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The MenThe Men’’s Health Centers Health CenterComprehensive Compassionate CareComprehensive Compassionate CareCardiometabolic Urology: The Future?Cardiometabolic Urology: The Future?

Martin Miner MDMartin Miner MDCoCo--Director Director The MenThe Men’’s Health Centers Health CenterMiriam Hospital Miriam Hospital Warren Alpert School of MedicineWarren Alpert School of MedicineWarren Alpert School of MedicineWarren Alpert School of MedicineBrown UniversityBrown UniversityProvidence, RI USA Providence, RI USA

Disclosures

Research Funding: GSK; Auxilium

Consultancy: Auxilium T Registry;Merck

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Why is Men’s Health Critical?Rationale: THE EDUCATIONAL MISSION

The standard for most US family medicine residency programs is a one-month rotation encompassing:

• “Randomly-defined” exposure to various surgical subspecialty fields, which may or may not include urologyp y , y y gy

• Widely varying educational goals and objectives• NO DEFINED MEN’S HEALTH CURRICULUM

Medical students and medicine residents at Brown University have expressed educational concerns regarding:

• Lack of exposure to and training in comprehensive, multi-disciplinary men’s health (we see male patients, but…)

• Lack of adequate training in primary care (office non• Lack of adequate training in primary care (office, non-surgical) urology (Sexual health is the portal to men’s health…)

• Lack of adequate training in andrology (What’s this ?)

Project Description

The development of a men’s health curriculum is a novel concept aimed at improving theis a novel concept aimed at improving the knowledge base in various subject areas for medical students, family medicine, and internal medicine residents

Dedicated men’s health center co-led by primary care and urologyprimary care and urology

Each clinic session accommodates an average of 12-16 patients on a referral basis

Allows for re-direction to primary care emphasis

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Curriculum

The development of a men’s health curriculum to include primary care urology is novel and innovativeinnovative

The principal framework is driven by the ACGME competencies of medical knowledge:

• Patient-centered care

• Practice-based learning and improvement

• Systems-based practice

• Professionalism

• Inter-professional and communication skills

• Interdepartmental and Interspecialty Links

Multidisciplinary Outreach

Cardiology-Partnership in finding vul

Internal Medicine-TD; Male Bone Health; CMB*

MHC

Partnership in finding vul pt

Neurology-TD & Chr HA;

-ED & MS; Parkinsons

Health

Urology

Pulmonary Medicine-OSA & TD

-COPD & TD & ED

Gynecology

Psychiatry-TD &

Depression;

Sex Rx

Oncology-Chemo TD; Rad TD

-ED in all Onc popuiations

-TD; Bone Health; CVD eval

Of ED pts-FSD

*Cardiometabolic (CMB)

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Aims

Diagnose and treat male sexual dysfunction General sexual dysfunction

S l d f ti l t d t ifi Sexual dysfunction related to specific disease states

Evaluate cardiometabolic risks of men with sexual dysfunction Cardiovascular risk stratification Prevention strategies and lifestyle Prevention strategies and lifestyle

counseling The benefits and risks of male hormonal

replacement therapyPsychological Evaluation and Therapy

Establish the Miriam/Brown MHC as a national leader in the emerging field of sexual medicine and cardiometabolic health

• Research

–Outcomes based

Computerized database

–Industry and NIH support• Resident/trainee Education

–Psychology/Psychiatrysyc o ogy/ syc at y

–Urology

–Int Medicine/Family Medicine

–Medical Student

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Goals

Offer sexual health services to patient groups not currently served

• After MI or CAD intervention

• Conditions where disease or treatment affects sexual function

– Post Abdominal/Pelvic Surgical Penile Rehabilitation

– Non urologic cancer patients eg general l H d ki Di C l t l CAoncology: Hodgkins Disease; Colorectal CA

– Chronic disease statesMS, Parkinson’s, COPD, Obesity, DM, Depression

OSA and other sleep disorders

Goals

• Expand management breadth where services exist

– General male sexual dysfunctionsGeneral male sexual dysfunctions• ED• Premature Ejaculation• Testosterone deficiency• Links to Obesity Treatment, Nutrition

