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Thyroid, Adrenals, and Sex Steroids - A Balancing Act

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This was the second presentation gibven on MZarch 29, 2019 at the Manlove Psychiagtric Group and Brain Injury Institute spring conference in Rapid City, SD.

In this presentation, Dr. Cady carefully goes over the necessity of integrating and overview and awareness of hormones and their levels in the elucidation of what truly is going on with the patient.

This was an overview lecture only. Dr. Cady will be presenting a 16 hour CME program in Austin Texas on June 22 and 23 for the National Procedures Institute, and will explore all aspects of all relevant hormones and what can be done to manage and optimize them.

Veröffentlicht in: Gesundheit & Medizin
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Thyroid, Adrenals, and Sex Steroids - A Balancing Act

  1. 1. Thyroid, Adrenals & Sex Hormones: A Balancing Act The Manlove Group Spring Conference Rapid City, South Dakota March 29, 2019 Louis B. Cady, MD – CEO & Founder – Cady Wellness InstituteLouis B. Cady, MD – CEO & Founder – Cady Wellness Institute Adjunct Professor – Indiana University School of Medicine Functional & Integrative Neuropsychiatry – Evansville, Indiana
  2. 2. Louis B. Cady, MD, FAPA – CEO & Founder – Cady Wellness InstituteLouis B. Cady, MD, FAPA – CEO & Founder – Cady Wellness Institute Adjunct Clinical Lecturer – Indiana University School of Medicine Department of Psychiatry Functional & Integrative Neuropsychiatry – Evansville, Indiana THYROID, ADRENALS, AND HORMONES: A Balancing Act The Manlove Group Spring Conference Rapid City, South Dakota March 23 2019
  3. 3. Framework for this presentation: “Slumber not in the tents of your fathers. The world is advancing. Advance with it.” - Giuseppe Mazzine
  4. 4. Orientation to this talk • Sketch in the fundamental differences between “wnl” and OPTIMAL • Quick review of hormones having to do with FATIGUE and DEPRESSION: – Thyroid – DHEA – Testosterone/estradiol/progesterone – IGF-1 (“foot soldier” of growth hormone) • Exposure to the literature/stimulation
  5. 5. American Journal of Health Promotion; November/December, 2002 19% of those surveyed were completely healthy with high levels of both physical and mental health and a low level of illness. 18.8% completely unhealthy, defined as having low levels of health with high levels of illness. Two-thirds of the adults reported some degree of mental or physical illness that kept them from being completely healthy. “Incompletely healthy.” HEALTH continuum DEAD O 66% “Incompletely healthy”
  6. 6. VISION: “We dramatically transform the lives of our patients and clients to levels of peak physical and mental health, supporting a lifetime of maximum performance and happiness.”
  7. 7. BODY M IN D A C TIO N S
  8. 8. Critical area of concern for men & women. Things that will make them: • Tired &/or depressed • Unable to cope • “Mean” • Stressed • Deficient in libido or in the bedroom • Demented
  9. 9. Depression & Anxiety Dx in 1 Easy Lesson DEPRESSION SIG: E- CAPS! • Sleep • Sadness • Interest loss • Guilt • *Energy • Concentration • Appetite • Psychomotor Sx • Suicidal thinking Gen. ANXIETY D.O. •Somatic Sx (“energy”,etc.) •WORRY •Irritability •Concentration •Keyed up •Insomnia (“sleep”) •Restlessness SWICKIR is Quicker: Worry + 3 = GAD (Baughman) 5of 9 with 1 of 2 x 2 weeks *MUST MUST MUST exclude “mood disorder due to a general medical condition”
  10. 10. ♦ Depressed mood 100% ♦ Reduced energy: 97%3 ♦ Fatigue or loss of energy: 94%2 ♦ Impaired concentration: 84%3 ♦ Tiredness:73%1 ♦ Hypersomnia: 10%–16%4 (Insomnia) Useful Target Symptoms in MDDUseful Target Symptoms in MDD 1. Tylee et al. Int Clin Psychopharmacol 1999;14:139-151. 2. Maurice-Tison et al. Br J Gen Pract 1998;48:1245-1246. 3. Baker et al. Comp Psychiatry 1971;12:354-65. 4. Horwath et al. J Affect Disord 1992;26:117-25. 5. Reynolds and Kupfer. Sleep 1987;10:199-215.
