So What About Low T?

1
So What About Low T?

• Louis B. Kasunic, DO, FACOFP
• Castle Rock Family Physicians
• May 3, 2014

2
For Your Consideration

• A few philosophical questions
• A discussion of condition prevalence
• Some screening suggestions
• A brief review of testosterone physiology
• Patient evaluation suggestions
• Treatment options
• Patient follow up suggestions

3
Testosterone
4
Testosterone Deficiency

• Why should we care?
• Andropause Medical condition or normal male
  aging? Is this a pharmaceutical industry
  construct or a valid male health issue?
• Have you ever asked yourself this question about
  female hormone replacement therapy?

5
Low Testosterone Review Prevalence

• Low testosterone (T) in men is a common condition
  which often goes undiagnosed
• Prevalence of low T in men over 45 years old in
  the U.S. estimated at about 40
• In studies of men with type 2 diabetes, about 50
  have low T

Mulligan T, et al. Int J Clin Pract.
200660(7)762-9. Dhindsa S, et al. J Clin
Endocrinol Metab. 2004895462-8.
6
Low T complications

• Increased body fat to lean body mass ratio
• Decreased bone mass and bone mineral density
• Decreased erectile function / sexual performance
• Anemia
• Decreased strength / vigor/ vitality
• Decreased libido
• Mood changes with an increase in depression
• Decreased Leydig cell counts
• Increased SHBG and lower Free (active) T

7
Hypogonadism in Males

• 2165 patients (45-96 yrs mean age 60 yrs) Pt
  age yrs Low T 45-54 34 55-64 40 65-74
  40 75-84 45 gt85 50
• Prevalence increases with aging

8
Conditions associated with low T

• Type II DM
• Obesity
• Chronic opiate use
• COPD
• Cancer
• HIV

• Rheumatoid Arthritis
• Corticosteroid use
• Chronic liver disease
• Chronic Renal disease

9
Diabetes and low T

• Dhindsa studies DM type II 33 low free T
• 44 low total TBMI correlates inversely with
  FT and TT inversely with LH and FSH
• Similar data demonstrated for insulin resistant
  and metabolic syndrome males

10
Hypogonadism, Obesity and Insulin Resistance

Insulin Sensitivity
Body Fat
T
E2
Aromatase
Altered Leydig cell function
E2 Estradiol
Kapoor et al. Clin Endocrinol 200563239-250.
Pitteloud et al. JCEM 2005902636-2641. Dhindsa
et al. Diabetes Care 2007301860-2.
11
Comorbidities in Hypogonadal Men(HIM Study)
70 60 50 40 30 20 10 0
Hypertension Hyperlipidemia Diabetes Obesity
Asthma/COPD
OR 1.84 (1.53, 2.22)
OR 1.47 (1.23, 1.76)
OR 2.09 (1.70, 2.58)
OR 2.38 (1.93, 2.93)
OR 1.40 (1.04, 1.86)
Hypogonadal
Eugonadal
p lt0.001 p 0.013 Mulligan et al. Int J
Clin Pract 200660(7)762-9.
12
Screening for Low T

• The Androgen Deficiency in Aging Males (ADAM)
  Questionnaire
• Do you have a decrease in libido (sex drive)?
• Do you have a lack of energy?
• Do you have a decrease in strength and/or
  endurance?
• Have you lost height?
• Have you noticed a decreased enjoyment of life?
• Are you sad and/or grumpy?
• Are your erections less strong?
• Have you noticed a recent deterioration in your
  ability to play sports?
• Are you falling asleep after dinner?
• Has there been a recent deterioration in your
  work performance?

If the answer is yes to question 1 or 7, or at
least three of the other questions, low
testosterone may be present.
Morley J et al. Metabolism 2000491239-42.
13
Case Presentation

• Past Medical History
• Type 2 diabetes
• No neuropathy
• Occasional ED
• No retinopathy
• Hypertension
• COPD

• History of Present Illness
• 50 year-old male
• ED, loss of libido x 2 years
• Poor recovery with exercise
• Always tired
• Recent belly fat weight gain
• Tobacco use 255,000 lifetime cigs

14
Case Presentation

• Medications
• metformin
• ipatroprium
• simvastatin
• valsartan
• aspirin

• Physical Exam
• BMI 32 kg/m2
• Waist circumference
• 40 inches
• BP 155/90 mm Hg

• Q. What are the labs you would order?

