Thyroid, Adrenals & Sex Hormones: A Balancing Act Louis B. Cady, MD – CEO & Founder – Cady Wellness Institute  Adjunct Pro...
Framework for this presentation: “ Slumber not in the tents of your fathers.  The world is advancing.  Advance with it.” -...
Orientation to this talk <ul><li>Sketch in the fundamental differences between “ wnl ”  and OPTIMAL </li></ul><ul><li>Quic...
American Journal of Health Promotion; November/December, 2002 19% of those surveyed were completely healthy  with high lev...
<ul><li>VISION:  “We dramatically transform the lives of our patients and clients to levels of peak physical and mental he...
BODY MIND ACTIONS
Critical area of concern for men & women.  Things that will make them: <ul><li>Tired &/or depressed </li></ul><ul><li>Unab...
How would you take care of a classic?
“ Age management”   “Conventional practice” There are fuel additives we can use to keep our cars burning cleaner and prese...
A Shrink meets the  “anti-aging” crowd <ul><li>Patient  “complaints” </li></ul><ul><li>Loss of energy </li></ul><ul><li>Lo...
Depression & Anxiety Dx in 1 Easy Lesson <ul><li>DEPRESSION SIG: E- CAPS! </li></ul><ul><li>Sleep </li></ul><ul><li>Sadnes...
<ul><li>Depressed mood 100% </li></ul><ul><li>Reduced energy : 97% 3   </li></ul><ul><li>Fatigue  or  loss of energy : 94%...
Stahl, SM.  Symptoms & Criuits, Part 1  Major Depressive Disorder.  “Brainstorms.”  J Clin Psych 64:11, Nov 2003:1282-1283...
Toward an INTEGRATED approach: Death Optimal Health Traditional Medicine Functional & Informed Lab Testing No  Disease = H...
 
 
Interesting lab values – Cady – 3/11/03: Lab Value Cenegenics Normal a.m.glucose 87 mg/dl 65 – 85 65 – 109 Fasting insulin...
Modern Medicine ’s Paradigm:  Two Standard Deviations – “if you are not sick, then you must be well.” “ NORMAL” OPTIMAL
4
Releasing  Factors Adrenal Gland Ovaries Testicles Thyroid Liver Testosterone Estrogen Cortisol DHEA Progesterone T3  &  T...
“ But the doctor told me my thyroid was fine.” <ul><li>Can be “ wnl ”  but suboptimal. </li></ul><ul><li>TSH frequently on...
“ the foot soldier” “ the evil twin ”
“ Thyrotropin (Thyroid-Stimulating Hormone or TSH).  Measuring TSH is the most sensitive indicator of hypothyroidism. ”  (...
“ the foot soldier” “ the evil twin ” CORTISOL Se
Yes, T-3 DOES get into the brain  (Transthyretin = carrier protein ) <ul><li>Terasaki, T. and Pardridge, W.M.: Stereospeci...
Transthyretin (a systemic amyloid precursor) may be protective for Alzheimer’s  (Why?) Li X et al.  J Neurosci 2011 Aug 31...
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 & Covi...
 
 
“ No duh” obvious thyroid teaching points: <ul><li>You must check the thyroid and you must check ALL OF IT (not just “TSH....
Fatigue from Adrenal Dysfunction -  The Worst Case Scensario:  Addison ’s Disease
Signs & Symptoms of Adrenal  FATIGUE <ul><li>Difficulty getting up in a.m. </li></ul><ul><li>Ongoing lethargy during the d...
“ Hypoadrenia” : The Adrenal Problem that most conventionally trained physicians don’t know about. <ul><li>Non-Addison ’s ...
The state of adrenal exhaustion can be determined Early-stage Chronic Stress Response Mid-stage Chronic Stress Response En...
DHEA – the critical hormone most doctors never check <ul><li>Produced in the adrenal cortex </li></ul><ul><ul><li>Humans a...
334  citations on  “DHEA with energy” – as of 07 29 2011
Why isn ’t adrenal fatigue diagnosed? <ul><li>Not severe enough to be an emergency </li></ul><ul><li>Symptoms can be attri...
Modern Medicine ’s Paradigm:  2 Standard Deviations –  a model “ NORMAL” OPTIMAL
432 citations on DHEA with depression as  of  9/5/2011 “ Neuroeconomic paramaters predicted to be related to suicidal beha...
Neurobiological & neuropsychiatric effects of DHEA & DHEAS  [Maninger N et al. Front Neuroendocrinology 2009] <ul><li>DHEA...
Source: Maninger, N et al : Front Neuroendocrinol. 2009 Jan;30(1):65-91. Epub 2008 Dec 3.
“ Women’s issues”
One destigmatizing notion: Estrogen as MAOI <ul><li>Estrogen & Testosterone (!) decrease  MAO </li></ul><ul><ul><li>Luin, ...
Estrogen-related mood disorders – reproductive life cycle factors.    Douma SL et al.  Adv. Nursing Sci. 2005.  28 (4):364...
Symptoms of estrogen imbalances*:  <ul><li>Hot flushes or flashes;  night sweats </li></ul><ul><li>Mood swings </li></ul><...
Psychoactive Progesterone* <ul><li>Increases  energy and libido </li></ul><ul><li>Has a  calming effect , acting like a be...
Testosterone: The “sexist” bias against women <ul><li>Fall in the circulating testosterone and the adrenal preandrogens mo...
Traditional vs.  Bio-identical  “HRT”: <ul><li>Synthetic   means that the molecule is not natural to the human body.  </li...
Women ’s Health Initiative Study <ul><li>Flawed study - it was designed as a  “Premarin & Provera” study, not a bioidentic...
Women ’s Health Initiative Study <ul><li>The results presented did not justify their overall broad conclusion:  </li></ul>...
