MEN’S HEALTHUNDERSTANDING LOW TESTOSTERONE 

bjectives:Discuss the importance of Testosterone in Men’s Health

Discuss the prevalence of Hypogonadism in various patient populations

dentify the clinical manifestations of Hypogonadism

Assess the barriers to diagnosis and management of Hypogonad

Review the treatment options for Hypogonadism

Why should YOU be concerned? What can YOU do to increase awareness and comfort in Men’s Health?

Characterized by:Deficiency in serum testosterone (T) levels ± changes in receptor sensitivitto androgens

Also known as:Testosterone Deficiency Syndrome (TDS)Late-onset Hypogonadism (LOH)Low Testosterone (Low T)

Formerly termed: Andropause

ypogonadism

YPOGONADISM:evalencenical Manifestations morbidities

What Percentage of Canadian Men between the Agof 40-82 have Low T?

A. 5‐10%

B. 10‐15%

C. 15‐20%

D. 20-25%

Crude prevalence rate in Canada: 25% of men aged 40 to 82 years are biochemically testosteronedeficient.

<10% of affected men receive T therapy

evalence of Hypogonadism

evalence of Hypogonadism: HIM Study 1

ck MF et al. Int J Clin Pract. 2006; 60:762-9.

nical Manifestations 1,2

Decreased libido Decreased vitality Fatigue Mood changes Insomnia Anemia Delayed ejaculation Flushes Erectile dysfunction Decreased muscle mass Increased visceral body fat Testicular atrophy Weakness Osteopenia/osteoporosis Loss of facial, axillary and pubic hair

Mild

Severe

Manifestations may present alone or in combinationClin Endocrinol Metab. 2004; 89:4789-4796.

t al. J Clin Endocrinol Metab. 2006;91:4335-4343.

nical Conditions Associated with Testosterone iciency 1,2

Type 2 diabetes mellitus

Metabolic syndrome

Chronic obstructive pulmonary disease

Osteoporosis or low trauma fracture at a young age 

Treatment with opioids, glucocorticoids or ketoconazole

End‐stage renal disease and maintenance hemodialysis

Infertility

. J Clin Endocrinol Metab. 2006;91:1995-2010.al. CUAJ. 2010;4:268-274.

Recommendation to screen in new Canadian Diabetes G

with these clinical conditions have high prevalence of low testosterone therefore measurement of testostmended

nadian Diabetes Association Guidelines (CDA) 201

YPOGONADISM:sessment & Diagnosis

sessment

valuate patient history and symptoms

omplete Androgen Deficiency in Aging Males (ADAM) uestionnaire

rder a serum Testosterone test

pogonadism Symptoms Cluster

Decreased lean bodymass, increased

sceral fat, decreasedBMD,decreased

body hair

Changes in mood, decreases in intellectual

activity, cognitive functions,fatigue, depressed mood

and irritability

Sleep disturbancesLibido &

erectile quality andfrequency

erdloff R, Behre HM et al. The Aging Male 2005;8(2):56-8.

AM Questionnaire1

ositive answer represents Yes to questions 1 or 7, or any 3 other questi

al. Metabolism. 2000;49:1239-1242.

1. Do you have a decrease in libido (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?6. Are you sad and/or grumpy?7. Are your erections less strong?8. Have you noticed a recent deterioration in your ability to play sports?9. Are you falling asleep after dinner?10.Has there been a recent deterioration in your work performance?

S  NO□□□□□□□□□□

rms of Circulating Testosterone

ty:  SHBG

m low T with either cFT or BT

ty:  SHBG

m low T with either cFT or BT

Slide 15

A5 Title is 40pt and not all capitalizedThere is a shade on the green box below - reflection of the Confirm low T with either cFT or BTPlease capitalize Low TAuthor, 3/25/2013

easurement Tests For Testosterone (T)

