the face of androgen deficiency. between 2.1% and 21% of men with ed have low testosterone,...
TRANSCRIPT
The face of Androgen deficiency
Erectile Dysfunction and Androgen Deficiency Are Independently Distributed Disorders
Between 2.1% and 21% of men with ED have low testosterone, depending on the test used to measure testosterone
Korenman et al. J Clin Endocrinol Metab. 1990;71:963-969.Buvat and Lemaire. J Urol. 1997;158:1764-1767.Nehra A. Mayo Clin Proc. 2000;75 Suppl:S40-S45.Shabsigh R. Int J Impot Res. 2003;15 Suppl 4:S9-S13.
AndrogenDeficiency
ErectileDysfunction
Issues covered:
Hormonal Diagnosis of Androgen deficiency
Etiological approach to Low T
Therapeutic aspects
Hormonal Diagnosis
Testosterone Measurement
Total T Free T Albumin bound T
Bound to SHBG
Which one to measure?
Bio availableTestosterone
Testosterone Measurements
Need to be measured close to 8 am
Assays at a reputable reference lab
Total T and calculated free T usually correlate
Free T is more accurate when SHBG is altered
ObesityDMRenal/HepaticThyroid ds
What defines a low Testosterone?
“Normal range” 300-900 ng/dl (age relevant)
Total T less than 200-250 = “low”Total T between 250 -300 = “Borderline”Free T (n=> 65 pg/ml) helps when total T is borderline or a Affected by changes in SHBG
OpioidsAnabolic steroidsGluco corticoids
T levels affected by drugs
Issues covered:
Hormonal Diagnosis of Androgen deficiency
Etiological approach to Low T
Therapeutic aspects
The Hypothalamic Pituitary Gonadal Axis
GnRH
LH FSH
Testosterone Spermatogenesis
-Inhibin
-T
-
Low TESTOSTERONE
High LH
HYPER GONADOTROPHICHYPOGONADISM
Klinefelter’s syndromeAdult testicular failureOrchitisTesticular traumaChemo/RadiationKetoconazole
Primary Gonadal Failure
High LH
Low LH
Low TESTOSTERONE
HYPOGONADOTROPHICHYPOGONADISM
Kallman SyndromePituitary failurePituitary tumorProlactinomaHemochromatosisHIVPrimary HypothyroidAnorexia Nervosa
Low LH
SteroidsAlcoholOpioids
Secondry Gonadal Failure
Normal LH
Low TESTOSTERONE
Seen in clinical practice in association withSeveral common conditions
Metabolic syndromeType 2 Diabetes
Aging
Obstructive Sleep Apnea
Androgen
Deficiency in the
Aging
Male
Age-Dependent Prevalence of Androgen Deficiency
*Hypogonadal: at least 1 free testosterone value <11.3 nmol/L (325 ng/dL).Harman et al. J Clin Endocrinol Metab. 2001;86:724-731.
% H
yp
og
on
ad
al *
50-59 60-69 70-79 >80Age (years)
12%
19%
28%
49%
0
10
20
30
40
50
60
12%22%
42%
68%
Hypogonadism defined as serum T <300 ng/dL
Issues covered:
Hormonal Diagnosis of Androgen deficiency
Etiological approach to Low T
Therapeutic aspects
Androgen Deficiency PoorConcentration
Ability
DecreasedHematopoiesis
DecreasedBody Hair
MuscleWasting
SexualDysfunction
IncreasedFat
Osteoporosis
IncreasedFractures
AACE Guidelines. Endocr Pract. 2002;8:439-456.Harman et al. J Clin Endocrinol Metab. 2001;86:724-731.
Clinical Problems Associated With Androgen Deficiency
Androgen deficiency in aging male: ”ADAM”
Total, free T dramatically decline after age 60
Symptoms and T levels may not correlate
ED can be multifactorial in males > 60
Age, depression, atherosclerosis, co morbidities and meds contribute to ED
Issues:
Sexual Enounter Profile (SEP) Questions
SEP consists of 5 questions rate from 1-5 for each 1.Were you able to achieve at least some erection?2.Were you able to insert your penis into your
partner’s vagina?3.Did your erection last long enough to have
successful intercourse?4.Were you satisfied with the hardness of your
erection?5.Were you satisfied with the overall sexual
experience?