Women ’s Health Initiative Study <ul><li>THE PARTICIPANTS: </li></ul><ul><li>2/3 of the women in the study were older than...
Women ’s Health Initiative Study Facts You Should Know <ul><li>In the first 1-3 years there was a higher incidence of M.I....
Women ’s Health Initiative Study  Facts You Should Know <ul><li>When the W.H.I. Study was organized, the subjects were not...
Hx of Baseline Health Characteristics (total # of participants 16,608) 37% 11% 2%
Traditional vs.  Bio-identical  “HRT”: <ul><li>Premarin raises C-reactive protein significantly.  </li></ul><ul><li>CRP is...
Some of the “10 reasons” to be  happy [Studd J.  Menopause Int. 2010 Mar;16(1):44-6 <ul><li>Trans-derm safer than oral </l...
50’ish year old female, post-menopausal, on no hormones <ul><li>On aggressive supplement regimen with daily MVI and others...
 
 
 
 
Treatment for this “normal” patient <ul><li>Armour thyroid – ¼ grain for 1 week, then ½ grain. (Aiming for T3 in “high 3’s...
 
What’s life like now? <ul><li>“ it’s like the colors of the rainbow have gotten more into the pink.” </li></ul><ul><li>“ M...
 
November 2009  “Alpha Male” issue <ul><li>Observational study of randomly selected men – Boston </li></ul><ul><li>3 cohort...
Fast food (low Zn) is bad for you. <ul><li>Fast food = high energy density = low essential micronutrient density, ESPECIAL...
Special needs - Zinc <ul><li>Low Zinc- associated with low testosterone </li></ul><ul><ul><li>Per USDA,  60% of US men bet...
Testosterone functions  (Men AND Women) <ul><li>Enhances sex drive </li></ul><ul><li>Builds muscle & decreases fat </li></...
“ Hence, among  older men reporting excellent asymptomatic health ,  age has no effect on serum T or E2  with a minor incr...
<ul><li>Decline in male sex steroids not as abrupt as menopause, but equally debilitating   </li></ul><ul><ul><li>Between ...
Andropause:  Characteristics of Change <ul><li>Insidious & unpredictable onset </li></ul><ul><li>Slow progression </li></u...
T vs Cognitive Function Rosario ER.  JAMA . 292(2004):1431-2
T vs Cognitive Function Rosario ER.  JAMA . 292(2004):1431-2 “ Testosterone depletion  likely precedes  and thus  may cont...
T vs Cognitive Function <ul><li>400 independently living men, 40-80yo </li></ul><ul><ul><li>100 in each age decade </li></...
T vs Mood in men <ul><li>Study: 278 men,  > 45yo, followed 2 years </li></ul><ul><li>Compared to eugonadal patients, hypog...
Treatment options – not just “the needle”
Testosterone and “Prostate Cancer risk” <ul><li>Prostate CA found 2.15 & 2.26 times  more likely  in lowest  compared to h...
HOW OBVIOUS DOES IT HAVE TO BE?    The Challenge of Empathic Listening  & CREATIVE THINKING Ron Hunt lost an eye but suffe...
Do you really want to try 100,000 miles without changing the oil?
Definition of ‘normal’ – “where your hormone levels are as lousy as everyone else’s.”  Neal Rouzier, MD “ NORMAL” OPTIMAL
American Journal of Health Promotion; November/December, 2002 HEALTH continuum DEAD OPTIMAL 66% “ Incompletely  healthy ” ...
“ For me, the practice of medicine has opened the door to the greatest adventure in life.  Medicine is like a hallway line...
Extra slides for further background follow in notes     Contact info: Louis B. Cady, M.D. www.cadywellness.com   Office: ...
Health  is a state of complete physical, mental and social well-being, and not merely the absence of disease or infirmity....
Cady response to DHEA:  March – May – 2 months… <ul><li>Dropped from 25.6% BF to 21.5% BF </li></ul><ul><li>Lost 3.3 inche...
The R-Factor Question* If we were meeting here three years  from today – and you were to look  back over those three years...
 
Indole-3-Carbinol – good with or without HRT (for women AND men) Estradiol 16 alpha-OH Estrone  (Ca) 4-OH Estrone (B) 2-OH...
ADAM Questionnaire <ul><li>Do you have a decrease in libido (sex drive)? </li></ul><ul><li>Do you have a lack of energy? <...
ADAM Questionnaire <ul><li>Are you sad and/or grumpy? </li></ul><ul><li>Are your erections less strong? </li></ul><ul><li>...
ADAM Questionnaire <ul><li>Positive result if yes to </li></ul><ul><ul><li>answer  1 or 7 </li></ul></ul><ul><ul><li>any t...
MENOPAUSE  FACTS and hormonal optimization facts: <ul><li>12 months of HRT increased skin elasticity by 5.2% </li></ul><ul...
Fatter upper body and decreased antioxidants in menopause <ul><li>Fat content increases in upper part of body (trunk and a...
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Thyroid, Adrenals, & Sex Hormones: A Balancing Act

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This is the lecture delivered on September 18, 2011, by Dr. Cady at the 2nd annual Integrated Medicine and Mental Health Conference in Sedona, Arizona.

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  • Giuseppe Mazzini (22 June 1805 – 10 March 1872), nicknamed &amp;quot;Soul of Italy,&amp;quot;[1] was an Italian politician, journalist and activist for the unification of Italy. His efforts helped bring about the independent and unified Italy[2] in place of the several separate states, many dominated by foreign powers, that existed until the 19th century. He also helped define the modern European movement for popular democracy in a republican state. [ citation needed ] – Source - Wikipedia
  • Depressed mood is the most commonly cited symptom in major depressive disorder. Studies have shown that fatigue and reduced energy are nearly as common as depressed mood. As many as 94%-97% of patients may experience reduced energy and fatigue, while 73% may complain of tiredness. Impaired concentration is also common and occurs in as many as 84% of patients. Hypersomnia, or excessive sleepiness as opposed to physical weariness, is less common and occurs in 10%-16% of patients.