  11. 11. Stahl, SM. Symptoms & Criuits, Part 1 Major Depressive Disorder. “Brainstorms.” J Clin Psych 64:11, Nov 2003:1282-1283. “Each symptom may be mediated by separate and distinct neuronal [AND PHYSIOLOGICAL – (Cady)] circuits.”
  12. 12. Death OptimalHealth Traditional Medicine Functional & Informed Lab TestingNoDisease=Health Vitamins, HRT, Nutrition, Exercise INTEGRATED Medicine Diagnose and Treat Disease New DrugsNew Drugs New SurgicalNew Surgical TechniquesTechniques Forestall and PREVENT Disease – Optimize Mood & Function Toward an INTEGRATED approach:
  13. 13. Modern Medicine’s Paradigm: Two Standard Deviations – “if you are not sick, then you must be well.” “NORMAL” OPTIMAL
  14. 14. 4
  15. 15. Releasing Factors Releasing Factors Adrenal Gland Adrenal Gland OvariesOvariesTesticlesTesticles ThyroidThyroidLiverLiver Testosterone EstrogenCortisol DHEA Progesterone T3 & T4 GHLH & FSH TSHProlactinACTH IGF-1 Pituitary Brain HypothalamusHypothalamus DHEA BreastsBreasts
  16. 16. “But the doctor told me my thyroid was fine.” • Can be “wnl” but suboptimal. • TSH frequently only thing checked. • Nothing known about Free T4 or Free T3. • Free T4 can be converted to Reverse T3 under stress (cortisol) • Free T4 can be underconverted to T3. • Can have normal levels (or slightly elevated levels) of everything and have auto-immune thyroid disease.
  17. 17. “the foot soldier” “the evil twin”
  18. 18. “Thyrotropin (Thyroid-Stimulating Hormone or TSH). Measuring TSH is the most sensitive indicator of hypothyroidism.” (hunh?!) http://www.umm.edu/patiented/articles/how_serious_hypothyroidism Accessed: 9/5/2011
  19. 19. “the foot soldier” “the evil twin” CORTISOL Se
  20. 20. Transthyretin (a systemic amyloid precursor) may be protective for Alzheimer’s (Why?) Li X et al. J Neurosci 2011 Aug 31;31(55):12483-90
  21. 21. Per HRSD – 17, remission in: 15.9% on Li 24.7% on T3 Per QIDS-SR16, remission in: 13.2% on Li 24.7% for T3 * * Fava & Covino: Augmentation/Combination Therapy in STAR*D Trial, Medscape Psychiatry LEVEL III RESULTS:
  22. 22. T3 and thyroid augmentation - depression • Pharmacological management of refractory depression. – Kennedy SH, Joffe RT. Can J Psychiatry. 1989 Jun;343(5):451-6. • Use of thyroid hormone shortens depressive illness. – 15 clinical studies, {1969-1987} with 353 patients – Vegt M et al. Acta Neuropsychiatr. 1991 Jun;3(2):17-21. • “Thyroid augmentation depression” – www.pubmed.gov: – 92 citations as of 03 04 2019
  23. 23. “the foot soldier” “the evil twin” CORTISOL Se
  24. 24. • BACKGROUND: • Clinicians may not consider using the thyroid hormone liothyronine sodium (levorotary isomer of triiodothyronine [T3]) for augmentation of antidepressant drugs in depressed patients who are also receiving the precursor hormone levothyroxine (levorotary isomer of thyroxine [T4]) for thyroid disease. We now report on the successful use of T3 augmentation therapy in seven of nine depressed patients who were also receiving T4 for thyroid disease.
  25. 25. “No duh” obvious thyroid teaching points: • You must check the thyroid and you must check ALL OF IT (not just “TSH.”) • Stress and/or selenium deficiency can PROFOUNDLY alter it. • Do you want “normal” or “optimal”?
