Hormones, Cognition, and Mood Changes in Older Adults

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HORMONES, COGNITION AND MOOD CHANGES IN OLDER ADULTS. This is Dr. Cady's lecture from the Age Management Medical Group meeting in las Vegas, NV, PRESENTED 12 2 2012.

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  • 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.
  • Noted that DHEA and DHEA-S are synthesized de novo in the brain. brain concentrations were higher than plasma concentrations and brain concentrations remained high after adrenalectomy and gonadectomy of rats [ 68; 69]. This is one of the reasons they have been referred to as “neurosteroids.” From the article: Mechanisms of action of DHEA and DHEAS in neurons. Has inhibitory effect at the GABA A receptor. DHEA and DHEAS act as agonists (green arrow) at the σ1 receptor (section 6 and 7.1), which subsequently may activate the NMDA receptor. DHEA inhibits Ca2+ 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: σ1, sigma 1 receptor; Akt, serine-threonine protein kinase Akt; Ca2+, calcium; da, dopamine; GABAA, 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.”
  • These symptoms correlate to decrease in bioavailable testosterone
  • And these numbers are just talking about totally testosterone which is just part of the problem. The amount of testosterone available to tissues is even less. The solid lines on the graph are the total testosterone levels and the lined bars are the free levels.
  • 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 < 200ng/dL or FT < 0.9ng/dL
  • Hypogonadal if TT < 200ng/dL or FT < 0.9ng/dL
  • Hormones, Cognition, and Mood Changes in Older Adults

    1. 1. Hormones, Cognitive Dysfunction & Depression in Older Adults Louis B. Cady, MD – CEO & Founder – Cady Wellness InstituteAdjunct Asst. Prof of Psychiatry – Indiana University School of Medicine Department of PsychiatryChild, Adolescent, Adult, Functional Neuropsychiatry – Evansville, IndianaAMMG Fall Conference – Nov. 2, 2012 – GeneralSession Curriculum 2:00 – 2:45 pm Las Vegas, NV - USA
    2. 2. “There are two objects of medical education: to healthe sick and to advance the science.”- Dr. Charles H. Mayo, MD “The glory of medicine is that it is always moving forward, that there is always more to learn.” H -2 - Dr. William J. Mayo
    3. 3. Purpose of this talk:• Real-world, clinical application of age management concepts• Avoiding “knee-jerk” reaction for “just depression.”• Understanding relevance of thyroid, cortisol and several other hormones in affective and cognitive dysfunction• Review of cost-effective ways of screening for hormonal and neurotransmitter abnormalities
    4. 4. How to get the MOST out of this presentation:
    5. 5. My bias: whatever works for thepatient; whatever it takes.
    6. 6. Topics:• Thyroid• Cortisol• DHEA• Estradiol/Progesterone• Testosterone• Lab techniques: saliva or blood?
