Download So What About Low T?

Louis B. Kasunic, DO, FACOFP
Castle Rock Family Physicians
May 3, 2014
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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
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Why should we care?
“Andropause”
Medical condition or normal male aging?
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Is this a pharmaceutical industry construct or
a valid male health issue?
Have you ever asked yourself this question
about female hormone replacement therapy?
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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. 2006;60(7):762-9.
Dhindsa S, et al. J Clin Endocrinol Metab. 2004;89:5462-8.
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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
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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%
>85
50%
Prevalence increases with aging
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Type II DM
Obesity
Chronic opiate use
COPD
Cancer
HIV
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Rheumatoid
Arthritis
Corticosteroid use
Chronic liver
disease
Chronic Renal
disease
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Dhindsa studies DM type II
33% low free T
44% low total T
BMI correlates inversely with FT and TT
inversely with LH and FSH
Similar data demonstrated for insulin resistant
and metabolic syndrome males
Insulin
Sensitivity
Body Fat
Endogenous T
T
E2
Aromatase
Kapoor et al. Clin Endocrinol 2005;63:239-250.
Pitteloud et al. JCEM 2005;90:2636-2641.
Dhindsa et al. Diabetes Care 2007;30:1860-2.
Altered Leydig cell function
E2 = Estradiol
70%
60%
50%
40%
30%
20%
10%
0%
* p <0.001
† p = 0.013
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
Mulligan et al. Int J Clin Pract 2006;60(7):762-9.
Eugonadal
The Androgen Deficiency in Aging Males (ADAM) Questionnaire
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
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 2000;49:1239-42.
History of Present
Illness
Past Medical History
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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
Type 2 diabetes
No neuropathy
Occasional ED
No retinopathy
Hypertension
COPD
13
Medications
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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?
 Hgb and Hct
 Hemoglobin A1c
 Lipid Profile
Hgb 15 g/dL/ Hct 45%
8%
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
 Hgb and Hct
not repeated
 Hemoglobin A1c
Not repeated
 Lipid profile
 Serum Total Testosterone (am)
 FSH and LH
Not repeated at one week
TT 195 ng/dL, FT 5.0 ng/dL
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
Is the patient hypogonadal?
Would you consider treatment with
appropriate testosterone therapy?
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Normalizing T levels
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Improved libido (? improve performance)
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Improved energy level
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Improved mood, sense of well-being
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Increase in lean body mass and strength
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Decrease in body fat mass
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Improved bone mineral density (effects on
fracture risk are currently unknown)
Bhasin S, et al. J Clin Endocrinol Metab. 2006;91(16):1995-2010.
Wang C, et al. J Clin Endocrinol Metab. 2004;89:2085-2098.
Petak SM, et al. AACE Clinical Practice Guidelines. Endocrine Practice. 2002;8(6):439-456.
Wang C, et al. J Clin Endocrinol Metab. 2000;85:2839-2853.
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†
Bhasin S, et al. J Clin Endocrinol Metab. 2006;91(16):1995-2010.
*Androderm® [package insert]. Corona, CA:Watson Pharma, Inc; February 2013
†Testopel in Drugs.com
SC = Subcutaneous
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
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Vigen et al Jama
2013
8709 T deficient
men
1223 T therapy
20% untreated and
26% treated men
death/MI/stroke
HR = 1.29
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Finkle et al.
PLoSOne 2014
Retrospective look
56K men T and
167K treated PDE5
inhibitor
T 1.36 nonfatal MI
>65yoa 2.19
<65 w cv dx 2.90
PDE5 1.1, 1.15, 1.4
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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
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Cost
Insurance coverage
Testosterone therapy =$$$$
[female HRT =$]
Controlled substance
Testosterone yes
[female HRT
no]
PO administration
Testosterone
no
[female HRT
yes]
1400
Upper limit of
normal range
Serum testosterone
concentration (ng/dL)
1200
1000
800
600
400
200
Lower limit of
normal range
0
0
3
6
Time (weeks)
IM = Intramuscular
9
12
15
Testosterone concentration
(ng/dL)
1400
5 g T-Gel
1200
10 g T-Gel
Upper limit of
normal range
1000
800
600
400
Lower limit of
normal range
200
0
0
4
8
12
16
20
Time (hours) after application
24
AndroGel® [prescribing information]. Marietta, GA: Solvay Pharmaceuticals, Inc.; December 2007.
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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. 2005;56:117-137
Bhasin S, et al. J Clin Endocrinol Metab. 2006;91(16):1995-2010
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Known or suspected prostate cancer
Breast cancer
Use in pregnant or breastfeeding women
Unexplained PSA elevation
Hematocrit >50%
Severe BPH symptoms
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AUA prostate symptom score >19 (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. 2006;91(16):1995-2010.
Petak SM, et al. AACE Clinical Practice Guidelines. Endocrine Practice 2002 8(6): 439-456.
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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 don’t 18 yr old males have prostate
cancer?
Evaluate patient after testosterone initiation, then annually for response to
treatment and symptom profile
Baseline
2-6
Months
Hematocrit
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PSA and DRE
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BMD
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T Concentrations
Annually
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In accordance with your prostate cancer
screening protocol
After 2 years of T therapy in hypogonadal
men with osteoporosis or osteopenia
DRE = Digital Rectal Exam
BMD = Bone Mineral Density
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Serum PSA >4 ng/ml
Increase in serum PSA >1.4 ng/mL within any 12
month period of T replacement
PSA velocity of >0.4 ng/mL/yr
• Only applicable if PSA data are available for a
period >2 years
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Prostatic abnormality on digital rectal exam
If AUA prostate symptom score >19
In Summary
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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
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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
Pearls?