  26. 26. “Hypoadrenia”: The Adrenal Problem that most conventionally trained physicians don’t know about. • Non-Addison’s hypoadrenia • Subclinical hypoadrenia • Neurasthenia • Adrenal neurasthenia • Adrenal apathy • Adrenal fatigue • “Adrenal burnout” • “Chronic fatigue syndrome”?!!
  27. 27. Fatigue from Adrenal Dysfunction - The Worst Case Scensario: Addison’s Disease
  28. 28. Signs & Symptoms of Adrenal FATIGUE • Difficulty getting up in a.m. • Ongoing lethargy during the day. • Continued fatigue not relieved by sleep. • Craving for salt or salty foods. • Increased effort to do daily tasks • LESS PRODUCTIVE • Decreased sex drive • Decreased ability to handle stress. • Light-headed when standing up quickly • Increased recovery time for illness • Generally less happy about life.
  29. 29. The state of adrenal exhaustion can be determined Early-stage Chronic Stress Response Mid-stage Chronic Stress Response End-stage (exhausted) Chronic Stress Response
  30. 30. DHEA – the critical hormone most doctors never check • Produced in the adrenal cortex – Humans and primates are unique in secreting large amounts • Immune system booster • Insulin regulator • Energy increase – remarkable • Boosts growth hormone – 20% in men; 30% in women in one study • [Yen, Morales Khorram – one year double-blind placebo controlled crossover experiment – with 100mg DHEA]
  31. 31. Pub Med search Jan 25, 2019 – “DHEA Supplementation” 421 citations • Improves sexual function in older premenopausal women with low baseline FSFI scores (Female Sexual Function Index) – Kushner VA. Endocrine 2018 Oct 11. • Ameliorates abnormal mitochondrial dynamics and mitophagy of cumulus cells in poor ovarian responders (in IVF work) . “DHEA may prevent mitochondrial dysfunction through regulating mitochondrial homeostasis and mitophagy.” – Li CJ et al. J Clin Med. 2018 Sep 20:7(10)
  32. 32. Pub Med search Jan 25, 2019 – “DHEA Supplementation”(cont.) • (mouse studies) - Improves insulin secretion of pancreas; increases insulin sensitivity of the liver, adipose tissue and muscle. (Not yet demonstrated to have effect in human AODM) – Aoki K et al. Viamin Horm. 2018; 108:365-365} • Several interesting studies noted correlations between DHEA and multiple physiological functions: – Neurological, cognition, memory, depression, decreased bone mineral density, obesity, diabetes, increased CV mortality, ERECTILE DYSFXN, and decreased libido. – Dehydroepiandrossterone and erectile function: A review. El- SakkaAI. World J Mens Health. 2018 Sep 36 (3):183-191
  33. 33. Dehydroepiandrosterone Monotherapy in Midlife-Onset Major and Minor Depression • Double blind, randomized, placebo–controlled, crossover study (Jan 4 1996 – August 31, 2002) at NIMH Midlife Outpatient Clinic – 23 men, 23 women, aged 45 – 65 – Midlife onset of major or minor depression. • “We find DHEA to be an effective treatment for midlife-onset major and minor depression.” Schmidt PJ, Daly RC, Bloch M, et al. Dehydroepiandrosterone monotherapy in midlife-onset major and minor depression. Arch Gen Psychiatry. 2005 Feb;62(2):154-162.
  34. 34. DHEA – some ‘faves” from the literature • DHEA treatment improves HRQOL with regard to mental well-being and sexuality. – Nordmark G, Bengtsson C, Larsson A, et al. Effects of dehydroepiandrosterone supplement on health-related quality of life in glucocorticoid treated female patients with systemic lupus erythematosus. Autoimmunity. 2005 Nov;38(7):531-540. • DHEA Tx could play a role in the prevention and tx of metabolic syndrome associated with abdominal obesity. – Villareal & Holloszy. JAMA. 2004 Nov 10;292(18):2243-8. • DHEA – modest and selective benefical effect on BMD & bone resorption in women. – Von Mühlen D, Laughlin GA, Kritz-Silverstein D, et al. Osteoporos Int. 2008 May;19(5):699-707. • Improved memory, recollection and mood; decreased trough cortisol levels. – Alhaj HA, Massey AE, McAllister-Williams RH. Effects of DHEA administration on episodic memory, cortisol and mood in healthy young men: a double-blind, placebo- controlled study. Psychopharmacology (Berl). 2006 Nov;188(4):541-551.
