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Dr. Claude Chauchard Paris, FRANCE Chairman & CEO - La Clinique de Paris Group Former Assistant Professor of Montpellier University . A memorandum on andropause management. Claude.ch@lcdpi.com. Anti-aging Medicine World Congress Monte Carlo, Monaco April 8-10, 2010. 1.

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a memorandum on andropause management

Dr. Claude Chauchard

Paris, FRANCE

Chairman & CEO - La Clinique de Paris Group

Former Assistant Professor of

Montpellier University

A memorandum on

andropause management

Claude.ch@lcdpi.com

Anti-aging Medicine World Congress

Monte Carlo, Monaco

April 8-10, 2010

1

© Claude Chauchard La Clinique de Paris 2009

goal of anti ageing medicine
Goal 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.ch@lcdpi.com

2

© Claude Chauchard La Clinique de Paris 2009

balanced hormone replacement therapy
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.ch@lcdpi.com

3

© Claude Chauchard La Clinique de Paris 2009

balanced hrt
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)

Claude.ch@lcdpi.com

4

© Claude Chauchard La Clinique de Paris 2009

slide5

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

    • Testosterone replacement therapy is safe and can provide dramatic benefits

Claude.ch@lcdpi.com

5

© Claude Chauchard La Clinique de Paris 2009

andropause menopause

Testosterone 

Estrogen 

Body Fat 

Body Fat 

Well being 

Well being 

Sexual function 

Sexual function 

Cardiovascular Disease 

Cardiovascular Disease 

Osteoporosis 

Osteoporosis 

Prostate Cancer 

Breast Cancer 

Andropause & Menopause

Claude.ch@lcdpi.com

6

© Claude Chauchard La Clinique de Paris 2009

symptoms of change of life
Symptoms of Change of Life

Male

Female

7

© Claude Chauchard La Clinique de Paris 2009

testosterone prostate
Testosterone & Prostate

8

© Claude Chauchard La Clinique de Paris

overview
Overview

ECBU

UIV

Bladder Full

Abdominal Sonography

9

© Claude Chauchard La Clinique de Paris

male menopause andropause
Male Menopause = Andropause
  • Less sudden in onset than female menopause
  • Just as severe in long term consequences
  • The cause …
  • Decreased bioavailable
  • TESTOSTERONE

Claude.ch@lcdpi.com

10

© Claude Chauchard La Clinique de Paris 2009

male menopause
Male Menopause
  • Fatigue
  • Depression
  • Irritability
  • Reduced libido and potency
    • Decreased desire and fantasies
    • Decreased morning erections
    • Decreased erectile tension
    • Longer recovery time between orgasms
    • Decreased intensity of orgasms

Claude.ch@lcdpi.com

11

© Claude Chauchard La Clinique de Paris 2009

male menopause12
Male Menopause
  • 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

Claude.ch@lcdpi.com

12

© Claude Chauchard La Clinique de Paris 2009

male menopause13
Male Menopause
  • Loss of drive and competitive edge
  • Stiffness and pain in muscles and joints
  • Falling level of fitness
  • Decreased effectiveness of workouts

Claude.ch@lcdpi.com

13

© Claude Chauchard La Clinique de Paris 2009

male menopause14
Male Menopause
  • The cause …
  • Decreased bioavailable

TESTOSTERONE

  • Plus
    • Stress
    • Alcohol
    • Increased fat especially abdominal fat
    • Lack of exercise

Claude.ch@lcdpi.com

14

© Claude Chauchard La Clinique de Paris 2009

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 year
  • Free T 1% per year
  • All T measures correlated with strength, BMD body composition, fat mass

Claude.ch@lcdpi.com

15

© Claude Chauchard La Clinique de Paris 2009

slide16

Sex Hormone Binding Globullin (SHBG) binds T > E

    • 20-60 nmol/l male
    • 40-120 nmol/l female
  • Free Androgen Index
  • Testosterone x 1000 / SHBG
  • T is tightly bound to SHBG and loosely bound to albumin
  • Free T is unbound to SHBG or albumin
  • Bioavailable T = unbound + loosely bound

Claude.ch@lcdpi.com

16

© Claude Chauchard La Clinique de Paris 2009

slide17

Serum Concentration (ng/dl)

800

700

Young Men

600

500

Claude.ch@lcdpi.com

Old Men

400

0

0400 0800 1200 1600 2000

Clock Time (Hours)

17

© Claude Chauchard La Clinique de Paris 2009

slide18

Hypothalamus

GnRH

Aromatase

DHT

Estrogens

Anterior

Pituitary

5-alpha Reductase

LH

FSH

TESTOSTERONE

Inhibin

Claude.ch@lcdpi.com

Leydig cell

Sperm

Sertoli cell

Testes

18

© Claude Chauchard La Clinique de Paris 2009

methods of trt
Methods 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 thatntransdermal
  • Weekly dose 100 mg
    • More physiologic stable levels
    • Less aromatization to Estradiol

