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ED, EjD, and Hypogonadism in Diabetic Males

ED, EjD, and Hypogonadism in Diabetic Males. Steven N. Gange, MD, FACS. 4252 S. Highland Drive. Lane Childs, MD Peter Fisher, MD Steven Gange, MD Scott Hopkins, MD Regan Brooks, PA-C Elizabeth Darling, PA-C. This is a talk about sex, and contains potentially offensive images….

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ED, EjD, and Hypogonadism in Diabetic Males

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  1. ED, EjD, and Hypogonadism in Diabetic Males Steven N. Gange, MD, FACS

  2. 4252 S. Highland Drive Lane Childs, MD Peter Fisher, MD Steven Gange, MD Scott Hopkins, MD Regan Brooks, PA-C Elizabeth Darling, PA-C

  3. This is a talk about sex, and containspotentially offensive images…

  4. Men’s Health Statistics Reality bites…

  5. With Respect to American Women, Men… • Die 7 years younger (1 year younger in 1920) • Die more often from all 15 leading causes of death (except Alzheimer’s) • Greater risk of serious chronic diseases, and suffer from them at an earlier age • Are twice as likely to die from heart disease (3 of 4 heart attack deaths under 65 are men)

  6. With Respect to American Women, Men… • More likely to be drug abusers, pathological gamblers, alcoholics, and smokers…

  7. With Respect to American Women, Men… • Are responsible for 8 of 10 car accidents!

  8. Men Avoid Doctors • Twice as many men than women have no regular source of medical care • Men comprise 70% of those who haven’t seen a doctor in the past 5 years • 25% of men would wait “as long as possible” to see a doctor

  9. And, yet… • What universally gets a man’s attention:

  10. Older Men Are Still Sexually Active 92% Sexual activity = Intercourse, masturbation and any activity that the participant considered “sexual” 83% 83% 100% 65% 80% 60% % of men with sexual activity in the last 4 weeks 40% 20% 0% Total 50-59 60-69 70-79 Age Rosen R. Multinational Survey of the Aging Male (MSAM-7). Presented at the Annual Meeting of the AUA ; May 26, 2002; Orlando, Fla.

  11. Massachusetts Male Aging Study:Prevalence of Erectile Dysfunction (ED) • In 2005, 30 million men are affected worldwide • By 2025, over 300 million men will have ED Feldman HA et al. J Urol. 1994;151:54-61.

  12. Major Risk Factors for ED: Aging Age-Adjusted Progression of ED 67 57 48 Prevalence (%) 40 Severe ED Moderate ED Mild ED Feldman HA, Goldstein I, Hatzichristou DG et al. Impotence and its medical and psychosocial correlates: results from the Massachusetts Male Aging Study. J Urol. 1994;151(1):54-61.

  13. Major Risk Factors for ED • Aging • Chronic diseases • Hypertension • Diabetes • Depression • Cardiovascular disease • Medications • Antihypertensives • Thiazide diuretics • Beta-blockers • Lifestyle • Stress • Alcohol abuse • Smoking Feldman HA et al. J Urol. 1994;151:54-61.

  14. ED and Endothelial Injury Precursors Diabetes Dyslipidemia OxidativeStress Hypertension Tobacco EndothelialCell Injury Vasoconstriction Atherosclerosis Erectile Dysfunction Thrombosis Outcomes Dzau et al. Am J Cardiol. 1997;80:33I-39I Cooke, Dzau. Annu Rev of Med. 1997;48:489-509 Solomon et al. Heart. 2003;89:251-254.