    7. 7. AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS MEDICAL GUIDELINES FOR CLINICAL PRACTICE FOR THE EVALUATION AND TREATMENT OF HYPERTHYROIDISM AND HYPOTHYROIDISM AACE Thyroid Task Force Chairman H. Jack Baskin, MD, MACE Committee Members Rhoda H. Cobin, MD, FACE Daniel S. Duick, MD, FACE Hossein Gharib, MD, FACE Richard B. Guttler, MD, FACE Michael M. Kaplan, MD, FACE Robert L. Segal, MD, FACE Reviewers Jeffrey R. Garber, MD, FACE Carlos R. Hamilton, Jr., MD, FACE Yehuda Handelsman, MD, FACP, FACE Richard Hellman, MD, FACP, FACE John S. Kukora, MD, FACS, FACE Philip Levy, MD, FACE Pasquale J. Palumbo, MD, MACE Steven M. Petak, MD, JD, FACE Herbert I. Rettinger, MD, MBA, FACE Helena W. Rodbard, MD, FACE F. John Service, MD, PhD, FACE, FACP, FRCPC Talla P. Shankar, MD, FACE Sheldon S. Stoffer, MD, FACE John B. Tourtelot, MD, FACE, CDR, USN 2006 AMENDED VERSION This amended version reflects a clarification to specify pertechnetate as the compound attached to 99mTc. ENDOCRINE PRACTICE V ol 8 No. 6 November/December 2002 457
    8. 8. • “Thyrotropin (Thyroid-Stimulating Hormone or TSH). Measuring TSH is the most sensitive indicator of hypothyroidism.” (hunh?!) – accessed 9/5/2011• “…blood tests for measuring levels of TSH and free thyroxine (T4) are the only definitive way to diagnose hypothyroidism” – 10/6/2012 http://www.umm.edu/patiented/articles/how_serious_hypothyroi
    9. 9. FEEDBACK INHIBITIONSelenium CORTISOLrequired! “the foot soldier” “the evil twin”
    10. 10. % Mineral depletion from the soilduring the past 100 years, by continent North America 85% South America 76% Asia 76% Africa 74% Europe 72% Australia 55% Source: UN Earth Summit Report 1992
    11. 11. Jrnl of Amer. College of Nutrition Vol 23, No. 6, 669-682 (2004).Objective: evaluate possible changes in USDA nutrient content data for43 crops between 1950 – 1999; consider potential causesMethods: ratios calculated for “R” 1999/1950Results: as a group, the 43 foods showed apparently, statistically reliabledeclines for 6 nutrients: protein, Ca, P, Fe, riboflavin, and ascorbic acid. - 6% decrease in protein - 38% decrease in riboflavinCONCLUSIONS: trade off between yield and nutrient content
    12. 12. SELENIUM DEFICIENCY in FASEB: • “Adaptive dysfunction of selenoproteins from the perspective of the ‘triage’ theory: why modest selenium deficiency may increase risk of diseases of aging.”Foundation of American McCann, J, Ames BM. FASEB J.Societies for Experimental 2011 Jun;25(6):1793-814.Biology
    13. 13. (permission granted to use photos & data)
    14. 14. (permission granted to use photos & data)
    15. 15. • Early 20’s college student• Weight gain, fatigue, brain fog• Saw “numerous” MD’s asking for help• Told “nothing is wrong with your thyroid; your labs are fine.” (permission granted to use photos & data)
    16. 16. (permission granted to use photos & data)
    17. 17. Useful Target Symptoms in Major Depression ♦ 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)1. Tylee et al. Int Clin Psychopharmacol 1999;14:139-151. 2. Maurice-Tison et al. Br J GenPract 1998;48:1245-1246. 3. Baker et al. Comp Psychiatry 1971;12:354-65. 4. Horwath etal. J Affect Disord 1992;26:117-25. 5. Reynolds and Kupfer. Sleep 1987;10:199-215.
    18. 18. Modern Medicine’s Paradigm:Two Standard Deviations – “if you are not sick, then you must be well.” “NORMAL” OPTIMAL? OPTIMAL
    19. 19. Average (normal) or optimal?• Would you like an normal wife (husband) or an optimal one?• Would you like a “normal” marriage or an exciting and optimal one?• Would you like a “normal” medical practice or an incredible, exciting, and (optimal!!) stimulating one?• Would you like “normal” labs or OPTIMAL ones?
    20. 20. Serum concentrations of Free T3, Free T4, morning cortisol,afternoon cortisol and change in cortisol concentrations.Adjustments for: age, sex, body mass index, hypertension, previousMI, heart failure, diabetes, NY Heart Assn. functional class,depressive symptoms and anxiety symptoms.Lower Free T3 = more physical fatigueLower Free T4 = more exertional fatigueLower morning cortisol and change in cortisol concentration = moremental fatigue.