  • Addison ’s disease, like so many medical conditions, has a history of being ignored, hidden, and misunderstood.  It is a rare disease that affects about one in every 100,000 Americans and is usually diagnosed around age forty. 
  • Asian J Androl. 2011 Aug 29. doi: 10.1038/aja.2011.116. [Epub ahead of print] Low DHEAS levels are associated with depressive symptoms in elderly Chinese men: results from a large study. Wong SY, Leung JC, Kwok T, Ohlsson C, Vandenput L, Leung PC, Woo J. Source School of Public Health and Primary Care, School of Public Health, The Chinese University of Hong Kong, Hong Kong, China. Abstract This study investigated the association between depressive symptoms in elderly Chinese men and the total testosterone, dehydroepiandrosterone (DHEA), DHEA sulphate (DHEAS), oestradiol and sex hormone-binding globulin (SHBG) levels, and the free androgen index. Cross-sectional data from 1147 community-dwelling elderly men, aged 65 and older, were used. Depressive symptoms were measured using the Chinese Geriatric Depression Scale (GDS). Total testosterone, free testosterone, DHEA, DHEAS, total oestradiol, the free androgen index and SHBG levels were assessed. DHEA was significantly associated with GDS score, and there was a trend towards DHEAS association, but this was not significant (β=-0.110, P=0.015; β=-0.074, P=0.055). However, no association was seen between depressive symptoms and total testosterone levels, free testosterone levels, oestradiol levels or SHBG levels. In terms of the presence of clinically relevant depressive symptoms, there were no statistically significant differences between patients in the lowest quartile of sex steroid hormone levels and those in other quartiles of sex steroid hormone levels. Similarly to Western studies, our study shows that DHEA and DHEAS levels are associated with depressive symptoms.Asian Journal of Andrology advance online publication, 29 August 2011; doi:10.1038/aja.2011.116.
  • Front Neuroendocrinol. 2009 Jan;30(1):65-91. Epub 2008 Dec 3. Neurobiological and neuropsychiatric effects of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS). Maninger N, Wolkowitz OM, Reus VI, Epel ES, Mellon SH. Graphic summary from the article, by the authors: Mechanisms of action of DHEA and DHEAS in neurons. “This cartoon summarizes many of the actions of DHEA and DHEAS described in detail in the text. DHEA and DHEAS have inhibitory effects (red blocking arrow) at the GABA A receptor (section 6 and 7.1). DHEA and DHEAS act as agonists (green arrow) at the σ 1 receptor (section 6 and 7.1), which subsequently may activate the NMDA receptor. DHEA inhibits Ca 2+ influx (red blocking arrow) into the mitochondria (section 7.1). DHEA influences embryonic neurite growth through stimulation (green arrow) of the NMDA receptor (section 7.2). DHEA increases (green arrow) kinase activity of Akt and decreases apoptosis, while DHEAS decreases (red blocking arrow) Akt and increases apoptosis (section 7.4). DHEAS increases (green arrows) TH mRNA and TH protein abundance (section 7.5) leading to increased catecholamine synthesis. DHEA and DHEAS stimulate (green arrows) actin depolymerization and submembrane actin filament disassembly and (green arrows), increasing secretion of catecholamines (“da” and “ne”) from secretory vesicles (section 7.5). DHEA and DHEAS inhibit (red blocking arrow) reactive oxygen species (ROS) activation of transcription mediated by NF-κB (section 7.6 and 7.7). DHEA inhibits (red blocking arrow) nuclear translocation of the glucocorticoid receptor (GR) (section 7.8). Mechanisms of action not pictured in this graph are: alterations of brain derived neurotrophic factor (BDNF) synthesis, inhibition of stress-activated protein kinase 3 (SAPK3) translocation, and inhibition of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSDl) activity. Abbreviations: σ 1 , sigma 1 receptor; Akt, serine-threonine protein kinase Akt; Ca 2+ , calcium; da, dopamine; GABA A , γ-aminobutyric acid type A receptor; GR, glucocorticoid receptor; ne, norepinephrine; NF-κB, nuclear factor kappa B; NMDA, N -methyl-D-aspartate receptor; ROS, reactive oxygen species; TH, tyrosine hydroxylase.”
  • One goal is to rectangularize the health span curve. I.e. to improve vitality from middle age onward.
  • These symptoms correlate to decrease in bioavailable testosterone
  • RIA (in-house after diethylether extraction) Total testosterone - T (RIA) 208-1141ng/dL, average 536+/-153ng/dL Bioavailable testosterone - BT (calculated) 78-470ng/dL, average 236+/-63ng/dL
  • Hypogonadal if TT &lt; 200ng/dL or FT &lt; 0.9ng/dL
  • Thyroid, Adrenals, & Sex Hormones: A Balancing Act

    1. 1. Thyroid, Adrenals & Sex Hormones: A Balancing Act Louis B. Cady, MD – CEO & Founder – Cady Wellness Institute Adjunct Professor – University of Southern Indiana Adjunct Professor – Indiana University School of Medicine Integrative Medicine for Mental Health Conference Sedona, Arizona September 17-18, 2011
    2. 2. Framework for this presentation: “ Slumber not in the tents of your fathers. The world is advancing. Advance with it.” - Giuseppe Mazzine
    3. 3. Orientation to this talk <ul><li>Sketch in the fundamental differences between “ wnl ” and OPTIMAL </li></ul><ul><li>Quick review of hormones having to do with FATIGUE and DEPRESSION: </li></ul><ul><ul><li>Thyroid </li></ul></ul><ul><ul><li>DHEA </li></ul></ul><ul><ul><li>Testosterone/estradiol/progesterone </li></ul></ul><ul><ul><li>IGF-1 (“food soldier” of growth hormone) </li></ul></ul><ul><li>Exposure to the literature/ stimulation </li></ul>
    4. 4. 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 OPTIMAL 66% “ Incompletely healthy”
    5. 5. <ul><li>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.” </li></ul>
    6. 6. BODY MIND ACTIONS
    7. 7. Critical area of concern for men & women. Things that will make them: <ul><li>Tired &/or depressed </li></ul><ul><li>Unable to cope </li></ul><ul><li>“ Mean” </li></ul><ul><li>Stressed </li></ul><ul><li>Deficient in libido or in the bedroom </li></ul><ul><li>Demented </li></ul>
    8. 8. How would you take care of a classic?