  15. Anatomy of an Erection

  16. Anatomy of an Erection

  17. Anatomy of an Erection

  18. How Inflow Affects Outflow

  19. Biochemistry of an Erection:The Nitric Oxide (NO) Story • Prior to 1990: an air pollutant • Named “Molecule of the Year” by Science magazine in 1992 • Nobel Prize in Medicine 1998 to 3 PhDs responsible for discovery

  20. Phosphodiesterases • Main role: termination of cyclic nucleotide second messenger signal, often cGMP • 11 PDE groups (PDE 1-11) • PDE-5 breaks down cGMP (the second messenger of Nitric Oxide—NO), reversing the muscle-relaxant effect of NO • PDE-5 is found in corpus cavernosum, vascular and visceral muscles, and in platelets

  21. N.O. Release Increases Penile Bloodflow Lue,T. NEJM 2000. 342:1802

  22. PDE-5 Terminates the Process and Slows Blood Flow Norepinephrine released Lue,T. NEJM 2000. 342:1802

  23. Ejaculation and Orgasm

  24. Ejaculatory Anatomy

  25. Components of Ejaculation • Seminal emission: semen is delivered into the posterior urethra • Propulsion of semen from the posterior urethra outside, involving muscular contractions of the epididymus, vas deferens, seminal vesicles, and prostate • Simultaneous bladder neck closure • Orgasm is the sensation that accompanies ejaculation in the male (it is rare for one to occur without the other)

  26. Erection and Ejaculation Necessities • Libido • Intact neural pathway • Adequate blood inflow • Expandable penis • Compressible veins • Continued stimulation • Prostate and seminal vesicles • Competent bladder neck

  27. Erection and Ejaculation Necessities • Libido • Intact neural pathway • Adequate blood inflow • Expandable penis • Compressible veins • Continued stimulation • Prostate and seminal vesicles • Competent bladder neck

  28. It doesn’t take much for a man with testosterone to become aroused

  29. Male Hypogonadism(symptomatic low testosterone level)

  30. Hypothalamus Production and Regulationof Testosterone GnRH Pituitary Free T 2% FSH Testosterone LH Albumin- bound T 38% SHBG-bound T 60% Testis 40% of serum testosterone is “bioavailable” Testosterone Adapted from Braunstein G.D.. In: Basic & Clinical Endocrinology. 5th ed. Stamford, Conn: Appleton & Lange; 1997:403-433. Sperm Adapted from Bagatell C.J., Bremner W.J.. N Engl J Med. 1996;334:707-715.

  31. Testosterone At Work Dihydrotestosterone (DHT) is the primary end-organ androgen

  32. Hypogonadism in the Aging Man • All components of testosterone decline with normal aging • Decline in Leydig cell count and function • Increase SHBG, lowers bioavailable T • Not all men with low testosterone have symptoms or need treatment Tenover J.L. Endocrinol Metab Clin North Am. 1998;27:969-987. Swerdoff, R.S. Summary of the Consensus Session from the 1st Annual Andropause Consensus Meeting. The Endocrine Society, April 2000.

  33. Age-Related Changes in Testosterone 20 (177) 18 (144) (151) 16 Testosterone (nmol/L) (109) 14 (43) (158) 12 10 30 40 50 60 70 80 90 Age (Years) Adapted from Harman S.M., et al. J Clin Endocrinol Metab. 2001;86:724-731.

  34. Rates of Low T in Selected Conditions Other Areas of Concern HIV/AIDS 30% of HIV-infected men and 50% of men with AIDS have low testosterone.2 Chronic Pain 74% of men consuming sustained-action oral opioids have low testosterone.3 Type 2 Diabetes Hyperlipidemia Hypertension Obesity 1. Mulligan, et al. Int J Clin Pract 2006 Jul;60(7):762–769 2. Dobs A.S. Clin Endocrinol Metab 1998;12:379-370 3. Daniell HW. J Pain 2002 Oct;3(5):377-84

  35. Potential Effects of Hypogonadism Long-term complications • Decline in libido and erectile function • Increased body fat mass • Decreased muscle mass, bone mass, and strength • Possibly: fatigue, mood / cognitive changes • Increased incidence of osteoporosis Tenover J.L.. Endocrinol Metab Clin North Am. 1998;27:969-987. Petak S.M., et al. AACE Clinical Practice Guidelines. Available at: http://www.aace.com/clin/guidelines/hypogonadism.html.

