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.
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
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?
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
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)
SHBG• Obesity (lowering SHBG): – Lower total testosterone – Normal free or bioavailable testosterone• Aging (increasing SHBG): – Higher total – Lower bioavailable testosterone.
―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
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
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)
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
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
Mean Steady-State Testosterone Concentrations in Patients Receiving AndroGel® Day 90Swerdloff RS, Wang C, Cunningham G, et al. JCEM. 2000;85:4500-4510.
Buccal TestosteroneDose: mucoadhesive table (30 mg) bidAdvantages :Consistent T levelDisadvantages :Local irritationGingivitisBitter tasteBID use
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
Testosterone Injections• Testosterone propionate in oil• Testosterone enanthate in oil (Delatestryl)• Testosterone cypionate in oil (Depotest)
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‖
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.
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
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
• 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.
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
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
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
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
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®
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