Education, & Reintroduction of Exercise

After prostate cancer therapy– After prostate cancer therapy• Penile rehabilitation• Urinary Incontinence Pelvic Floor

Strengthening/Conditioning PT Specialist

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Goals • Expand the evaluation to include underlying risks

associated with sexual dysfunction– Cardiovascular disease (CAD)

P t A t i l A i A ti Stiff C t l– Premature Arterial Aging: Aortic Stiffness Central Arterial Pressure; Pulse Wave Velocity

• SphygmoCor• EndoPat: measure Endothelial Function

– Metabolic syndrome (Individual components)– Diabetes Mellitus– Obesity– Dyslipidemia (Inc TG/ Dec HDL)– Psychological Evaluation for anxiety, depression,

relational disorders esp performance anxiety

MHC: Multidisciplinary Approach• Psychology

– John Wincze PhD• Elected Member/ Former President• International Academy of Sex Research Therapistsy f p

• Medicine– Martin Miner MD

• Fellow Sexual Medicine Society of North America• Fellow Am Academy of Family Practice

• Urology– Mark Sigman MD Nutrition– Kathleen Hwang MD -- Mary Flynn PhD

• Urology/Andrology• Male Pelvic Floor Therapy

-- Christy Cielsa PT

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MHC: Age Range of Patients

MHC: Current Referral Base

Referring Practices

40

60

80

100

120

140

160

180

Nu

mb

er o

f P

atie

nts

Ref

erre

d

60% Urology30% Int Med10% Other

0

20

Ob/

Gyn

Orth

oped

ics

Car

diol

ogy

Psyc

hiat

ryEn

docr

inol

ogy

Pulm

onar

y

Onc

olog

ySe

lf R

efer

ral

Inte

rnal

Med

icin

e

Uro

logy

Type of Practice

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Men’ s Health

Why is the relation between ED and CVD important?

The size of the problem

The number of men with ED will increase from152 million men in 1995 to 322 million men by 2025

North America 9.1 million

South/CentralAfrica

19 3 million

Europe 11.9 million

Asia 113 million

152 million men in 1995 to 322 million men by 2025

South/CentralAmerica andCaribbean

15.6 million

19.3 million

Oceania 0.9 million

Adapted from McKinlay JB. Int J Impot Res. 2000;12(suppl 4):S6-S11.

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ED is a remarkably common condition.

ED in a substantial majority of men is

The Prevalence of EDThe Prevalence of ED

majority of men is due to underlying vascular causes.

ED is highly Associations Between ED

and Various Comorbid StatesAssociations Between ED

and Various Comorbid States

n=2536, ED 18.5 %n=2536, ED 18.5 %

prevalent in men with vascular risk factors for CVD.

Christopher S Saigal, Hunter Wessells, Jennifer Pace, Matt Schonlau, Timothy J Wilt. Predictors and

prevalence of erectile dysfunction in a racially diverse population. Arch Intern Med. 2006;166:207-212 *

Christopher S Saigal, Hunter Wessells, Jennifer Pace, Matt Schonlau, Timothy J Wilt. Predictors and

prevalence of erectile dysfunction in a racially diverse population. Arch Intern Med. 2006;166:207-212 *

Prevalence of ED in Patients With CV Pathologic Conditions or RisksPrevalence of ED in Patients With CV Pathologic Conditions or Risks

Condition Condition Estimated Prevalence Estimated Prevalence

of ED, % of ED, % ReferencesReferences

Age >40 yAge >40 y 33–89 Bacon et al, Bai et al, Chew et al, Feldman et al, Moreira et al, Morillo et al, Safarinejad, Shiri et al

Type 2 diabetesType 2 diabetes 2020––8686 Alonso et al, Klein et al, McCulloch et al, Siu et al, Yamasaki et al

HypertensionHypertension 27–68 Burchardt et al, Cuellar et al, Jensen et al

CADCAD 42–75 Dhabuwala et al, Diokno et al, Kloner et al, Montorsi et al, Solomon et al, Wabrek et al

Heart failureHeart failure 75 Jaarsma et al

DepressionDepression 25–90 Araujo et al

ObesityObesity Increased prevalence Esposito and Giugliano, Esposito et al, Gunduz et al

HyperlipidemiaHyperlipidemia Increased prevalence Nikoobakht et al, Saltzman et al, Wei et al

SmokingSmoking Increased prevalence Gades et al, Mannino et al, Mirone et al

MedicationMedication Increased prevalence Derby et al

CAD, coronary artery disease; CV, cardiovascular; ED, erectile dysfunction.

