testosterone final
- 1. TESTOSTERONE Decoding Some of the Controversies Tarek Pacha DO
- 2. HYPOGONADISM: TYPES 1. Primary Testicular malfunction (congenital, drugs, trauma) Elevated LH 2. Secondary Hypothalamic dysfunction (mass) Pituitary dysfunction (mass) Low or normal LH 3. ADAM (androgen decline of the aging man) Normal LH
- 3. PRIMARY HYPOGONADISM Klinefelter’s Syndrome (most common) Chromosome abnormalities XX male XYY syndrome Noonan Syndrome Leydig Cell Dysfunction Myotonic Dystrophy
- 4. SECONDARY Chemotherapeutic drugs Alcohol Meds Radiation Orchitis (Mumps) HIV Testicular trauma Torsion Pituitary tumor Systemic Dx (Diabetes, Metabolic syndrome, renal failure) aging Unknown
- 5. ADAM Androgen decline in the aging male A.K.A Andropause Asymptomatic decrease in Testosterone as men age See next slide As men age SHBG (sex hormone binding globulin) increases decreases bioavailable T
- 7. EPIDEMIOLOGY 10%-20% Low T associated with Metabolic Syndrome Obesity Type 11 DM Renal insufficiency (high prolactinlow T) Opioid abuse Steroid use Decreased Survival*
- 8. HISTORY Cryptorchidism Scrotal or inguinal surgery Pituitary surgery/radiation Prior fertility Development of secondary sex characteristics Renal or hepatic failure Chemo Prior use of anabolic steroids Stress Cortisol steal phenomenon*
- 9. SYMPTOMS Pre-Pubertal Outside the scope of this talk Post-Pubertal Decreased Libido Diminished Erections Fatigue Foggy thinking Mood disturbance Note: Ask about visual disturbances (rule out Pituitary tumor)
- 11. AMS (AGING MALE SURVEY) More rigorous 17 questions with 5 point scale ADAM survey easier
- 12. PHYSICAL EXAM Bodily hair Habitus Gynecomastia Genital exam Size of penis Size and presence of testicles Prostate exam
- 13. CLINICAL CHALLENGE Symptoms can be non-specific! Is it another condition? ?Thyroid ?anemia ?Depression ?normal aging Men with asymptomatic Testosterone Up to 25%*!!!
- 14. THE GOAL Correctly identify meaningful low testosterone and then supplement to alleviate symptoms and enhance quality of life.
- 15. VENN DIAGRAM ADA M Low TT Therapy Helps
- 16. TESTOSTERONE IN THE BLOOD Testosterone Bound *SHB G (45%) Free (2-3%) Bound Albumin (50%) Bioavailable (active) 1. Not bioavailable 2. Increase when you agedec T*Sex Hormone Binding Globulin
- 17. LAB CONSIDERATIONS Challenging Large range Factors that affect levels Time of day (better to check in AM) Seasonal Age Ethnicity Concomitant illness Meds (Opiate and glucocorticoids) Any condition that affects SHBG (age, meds, illness)
- 18. LABS Total Testosterone Collect Total Testosterone before 11 AM Diurnal: Highest level in the AM Two Measurements 1 week apart Free Testosterone Useful if Total T is equivocal Calculated Value Based on Albumin and SHBG <65 pg/ml (consider treatment)
- 19. LABS LH Elevated: Primary Decreased or Normal: Secondary Note: FSH not usually needed. Prolactin Rule out pituitary adenoma Other labs for differential TSH CBC Etc.
- 20. TESTOSTERONE RANGE Total T: No Consensus! 300-1200 (depends on lab) General guidelines >400 No treatment <230 no need to obtain free T. Treat 230-399 Obtain Free T Treat based on symptoms
- 21. CONTRAINDICATIONS TO TESTOSTERONE REPLACEMENT THERAPY (TRT) Elevated PSA Untreated prostate cancer Metastatic prostate cancer Biochemical recurrence (PSA elevation after definitive tx) Uncontrolled CHF Polycythemia Men seeking fertility
- 22. QUESTIONS??? CONTROVERSY! Does T supplementation increase cardiovascular risk? Should I give Testosterone in a patient with a history of prostate cancer? Is there a threshold T level? Are thresholds unique? Do I treat patients with “low T” that are not symptomatic? Do I treat a patient with normal Total T, but Low Free T? What do I do when I give Testosterone and there is no improvement?
- 23. SCENARIO 1 Aging male Low T Asymptomatic What do you think?
- 24. ANSWER 1 NO Supplementation!
- 25. SCENARIO 2 Aging male Low normal or borderline T Symptomatic What do you think?
- 26. ANSWER 2 Yes Supplement for 3-6 months then re-evaluate Don’t forget to check other conditions that mimic Low T
- 27. SCENARIO 3 Aging male normal Total T low free T Symptomatic What do you think?
- 28. ANSWER 3 Treat and reevaluate in 3-6 months Don’t forget to check other conditions that mimic Low T If the above patient was asymptomatic don’t treat
- 29. SCENARIO 4 Aging Male Patient A: Normal (375) Patient B: Normal (550) Symptomatic All other labs and work up negative What do you think?