    9. 9. “ Age management” “Conventional practice” There are fuel additives we can use to keep our cars burning cleaner and preserve engines. No fuel additives should be used. They are unnatural. Gas is all that is required. We should use optimal quality of gas. Cheap gas causes “pinging” which is hard on the engine. The quality of the gas is irrelevant. Anything that the motor will burn is adequate. We should take our car in for preventive maintenance before anything breaks. Preventive maintenance? This is silly! Wait until something breaks, then have the car towed in so the mechanic can really tell what is wrong.
    10. 10. A Shrink meets the “anti-aging” crowd <ul><li>Patient “complaints” </li></ul><ul><li>Loss of energy </li></ul><ul><li>Loss of stamina </li></ul><ul><li>Loss of libido </li></ul><ul><li>Weight gain </li></ul><ul><li>Loss of zest for life </li></ul><ul><li>Loss of interest in career </li></ul><ul><li>“ I’ve felt like I’ve been aging since I was 35.” </li></ul><ul><li>Personal experience </li></ul><ul><li>Previous state: “energy to burn” </li></ul><ul><li>“ Snooze bar syndrome” </li></ul><ul><li>“ Piles syndrome” </li></ul><ul><li>“ Why can’t I make myself exercise?” </li></ul><ul><li>Car wash MSE! </li></ul>
    11. 11. Depression & Anxiety Dx in 1 Easy Lesson <ul><li>DEPRESSION SIG: E- CAPS! </li></ul><ul><li>Sleep </li></ul><ul><li>Sadness </li></ul><ul><li>Interest loss </li></ul><ul><li>Guilt </li></ul><ul><li>*Energy </li></ul><ul><li>Concentration </li></ul><ul><li>Appetite </li></ul><ul><li>Psychomotor Sx </li></ul><ul><li>Suicidal thinking </li></ul><ul><li>Gen. ANXIETY D.O. </li></ul><ul><li>Somatic Sx ( “ energy ”,etc.) </li></ul><ul><li>WORRY </li></ul><ul><li>Irritability </li></ul><ul><li>Concentration </li></ul><ul><li>Keyed up </li></ul><ul><li>Insomnia ( “sleep”) </li></ul><ul><li>Restlessness </li></ul>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”
    12. 12. <ul><li>Depressed mood 100% </li></ul><ul><li>Reduced energy : 97% 3 </li></ul><ul><li>Fatigue or loss of energy : 94% 2 </li></ul><ul><li>Impaired concentration: 84% 3 </li></ul><ul><li>Tiredness : 73% 1 </li></ul><ul><li>Hypersomnia : 10%–16% 4 (Insomnia) </li></ul>Useful 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.
    13. 13. 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.”
    14. 14. Toward an INTEGRATED approach: Death Optimal Health Traditional Medicine Functional & Informed Lab Testing No Disease = Health Vitamins , HRT, Nutrition, Exercise INTEGRATED Medicine Diagnose and Treat Disease New Drugs New Surgical Techniques Forestall and PREVENT Disease – Optimize Mood & Function
    15. 17. Interesting lab values – Cady – 3/11/03: Lab Value Cenegenics Normal a.m.glucose 87 mg/dl 65 – 85 65 – 109 Fasting insulin 3 u U/ml <5 <20 HgB A1C 4.9 % <5.1% < 6.0 % Cholesterol 241 mg/dl <200 <200 Triglycerides 42 mg/dl <120 <150 Cor. Risk ratio 3.3 <4.0 Av = 5 – 6 Homocysteine 7.9 <8.0 5.4-11.4 DHEA-S 148 350 – 500 59 – 452
    16. 18. Modern Medicine ’s Paradigm: Two Standard Deviations – “if you are not sick, then you must be well.” “ NORMAL” OPTIMAL
    17. 19. 4
    18. 20. Releasing Factors Adrenal Gland Ovaries Testicles Thyroid Liver Testosterone Estrogen Cortisol DHEA Progesterone T3 & T4 GH LH & FSH TSH Prolactin ACTH IGF-1 Pituitary Brain Hypothalamus DHEA
    19. 21. “ But the doctor told me my thyroid was fine.” <ul><li>Can be “ wnl ” but suboptimal. </li></ul><ul><li>TSH frequently only thing checked. </li></ul><ul><li>Nothing known about Free T4 or Free T3. </li></ul><ul><li>Free T4 can be converted to Reverse T3 under stress (cortisol) </li></ul><ul><li>Free T4 can be underconverted to T3. </li></ul><ul><li>Can have normal levels (or slightly elevated levels) of everything and have auto-immune thyroid disease. </li></ul>
    20. 22. “ the foot soldier” “ the evil twin ”
    21. 23. “ 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_000038_6.htm Accessed: 9/5/2011
    22. 24. “ the foot soldier” “ the evil twin ” CORTISOL Se