Measured Bioavailable Testosterone (BT) is the gold standard Ammonium sulphate precipitation correlates well with symptoms of TDS 1

f measured BT is unavailable or unaffordable, acceptable alternatives are 2,3: Total Testosterone (TT) or Calculated free T (cFT) or Calculated bioavailable T (cBT) Free calculator for cFT and cBT4: http://www.issam.ch/freetesto.htm

et al. J Clin Endocrinol Metab. 2007;92:405-413.A, et al. J Clin Endocrinol Metab. 1999;84:3666-3672.et al. CUAJ. 2010;4:268-274.l Society for The Study of the Aging Male. Free & Bioavailable Testosterone calculator. http://www.issam.ch/freetesto.htm. Accessed March 29, 2010.

stosterone Deficiency Syndrome (TDS): Diagnosticaluation

Karyotype [Klinefeltersyndrome]

Prolactin, iron, other pituitaryhormones, MRI [under certain

circumstances]

Low T, high LH+FSH (1°) Normal T, LH+FSH

Confirmed low T [e.g. Total T <9.8‐10.4 nmol/L; or cFT or         BT <normal (e.g. free T <0.17‐0.31 nmol/L, BT < 4 nmol/L)]

Morning Total T

Low T

History and physical (symptoms and signs)

Exclude reversible illness, drugs, nutritional deficiencyRepeat T [use cFT or BT If suspect altered SHBG)

LH+FSH SFA (if fertility issue)

Low T, low or normal LH+FSH (2°)

Normal T

Follow‐up

<9.8-10.4 nmol/L

asin S et al. J Clin Endocrinol Metab 2010; 95:2536-2559.

alues vary between laboratories

No equipment standardization

RecommendationsConsistently employ the same local laboratoryAchieve awareness of: Accuracy Precision Definition of normal values

t-Off Values For Normal T

WHAT IF THE PATIENT HAS SYMPTOMS BUT ISLOW OR BORDERLINE?

epeat TPlus, measures of:

SHBGLuteinizing hormone (LH), Follicle-stimulating (FSH)Prolactin

Other tests/serum markers that may be included:Complete blood count (CBC)FerritinThyroid-stimulating hormone (TSH)Prostate-specific antigen (PSA)Digital rectal exam (DRE)

Consider a 3 month trial if patient is low normal with symptoms

w/Borderline T

TREATMENT •MONITORING • SAFETY 

teria for Treatment

Signs or symptoms

Biochemical evidence

Diagnosis

anced:erall health/survivalengthual desire/Erectile functionrgyotional well‐beingy improve some symptoms of MetSgnitionne mineral densitycemic controldiovascular health

uced:dy fat

umented Benefits of Treatment

oals Symptom improvementAchievement of physiological T levels

everal safe and effective formulations available

tosterone Replacement Therapy (TRT)

osterone Formulations in Canadaame Trade Name Dosage Advantage(s)/

Disadvantage(s)

cular Injections - Supply issues

e cypionate Depo-testosterone1 200 mg every 2 weeks (400 mg max per month)

• Effective• Long-acting• Supraphysiologic T• Waning effect (2-3 weeks)e enanthate Delatestryl2 100-400 mg every 1-4 weeks

cations – Generic formulations available

e undecanoate Andriol3pms-Testosterone4 120-160 mg daily divided in 2 dosesa

• Convenient • Absorption issues• Supraphysiologic DHT

mals

e patch Androderm5 2.5 or 5 mg patch applied daily• Consistent T levels • Visibility• Significant skin reactions

e gels AndroGel6Testim7 5-10 g daily

• Consistent T levels• Minor skin reactions• Secondary exposure

e solution Axiron 60 mg daily•Consistent T levels• Minor skin reactions• Secondary exposure

in Appendix A

tosterone Blood Level According to the Modeministration

IM Injection or sc q 2 weeksthe day before the injection

Skin patch q 24 hoursmeasured any time

Gel q 24 hoursmeasured any time

e Effect of Food on Absorption of Testosteronedecanoate 1

onograph: Andriol (testosterone undecanoate capsules) 40 mg. Kirkland, Québec: Schering-Plough Canada Inc.; 2008.

osterone Undecanoate should be taken with a normal meal or breakfast to eve proper T levels

al. CUAJ. 2010;4:268-274.

