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 prolactinlow 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)

10. VALUABLE SCREENING TOOL

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 agedec
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