A memorandum on andropause management Dr Claude Chauchard

A memorandum on andropause management Dr. Claude Chauchard Claude. ch@lcdpi. com Paris, FRANCE Chairman & CEO - La Clinique de Paris Group Former Assistant Professor of Montpellier University Anti-aging Medicine World Congress Monte Carlo, Monaco April 8 -10, 2010 © Claude Chauchard La Clinique de Paris 2009 1

Goal of Anti-Ageing Medicine Ø Increase Health Span not just lifespan Claude. ch@lcdpi. com Ø Increase lifespan if: strong and vigorous happy content creative spiritually satisfied Ø No one wants to live longer with debility or chronic illness or cognitive impairment © Claude Chauchard La Clinique de Paris 2009 2

Balanced hormone replacement therapy All hormones restored to 25 -30 years old Claude. ch@lcdpi. com 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 3

Claude. ch@lcdpi. com Balanced HRT Human growth hormone DHEA, Pregnenolone, Melatonin Testosterone in men and women Estrogens and Progesterone in women (Bioidentical hormones) Not Premarin or Provera (MPA) Thyroid (T 3 and T 4, not just T 4) © Claude Chauchard La Clinique de Paris 2009 4

Claude. ch@lcdpi. com 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 Chauchard La Clinique de Paris 2009 5

Claude. ch@lcdpi. com Andropause & Menopause Testosterone Estrogen Body Fat Well being Sexual function Cardiovascular Disease Osteoporosis Prostate Cancer Breast Cancer © Claude Chauchard La Clinique de Paris 2009 6

Symptoms of Change of Life Male © Claude Chauchard La Clinique de Paris 2009 Female 7

Testosterone & Prostate © Claude Chauchard La Clinique de Paris 8

Overview Bladder Full Abdominal Sonography Bone Densit y UIV Prostate Sonograp hy – study of urinary flow Clinical Symptom s of Male Menopau se How to evaluate the right patient for HRT and Prostate Prevention? CBP Kidney & Liver Function Blood Pressu re Prostate condition Rectal Touch (smooth or not) ECBU FSH, LH, Test. , Free T, SHBG, E 2 PSA Free PSA Velocity © Claude Chauchard La Clinique de Paris Loss Hair on Legs Physic al Exam Fat Mass Lean Mass 9

Male Menopause = Andropause Less sudden in onset than female Claude. ch@lcdpi. com menopause Just as severe in long term consequences The cause … Decreased bioavailable TESTOSTERONE © Claude Chauchard La Clinique de Paris 2009 10

Male Menopause Fatigue Claude. ch@lcdpi. com 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 Chauchard La Clinique de Paris 2009 11

Male Menopause Increased aging of heart and circulation Claude. ch@lcdpi. com ◦ Increased MI’s and CVA’s ◦ Decreased hemodynamic function Increased brain aging ◦ Decreased memory ◦ Decreased intelligence ◦ Increased Dementia, Alzheimer’s © Claude Chauchard La Clinique de Paris 2009 12

Male Menopause Claude. ch@lcdpi. com Loss of drive and competitive edge Stiffness Falling and pain in muscles and joints level of fitness Decreased effectiveness of workouts © Claude Chauchard La Clinique de Paris 2009 13

Male Menopause The cause … Claude. ch@lcdpi. com Decreased bioavailable TESTOSTERONE Plus ◦ Stress ◦ Alcohol ◦ Increased fat especially abdominal fat ◦ Lack of exercise © Claude Chauchard La Clinique de Paris 2009 14

Does T decline with age ? Older studies showed no difference Claude. ch@lcdpi. com ◦ Did not measure free T ◦ Did not get AM samples Total T, Free T, Bioavailable T, E 1 and E 2 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 Chauchard La Clinique de Paris 2009 15

Sex Hormone Binding Globullin (SHBG) binds T >E ◦ 20 -60 nmol/l male Claude. ch@lcdpi. com ◦ 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 Chauchard La Clinique de Paris 2009 16

Serum Concentration (ng/dl) Claude. ch@lcdpi. com 800 700 Young Men 600 500 Old Men 400 0 0400 0800 1200 1600 2000 Clock Time (Hours) © Claude Chauchard La Clinique de Paris 2009 17

Hypothalamus Gn. RH Claude. ch@lcdpi. com Estrogens Aromatase LH FSH Inhibin Sperm Sertoli cell DHT Anterior Pituitary 5 -alpha Reductase TESTOSTERONE Leydig cell Testes © Claude Chauchard La Clinique de Paris 2009 18

Methods of TRT Injections Older of T enathate or T cypionate method 200 mg q 2 weeks Claude. ch@lcdpi. com ◦ 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 © Claude Chauchard La Clinique de Paris 2009 19