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Risk Factors of ED

Traditional

• Age• High LDL• Low HDL

Underlying

• Obesity• Sedentary

lifestyle

Emerging

• Insulin resistance

• Metabolic • Hypertension• Diabetes• Smoking

• Artherogenicdiet

Syndrome

Cardiovascular DiseaseRisk Stratification in the Asymptomatic Patient The Framingham Score and National Cholesterol

Education Program Adult Treatment Panel are theEducation Program Adult Treatment Panel are the predominant methods of identifying levels of risk for CHD.

• Typically patients are stratified into 3 categories based on

10 - year risk:

– Low (less than 10%)

– Intermediate (10-20%)

– High (>20%)

• Calculations include: age, cholesterol level, HDL cholesterol, BP, smoking and diabetes

• None include ED

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Erectile Dysfunction and S b tErectile Dysfunction and S b t

Does ED Predict CVD in an Asymptomatic Male?Does ED serve as a Surrogate Measure in Preventative

Interventions for Cardiac Disease?

Subsequent Cardiovascular Disease

Thompson IM, Tangen CM, Goodman PJ, Probstfield JL

Subsequent Cardiovascular Disease

Thompson IM, Tangen CM, Goodman PJ, Probstfield JLJL, Moinpour CM, Coltman CA. JAMA. 2005;294:2996-3002.JL, Moinpour CM, Coltman CA. JAMA. 2005;294:2996-3002.

Study Population/Design Highlights

9,457 men age 55+ randomized to placebo in Prostate Cancer Prevention Trial (PCPT)Prostate Cancer Prevention Trial (PCPT)

• 8,063 (85%) men with no CVD at study entry

• 3,816 (47%) with prevalent ED, 2,420 (57%) reported incident ED after 5 y

Followed for 7 years for development of CVD255 CVD t• 255 CVD events

Thompson et al. JAMA 2005;294:2996-3002

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ED and Subsequent Cardiovascular Events Incident ED significantly

increased the risk of myocardial infarction or angina. C i t

HR( 4247)

PV l

g

2% had CV event 1 year after incident ED.

11% had CV event by 5 years after incident ED.

ED may be considered a

SmokingSmoking 1.461.46 .02.02

Family hx Family hx MIMI

1.461.46 .001.001

DiabetesDiabetes 2.342.34 <.001<.001

Covariates

(n=4247) Value

ED may be considered a harbinger of CV events in some men with an associated risk similar to current smoking, or family history of MI.

Thompson I. JAMA. 294(23):2996-3002, 2005.

DiabetesDiabetes 2.342.34 .001.001

AntiAnti--HTN RxHTN Rx 1.741.74 <.001<.001

Incident EDIncident ED 1.461.46 <.001<.001

A Population-Based,

What about the implications of ED in a broad populationWithout diabetes and CAD?

A Population Based, Longitudinal Study of Erectile Dysfunction and Future Coronary Artery Disease

Inman B, St. Sauver J, Jacobson D, McGree M, Nehra A, Jacobsen S. Mayo Clinic Proceedings; Feb. 2009

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Incidence of Coronary Artery Disease with Respect to Age and ED Status

Overall new incident CAD developed in 156 /1402 (11%) of men, followed from 1996-2005.

14 7% MI60

ars

• 14.7% MI

• 78.8% angiographic

• 6.4% sudden death

Association between ED and incident CAD declined with increasing age.

ED presence in men > 70 years old was of no prognostic10

20

30

40

50

EDNo ED

e p

er 1

000

per

son

-yea

old was of no prognostic significance.

Men with ED at age 40 had an 80% higher risk for subsequent CAD over 9 years.

0

10

40 - 49 50 - 59 60 - 69 > 70

Inci

den

ce

Inman B. Mayo Clinic Proc Inman B. Mayo Clinic Proc 2009;84(2):1082009;84(2):108--113.113.