    21. 21. Aim: evaluate biological factors assoc. with suicide attempts innaturalistic sample439 patients with major depression, bipolar and psychoticdisorders consecutively assessed in the ER of an Italian Hospital(Jan 2008-Dec 2009)Suicide attempters were 2.27 times less likely to have higher FreeT3 values than non-attempters (odds ratio = 0.44; 95% CI; p=0.01)(prolactin level differences failed to reach significance)
    22. 22. Treatment resistant depression is a common challenge.Best augmenting strategies available:-Lithium-Thyroid hormone-Anti-anxiety medications-Atypical antipsychotics.
    23. 23. LEVEL III RESULTS: Per HDRS – 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
    24. 24. 63 patients with “subclinical hypothyroidism”HAM-D and MADRS scales with serum TSH Free T4, free T3TPO AB and Tg-AB levels Prevalence of depressive symptoms in this population was 63.5% “This study suggests the importance of a psychiatric evaluation in patients affected by subclinical hypothyroidism.” Hunh?
    25. 25. Aim: Evaluate relationship of subclinical hypothyroidism andcognition in the elderly.- 337 outpatients; {177 = men; 160 = women}MMSE scores were SIGNIFICANTLY lower insubclinical hypothyroid patients compared toeuthyroid (p<0.03)“Patients with subclinical hypothyroidism had aprobability about 2 times greater (RR = 2.028, p<0.05) ofdeveloping cognitive impairment.”
    26. 26. The Glamorous Grandmother• 4/8/11 – 80 yo returned to practice. No real complaints. History of depression. On des- methylvenlafaxine. – Daughter “handling her finances”• 5/2/11 – “doing terrible.” – TSH 3.84, Free T3 2.8 – on 50 MICROgrams T4 – Fasting BS 120; HgBA1C 6.5% – Fasting insulin 36 (!!!) {3 – 25} – Progesterone – 0.2 {0.2 – 1.4 follicular} – Total testosterone 11 – DHEA-S = 25 MICROgrams/dL (!!) • Age adjusted {10 – 90} . Optimal = {c. 350-500} • Rouzier = {300 –females, 600 males}
    27. 27. G.G. - interventions 5/2/11 & Follow-up• Interventions: – DHEA – 25 mg SR q a.m. – Progesterone 50 mg then 100 mg HS, transdermal. – Testosterone – 2 mg for one week, then 4 mg transdermal – Referred to better MD for intervention with AODM.• 6/13/2011 – improvement in fatigue. Labs rechecked.• 7/11/2011 – “feeling wonderful”
    28. 28. G.G. – labs before and after 4/11/11 interventions 7/11/11 changesTSH 3.84 Raise T4 from 0.01 (L) none 50 – 75 ugFT4 1.16 “ 1.24 “FT3 2.8 “ 3.3 “Progesterone <0.2 100mg topical 0.9 None HSTestosterone 11 4mg topical 15 4 mg LABIALDHEA-S 25 25 mg SR n/a continue
    29. 29. 24 post-menopausal women with intact uterus. Neuropsychtesting. No hormone therapy used in the past. Recruited bynewspaper ads.Randomized to CEE + PL, CEE + MPA, CEE +MP (Micronized progesterone)Mood improved in all groups.CEE + MP performed significantly better on a test ofworking memory than the other two groups.
    30. 30. Medroxyprogesterone in women and rats• MPA – used in hormone therapy and as DepoProvera, is implicated in detrimental cognitive effects in women.• In ovariectomized rodents – MPA impairs cognition and alters the GABA- ergic system.• Findings suggest that MPA treatment leads to LONG-LASTING cognitive impairments in the rodent, even in the absence of ongoing circulating MPA Braden BS, et al. Cognitive-impairing effects of medroxyprogesterone acetate in the rat: independent and interactive effects across time. Psychopharmacology (Berl). 2011 Nov;218(2):405-18. Epub 2011 May 12.