Mulhall JP et al. J Urol. 2003;170:353-358.
Depression“Burn out”StressHostilityBored with partnerLoss of attractionHostilityGuilt
?TestosteroneDeficiency
Androgen TherapyNOT recommended unlessthe Testosteronelevel is low!!
Testosterone Replacement: Initiation and Risk Assessment Examination/laboratory tests
Digital rectal examination, PSA, breast evaluation
Eliminate absolute contraindications Prostate cancer Breast cancer
Consider relative contraindications Sleep apnea, Polycythemia
Rhoden EL, Morgentaler A. N Engl J Med 2004;350:482-492; accessed January 29, 2004. Endocr Pract. 2002;8:439-456.
Testosterone Replacement Options
Parenteral Testosterone Cypionate Enanthate 200 q 2 weeks Dermal patch: (Androderm) 5 mg patches
Gel: Androgel1% or 1.62% Testim Fortesta 2% Liquid
Axiron
Buccal
Gum (Striant)
Pellets
Effects of Testosterone Therapy on Prostate-Specific Antigen (PSA)
N=54; P<.01; PSA=prostate-specific antigen.*Testosterone replacement in hypogonadal men defined as testosterone <300 ng/dL.Gerstenbluth et al. J Androl. 2002;23:922-929.
Mean follow-up=30.2 monthsMean age= 60.4 years
652 Hypogonadal men (T<300ng/dL)Dose=200-300 mg, q 2-4 Weeks6 Biopsies, 1 prostate cancer
0.96
0.0
0.5
1.0
1.5
2.0
2.5
3.0
Seru
m P
SA
(n
g/m
L)
Pretreatment
Posttreatment
Androgen Deficiency in Men:Summary
Aging is associated with In prevalence of androgen deficiency
Testosterone replacement in hypogonadal men Strength, lean body mass Bone mass Libido Sense of “well-being”
May augment the treatment of ED with PD5 inhibitors
Effect of Testosterone on Response to Sildenafil in Men with ED
Erectile dysfunction and low testosterone frequently occur together
Study to evaluate whether the addition of testosterone to sildenafil improves erectile function in men with low T (total T <330 ng/dl or free T < 50 pg/ml)
140 Men 40 -70 y/o with EFD of IIEF scores of <25 randomized to 10-g daily of transdermal testosterone gel or placebo after sildenafil dose was optimized
EFD score improvement analyzed after 14 weeksSpitzer, M. et.al… Ann Internal Med.
2012;157:681-691
Effect of Testosterone on Response to Sildenafil in Men with ED
Characteristics Testosterone (n=70)
Placebo (n=70)
Age, y 55.1 54.6
BMI, kg/m2 31.5 32.7
Diabetes , n 13 14
Hypertension, n 35 32
Cardiovascular disease, n
35 32
Total Testosterone, ng/dl
248 254
Free Testosterone, pg/ml
45 47
EFD of IIEF score 12 12
Baseline Characteristics at Randomization
Spitzer, M. et.al… Ann Internal Med. 2012;157:681-691
Effect of Testosterone on Response to Sildenafil in Men with ED
Characteristics Testosterone (n=70)
Placebo (n=70)
Increase in EFD Score(after Sildenafil optimized)
7.7 [95% CI, 6.5 to 8.8](Compared to baseline EFD Scores)
Total Testosterone, ng/dl(after Sildenafil optimized)
364 347
Total Testosterone, ng/dl(after 14 weeks of Tx.)
649 No Change
Increase in EFD Score(after Testosterone Tx)
2.2 [CI, -0.8 to 5.1](Compared to placebo)
Results
There was no effect of age, BMI, disease state, initial T level,EFD score, or response to sildenafil alone on the results
Spitzer, M. et.al… Ann Internal Med. 2012;157:681-691
There was no additional benefit of adding testosterone therapy to optimized sildenafil treatment on ED (though there was also no increase in adverse events)
However, this should not preclude use of testosterone for its other beneficial effects
A confounder may be the 100 ng/ml increase in testosterone seen in the sildenafil run-in period
Effect of Testosterone on Response to Sildenafil in Men with ED
Spitzer, M. et.al… Ann Internal Med. 2012;157:681-691