A memorandum on andropause management Dr. Claude Chauchard Paris, FRANCE Chairman & CEO - La Clinique de Paris Group Former Assistant Professor of Montpellier University 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 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 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 Claude.ch@lcdpi.com 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

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

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

Testosterone & Prostate 8 © Claude Chauchard La Clinique de Paris

How to evaluate the right patient for HRT and Prostate Prevention? Overview How to evaluate the right patient for HRT and Prostate Prevention? Clinical Symptoms of Male Menopause Physical Exam Blood Pressure Prostate condition - Rectal Touch (smooth or not) Lean Mass Fat Mass Loss Hair on Legs PSA Free PSA PSA Velocity FSH, LH, Test., Free T, SHBG, E2 CBP Kidney & Liver Function Prostate Sonography – study of urinary flow Bone Density Abdominal Sonography Bladder Full UIV ECBU 9 © Claude Chauchard La Clinique de Paris

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 Claude.ch@lcdpi.com 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 Menopause Claude.ch@lcdpi.com 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 Menopause Claude.ch@lcdpi.com 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 Menopause TESTOSTERONE Claude.ch@lcdpi.com 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 ? Claude.ch@lcdpi.com 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

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

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

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

Methods of TRT Claude.ch@lcdpi.com 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 Claude.ch@lcdpi.com 19 © Claude Chauchard La Clinique de Paris 2009

Methods of TRT Claude.ch@lcdpi.com 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 Claude.ch@lcdpi.com 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

Transdermal Claude.ch@lcdpi.com Androgel Compounding pharmacies 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 Claude.ch@lcdpi.com 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 Claude.ch@lcdpi.com 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 Claude.ch@lcdpi.com 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 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.ch@lcdpi.com 25 © Claude Chauchard La Clinique de Paris 2009

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 Claude.ch@lcdpi.com 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 Claude.ch@lcdpi.com 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

HCG Claude.ch@lcdpi.com 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

Claude.ch@lcdpi.com Improved with patch and gel With gel but not patch 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

Claude.ch@lcdpi.com 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 Claude.ch@lcdpi.com 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 > 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 Claude.ch@lcdpi.com 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) 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 ? 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 Claude.ch@lcdpi.com 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: 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: Heart Disease Diabetes Insulin Resistance Alzheimer Osteoporosis Claude.ch@lcdpi.com 39 © Claude Chauchard La Clinique de Paris 2009

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 Claude.ch@lcdpi.com All my wishes to you 41