  35. 35. Why isn’t adrenal fatigue diagnosed? • Not severe enough to be an emergency • Symptoms can be attributed to other things, including “just neurotic” or “avoidant” • “Functional medicine” testing not typically done (& rarely is DHEA-S checked) • Modern medicine focuses on the treatment of sickness, not “less than optimal” function. • “Bell Curve” paradigm
  36. 36. Modern Medicine’s Paradigm: 2 Standard Deviations – a model “NORMAL” OPTIMAL
  37. 37. 432 citations on DHEA with depression as of 9/5/2011 “Neuroeconomic paramaters predicted to be related to suicidal behavior.” DHEA is related to these, acting in amygdala. Low levels of DHEA/DHEA-S assoc. with depression, as per Western studies. “DHEA was significantly assoc. w/ [Chinese] Geriatric Depression Scale (GDS).”
  38. 38. 628 citations on DHEA with depression as of 3/4/2019
  39. 39. Neurobiological & neuropsychiatric effects of DHEA & DHEAS [Maninger N et al. Front Neuroendocrinology 2009] • DHEA & DHEAS synthesized in adrenals AND BRAIN. • Biological actions of DHEA/DHEA-S: – Neuroprotection – Neurite growth – Antagonistic effects on oxidants & glucocorticoids • “accumulating data suggest abnormal DHEA (S) concentrations in several neuropsychiatric conditions.”
  40. 40. Key concept “ADRENALS BEFORE THYROID.”
  41. 41. 59 year old female, post-menopausal, on no hormones • On aggressive supplement regimen with daily MVI and others • Not ill • Top rated medical care with previous labs done • Nothing identified as seriously abnormal • “Just interested in having my hormones checked.”
  42. 42. Relevant labs – 59 yo female • CBC, CMP wnl • TFT’s – TSH 1.670 {0.45 – 4.5] – Free T4 1.12 {0.82-1.778} – Free T3 2.7 {2.0 – 4.4} • Vitamin D 23.6 (L) {30 – 100; 50 – 80} • Hormones – DHEA-S 148.5 {“18.9 – 205.0”} – Total testosterone 15 {“3 – 41”} – Free Testosterone 0.5 {0.0 – 2.2} – Estradiol 12.7 {12.5 – 166 follicular, vs <6.0 – 54.7 = post-menopausal} – Progesterone 0.3 {0.2 – 1.5 vs. 0.1 – 0.8} – IGF -1 100 {81-225} • CRP 5.1(H) {0 – 4.9}
  43. 43. Treatment for this “normal” patient 1. porcine thyroid (T4 + T3 + T2 + T1) – ¼ grain for 1 week, then ½ grain. (Aiming for T3 in “high 3’s.” 2. DHEA – 25 mg SR micronized, compounded – in a.m. 3. Progesterone – 50 mg SR compounded – at night. 4. Testosterone – 3mg topical per day x 1 wk, then 6 mg. “Decrease dosing as needed for side effects.” 5. Vitamin D – 5,000 IU twice daily x 3 weeks, then decrease to one dose per day. 6. Fish oil – 4.6 grams (c. 1660 mg EPA and 1,250 mg DHA by compound weight, plus misc. Omega 3)
  44. 44. What’s life like now? • “it’s like the colors of the rainbow have gotten more into the pink.” • “My computer will survive – I use to ‘lose it’ over my computer. I would swear obscenities.” • “I’ve gotten into a zen like mode. Handling everything that life can throw at me.” • “It’s almost as if I’ve taken a pill or drug that jus makes me handle everything that life is throwing at me. I can roll with it.” • “I’m not irritable any more. Time pressure has just one away.”
