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Testosterone

TestosteroneDecoding Some of the Controversies

Tarek Pacha DO

Hypogonadism: Types1. Primary Testicular malfunction (congenital, drugs, trauma)Elevated LH2. SecondaryHypothalamic dysfunction (mass)Pituitary dysfunction (mass)Low or normal LH3. ADAM (androgen decline of the aging man)Normal LH

Primary HypogonadismKlinefelters Syndrome (most common)Chromosome abnormalitiesXX maleXYY syndromeNoonan SyndromeLeydig Cell DysfunctionMyotonic Dystrophy

Dont read the whole list. Just let audience understand that it exits. Dont spend much time on this slide3

SecondaryChemotherapeutic drugsAlcoholMedsRadiationOrchitis (Mumps)HIVTesticular traumaTorsionPituitary tumorSystemic Dx (Diabetes, Metabolic syndrome, renal failure)agingUnknown

This is an important slide: Take a few moments to highlight these risk factors for acquired hypogonadism. 4

AdamAndrogen decline in the aging maleA.K.A AndropauseAsymptomatic decrease in Testosterone as men ageSee next slideAs men age SHBG (sex hormone binding globulin) increases decreases bioavailable T

Point out that the decline begins around 40 yo and will decline until death6

Epidemiology10%-20%Low T associated withMetabolic SyndromeObesityType 11 DMRenal insufficiency (high prolactinlow T)Opioid abuseSteroid useDecreased Survival*

*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;20:613-6207

HistoryCryptorchidismScrotal or inguinal surgeryPituitary surgery/radiationPrior fertilityDevelopment of secondary sex characteristicsRenal or hepatic failureChemoPrior use of anabolic steroidsStress Cortisol steal phenomenon*

Men under heavy stress will have lower testosterone because will preferentially make cortisol instead of androgen (Cortisol will steal the precursors of androgens)8

Symptoms Pre-PubertalOutside the scope of this talkPost-PubertalDecreased Libido Diminished ErectionsFatigueFoggy thinkingMood disturbanceNote: Ask about visual disturbances (rule out Pituitary tumor)

Valuable Screening tool

AMS (Aging Male survey)More rigorous17 questions with 5 point scale

ADAM survey easier

Physical ExamBodily hairHabitusGynecomastiaGenital examSize of penisSize and presence of testiclesProstate exam

Clinical ChallengeSymptoms can be non-specific!Is it another condition??Thyroid?anemia?Depression?normal agingMen with asymptomatic TestosteroneUp to 25%*!!!

*Araujo, Andre. Prevalence of Symptomatic Androgen Deficiency in Men. JCEM July 201313

The GoalCorrectly identify meaningful low testosterone and then supplement to alleviate symptoms and enhance quality of life.

Venn Diagram

ADAMLow TT Therapy Helps

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 dont have any benefit from T therapy even if they are hypogonadal. 15

Testosterone in the bloodTestosteroneBound *SHBG(45%)Free(2-3%)Bound Albumin(50%)Bioavailable (active)Not bioavailableIncrease when you agedec T*Sex Hormone Binding Globulin

Original slide 16

Lab considerationsChallengingLarge rangeFactors that affect levelsTime of day (better to check in AM)SeasonalAgeEthnicityConcomitant illness Meds (Opiate and glucocorticoids) Any condition that affects SHBG (age, meds, illness)

LabsTotal TestosteroneCollect Total Testosterone before 11 AMDiurnal: Highest level in the AM Two Measurements1 week apartFree TestosteroneUseful if Total T is equivocalCalculated ValueBased on Albumin and SHBG400 No treatment500, I will not supplementIf patient is symptomatic and no other cause is identified I will raise the level to above 500 and then re-evaluate.

Scenario 5Pt with history of known hx prostate cancer. Last 3 PSAs were 0T is 150Symptomatic

Would you supplement?

Answer 5Yes!Previously, the answer was NoSaturation levelTestosterone does fuel prostate cancer growthTo a saturation pointAny level past the saturation point does not affect malignancy potentialTRT does not appear to increase your risk for prostate cancerLow T is associated with more aggressive cancer (higher Gleason scores)*Caution is always prudent

*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;185:1256-6032

Monitoring your patient on TRT1st Labs @ 3 monthsQuarterly for first yearQ6 months for 2nd yearAnnually if no problemsTotal TPSAH+HNote: no need to check liver enzymes (no oral forms available)

How to deal with abnormal labs during TRTPSA20% increase or increases >1.4 consider prostate bxPSA velocity If PSA .35/yr (need 3 PSA values)If PSA >4: an increase > .75/yr (need 3 PSA values)Consider prostate bx

How to deal with abnormal labs during TRTHematocrit/Hgb>55% / 18Donate blood q3-6 monthsReduce doseTemporarily Stop supplementation

How long to wait for efficacy?Libido usually improves 1st around 3 monthsIf there is not any improvement in 6 monthsLook for other causeUse ADAM or AMS survey to assess response

What are the benefits of TRTImprove waist circumference*Fasting glucose*Improved Insulin resistanceBMI*Biochemical surrogate markers for atherosclerosis*Improved erectionsBetter response to PDE5i after 6 months of therapy**

*J Sex Med. 2010;7:3495-503 ** J sex Med. 2011; 8 (11):3204-1337

Side Effects of TRTIrritabilityGynecomastiaWorsening lower urinary track symptomsPolycythemiaNew or worsening sleep apnea (Data is weak)

Is TRT a cardiovascular risk?No!JAMA article (JAMA 2014; 311:961)Reported more CV events in the T groupAuthors acknowledged that they miscategorized more than 1000 pts. Contamination of one arm in study: They included 100 womenUsed complex statistics that manipulated more than 50 variablesMultiple societies have written to JAMA to remove the article for multiple methodological flaws.

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 CHFThere 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?

I can get you the references of these studies. Mention just to support your opinion. *AM J Med 2011; 124:57840

Testosterone TrialRCT Double blinded (sponsored by National institute of aging)Start: Nov 2009 End: June 2015Goal:Will 1 year of TRT in men with hypogonadism lead to improvement in:Walking speedSexual activityVitality scaleVerbal memory testCorrection of anemiaSub trialCardiovascular trial to evaluate cardiovascular riskBone trial to show an increase in Bone Muscular Density

References:Androgen Deficiency and Testosterone Replacement. Springer 2013Urological Mens Health. Springer 2012Testosterone Deficiency in Men. Jones, Hugh. Oxford 2011