*

Can we use ED as a means of detecting cardiovascularof detecting cardiovascular disease?

Can we use ED as a means of preventing

cardiovascular disease?

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Time interval between ED onset and CADED Prevalence and Time of Onset in 300

Consecutive Men With Acute Chest Pain and CAD

InIn 67% 67% of 300 pts, symptoms of ED had started before the of 300 pts, symptoms of ED had started before the symptoms of CAD (mean 39 months)symptoms of CAD (mean 39 months) –– retrospectiveretrospectivesymptoms of CAD (mean 39 months) symptoms of CAD (mean 39 months) retrospective retrospective

studystudy

Mean age, 62.5 y ED prevalence, 49% (147/300)Mean age, 62.5 y ED prevalence, 49% (147/300)MontorsiMontorsi F, et alF, et al.. EurEur UrolUrol 20032003

I l t ll ti t ED60

80

100

, m

o

Ptrend=.016

MontorsiMontorsi P, et al. P, et al. EurEur Heart J 2006Heart J 2006

In almost all patients, ED onset on average2-5 y before CAD

1-VD 2-VD 3-VD0

20

40

Inte

rval

Clinical spectrum of coronary artery disease

CVDsCVDs2-5 years2-5 years

*

EDED

DeBusk, Erectile Dysfunction Therapy in Special Populations and Applications: Coronary Artery Disease. Am J Cardiol 2005;96: 62M–66M

DeBusk, Erectile Dysfunction Therapy in Special Populations and Applications: Coronary Artery Disease. Am J Cardiol 2005;96: 62M–66M

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The Endothelium: A Living Organ

SmoothSmoothmusclemuscle

Arteriolelumen

Endothelium

ED May Be a Sign of Endothelial Damage: Part 1

Cigarette smoking1

Poor lifestyle choices increase oxidative stress in endothelial cells, causing early injury1

High-fatmeals1

g gObesity1

Psychological stress2

Sedentarybehavior1

ImpairedImpairedImpairedImpaired

OxidativeOxidativestressstress

NO=nitric oxide.

1. Jackson G. Int J Clin Pract. 2004;58:431. 2. Hornstein C. Vertex. 2004;15(suppl):21-31. 3. Maas R et al. Vasc Med. 2002;7:213-225.

Endothelial cellEndothelial cell

Impaired Impaired NO NO

productionproduction33

Endothelial cellEndothelial cell

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ED May Be a Sign of Endothelial Damage: Part 2

Anxiety/

ED may occur with the early endothelial cell damage before other serious diseases are manifest1-3

Anxiety/ Depression4

Early endothelial damageEarly endothelial damageVascular damageVascular damage

Endothelial cell:Endothelial cell:Early endothelial damageEarly endothelial damage

Vascular damageVascular damage8,118,11

Hyperlipidemia5-7

ED3,8

Visceral Obesity 10,11 7 Diabetes5,6,9

Atherosclerotic changesAtherosclerotic changes

1. Billups KL. Curr Sexual Health Rep. 2004;1:137-141. 2. Montorsi P et al. Eur Urol. 2003;352-354. 3. Kaiser DR et al. J Am Coll Cardiol. 2004;43:179-184. 4. Broadley AJM et al. Heart. 2002;88:521-524. 5. Maas R et al. Vasc Med. 2002;7:213-225. 6. Solomon H et al. Heart.

2003;89:251-254. 7. Hurairah H, Ferro A. Int J Clin Pract. 2004;58:173-183. 8. Bocchio M et al. J Urol. 2004;171:1601-1604. 9. DeAngelis L et al. Diabetologia. 2001;44:1155-1160. 10. Jackson G. Int J Clin Pract. 2004;58:431. 11. Deedwania PC. J Am Coll Cardiol. 2000;35:67-70.