  45. 45. Fast food (low Zn) is bad for you. • Fast food = high energy density = low essential micronutrient density, ESPECIALLY ZINC • Antioxidant processes are dependent on Zinc • Fast food = severe decrease in antioxidant vitamins and zinc, correlating with inflammation in testicular tissue – with underdevelopment of testicular tissue and decreased testosterone levels
  46. 46. Special needs - Zinc • Low Zinc- associated with low testosterone – Per USDA, 60% of US men between 20 – 49 years of age do not get enough. – N.B.: Do not supplement with > 50 mg daily (can interfere with Cu+ metabolism) • Tsai, E.C., Boyko, E.J., Leonetti, D.L., & Fujimoto, W.Y. (2000). Low serum testosterone level as a predictor of increased visceral fat in Japanese- American men. International Journal of Obesity and Related Metabolic Dis 24, 485-491
  47. 47. Testosterone functions (Men AND Women) • Enhances sex drive • Builds muscle & decreases fat • Elevates mood • Prevents osteoporosis • Improves memory • Lowers cholesterol • Protects against heart disease
  48. 48. “Hence, among older men reporting excellent asymptomatic health, age has no effect on serum T or E2 with a minor increase in DHT while obesity decreases serum androgens…”
  49. 49. • Decline in male sex steroids not as abrupt as menopause, but equally debilitating –Between 40 – 70, average male loses: • Nearly 2" of height • 15% of bone density • 10 – 20 pounds of muscle •At 70 yoa, 15% completely impotent Testosterone (Men)
  50. 50. Andropause: Characteristics of Change • Insidious & unpredictable onset • Slow progression • Subtle & variable manifestations • Cannot be linked directly to a decrease in the hormone testosterone • Very different from menopause in women! Charlton R. JMHG. 1(2004): 55-9 Kaufman JM. Endocrine Reviews. 26(2005):833-76
  51. 51. T vs Cognitive Function Rosario ER. JAMA. 292(2004):1431-2
  52. 52. T vs Cognitive Function Rosario ER. JAMA. 2004(292):1431-2 “Testosterone depletion likely precedes and thus may contribute to rather than result from the development of AD, since low brain testosterone is observed in men with early indications of AD neuropathology”
  53. 53. CLINICAL VIGNETTE
  54. 54. #1: The Case of the Phrustrated Pharmacist (8/3/2014) • 73 yo MWM retired (2009) R.Ph. “burned out.” Essentially sitting home depressed, not going anywhere • Presenting Rx: – Fluoxetine – 40 mg – Quetiapine – 50 mg XR for sleep (??) – Hydralazine, amlodipine, simvastatin, metformin, ASA • ROS: Decrease in libido, Profound fatigue
  55. 55. Mental Status Examination • Depression: – Sad/depressed/down in the dumps – Lack of/loss of interest in things – Trouble concentrating – Insomnia/trouble sleeping at times – Decreased energy – Guilty/worthless – which is irrational – he has nothing to feel guilty about it. (6 total symptoms; 5 = required) • Other symptoms: – Weakness, hopeless, feeling life is not worth living, sleeping too much, loss of libido, and full diagnostic criteria met for generalized anxiety disorder
  56. 56. Relevant Markers • Thyroid Functions – TSH 0.43 {0.34 – 5.61} – Free T4 1.34 {0.587 – 1.64} – Free T3 2.8 {2.0 – 4.4} – Reverse T3 32.1 (H) {9.2 – 24.1} • Sex Hormone – LH 8.7 (H) {1.24 – 8.62} – Total testosterone 199 (L) {348 – 1197} – Free Testosterone 3.6 (L) {6.6 – 18.1} – PSA 0.24 {0.0 – 4.0] – Estradiol 13.6 {7.6 – 42.6} • Coenzyme Q10 0.75 {0.37-2.20}
  57. 57. Interventions – 8/14/2013 • Testosterone IM – 200 mg ASAP, then 100 mg every 4 days until levels better • DHEA – 25 mg timed release • Liothyronine – timed release • High potency MVI (200% Selenium; 100% Zinc RDA) • (Continued fluoxetine)
