL)
SHBG
SHBG
• Obesity (lowering SHBG): – Lower total testosterone– Normal free or bioavailable testosterone
• Aging (increasing SHBG):– Higher total – Lower bioavailable testosterone.
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“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
LH/FSH
• LH: primary VS secondary • FSH: reflect spermatogenesis
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
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
CONTRAINDICATIONS TO TRT:
• Prostate CA• Breast CA• Untreated prolactinoma
RELATIVE CONTRAINDICATIONS:
• PSA >4.0 or accelerated >0.75• Hb/Hc> 18/55• Sleep Apnea• Cardiac, Hepatic, Renal Dz
POTENTIAL RISKS
1. Bladder outlet symptoms due to increase in prostate volume
2. Stimulation of growth in previously undiagnosed prostate cancer
3. Edema in patients with preexisting dz 4. Gynecomastia & Weight gain
5. Erythrocytosis (monitor H/H)6. Precipitation or worsening of sleep apnea7. Acne8. Decreased sperm production9. CVD??: Adverse lipid: LDL, HDL
DRUG INTERACTIONS:
• Diabetic Medications• Propranolol• Oxyphenbutazone
TESTOSTERONE DELIVERY SYSTEMS
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TESTOSTERONE DELIVERY SYSTEMS
• Trans-dermal: consistent, ? adequate T level, no First-pass effect through the liver1. Gels2. Patches3. Pellets4. Buccal
• IM• Orals: xxxxx
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 bathing
Products :
-AndroGel® 5-10 g per day
-Testim™ 5-10 g per day (50 mg testosterone)
Advantages : Once-a-day dosing Normalizes testosterone in 24 hrs Convenient application sites More potent & Less skin irritation than patches
Disadvantages : Potential for transfer to partner ?? pregnant or child More expensive than other forms of therapyMay elevate ESTROGENS
Testosterone Gels
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
Testosterone Patches: Androderm®5 mg per day
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.
Dose: mucoadhesive table (30 mg) bid
Advantages : Consistent T level
Disadvantages :Local irritationGingivitisBitter taste BID use
Buccal Testosterone
• Pellets are slowly released pure T crystals: 100 mg• Local anesthetic , 6-10 pellets are introduced by a
needle into 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
Testosterone pellets: Testopel
• Testosterone propionate in oil • Testosterone enanthate in oil
(Delatestryl)• Testosterone cypionate in oil (Depotest)
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Testosterone Injections
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.
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.
Injection doses
• Testosterone Cypionate IM in oil (Depotest): 100 mg QW
--double dose “front load”• Glutes: 22 ga 1 ½” • Thighs: 25 ga 1”
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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.
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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)
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
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
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FOLLOW-UP LABS (con’t)
• Once dose is titrated:
--q 6 months or yearly
--Include PSA
--Perform Digital Rectal Exam (DRE)
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
Testicular atrophy nightmare!!!!!!!!
• 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.
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CRISLER HCG PROTOCOLmodified
• -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
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
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•Do we have other adjunctive for
TRT!!!!!!
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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
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Clomiphene: SERM’s
• -- Racemic mixture (antagonist AND agonist)
-- May bring untoward visual effects -- May bring untoward emotional
effects
Raloxifen : SERM’s
• --Great estrogen antagonism --MUCH more expensive
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DHEA
• -- Effect??
• --25mg BID --100mg QD can elevate E1
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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
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®
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ANABOLIC STEROIDS
O
O
OH
HH
H
CH3
H
OXANDROLONE (OXANDRIN)
OH
HH
H
N
O
C CH
DANAZOL (DANOCRINE)
Also classified as 17-alpha alkylated androgens
Long list of SEs
DANAZOLE
• Non aromatizable androgen• 300 -600 mg/d• Used in gynecomastia ??• Weight gain • Acne
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Androgenic steroids Abuse
Young Athletes
Superphysiologic doses
• Suppress LH/FSH • Inhibits spermatogenesis• Testicular atrophy• Lower HDL• Testosterone / epitestosterone < 6
Symptoms
• Gynecomastia• Acne• Small testicular volume
WHAT IS THE FUTURE OF TRT?
• Elevating T to healthy, happy levels• Estrogen metabolism• Actions at the androgen, estrogen
receptors• Restoring endocrine pathways
دعوانا آخر و
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لله الحمد أنالعالمين رب
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