Duration of Treatment (months)

Symptom

Improvem

ent

0 3 6 12

Enhanced libido

Improved emotional well-being

Increased energy

Reduced ED

Increased strength

Enhanced BMD

Improved cognition

Enhanced cardiovascular health

Decreased body fat

Improvement in some components of MetS

olic Syndrome

0 3 6 12

eline of Symptom Improvement1

e Effects of Testosterone Formulations

Reported Side Effects for Testosterone Products 1,2,3,4

ication Site Reaction: Irritation, Redness, Rash High Blood Pressure

e Increased RBC Count

rged Prostate Prolonged or Painful Erection

nge in Mood / Depression Aggression / Aggressive Behaviour

p Disturbances Breast Pain

st Enlargement Weight Gain

Loss / Baldness Dizziness

dache

of testosterone products may have side effects

ng Information: Depo-Testosterone (testosterone cypionate injection USP, Sterile Solution) 100 mg/mL. Kirkland, Québec: Pfizer Canada Inc.; 2007.ng Information: Delatestryl (testosterone enanthate, Solution for Injection) 200 mg/mL. Mississauga, Ontario: Theramed Corporation; 2007.Monograph: Andriol (testosterone undecanoate capsules) 40 mg. Kirkland, Québec: Schering-Plough Canada Inc.; 2008.Monograph: pms-Testosterone (testosterone undecanoate capsules) 40 mg. Montréal, Québec: Pharmascience Inc.; 2009.

on-response may be indicative of:CompliancePoor absorption (oral)Insufficient doseUnsatisfactory formulationSymptoms unrelated to TDS

ED patients who fail T or PDE5i alone:Consider T plus PDE5iong-term lack of response:Consider referral to a specialist (endocrinologist/urologist)

n-Response

aselineTestosterone measurement 1,2

Hematological assessment 1,2

DRE & PSA 1,2

Repeat q 3 months over first year, then annually 1,2

Maintain testosterone in lower to middle range expected in young adults 1,2

nitoring: Recommendations for Follow-Up

, Swerdloff R, Behre HM et al. The Aging Male 2005;8(2):56-8.unningham GR, Hayes FJ et al. J Clin Endocrinol Metab 2006;1995-2010.

uspected or confirmed carcinoma of the prostate or breast1,2

Significant polycythemia (hematocrit>50%)1,2

Untreated sleep apnea1,2

Severe heart failure (eg, class III or IV)1,2

Severe symptoms of lower urinary tract obstruction1,2

Clinical evidence of bladder outflow obstruction1

Undiagnosed prostate nodule or induration2

Unexplained elevation in PSA2

ntraindications to Treatment

E, Swerdloff R, Behre HM et al. The Aging Male 2005;8(2):56-8.unningham GR, Hayes FJ et al. J Clin Endocrinol Metab 2006;1995-2010.

QUESTIONS ABOUT THE PROSTATE?

urrent evidenceno increase in PCa rates in clinical trials of TRT in normal men or men at increased risk for PCa

no relationship of PCa risk with serum testosterone levels

no reduced risk of PCa in men with low testosterone

ostate Safety: Historical Review

aler, A. Euro Urol 2006;50:935-939.

ects of Testosterone on Prostatic Outcomes eta-analysis of 51 testosterone studies

o significant effect on prostate cancer incidence

o significant effect on the need for prostate biopsy

o significant effect on rate of PSA levels > 4 ng/ml or significant crease in PSA during treatment > 1.4 ng/ml above baseline

o significant effect on a composite prostate endpointBalsells M et al. J Clin Endocrinol Metab 2010;95:2560-2575.

nclusiontosterone Deficiency Syndrome (TDS) is a common condition

S has an impact on individuals Quality of Life

yers have an important role to play in educating and increasing areness in Men’s Health

Payers can engage with their employers and create an opportunity for increawareness ▪ Support Health Learning Days in the workplace▪ Increase access to learning - bring in healthcare professionals / screening clinic

the workplace

▪QUESTIONS AND ANSWERS

THANK YOU FOR YOUR PARTICIPATION