Atherosclerotic changesAtherosclerotic changes

Early endothelial dysfunction may lead to atherosclerosis and vascular remodeling10,11

Early endothelial dysfunction may lead to atherosclerosis and vascular remodeling10,11

ED and Probability of Future CADED and Probability of Future CAD

18

16

14

12

10

8

6

10

-Ye

ar

CH

D r

isk

, %(M

ea

n, 9

5%

Cl)

CAD, coronary artery disease; CHD, coronary heart disease; CI, confidence interval; ED, erectile dysfunction; IIEF, International Index of Erectile Function; IIEF5, International Index of Erectile Function-5 questionnaire.

Reproduced with permission from Ponholzer A et al. Eur Urol. 2005;48(3):512-518.

Severe EDIIEF: 5-7

n=56

6

Moderate EDIIEF: 8-16

n=94

Mild EDIIEF: 17-21

n=495

No EDIIEF: 22-25

n=1213

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Why ED occurs before other vascular diseases?

The small diameter of theEarly Late

PenileThe small diameter of the cavernosal arteries.

The penis is a vascular organ, sensitive to changes in oxidative stress and NO levels.

The high content of endothelium and smooth muscle on a per

ED

angina/infarction

Stroke

Penile1-2 mm

Coronary3-4 mm

Carotid5-7 mm

**

and smooth muscle on a per gram tissue basis (compared to other organs).

Claudication

Femoral6-8 mm

Montorsi et al. The Artery Size Hypothesis: A Macrovascular Link Between Erectile Dysfunction and

Coronary Artery Disease. Curr Opin Urol. Am J Cardiol 2005;96:19M–

23M.

Montorsi et al. The Artery Size Hypothesis: A Macrovascular Link Between Erectile Dysfunction and

Coronary Artery Disease. Curr Opin Urol. Am J Cardiol 2005;96:19M–

23M.

Atherosclerosis in Coronary Vessels

Atherosclerosis in Penile Arteries

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Conclusions ED and CHD frequently coexist, especially in

ld (> 70)older men (> 70)

ED may occur in the absence of coronary symptoms ie. ED precedes coronary ishemia perhaps even more so in younger men (<60)

ED may precede a CAD event by years (ave 2-5)

Aggressive CVD risk reduction should be considered for all men with organic ED and no cardiac symptoms

Conclusion

“These data could serve as a basis for preventing life‐threatening events by risk factor management and lifestyle modification in men with ED”

Ponholzer A et al Eur Urol2005;48:512-8

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Testosterone Therapy: Where Have We BeenWhere Have We Been,Where Are We Going?

0

Survival of Treated Versus Untreated Testosterone-Deficient Men in VA Population

• 1031 Men aged > 40 yrs, Testosterone < 250 ng/dL • Mortality: 10.3% treated, 20.7% untreated (p<0.0001)

urv

ival

by

Test

ost

ero

ne

Trea

tmen

t, %

Log rank P=.029

1.00

0.90

Untreated

VA, US Department of Veterans Affairs.

Shores MM et al. J Clin Endocrinol Metab. 2012 Apr 11 [Epub ahead of print].

Su

0.80

0 12 24 36 48Time Since Testosterone Test Date, mo

1016 639 557 496 19315 301 321 323 146

UntreatedTreated

At risk, n

Treated

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TRT Improves Survival in Men With T2DM

• Six year follow up study• Six year follow-up study• N=587

• Effect of baseline T and TRT on all-cause

mortality in hypogonadal men with

T2DMT2DM• Low T predicts

increased mortality by hazard ratio of ~2.0

(20% vs 10%)Muraleedharan V, Jones H et al. Early Online 2012 Diabetes Care

TRT Improves Survival in Men with T2DM-results Mortality rate was significantly higher in patients with low

TT without TRT compared to patients with normal TTp p

Low TT patients with TRT had lower mortality rate

510152025

ort

alit

y R

ate p=0.001

p=0.049

0

Muraleedharan V, Jones H et al. Diabetes Care 2012

Normal TT (>10.4 nmol/L)(300 ng/dL) (31/338)Low TT (≤10.4 nmol/L) without TRT(36/182)Low TT receiving TRT for ≥2 y (5/58)

Mo

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Testosterone Therapy Effects on Diabetes TIMES2 Study

• A 12-month, multicenter, prospective, randomized, double-blind, placebo-controlled study

Study Design

• 220 hypogonadal men with T2DM and MetSPopulation

• Significantly improved:• Insulin resistance in all patients by 15.2% at 6

months; 16.4% at 12 months• HDL -0.049 mmol/L and LDL cholesterol -0.210

mmol/L, lipoprotein a -0.31 mmol/L in selected groups

• Erectile Function increase of 4.8 on IIEF-5

Results

Jones TH et al. Diabetes Care. 2011;34(4):828-837.