  58. 58. The Phrustrated Pharmacist: What Happened? • 11/26/2013 – (3 ½ months later) – Going to all grandchildren’s soccer games – Out mowing his yard and mulching leaves – Depressive symptoms ELIMINATED – Appetite has gone up; but clothes fitting better – Plenty of energy • 1/16/2014 – “I’ve been doing good – I’m doing everything. I walk the dog every day. I go to the soccer games.” – Has gone to get OSA checked – Has lost so much weight (60 lbs.) he’s using clothes pins on pajamas
  59. 59. What Happened to Labs (1/6/2014)? • Thyroid functions – TSH 0.47 {0.34 – 5.61} – Free T4 0.67 {0.587 – 1.64} – Free T3 3.8  {2.0 – 4.4} – Reverse T3 14.5  {9.2 – 24.1} • Hormones (Rx of 80 mg T twice weekly) – Total testosterone 582 {348 – 1197} – Free Testosterone 12.0 {6.6 – 18.1} – DHEA-Sulfate 378 (“H”) {30.9 – 295.6”; OPTIMAL RANGE – per Cenegenics is about 500
  60. 60. Final Follow-up of Frustrated Pharmacist – 4/15/2014 • Animated and alert • Got hired to tutor pharmacology at local community college • Playing in handbell choir again – “I’m not very good – they let me play the half notes and whole notes with the great big bells.” • Quipped about a customer he recalled who came in (in past) and asked for “methyl-testosteroney.” • On CPAP for six weeks, Doing well
  61. 61. Teaching Points • No change in antidepressants required to ELIMINATE depression • Thyroid and testosterone optimized • High potency nutritional supplementation given • Appropriate allopathic care given • Predictable results occurred • BUT WHAT ABOUT THE LAST 20 YEARS? • This way of thinking works in ALL specialties
  62. 62. Testosterone and “Prostate Cancer risk” • Prostate CA found 2.15 & 2.26 times more likely in lowest compared to highest tertile of total and free testosterone • “. . . there are several papers showing a relationship between LOW testosterone and prostate cancer. Specifically, low testosterone has been associated with high-grade tumors, advanced stage of presentation, and worse prognosis.” Morgentaler A. Eur Urol. 50(2006):935-9 Morgentaler A. Urology. 68(2006):1263-7
  63. 63. Risk of Venous Thromboembolism in Men Receiving Testosterone Therapy • 30,572 men >/=40 years of age. In nation’s largest commercial insurance programs – 1/1/2007 – 12/31/2014. • Identified cases – men with dx of VTE who received anticoagulant drug in the 60 days after their diagnosis. • “Exposure to testosterone therapy in the 154 days before the even/index date was not associated with an increased risk of VTE.” Baillargeon J et al (incl. Morgentaler) – Mayo Clinic Proceedings, August 2015, vol 90, issue 8: 1038-1045.
  64. 64. Risk of Venous Thromboembolism in Men Receiving Testosterone Therapy • “Having filled a prescription for testosterone therapy was not associated with an increased risk of VTE in commercially insured middle-aged and older men.” Baillargeon J et al (incl. Morgentaler) – Mayo Clinic Proceedings, August 2015, vol 90, issue 8: 1038-1045.
  65. 65. A 2nd Paper on Risks of Testosterone • “In this population of older men with limitations in mobility and a high prevalence of chronic disease, the application of a testosterone gel was associated with an increased risk of cardiovascular adverse events.” • Subjects: 65 yo or older, mobility limitations; testosterone level of {100-350 ng/dL} – Baseline: “a high prevalence rate” of HTN, DM, hyperlipidemia, and obesity” Basaria S et al. Adverse events associated with testosterone administration. N Engl J Med 2010 Jul8;363(2)
  66. 66. “For me, the practice of medicine has opened the door to the greatest adventure in life. Medicine is like a hallway lined with doors, each door opening into a different room, and each room opening into another hallway, again lined with doors. Medicine is always wonderful and never will be finished.” - Charles H. Mayo, M.D.