  36. Hormones and Osteoporosis Annual Fracture Incidence Donaldson L..F, et al. J Epidemiol Community Health. 1990;44:241-245.

  37. Testosterone and Sex • ED exclusively related to hypogonadism is rare (5%) • In hypogonadal men with ED, return to low level of normal testosterone range is adequate • Libido is most likely to improve with treatment • Spermatogenesis is greatly reduced with testosterone replacement, and may not be reversible with cessation Bhasis, S., Mayo Clin Proc 2000; 75: S70. Leungwattanakij, S., et al, Mediguide to Urology, 2000; 13:1.

  38. Diagnostic Testosterone Testing: Initial Tests • Serum Total Testosterone (free plus protein-bound) Morning sample recommended in young men Reasonable screening tool • Serum Free Testosterone (nonprotein-bound) Better in older/obese men • Serum Bioavailable T (free plus albumin-bound) Measures albumin-bound and free testosterone Best test, most expensive . Tenover J.L.. Endocrinol Metab Clin North Am. 1998;27:969-987. Braunstein G.D.. In: Basic & Clinical Endocrinology. 5th ed. Stamford, Conn: Appleton & Lange; 1997:403.

  39. Diagnostic Testosterone Testing: Additional Tests • LH and FSH • Serum Prolactin • Baseline PSA, Hematocrit Tenover J.L.. Endocrinol Metab Clin North Am. 1998;27:969-987.

  40. Risks of Testosterone Replacement Therapy (TRT) • Hepatic adverse effects with oral therapy • Polycythemia • Edema • Gynecomastia • Precipitation or worsening of sleep apnea • Infertility • Acceleration of BPH or Prostate Cancer Petak S.M., et al. AACE Clinical Practice Guidelines. Available at: http://www.aace.com/clin/guidelines/hypogonadism.html. S.Leungwattanakij, et al. Mediguide to Urology 2000; 13:1.

  41. Absolute Contraindications of TRT • Male breast cancer • Known or suspected prostate cancer • Hematocrit > 55% • Known or suspected sensitivity to ingredients used in testosterone therapy systems Petak S.M., et al. AACE Clinical Practice Guidelines. Available at: http://www.aace.com/clin/guidelines/hypogonadism.html. Cunningham, G.R. Summary of the Consensus Session from the 2nd Annual Andropause Consensus Meeting. The Endocrine Society, April 2001.

  42. Testosterone Delivery Systems • Oral and transmucosal tablets • Injectables • Transdermal patches • Transdermal gel Petak S.M., et al. AACE Clinical Practice Guidelines. Available at: http://www.aace.com/clin/guidelines/hypogonadism.html. Bals-Pratsch M./, et al. Acta Endocrinol (Copenh). 1988;118:7-13. Arver S., et al. J Urol. 1996;155:1604-1608.

  43. Oral Testosterone • Oral free- and methyl-testosterone: 98% first pass effect in liver; hepatotoxic • Transmucosal delivery (Striant): - twice a day - doesn’t fully dissolve Leungwattanakij, S. et al, Mediguide to Urology, 2000; 13:1.

  44. Injectable Delivery Systems • Testosterone enanthate and cipionate (t1/2 = 4.5 d) 200 mg injection dosed every 14 to 21 days 100 mg every week minimizes troughs • Testosterone proprionate (t1/2 = 0.8 d) must inject every 2-3 days Leungwattanakij, S. et al, Mediguide to Urology, 200; 13:1.

  45. Testosterone Enanthate 250 mg Administered IM Every 3 Weeks Behre HM, et al. In: Testosterone: Action, Deficiency, Substitution. Berlin, Germany: Springer-Verlag; 1998:329-348.

  46. Transdermal Patches • Androderm 5 mg/d, applied to back, abdomen, etc High rate of skin irritation Leungwattanakij, S. et al, Mediguide to Urology, 200; 13:1.

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