    23. 25. Yes, T-3 DOES get into the brain (Transthyretin = carrier protein ) <ul><li>Terasaki, T. and Pardridge, W.M.: Stereospecificity of triiodothyronine transport into brain, liver, and salivary gland: role of carrier- and plasma protein-mediated transport. Endocrinology , 121(3):1185-1191, 1987. </li></ul><ul><li>http://www.kingpharm.com/uploads/pdf_inserts/Cytomel_PI.pdf . </li></ul><ul><li>Mooradian, A.D.: Blood-brain transport of triiodothyronine is reduced in aged rats. Mech. Ageing Dev ., 52(2-3):141-147, 1990. </li></ul><ul><li>Cheng, L.Y., Outterbridge, L.V., Covatta, N.D., et al.: Film autoradiography identifies unique features of [125I]3,3'5'-(reverse) triiodothyronine transport from blood to brain. J. Neurophysiol ., 72(1):380-391, 1994. </li></ul><ul><li>Rudas, P. and Bartha, T.: Thyroxine and triiodothyronine uptake by the brain of chickens. Acta Vet. Hung , 41(3-4):395-408, 1993. </li></ul>Or: The idiocy of T4 only thyroid treatment…
    24. 26. 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
    25. 27. 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:
    26. 30. “ No duh” obvious thyroid teaching points: <ul><li>You must check the thyroid and you must check ALL OF IT (not just “TSH.”) </li></ul><ul><li>Stress and/or selenium deficiency can PROFOUNDLY alter it. </li></ul><ul><li>Do you want “normal” or “optimal”? </li></ul>
    27. 31. Fatigue from Adrenal Dysfunction - The Worst Case Scensario: Addison ’s Disease
    28. 32. Signs & Symptoms of Adrenal FATIGUE <ul><li>Difficulty getting up in a.m. </li></ul><ul><li>Ongoing lethargy during the day. </li></ul><ul><li>Continued fatigue not relieved by sleep. </li></ul><ul><li>Craving for salt or salty foods. </li></ul><ul><li>Increased effort to do daily tasks </li></ul><ul><li>LESS PRODUCTIVE </li></ul><ul><li>Decreased sex drive </li></ul><ul><li>Decreased ability to handle stress. </li></ul><ul><li>Light-headed when standing up quickly </li></ul><ul><li>Increased recovery time for illness </li></ul><ul><li>Generally less happy about life. </li></ul>
    29. 33. “ Hypoadrenia” : The Adrenal Problem that most conventionally trained physicians don’t know about. <ul><li>Non-Addison ’s hypoadrenia </li></ul><ul><li>Subclinical hypoadrenia </li></ul><ul><li>Neurasthenia </li></ul><ul><li>Adrenal neurasthenia </li></ul><ul><li>Adrenal apathy </li></ul><ul><li>Adrenal fatigue </li></ul><ul><li>“ Adrenal burnout” </li></ul><ul><li>“ Chronic fatigue syndrome”?!! </li></ul>Modern medicine does not recognize it.
    30. 34. The state of adrenal exhaustion can be determined Early-stage Chronic Stress Response Mid-stage Chronic Stress Response End-stage (exhausted) Chronic Stress Response
    31. 35. DHEA – the critical hormone most doctors never check <ul><li>Produced in the adrenal cortex </li></ul><ul><ul><li>Humans and primates are unique in secreting large amounts </li></ul></ul><ul><li>Immune system booster </li></ul><ul><li>Insulin regulator </li></ul><ul><li>Energy increase – remarkable </li></ul><ul><li>Boosts growth hormone </li></ul><ul><ul><li>20% in men; 30% in women in one study </li></ul></ul><ul><ul><ul><li>[Yen, Morales Khorram – one year double-blind placebo controlled crossover experiment – with 100mg DHEA] </li></ul></ul></ul>
    32. 36. 334 citations on “DHEA with energy” – as of 07 29 2011
    33. 37. Why isn ’t adrenal fatigue diagnosed? <ul><li>Not severe enough to be an emergency </li></ul><ul><li>Symptoms can be attributed to other things, including “just neurotic” or “avoidant” </li></ul><ul><li>“ Functional medicine” testing not typically done (& rarely is DHEA-S checked) </li></ul><ul><li>Modern medicine focuses on the treatment of sickness, not “less than optimal” function. </li></ul><ul><li>“ Bell Curve” paradigm </li></ul>
    34. 38. Modern Medicine ’s Paradigm: 2 Standard Deviations – a model “ NORMAL” OPTIMAL
    35. 39. 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).”
    36. 40. Neurobiological & neuropsychiatric effects of DHEA & DHEAS [Maninger N et al. Front Neuroendocrinology 2009] <ul><li>DHEA & DHEAS synthesized in adrenals AND BRAIN. </li></ul><ul><li>Biological actions of DHEA/DHEA-S: </li></ul><ul><ul><li>Neuroprotection </li></ul></ul><ul><ul><li>Neurite growth </li></ul></ul><ul><ul><li>Antagonistic effects on oxidants & glucocorticoids </li></ul></ul><ul><li>“ accumulating data suggest abnormal DHEA (S) concentrations in several neuropsychiatric conditions.” </li></ul>
    37. 41. Source: Maninger, N et al : Front Neuroendocrinol. 2009 Jan;30(1):65-91. Epub 2008 Dec 3.
