the face of androgen deficiency. between 2.1% and 21% of men with ed have low testosterone,...

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