A memorandum on andropause management Dr. Claude Chauchard Paris, FRANCE Chairman & CEO - La...

A memorandum on A memorandum on

andropause managementandropause management

Dr. Claude Chauchard

Paris, FRANCE

Chairman & CEO - La Clinique de Paris Group

Former Assistant Professor of

Montpellier University

Anti-aging Medicine World Congress Anti-aging Medicine World Congress

Monte Carlo, MonacoMonte Carlo, Monaco

April 8-10, 2010April 8-10, 2010

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© Claude Chauchard La Clinique de Paris 2009 1

Goal of Anti-Ageing MedicineGoal of Anti-Ageing Medicine

Increase Health Span not just lifespan

Increase lifespan if:

strong and vigorous

happy content creative

spiritually satisfied

No one wants to live longer with

debility or chronic illness or cognitive

impairment© Claude Chauchard La Clinique de Paris 2009

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2

Balanced hormone replacement therapy

All hormones restored to 25-30 years

old level and monitored by regular

serum levels

Natural (Bioidentical) hormones

Identical molecular structure to hormones

produced by human female or male

Not xeno hormones or horse hormones

Synthetically produced

© Claude Chauchard La Clinique de Paris 2009

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3

Balanced HRT

Human growth hormone

DHEA, Pregnenolone, Melatonin

Testosterone in men and women

Estrogens and Progesterone in

women (Bio-identical hormones)

Not Premarin or Provera (MPA)

Thyroid (T3 and T4, not just T4)


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4

We age because our hormones decline, our hormones don’t decline because we age

Testosterone replacement therapy is safe and can provide dramatic benefits


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5

Andropause & Menopause

Breast Cancer Prostate Cancer

Osteoporosis Osteoporosis

Cardiovascular Disease

Cardiovascular Disease

Sexual function Sexual function

Well being Well being

Body Fat Body Fat

Estrogen Testosterone


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6

Symptoms of Change of LifeSymptoms of Change of Life


Male Female

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Testosterone & ProstateTestosterone & Prostate

8© Claude Chauchard La Clinique de Paris

OverviewOverview

9© Claude Chauchard La Clinique de Paris

ECBUECBU

UIVUIV

Bladder Bladder FullFull

Abdominal Abdominal SonographSonograph

yy

Male Menopause = AndropauseMale Menopause = Andropause

Less sudden in onset than female

menopause

Just as severe in long term

consequences

The cause …

Decreased bioavailable

TESTOSTERONE


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10

Male MenopauseMale Menopause

FatigueDepressionIrritabilityReduced libido and potency

◦ Decreased desire and fantasies

◦ Decreased morning erections

◦ Decreased erectile tension

◦ Longer recovery time between orgasms

◦ Decreased intensity of orgasms


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11


Increased aging of heart and circulation

◦Increased MI’s and CVA’s

◦Decreased hemodynamic function

Increased brain aging

◦Decreased memory

◦Decreased intelligence

◦Increased Dementia, Alzheimer’s


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Loss of drive and competitive edge

Stiffness and pain in muscles and

joints

Falling level of fitness

Decreased effectiveness of workouts


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13


The cause …

Decreased bioavailable

TESTOSTERONEPlus

◦ Stress

◦ Alcohol

◦ Increased fat especially abdominal fat

◦ Lack of exercise


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14

Does T decline with age ?Does T decline with age ?

Older studies showed no difference◦ Did not measure free T◦ Did not get AM samples

Total T, Free T, Bioavailable T, E1 and E2 decline with age

T declines 10 ng/dl per yearFree T 1% per yearAll T measures correlated with strength,

BMD body composition, fat mass


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15

Sex Hormone Binding Globullin (SHBG) binds T > E

◦ 20-60 nmol/l male

◦ 40-120 nmol/l femaleFree Androgen IndexTestosterone x 1000 / SHBGT is tightly bound to SHBG and loosely

bound to albuminFree T is unbound to SHBG or albuminBioavailable T = unbound + loosely bound


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0 0400 0800 1200 1600 2000

Clock Time (Hours)

400

500

600

700

800S

eru

m C

on

cen

trati

on

(n

g/d

l)

Old Men

Young Men


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17

Hypothalamus

GnRH

AnteriorPituitary

Estrogens

FSH

Aromatase

LH TESTOSTERONE

DHT

5-alpha Reductase

Testes

Leydig cell

Sperm Sertoli cell

Inhibin


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18

Methods of TRTMethods of TRT

Injections of T enathate or T cypionate

Older method 200 mg q 2 weeks

◦ Roller coaster effect

◦ Suprahysiologic levels followed by low levels

◦ More aromatization to Estradiol

◦ More polycythemia

◦ Less DHT increase thatn transdermal

Weekly dose 100 mg

◦ More physiologic stable levels

◦ Less aromatization to Estradiol


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19

Oral – Methyltestosterone

◦ Hepatotoxic, contraindicated

Oral – T undecanoate (Andriol)

◦ Lymphatic absorption, no hepatic toxicity

reported

◦ Must use TID

◦ No available in US

Subcutaneous pellets

◦ Minor surgical procedure

◦ Last 2-3 months

Methods of TRT


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20

TransdermalTransdermal

Well absorbed as proven by serum levels

More DHT since hair follicles contain 5

alpha reductase

Steady state after 24 hours

Scrotal (Testoderm) – shaved scrotum

required, inconvenient, high DHT

Patches (Androderm) – Delivers 5 mg per

day, inconvenient, expensive


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21

TransdermalTransdermal

Androgel

◦ 1% transdermal gel

◦ Commercially available

◦ 50, 75 or 100 mg packages

Compounding pharmacies

◦ Can custom produce transdermal gel

◦ Can titrate to serum levels by varying

percentage 1-20 and dose

◦ Preferred method in most men


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22

T gel precautionsT gel precautions

Avoid scrotum (increased DHT)

Avoid getting gel on females and kids

Rub in well over large surface area

Can increase hair growth in area of application but (unfortunately) not on head


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Dihydro TestosteroneDihydro Testosterone

More potent than T (2-5x)

Conversion of T to DHT via 5-alpha-

reductase

Not aromatizeable to Estrogens

Is DHT an important beneficial androgen

or is DHT the evil twin of Testosterone ?