Methods of TRT Oral – Methyltestosterone ◦ Hepatotoxic, contraindicated Claude. ch@lcdpi. com 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 Chauchard La Clinique de Paris 2009 20

Transdermal Well absorbed as proven by serum levels Claude. ch@lcdpi. com 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 Chauchard La Clinique de Paris 2009 21

Transdermal Androgel ◦ 1% transdermal gel Claude. ch@lcdpi. com ◦ 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 Chauchard La Clinique de Paris 2009 22

Claude. ch@lcdpi. com 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 Chauchard La Clinique de Paris 2009 23

Dihydro Testosterone More potent than T (2 -5 x) Claude. ch@lcdpi. com Conversion of T to DHT via 5 -alpha- reductase Not Is aromatizeable to Estrogens DHT an important beneficial androgen or is DHT the evil twin of Testosterone ? © Claude Chauchard La Clinique de Paris 2009 24

DHT Gel 70 mg Vs. Placebo Claude. ch@lcdpi. com Men > 60 yo, T < 15 n. Mol/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 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 © Claude Chauchard La Clinique de Paris 2009 25

DHT RT Reduces Prostate Size 1. 8 year study Claude. ch@lcdpi. com BPH De requires both DHT and E 2 Lignieres B Transdermal dihydrotestosterone treatment of ‘andropause’ ◦ Ann Med 1993 Jun; 25(3): 235 -41 © Claude Chauchard La Clinique de Paris 2009 26

DHT For Andropause Claude. ch@lcdpi. com DHT gel 125 -250 mg/day vs Placebo x 6 months Improved erections and morning erections Decreased LH, FSH, E 2, 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 Chauchard La Clinique de Paris 2009 27

HCG Injections Human Chorionic Gonadotropin (HCG) Claude. ch@lcdpi. com 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 Chauchard La Clinique de Paris 2009 28

HCG there is no Leydig cell failure can treat hypogonadism with HCG injections Claude. ch@lcdpi. com If 2000 -5000 No units per week 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 Chauchard La Clinique de Paris 2009 29

Improved with patch and gel ◦ Sexual function Claude. ch@lcdpi. com ◦ 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 Chauchard La Clinique de Paris 2009 30

No change in lipid profile including HDL Skin Irritation ◦ 5. 5% gel, 66% patch Hg/Hct increase in 100 mg gel group Claude. ch@lcdpi. com ◦ 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 Chauchard La Clinique de Paris 2009 31

Sex Improved ◦ Enjoyment with partner Claude. ch@lcdpi. com ◦ Erection firmness ◦ Sexual performance ◦ Sexual desire Not related to dose or method of delivery or serum T obtained © Claude Chauchard La Clinique de Paris 2009 32

T and Erectile Function T > Placebo Claude. ch@lcdpi. com Transdermal (81%) > Oral (51%) or IM (53%) All statis. Significant Jain P et al. TESTOSTERONE SUPPLEMENTATION FOR ERECTILE DYSFUNCTION: RESULTS OF A METAANALYSIS : J Urol 2000 Aug; 164(2): 371 -375 © Claude Chauchard La Clinique de Paris 2009 33

T and Memory supplementation increased working memory in men Claude. ch@lcdpi. com T 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 Chauchard La Clinique de Paris 2009 34

T and Mood (and Erections) Effective when psych drugs do not work in Claude. ch@lcdpi. com 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 Chauchard La Clinique de Paris 2009 35

Does TRT increase angry behavior ? No Claude. ch@lcdpi. com Tricker R et al. The effects of supraphysiological doses of testosterone on angry behavior in healthy eugonadal mena clinical research center study J Clin Endocrinol Metab 1996 Oct; 81(10): 3754 -8 © Claude Chauchard La Clinique de Paris 2009 36

Claude. ch@lcdpi. com 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 Chauchard La Clinique de Paris 2009 37

Testosterone Replacement in men improves: Libido Claude. ch@lcdpi. com Erectile Function Mood Memory Angina Type 2 diabetes Muscle mass Fat © Claude Chauchard La Clinique de Paris 2009 38

Testosterone Replacement in men may prevent: Claude. ch@lcdpi. com Heart Disease Diabetes Insulin Resistance Alzheimer Osteoporosis © Claude Chauchard La Clinique de Paris 2009 39

Claude. ch@lcdpi. com Sexy Increased libido Increased sexual pleasure and performance Improved body image © Claude Chauchard La Clinique de Paris 2009 40

Claude. ch@lcdpi. com This is how much the male hormone replacement can keep younger All my wishes to you 41