15
Laboratory Tests
Hgb and Hct Hgb 15 g/dL/ Hct 45
Hemoglobin A1c 8
Lipid Profile TC 250 mg/dL, LDL 179 mg/dL, HDL 37 mg/dL, TG 220 mg/dL, LDL-p 2600
Serum Total Testosterone TT 205 ng/dL, FT 5.0 ng/dL
CIMT 18 years and soft plaque
TSH 1.5mIU/ml

CMP normal
PSA 1.1 ng/mL
16
Laboratory Tests
Hgb and Hct not repeated
Hemoglobin A1c Not repeated
Lipid profile Not repeated at one week
Serum Total Testosterone (am) TT 195 ng/dL, FT 5.0 ng/dL
FSH and LH FSH 2.9 IU/L, LH 3.5 IU/L
SHBG 22 nmol/L
Serum Prolactin 12 ng/mL
TSH Not repeated
PSA Not repeated
17
Your Diagnosis

• Is the patient hypogonadal?

• Would you consider treatment with appropriate
  testosterone therapy?

18
Testosterone Replacement Therapy
19
Testosterone Replacement Therapy Potential
Benefits

• Normalizing T levels
• Improved libido (? improve performance)
• Improved energy level
• Improved mood, sense of well-being
• Increase in lean body mass and strength
• Decrease in body fat mass
• Improved bone mineral density (effects on
  fracture risk are currently unknown)

Bhasin S, et al. J Clin Endocrinol Metab.
200691(16)1995-2010. Wang C, et al. J Clin
Endocrinol Metab. 2004892085-2098. Petak SM,
et al. AACE Clinical Practice Guidelines.
Endocrine Practice. 20028(6)439-456. Wang C, et
al. J Clin Endocrinol Metab. 2000852839-2853.
20
Testosterone Replacement Therapy Recommended
Dosing and Administration

• Intramuscular
• Testosterone enanthate or cypionate
• 100-200 mg weekly or 200-400 mg every 2 weeks
• Testosterone undecanoate 750mg/3ml Q 10 weeks
• Transdermal Patches (Nonscrotal)
• 4 mg applied nightly for 24 hours
• Transdermal Gels 1
• 5- ? g applied daily
• Buccal Tablets
• 30 mg tablet applied every 12 hours
• Pellets
• 150-450 mg implanted SC every 3-6 months

SC Subcutaneous
Bhasin S, et al. J Clin Endocrinol Metab.
200691(16)1995-2010. Androderm package
insert. Corona, CAWatson Pharma, Inc February
2013 Testopel in Drugs.com
21
Testosterone Formulation Specific Adverse Events

• Intramuscular
• Peaks and valleys in serum T levels
• Fluctuation in mood
• Office visits
• Pain at injection site
• Occasional excessive erythrocytosis
• Pulmonary oil microembolism
• Transdermal Patches
• Skin irritation at application site

• Transdermal Gels
• Risk for transfer
• odor
• Buccal Tablets
• Gum irritation
• Taste alteration
• Pellets
• Infection
• Expulsion of pellet

.
22
Testosterone and CV Risk

• Vigen et al Jama 2013
• 8709 T deficient men
• 1223 T therapy
• 20 untreated and 26 treated men death/MI/stroke
• HR 1.29

• Finkle et al. PLoSOne 2014
• Retrospective look 56K men T and 167K treated
  PDE5 inhibitor
• T 1.36 nonfatal MI
• gt65yoa 2.19
• lt65 w cv dx 2.90
• PDE5 1.1, 1.15, 1.4

23
Testosterone and CV Risk

• Xu et al. BMC Med 2013Meta analysis randomized
  placebo controlled trials of T therapy
  Odds ratio (OR) CV event 1.54
• Analysis by funding source Pharmaceutical
  funding OR 0.89 Not funded by pharma OR
  2.06