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24

DHT Gel 70mg Vs. PlaceboDHT Gel 70mg Vs. Placebo

Men > 60 yo, T < 15 nMol/l = 428 ng/dlDecreased LDL, no change HDL Increased Hemoglobin/HematocritDecreased Fat MassKnee strength increased not other muscles No change QOLNo change PSA or prostate volume Ly LP et al. Randomized Clinical Trial of Transdermal

Dihydrotestosterone Gel on Muscular Strength, Mobility and Quality of Life in Older Men with Partial Androgen Deficiency

J Clin Endocrinol Metab 2001 88:4078-4088


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25

DHT RT Reduces Prostate SizeDHT RT Reduces Prostate Size

1.8 year study

BPH requires both DHT and E2

De Lignieres B Transdermal

dihydrotestosterone treatment of

‘andropause’

◦Ann Med 1993 Jun; 25(3):235-41


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26

DHT For AndropauseDHT For Andropause

DHT gel 125-250 mg/day vs Placebo x 6 months

Improved erections and morning erectionsDecreased LH, FSH, E2, T and SHBGNo change lipids or hepatic functionHg/Hct increasedNo change in prostate weight or PSA

Kunelius P et al. The effects of transdermal dihydrotestosterone in the aging male: a prospective, randomized, double blind study. J Clin Endocrinol Metab 2002 Apr; 57(4):1457-72


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27

HCG InjectionsHCG Injections

Human Chorionic Gonadotropin (HCG)

Polypeptide hormone produced by the

human placenta

Alpha and beta sub-unit

Alpha sub-unit is essentially identical to

the alpha sub-units of LH and FSH


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28

HCGHCG

If there is no Leydig cell failure can treat hypogonadism with HCG injections

2000-5000 units per weekNo decrease in testicular size or sperm

countCan use as TRT (measure free T to confirm

success) or cycle with TRT every 6 months

Zilzmann M Hormone substitution in male hypogonadiam Mol Cell Endocrinol 2000 Mar 30; 161(1-2):73-88


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Improved with patch and gel◦ Sexual function

◦ Mood

◦ Muscle strength, leg > arm

◦ Subjects did not exercise

With gel but not patch◦ Improved lean body mass and fat mass

◦ Correlated with serum level of T obtained


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No change in lipid profile including HDL Skin Irritation

◦ 5.5% gel, 66% patchHg/Hct increase in 100 mg gel group

◦ Mean 1.3/4.1PSA

◦ Small increase with gel but not patch◦ Correlated with serum T◦ Remained within normal range◦ Stabilized on day 90◦ 50 mg 0.17 increase 100 mg 0.2

increaseProstate symptom score : no change


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31

S e xS e x

Improved◦ Enjoyment with partner

◦ Erection firmness

◦ Sexual performance

◦ Sexual desire

Not related to dose or method of delivery or serum T obtained


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32

T and Erectile FunctionT and Erectile Function

T > Placebo

Transdermal (81%) > Oral (51%) or IM

(53%)

All statis. Significant

Jain P et al. TESTOSTERONE

SUPPLEMENTATION FOR ERECTILE

DYSFUNCTION: RESULTS OF A META-

ANALYSIS : J Urol 2000 Aug; 164(2):371-375


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T and MemoryT and Memory

T supplementation increased working memory in men

No similar charge with estrogen in women

Janowsky J et al. Sex Steroids modify working memory J Cogn Neurosci 2000 May; 12(3):407-14


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34

T and Mood (and Erections)T and Mood (and Erections)

Effective when psych drugs do not work

in pts with low T Cooper MA. Testosterone Replacement Therapy for Anxlety Am J

Psychiatry 157:1884, Novermber 2000

TRT increases nocturnal and

spontaneous erections and improves

mood. Burris A et al. A long-term, prospective study of the physiologic and

behavioral effects of hormone replacement in untreated hypogonadal

men. J Androl 1993 Jul-Aug; 13(4):297-304.


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35

Does TRT increase angry Does TRT increase angry behavior ?behavior ?

No

Tricker R et al. The effects of

supraphysiological doses of testosterone

on angry behavior in healthy eugonadal

men- a clinical research center study

J Clin Endocrinol Metab 1996 Oct; 81(10):3754-8


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Adverse EffectsAdverse Effects

Fluid retention (rare)

Does TRT accelerate male pattern

hair loss ? No Info.

Possible increase in sleep apnea

Possible decrease in testicular size

Decreased sperm count


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37

Testosterone Replacement in Testosterone Replacement in men improves:men improves:

LibidoErectile FunctionMoodMemoryAnginaType 2 diabetesMuscle massFat


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38

Testosterone Replacement in Testosterone Replacement in men may prevent:men may prevent:

Heart DiseaseDiabetesInsulin ResistanceAlzheimer Osteoporosis


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39

SexySexy

Increased libido

Increased sexual pleasure and

performance

Improved body image


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40

This is how much the male This is how much the male hormone replacement can keep hormone replacement can keep

you youngeryou younger

All my wishes to youAll my wishes to [email protected]

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