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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.

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A memorandum on andropause management

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  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

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

  8. Testosterone & Prostate 8 © Claude Chauchard La Clinique de Paris

  9. Overview ECBU UIV Bladder Full Abdominal Sonography 9 © Claude Chauchard La Clinique de Paris

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  21. 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

  22. 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

  23. 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

  24. 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

  25. 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

  26. 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

  27. 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

  28. 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

  29. 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

  30. 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

  31. 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

  32. 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

  33. 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

  34. 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

  35. 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

  36. 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

  37. 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

  38. 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

  39. 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

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

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

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