    38. 42. “ Women’s issues”
    39. 43. One destigmatizing notion: Estrogen as MAOI <ul><li>Estrogen & Testosterone (!) decrease MAO </li></ul><ul><ul><li>Luin, VN. Brain Res. 1975;86:273-306 </li></ul></ul><ul><li>Platelet MAO levels inversely correlated to estradiol levels </li></ul><ul><ul><li>Klaiber EL et al. Psychoneuroendo- crinology. 1997 Oct;22(7):549-58. </li></ul></ul><ul><li>Estrogen decreases MAO-A & MAO-B </li></ul><ul><ul><li>Holschneider DP et al. Life Sci. 1998;63(3):155-60 </li></ul></ul>
    40. 44. Estrogen-related mood disorders – reproductive life cycle factors. Douma SL et al. Adv. Nursing Sci. 2005. 28 (4):364-375 <ul><li>“ Clinical recovery from depression postpartum, perimenopause , and postmenopause through restoration of stable/optimal levels of estrogen has been noted.” </li></ul>
    41. 45. Symptoms of estrogen imbalances*: <ul><li>Hot flushes or flashes; night sweats </li></ul><ul><li>Mood swings </li></ul><ul><li>DEPRESSION, and/or anxiety, panic attacks </li></ul><ul><li>“ Concentration” issues: Memory, communication, and attention span loss, “brain fog.” (Think: “MORE MAO.”) </li></ul><ul><li>Insomnia </li></ul><ul><li>Weight gain – “appetite changes” </li></ul><ul><li>SOMATIC symptoms : aches and pain </li></ul><ul><li>General deterioration: Incontinence, digestive disturbances, sensory function loss, aging skin . . . thinning, wrinkles, sagging </li></ul>* Adapted from Whitney Gabhart, N.D.
    42. 46. Psychoactive Progesterone* <ul><li>Increases energy and libido </li></ul><ul><li>Has a calming effect , acting like a benzodiazepine to the brain (HS dosing) </li></ul><ul><li>Enhances mood </li></ul><ul><li>Balances blood sugar (appetite) </li></ul><ul><li>Regulates fluid balance, sodium mineral balance </li></ul><ul><li>Necessary for fertility </li></ul><ul><li>Helps relieve menopausal symptoms </li></ul><ul><li>Decreases risk of endometrial cancer and may help protect against breast cancer, fibrocystic breasts, and osteoporosis </li></ul>* Adapted from Whitney Gabhart, N.D.
    43. 47. Testosterone: The “sexist” bias against women <ul><li>Fall in the circulating testosterone and the adrenal preandrogens most closely parallel increasing age. </li></ul><ul><li>Accelerated decrease occurs in the years preceding menopause (like estrogen). </li></ul><ul><li>Their loss affects: libido , vasomotor symptoms (hot flashes) , mood , well-being , bone structure, and muscle mass. </li></ul><ul><ul><li>Burd, Bachmann. Androgen replacement in menopause. Curr Womens Health Rep. 2001 Dec; 1(3):202-5. </li></ul></ul>
    44. 48. Traditional vs. Bio-identical “HRT”: <ul><li>Synthetic means that the molecule is not natural to the human body. </li></ul><ul><li>Bio-identical hormone is one whose molecule is identical to that made by a human organ.  </li></ul>SV2003-
    45. 49. Women ’s Health Initiative Study <ul><li>Flawed study - it was designed as a “Premarin & Provera” study, not a bioidentical estrogen study. </li></ul><ul><li>Premarin is a non-bio-identical substance </li></ul><ul><li>Provera is a non-bio-identical substance </li></ul><ul><li>Premarin is an equine derived array of 30+ female horse hormones . </li></ul>SV2003-
    46. 50. Women ’s Health Initiative Study <ul><li>The results presented did not justify their overall broad conclusion: </li></ul><ul><li>“ Premarin & Provera yielded these findings; therefore, Hormone Replacement Therapy is not appropriate for women.” </li></ul>SV2003-
    47. 51. Women ’s Health Initiative Study <ul><li>THE PARTICIPANTS: </li></ul><ul><li>2/3 of the women in the study were older than sixty </li></ul><ul><li>Of these women, most were first-time users of HRT. </li></ul><ul><li>Had already experienced cessation of endogenous hormone production (for a DECADE!!!) , therefore, at risk for: </li></ul><ul><ul><li>Heart attacks, strokes, clots, cancer </li></ul></ul>SV2003-
    48. 52. Women ’s Health Initiative Study Facts You Should Know <ul><li>In the first 1-3 years there was a higher incidence of M.I. ’s. </li></ul><ul><li>Patients who stayed on that program beyond the 8 th year started to actually outperform women on placebo. </li></ul><ul><li>WHY???? </li></ul>SV2003-
    49. 53. Women ’s Health Initiative Study Facts You Should Know <ul><li>When the W.H.I. Study was organized, the subjects were not prescreened for heart disease. </li></ul><ul><li>Without prescreening, a group of women was included with pre-existing heart disease. </li></ul>SV2003-
    50. 54. Hx of Baseline Health Characteristics (total # of participants 16,608) 37% 11% 2%
    51. 55. Traditional vs. Bio-identical “HRT”: <ul><li>Premarin raises C-reactive protein significantly. </li></ul><ul><li>CRP is an inflammation marker. </li></ul><ul><li>Inflammation is either the root cause (e.g., rupturing plaque ), or a strongly contributing cause, of both Cancer & Heart Disease . </li></ul>SV2003-
    52. 56. Some of the “10 reasons” to be happy [Studd J. Menopause Int. 2010 Mar;16(1):44-6 <ul><li>Trans-derm safer than oral </li></ul><ul><ul><li>Coag factors not induced in liver </li></ul></ul><ul><li>Safe for tx of flushes, sweats, vaginal dryness </li></ul><ul><li>Estrogens prevent osteoporotic fracutres – should be FIRST CHOICE rather bisphosphonates </li></ul><ul><li>HRT protects intervertebral discs </li></ul><ul><li>Est + T helps “reproductive depression” </li></ul><ul><li>Improves energy & libido </li></ul><ul><li>Reduces incidence of heart attakcs. </li></ul><ul><li>Beneficial effects on collagen </li></ul><ul><li>Note 1 % increased lifetime risk of breast cancer </li></ul>
    53. 57. 50’ish year old female, post-menopausal, on no hormones <ul><li>On aggressive supplement regimen with daily MVI and others </li></ul><ul><li>Not ill </li></ul><ul><li>Top rated medical care with previous labs done </li></ul><ul><li>Nothing identified as seriously abnormal </li></ul><ul><li>“ Just interested in having my hormones checked.” </li></ul>