- 30. ANSWER 4 Controversial! Is there a threshold? Don’t know Do Thresholds differ among patients? Don’t know Personal Experience (not supported in the literature) If >500, I will not supplement If patient is symptomatic and no other cause is identified I will raise the level to above 500 and then re-evaluate.
- 31. SCENARIO 5 Pt with history of known hx prostate cancer. Last 3 PSAs were 0 T is 150 Symptomatic Would you supplement?
- 32. ANSWER 5 Yes! Previously, the answer was No Saturation level Testosterone does fuel prostate cancer growth To a saturation point Any level past the saturation point does not affect malignancy potential TRT does not appear to increase your risk for prostate cancer Low T is associated with more aggressive cancer (higher Gleason scores)* Caution is always prudent
- 33. MONITORING YOUR PATIENT ON TRT 1st Labs @ 3 months Quarterly for first year Q6 months for 2nd year Annually if no problems Total T PSA H+H Note: no need to check liver enzymes (no oral forms available)
- 34. HOW TO DEAL WITH ABNORMAL LABS DURING TRT PSA <20% increase is expected >20% increase or increases >1.4 consider prostate bx PSA velocity If PSA <4: an increase > .35/yr (need 3 PSA values) If PSA >4: an increase > .75/yr (need 3 PSA values) Consider prostate bx
- 35. HOW TO DEAL WITH ABNORMAL LABS DURING TRT Hematocrit/Hgb >55% / 18 Donate blood q3-6 months Reduce dose Temporarily Stop supplementation
- 36. HOW LONG TO WAIT FOR EFFICACY? Libido usually improves 1st around 3 months If there is not any improvement in 6 months Look for other cause Use ADAM or AMS survey to assess response
- 37. WHAT ARE THE BENEFITS OF TRT Improve waist circumference* Fasting glucose* Improved Insulin resistance BMI* Biochemical surrogate markers for atherosclerosis* Improved erections Better response to PDE5i after 6 months of therapy**
- 38. SIDE EFFECTS OF TRT Irritability Gynecomastia Worsening lower urinary track symptoms Polycythemia New or worsening sleep apnea (Data is weak)
- 39. IS TRT A CARDIOVASCULAR RISK? No! JAMA article (JAMA 2014; 311:961) Reported more CV events in the T group Authors acknowledged that they miscategorized more than 1000 pts. Contamination of one arm in study: They included 100 women Used complex statistics that manipulated more than 50 variables Multiple societies have written to JAMA to remove the article for multiple methodological flaws.
- 40. CONT. 9 of 11 longitudinal studies shown: Increased mortality in patients with low T *Men with exercise induced angina had longer angina-free exercise tolerance with TRT + improved function in pts with CHF There is no convincing proof that TRT increases cardiovascular risk! Question: If there are so many benefits for T supplementation, what about asymptomatic men with Low T?
- 41. TESTOSTERONE TRIAL RCT Double blinded (sponsored by National institute of aging) Start: Nov 2009 End: June 2015 Goal: Will 1 year of TRT in men with hypogonadism lead to improvement in: Walking speed Sexual activity Vitality scale Verbal memory test Correction of anemia Sub trial Cardiovascular trial to evaluate cardiovascular risk Bone trial to show an increase in Bone Muscular Density
- 42. REFERENCES: Androgen Deficiency and Testosterone Replacement. Springer 2013 Urological Men’s Health. Springer 2012 Testosterone Deficiency in Men. Jones, Hugh. Oxford 2011
Editor's Notes
- #4: Don’t read the whole list. Just let audience understand that it exits. Don’t spend much time on this slide
- #5: This is an important slide: Take a few moments to highlight these risk factors for acquired hypogonadism.
- #7: Point out that the decline begins around 40 yo and will decline until death
- #8: *Studies upon request: 1.) Eur Heart J. 2010; 31: 1494-501. 2.) J Clin Endocrinol Metab. 2011; 96 (10): 3007-19. 3. J AM Soc Nephrol. 2009;20:613-620
- #9: Men under heavy stress will have lower testosterone because will preferentially make cortisol instead of androgen (Cortisol will steal the precursors of androgens)
- #14: *Araujo, Andre. Prevalence of Symptomatic Androgen Deficiency in Men. JCEM July 2013
- #16: I made this slide: I proud of it ! It just shows that only a select patients with Low T and ADAM actually benefit from T therapy. Thus, many men don’t have any benefit from T therapy even if they are hypogonadal.
- #17: Original slide
- #19: *Crucial to rule out Pituitary tumor or hyperplasia
- #33: *J Urol. 2011; 186; 1400-1405. There is another study in which men on AS with low T were receiving T and there was not evidence of local progression or mets. I probably would not mention this to this group of people. Probably fair game to group of Urologist (see J Urol. 2011;185:1256-60
- #38: *J Sex Med. 2010;7:3495-503 ** J sex Med. 2011; 8 (11):3204-13
- #41: I can get you the references of these studies. Mention just to support your opinion. *AM J Med 2011; 124:578