  67. 67. “For me, the practice of medicine has opened the door to the greatest adventure in life. Medicine is like a hallway lined with doors, each door opening into a different room, and each room opening into another hallway, again lined with doors. Medicine is always wonderful and never will be finished.” - Charles H. Mayo, M.D.
  68. 68. Appendix
  69. 69. Extra slides for further background follow in notes  Contact info: Louis B. Cady, M.D. www.cadywellness.com Office: 812-429-0772
  70. 70. Fundamental Concepts Regarding Testosterone Deficiency & Treatment: International Expert Consensus Resolutions • International expert consensus panel convened in Prague, Czech Republic on Oct 2, 2015. • Specialties represented: – Urology, endocrinology, diabetology, internal medicine, and basic science research. – Nine resolutions were debated, with unanimous approval. Morgentaler A et al. – Mayo Clinic Proceedings. 2016 Jul;91(7):881-96.
  71. 71. 9 Unanimous Resolutions 1. TD (testosterone deficiency) is well established, clinically significant, and affects male sexuality. 2. S/Sxs of TD occur as a result of low levels of T and may benefit from treatment regardless of whether there is an identified underlying etiology. 3. TD is a global health concern. 4. T therapy for men is effective, rational, and evidence-based. Morgentaler A et al. – Mayo Clinic Proceedings. 2016 Jul;91(7):881-96.
  72. 72. 9 Unanimous Resolutions 5. There is no T threshold that reliably distinguishes those who will reliably respond to tx from those who will not. 6. There is no scientific basis for any age- specific recommendations against the use of T therapy in men 7. The evidence does not support increased risks of cardiac event with T therapy. Morgentaler A et al. – Mayo Clinic Proceedings. 2016 Jul;91(7):881-96.
  73. 73. 9 Unanimous Resolutions 8. The evidence does not support increased risk of prostate cancer with T therapy. 9. The evidence supports a major research initiative to explore possible benefits of T therapy for cardiometabolic disease, including diabetes. “These resolutions may be considered points of agreement by a broad range of experts based on the best available science." Morgentaler A et al. – Mayo Clinic Proceedings. 2016 Jul;91(7):881-96.
  74. 74. T vs Cognitive Function • 400 independently living men, 40-80yo – 100 in each age decade – MMSE 21-30, average 28 – TT: 208-1141ng/dL; Bio-avail T 78-470ng/dL • HIGHER T = better cognitive performance in OLDEST AGE category • Men with lowest 1/5 T = worse than men with highest 1/5 T • Highest Bio-available T more significant than TT, age, intelligence level, mood, smoking, and alcohol. Muller M. Neurology. 64(2005):866-71
  75. 75. T vs Mood in men • Study: 278 men, >45yo, followed 2 years • Compared to eugonadal patients, hypogonadal men w/TT <200ng/dL had – 4-fold increase risk of depression – Significantly shorter time to depression diagnosis • Depression risk inversely related to TT w/statistical significance <280ng/dL Shores MM, Arch Gen Psychiatry. 61(2004):162-7
  76. 76. Treatment options – not just “the needle”
  77. 77. Health is a state of complete physical, mental and social well-being, and not merely the absence of disease or infirmity. - World Health Organization
  78. 78. ADAM Questionnaire • Do you have a decrease in libido (sex drive)? • Do you have a lack of energy? • Do you have a decrease in strength and/or endurance? • Have you lost height? • Have you noticed a decreased “enjoyment of life”? Tancredi A. Eur J Endocrinol. 151(2004):355-60
  79. 79. ADAM Questionnaire • Are you sad and/or grumpy? • Are your erections less strong? • Have you noted a recent deterioration in your ability to play sport? • Are you falling asleep after dinner? • Has there been a recent deterioration in your work performance? Tancredi A. Eur J Endocrinol. 151(2004):355-60
  80. 80. ADAM Questionnaire • Positive result if yes to – answer 1 or 7 – any three other questions • High sensitivity (~80%) to identifying aging males w/low free testosterone levels • Low specificity (~20%) • Validated in other languages Tancredi A. Eur J Endocrinol. 151(2004):355-60

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