    54. 62. Treatment for this “normal” patient <ul><li>Armour thyroid – ¼ grain for 1 week, then ½ grain. (Aiming for T3 in “high 3’s.” </li></ul><ul><li>DHEA – 25 mg SR micronized, compounded – in a.m. </li></ul><ul><li>Progesterone – 50 mg SR compounded – at night. </li></ul><ul><li>Testosterone – 3mg topical per day x 1 wk, then 6 mg. “Decrease dosing as needed for side effects.” </li></ul><ul><li>Vitamin D – 5,000 IU twice daily x 3 weeks, then decrease to one dose per day. </li></ul><ul><li>Fish oil – 4.6 grams (c. 1660 mg EPA and 1,250 mg DHA by compound weight, plus misc. Omega 3) </li></ul>
    55. 64. What’s life like now? <ul><li>“ it’s like the colors of the rainbow have gotten more into the pink.” </li></ul><ul><li>“ My computer will survive – I use to ‘lose it’ over my computer. I would swear obscenities.” </li></ul><ul><li>“ I’ve gotten into a zen like mode. Handling everything that life can throw at me.” </li></ul><ul><li>“ 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.” </li></ul><ul><li>“ I’m not irritable any more. Time pressure has just one away.” </li></ul>
    56. 66. November 2009 “Alpha Male” issue <ul><li>Observational study of randomly selected men – Boston </li></ul><ul><li>3 cohorts of men: 1987-1989; 1995-1997; 2002 -2004. </li></ul><ul><li>1374, 906, and 489 men, respectively. </li></ul><ul><li>“ Age independent decline in T that does not appear to be attributable to observed changes in explanatory factors, including lifestyle characteristics such as smoking and obesity.” </li></ul><ul><li>“ Recent years have seen a SUBSTANTIAL , and as yet UNRECOGNIZED age-independent population-level decrease in T in American men.” Travison, Araujo, et al. Jrnl of Clin. Endocrinol & Metabol 92:1; 196-202. </li></ul>
    57. 67. Fast food (low Zn) is bad for you. <ul><li>Fast food = high energy density = low essential micronutrient density, ESPECIALLY ZINC </li></ul><ul><li>Antioxidant processes are dependent on Zinc </li></ul><ul><li>Fast food = severe decrease in antioxidant vitamins and zinc, correlating with inflammation in testicular tissue – with underdevelopment of testicular tissue and decreased testosterone levels </li></ul>
    58. 68. Special needs - Zinc <ul><li>Low Zinc- associated with low testosterone </li></ul><ul><ul><li>Per USDA, 60% of US men between 20 – 49 years of age do not get enough . </li></ul></ul><ul><ul><li>N.B.: Do not supplement with > 50 mg daily (can interfere with Cu+ metabolism) </li></ul></ul><ul><ul><ul><li>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 Disorders, 24, 485-491 </li></ul></ul></ul>
    59. 69. Testosterone functions (Men AND Women) <ul><li>Enhances sex drive </li></ul><ul><li>Builds muscle & decreases fat </li></ul><ul><li>Elevates mood </li></ul><ul><li>Prevents osteoporosis </li></ul><ul><li>Improves memory </li></ul><ul><li>Lowers cholesterol </li></ul><ul><li>Protects against heart disease </li></ul>
    60. 70. “ 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…”
    61. 71. <ul><li>Decline in male sex steroids not as abrupt as menopause, but equally debilitating </li></ul><ul><ul><li>Between 40 – 70, average male loses: </li></ul></ul><ul><ul><ul><li>Nearly 2&quot; of height </li></ul></ul></ul><ul><ul><ul><li>15% of bone density </li></ul></ul></ul><ul><ul><ul><li>10 – 20 pounds of muscle </li></ul></ul></ul><ul><li>At 70 yoa, 15% completely impotent </li></ul>Testosterone (Men)
    62. 72. Andropause: Characteristics of Change <ul><li>Insidious & unpredictable onset </li></ul><ul><li>Slow progression </li></ul><ul><li>Subtle & variable manifestations </li></ul><ul><li>Cannot be linked directly to a decrease in the hormone testosterone </li></ul><ul><li>Very different from menopause in women! </li></ul>Charlton R. JMHG . 1(2004): 55-9 Kaufman JM. Endocrine Reviews . 26(2005):833-76
    63. 73. T vs Cognitive Function Rosario ER. JAMA . 292(2004):1431-2
    64. 74. T vs Cognitive Function Rosario ER. JAMA . 292(2004):1431-2 “ Testosterone depletion likely precedes and thus may contribute t o rather than result from the development of AD, since low brain testosterone is observed in men with early indications of AD neuropathology”
    65. 75. T vs Cognitive Function <ul><li>400 independently living men, 40-80yo </li></ul><ul><ul><li>100 in each age decade </li></ul></ul><ul><ul><li>MMSE 21-30, average 28 </li></ul></ul><ul><ul><li>TT: 208-1141ng/dL; Bio-avail T 78-470ng/dL </li></ul></ul><ul><li>HIGHER T = better cognitive performance in OLDEST AGE category </li></ul><ul><li>Men with lowest 1/5 T = worse than men with highest 1/5 T </li></ul><ul><li>Highest Bio-available T more significant than TT, age, intelligence level, mood, smoking, and alcohol. </li></ul>Muller M. Neurology . 64(2005):866-71
    66. 76. T vs Mood in men <ul><li>Study: 278 men, > 45yo, followed 2 years </li></ul><ul><li>Compared to eugonadal patients, hypogonadal men w/TT < 200ng/dL had </li></ul><ul><ul><li>4-fold increase risk of depression </li></ul></ul><ul><ul><li>Significantly shorter time to depression diagnosis </li></ul></ul><ul><li>Depression risk inversely related to TT w/statistical significance < 280ng/dL </li></ul>Shores MM, Arch Gen Psychiatry . 61(2004):162-7
    67. 77. Treatment options – not just “the needle”
    68. 78. Testosterone and “Prostate Cancer risk” <ul><li>Prostate CA found 2.15 & 2.26 times more likely in lowest compared to highest tertile of total and free testosterone </li></ul><ul><li>“ . . . 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 .” </li></ul>Morgentaler A. Eur Urol . 50(2006):935-9 Morgentaler A. Urology . 68(2006):1263-7
    69. 79. HOW OBVIOUS DOES IT HAVE TO BE? The Challenge of Empathic Listening & CREATIVE THINKING Ron Hunt lost an eye but suffered no brain damage after a freak accident with a large drill bit. (ABCNEWS.com)
    70. 80. Do you really want to try 100,000 miles without changing the oil?