24
Other therapeutic considerations

• Cost Insurance coverage
• Testosterone therapy female HRT
• Controlled substance Testosterone
  yes female HRT no
• PO administration Testosterone no female
  HRT yes

25
Testosterone Enanthate 250 mg Administered IM
Every 3 Weeks
1400
Upper limit of normal range
1200
1000
800
Serum testosteroneconcentration (ng/dL)
600
400
200
Lower limit of normal range
0
0
3
15
6
9
12
Time (weeks)
IM Intramuscular
26
Testosterone Gel Mean Steady State Concentrations
on Day 30
1400
10 g T-Gel
5 g T-Gel
1200
Upper limit of normal range
1000
800
Testosterone concentration (ng/dL)
600
400
Lower limit of normal range
200
0
0 4 8 12 16 20 24
Time (hours) after application
AndroGel prescribing information. Marietta,
GA Solvay Pharmaceuticals, Inc. December 2007.
27
Testosterone Replacement Therapy Potential Risks

• Stimulation of growth in previously undiagnosed
  prostate cancer
• Increased risk of bladder outlet symptoms due to
  increase in prostate volume
• Erythrocytosis
• Worsening of sleep apnea
• Acne
• Decreased sperm production
• Edema in patients with preexisting cardiac,
  renal, or hepatic disease
• Pulmonary Oil Microembolism

Hijazi R, Cunningham G. Annu Rev Med.
200556117-137 Bhasin S, et al. J Clin
Endocrinol Metab. 200691(16)1995-2010
28
Testosterone Replacement Therapy Precautions or
Contraindications

• Known or suspected prostate cancer
• Breast cancer
• Use in pregnant or breastfeeding women
• Unexplained PSA elevation
• Hematocrit gt50
• Severe BPH symptoms
• AUA prostate symptom score gt19 (severe)
• Unstable severe heart failure
• Untreated prolactinoma
• Untreated sleep apnea

PSA Prostate Specific Antigen, BPH Benign
Prostatic Hyperplasia, AUA American Urological
Association Bhasin S, et al. J Clin Endocrinol
Metab. 200691(16)1995-2010. Petak SM, et al.
AACE Clinical Practice Guidelines. Endocrine
Practice 2002 8(6) 439-456.
29
Prostate and Testosterone

• Wolffian and mullerian ducts in utero prostate
  or uterus
• Unopposed E2 on adult uterus inc risk of
  cancer -opposed by progesterone
• Unopposed E2 on adult prostate inc risk of
  cancer -opposed by testosterone
• If high T leads to prostate cancer (never proven)
  then why dont 18 yr old males have prostate
  cancer?

30
Monitoring Suggestions
Evaluate patient after testosterone initiation,
then annually for response to treatment and
symptom profile
Baseline 2-6 Months Annually
T Concentrations ? ? ?
Hematocrit ? ? ?
PSA and DRE ? ? In accordance with your prostate cancer screening protocol
BMD ? After 2 years of T therapy in hypogonadal men with osteoporosis or osteopenia
DRE Digital Rectal Exam BMD Bone Mineral
Density

31
Reasons to Obtain Urology Consultation

• Serum PSA gt4 ng/ml
• Increase in serum PSA gt1.4 ng/mL within any 12
  month period of T replacement
• PSA velocity of gt0.4 ng/mL/yr
• Only applicable if PSA data are available for a
  period gt2 years
• Prostatic abnormality on digital rectal exam
• If AUA prostate symptom score gt19

32
In Summary

• Low Testosterone is more common with increasing
  age and a number of other common medical
  conditions. It is characterized by serum
  concentrations below 300ng/ml
• With symptoms/ signs which may include changes in
  energy, libido, mood, body fat/lean mass ratio
  and bone mineral density
• Replacement therapy can increase T levels to
  normal ranges which may improve symptoms
• Multiple testosterone formulations are available
• Testosterone replacement / supplementation may be
  indicated based upon patient and physician
  preference
• Testosterone concentrations, PSA levels, DRE,
  hematocrit, AUA score, and BMD should be
  monitored during replacement supplementation
  therapy

33
Questions?

• Pearls?