Claude.ch@lcdpi.com

19

© Claude Chauchard La Clinique de Paris 2009

slide20

Methods of TRT

  • 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

Claude.ch@lcdpi.com

20

© Claude Chauchard La Clinique de Paris 2009

transdermal
Transdermal
  • 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

Claude.ch@lcdpi.com

21

© Claude Chauchard La Clinique de Paris 2009

transdermal22
Transdermal
  • 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

Claude.ch@lcdpi.com

22

© Claude Chauchard La Clinique de Paris 2009

t gel precautions
T 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

Claude.ch@lcdpi.com

23

© Claude Chauchard La Clinique de Paris 2009

dihydro testosterone
Dihydro 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 ?

Claude.ch@lcdpi.com

24

© Claude Chauchard La Clinique de Paris 2009

dht gel 70mg vs placebo
DHT Gel 70mg Vs. Placebo
  • Men > 60 yo, T < 15 nMol/l = 428 ng/dl
  • Decreased LDL, no change HDL
  • Increased Hemoglobin/Hematocrit
  • Decreased Fat Mass
  • Knee strength increased not other muscles
  • No change QOL
  • No change PSA or prostate volume

Ly LP et al. Randomized Clinical Trial of TransdermalDihydrotestosterone Gel on Muscular Strength, Mobility and Quality of Life in Older Men with Partial Androgen Deficiency

J ClinEndocrinolMetab 2001 88:4078-4088

Claude.ch@lcdpi.com

25

© Claude Chauchard La Clinique de Paris 2009

dht rt reduces prostate size
DHT 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

Claude.ch@lcdpi.com

26

© Claude Chauchard La Clinique de Paris 2009

dht for andropause
DHT For Andropause
  • DHT gel 125-250 mg/day vs Placebo x 6 months
  • Improved erections and morning erections
  • Decreased LH, FSH, E2, T and SHBG
  • No change lipids or hepatic function
  • Hg/Hct increased
  • No 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

Claude.ch@lcdpi.com

27

© Claude Chauchard La Clinique de Paris 2009

hcg injections
HCG 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

Claude.ch@lcdpi.com

28

© Claude Chauchard La Clinique de Paris 2009

slide29
HCG
  • If there is no Leydig cell failure can treat hypogonadism with HCG injections
  • 2000-5000 units per week
  • No decrease in testicular size or sperm count
  • Can 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

Claude.ch@lcdpi.com

29

© Claude Chauchard La Clinique de Paris 2009

slide30

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

Claude.ch@lcdpi.com

30

© Claude Chauchard La Clinique de Paris 2009

slide31

No change in lipid profile including HDL

  • Skin Irritation
    • 5.5% gel, 66% patch
  • Hg/Hct increase in 100 mg gel group
    • Mean 1.3/4.1
  • PSA
    • 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 increase
  • Prostate symptom score : no change

Claude.ch@lcdpi.com

31

© Claude Chauchard La Clinique de Paris 2009

s e x
S e x
  • Improved
    • Enjoyment with partner
    • Erection firmness
    • Sexual performance
    • Sexual desire
  • Not related to dose or method of delivery or serum T obtained

Claude.ch@lcdpi.com

32

© Claude Chauchard La Clinique de Paris 2009

t and erectile function
T 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

Claude.ch@lcdpi.com

33

© Claude Chauchard La Clinique de Paris 2009

t and memory
T 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

Claude.ch@lcdpi.com

34

© Claude Chauchard La Clinique de Paris 2009

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.

Claude.ch@lcdpi.com

35

© Claude Chauchard La Clinique de Paris 2009

does trt increase angry behavior
Does TRT increase angry 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

Claude.ch@lcdpi.com

36

© Claude Chauchard La Clinique de Paris 2009

adverse effects
Adverse 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

Claude.ch@lcdpi.com

37

© Claude Chauchard La Clinique de Paris 2009

testosterone replacement in men improves
Testosterone Replacement in men improves:
  • Libido
  • Erectile Function
  • Mood
  • Memory
  • Angina
  • Type 2 diabetes
  • Muscle mass
  • Fat

Claude.ch@lcdpi.com

38

© Claude Chauchard La Clinique de Paris 2009

testosterone replacement in men may prevent
Testosterone Replacement in men may prevent:
  • Heart Disease
  • Diabetes
  • Insulin Resistance
  • Alzheimer
  • Osteoporosis

Claude.ch@lcdpi.com

39

© Claude Chauchard La Clinique de Paris 2009

slide40
Sexy
  • Increased libido
  • Increased sexual pleasure and performance
  • Improved body image

Claude.ch@lcdpi.com

40

© Claude Chauchard La Clinique de Paris 2009

this is how much the male hormone replacement can keep you younger
This is how much the male hormone replacement can keep you younger

Claude.ch@lcdpi.com

All my wishes to you

41