    71. 81. Definition of ‘normal’ – “where your hormone levels are as lousy as everyone else’s.” Neal Rouzier, MD “ NORMAL” OPTIMAL
    72. 82. American Journal of Health Promotion; November/December, 2002 HEALTH continuum DEAD OPTIMAL 66% “ Incompletely healthy ” * *“treatment resistant”?
    73. 83. “ 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.
    74. 84. Extra slides for further background follow in notes  Contact info: Louis B. Cady, M.D. www.cadywellness.com Office: 812-429-0772
    75. 85. Health is a state of complete physical, mental and social well-being, and not merely the absence of disease or infirmity.  -  World Health Organization
    76. 86. Cady response to DHEA: March – May – 2 months… <ul><li>Dropped from 25.6% BF to 21.5% BF </li></ul><ul><li>Lost 3.3 inches off waist </li></ul><ul><li>Lost 8 pounds of fat </li></ul><ul><li>Gained 4 pounds of muscle </li></ul><ul><ul><li>March: 48,439 grams = 106.57 lbs of muscle </li></ul></ul><ul><ul><li>May 50, 251 grams = 110.55 lbs of muscle </li></ul></ul><ul><li>Cybex: 47.724 sec down to 40.726 sec </li></ul>
    77. 87. The R-Factor Question* If we were meeting here three years from today – and you were to look back over those three years all the way back to today – what has to have happened during that period …for you to feel happy about your progress and what you have accomplished and the changes made? *Adapted from The Dan Sullivan Question © Dan Sullivan May 2010
    78. 89. Indole-3-Carbinol – good with or without HRT (for women AND men) Estradiol 16 alpha-OH Estrone (Ca) 4-OH Estrone (B) 2-OH Estrone (B) I3C “ I-3 C raises the 2:16-OH Estrogen ratio” N.B.: available from LabCorp
    79. 90. ADAM Questionnaire <ul><li>Do you have a decrease in libido (sex drive)? </li></ul><ul><li>Do you have a lack of energy? </li></ul><ul><li>Do you have a decrease in strength and/or endurance? </li></ul><ul><li>Have you lost height? </li></ul><ul><li>Have you noticed a decreased “enjoyment of life”? </li></ul>Tancredi A. Eur J Endocrinol . 151(2004):355-60
    80. 91. ADAM Questionnaire <ul><li>Are you sad and/or grumpy? </li></ul><ul><li>Are your erections less strong? </li></ul><ul><li>Have you noted a recent deterioration in your ability to play sport? </li></ul><ul><li>Are you falling asleep after dinner? </li></ul><ul><li>Has there been a recent deterioration in your work performance? </li></ul>Tancredi A. Eur J Endocrinol . 151(2004):355-60
    81. 92. ADAM Questionnaire <ul><li>Positive result if yes to </li></ul><ul><ul><li>answer 1 or 7 </li></ul></ul><ul><ul><li>any three other questions </li></ul></ul><ul><li>High sensitivity (~80%) to identifying aging males w/low free testosterone levels </li></ul><ul><li>Low specificity (~20%) </li></ul><ul><li>Validated in other languages </li></ul>Tancredi A. Eur J Endocrinol . 151(2004):355-60
    82. 93. MENOPAUSE FACTS and hormonal optimization facts: <ul><li>12 months of HRT increased skin elasticity by 5.2% </li></ul><ul><li>Post menopause, women lose .55% skin elasticity each year. </li></ul><ul><ul><li>Sumino H, et al. Effects of aging, menopause, and HRT on forearm skin elasticity in women. J Am Geriatr Soc. 2004 June; 52(6):945-9 </li></ul></ul>SV2003-
    83. 94. Fatter upper body and decreased antioxidants in menopause <ul><li>Fat content increases in upper part of body (trunk and arms) </li></ul><ul><li>Antioxidant status decreases. </li></ul><ul><ul><li>Pansini F, et al. Oxidative stress, body fat composition, and endocrine status in pre- and postmenopausal women. Menopause. 2008 Jan-Feb; 15(1):112-8. </li></ul></ul>
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