Testosterone Therapy

In late 1980s, rarely used and almost not at all in urologyin urology

Reserved for men with unequivocal or severe testosterone deficiencies

• Absent testes

• Pituitary/hypothalamic tumors or resection

• Genetic abnormalities, eg, Klinefelter syndrome

Not recognized as useful in otherwise healthy men with sexual or other symptoms

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Current Status of Testosterone Therapy

Growing awareness of benefits for men who are symptomatic and testosterone deficientsymptomatic and testosterone-deficient

• ED

• Diminished libido

• Chronic fatigue

• Poor bone mineral density

• Decreased sense of vitality and well-being

Ongoing debate about usefulness for mid-life blues or male menopause

ED, erectile dysfunction.

Conclusions

A relationship exists between TD and MetS d it i di id l t i il and its individual components; similar cross-

sectional studies have demonstrated an association between TD and T2DM

Prospective studies have demonstrated that a low T at baseline can predict the development of T2DM

Visceral adiposity induces hypogonadotrophic hypogonadism

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Conclusions

TRT appears to improve insulin sensitivity and potentially glycemic control in TD men with T2DMpotentially glycemic control in TD men with T2DM

Men with erectile dysfunction, diminished desire, impaired orgasmic function, and metabolic diseases including MetS and T2DM should be screened for TD and treated with TRT

The issue of TRT in preventing CVD needs further study.

New Topics of T Repletion:

Emerging data that testosterone therapy may no longer be contraindicated for men with localized prostate cancer

Testosterone therapy may provide benefits for voiding despite conventional belief that higher testosterone levels cause BPH growth

T and Bone Health in Men

Testosterone may improve insulin resistance, ameliorate early type 2 DM, improve CVD and all cause mortalityy yp , p y

Provocative, no consensus

Will be fascinating to see what we learn in next 5-10 years

BPH, benign prostatic hyperplasia.

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The Future

Testosterone therapy for general health and longevity?and longevity?

Several publications showing associations between low testosterone and atherosclerosis, risk of diabetes and metabolic syndrome, and increased mortality

Ca sal relationship ers s mere association? Causal relationship versus mere association?

Barriers to Success of Men’s Health Center Unclear boundaries and newly recognized fears regarding

cardiometabolic risk screening crossing specialties and increasing costs (PCP vs ED spec; Inc $ testing)

Ensure receptivity and lack of threat to referring providers Ensure receptivity and lack of threat to referring providers-Refer back to PCP with faxed evaluation and non-threatening evidence-based recommendations

Must “vette” cardiometabolic workup with local and national preventative cardiologists: the workup must be evidence-based, cost-effective, and individualized to each patient

Establishing a computerized data base from the start E i b h i d d i id ll Engaging both community and academic providers as well as

allowing self-referral Ensure timely access Ensure cross-specialty patient discussions at weekly meeting

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What is the offer to our patients?

• A relevant issue: the value of a holistic approachto their health including sexual medicineto their health including sexual medicine

• It is 180* different from sports-page penileinjection clinic (Boston Medical)

• It is a coherent message: everything is linkedand all should be taken into account

• Patients are investing in quality of lifeg q y• One-stop Shopping: Links to Exercise; Diet;

Preventative Medicine

Who are our patients-clients?Why a Men’s Health Center?

Men above 35 y.oy

Worried about their health

Want to improve their global performance

Want to prevent age-related problems

Want to be active and healthy

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Future Long-term Goals of Men’s Health Center:

Incorporate Female Sexual Dysfunction and Partners for therapy beyond couplesPartners for therapy beyond couples counseling

Develop referral algorithms/links for other specialties: oncology; cardiology; pulmonary (COPD & OSA)

Establish the service of Male Bone Health Establish the service of Male Bone Health

Publish outcomes research