    31. 31. The glamorous grandmother – post tune-up: DHEA, thyroid, testosterone, progesterone Photos removed for internet slideshare and .pdf postings9/28/2011 (permission granted to use photos & data) 01/26/2012
    32. 32. Photos removed for internet slideshareand .pdf postings October 12, 2012 – used with permission
    33. 33. Conclusions regarding thyroid• It’s not just about eyebrows (or reflexes)• Low or subclinical hypothyroidism associated with: – Depression – More exertional and mental fatigue – Higher risk of suicide • Poorer cognition • 2 x likelier to have cognitive impairment.
    34. 34. The state of adrenal exhaustion can be determined• 53 year old male executive• Partner in four businesses.• “The last year or so, I’m more tired… don’t have the energy… I’m having more trouble getting out of bed in the morning.”
    35. 35. Other hormone markers by salivary & conventional testing• DHEA 120.12 pg/ml (L) {137 – 336}• Testosterone 59.06 pg/ml {30.1 – 142.5, males, not on tx}• DHEA-S 128.0 ug/dL {“25 – 240”; optimal more like 350 – 500}• Testosterone 820 ng/dL {250 – 1100}• Free T 87.7 pg/ml {35.0 – 155.0}• IGF-1 81 mg/ml(L) {“91 – 246”}• TSH 1.20 uIU/ml {0.40 – 4.50• Free T4 1.7 mg/ml {0.8 – 1.8}• Free T3 303 pg/ml {230 – 420}• Reverse T3 44 (H!) ng/dL {11 – 32}
    36. 36. DHEA – the critical hormone most conventional doctors never check• Produced in the adrenal cortex – Humans and primates are unique in secreting large amounts – “the most abundant steroid hormone in the human body.” (Maninger et al. Front. Neuroendocrinol. 2009 Jan; 30(1):65-91.)• 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]• Antidepressant effects
    37. 37. 349 citations on “DHEA with energy” – as of of 10/3/2012
    38. 38. From secretory vesiclesManninger, N et al. Neurobiological & neuropsychiatric effects of DHEA and DHEA
    39. 39. DHEA – other interesting points• No nuclear receptor for DHEA or DHEA-S ever found; mechanisms of action are not fully understood• Some actions may be through conversion into more potent sex steroids and activation of androgen or estrogen receptors in tissue.• May have effects through intermediate metabolites.• Neural growth (from animal studies) – DHEA – increases axon length – DHEA-S – stimulated dendrite growth.• DHEA-S promoted survival of adult human cortical brain tissue in vitro. – DHEA increased neurogenesis in addition to neuronal survivalManninger, N et al. Neurobiological & neuropsychiatric effects of DHEA and DHEA
    40. 40. DHEA has been correlated with lower susceptibility to anxietyand mood disturbance.Behavioral task – series of anagram puzzlesfrom possible to IMPOSSIBLE.Other indices: ACT scores, # of college classes droppedor failed, current GPAHigher DHEA: cortisol ratio associated with“lowest probability of failing the task.”
    41. 41. 91 students ½ male, ½ female – taking OrganicChemistry in the USA.Displacement activities (DA’s) screened for by videorecording during tests.A logistical model built on GPA, DA’s, andsalivary hormone levels of cortisol andDHEA correctly predicted 90% of thestudents who passed the class.
    42. 42. Treatment for the Stressed Executive• Empirically started at ¼ grain Armour with increase to ½ grain at first appt (based on previous thyroid tests) – This was continued at next appt per labs.• Start on DHEA 25 mg extended release tablets, then increase to 2– 3 tablets as needed and as tolerated. (Ultimately increased to 100 mg SR per day)• High potency MVI with high dose B, C, minerals.
    43. 43. Five month follow-up• “I think all the stuff is working. My energy level is good. If there’s anything lingering – it’s just stress from work stuff. I actually feel pretty good.”• “0 – 10 energy scale” probe: – 24 – 25 yoa – maximum energy “10” – July 2011 (before labs and interventions) – “4” – October 2011 – “5 – 6” – January 2012 – “8”
    44. 44. July 2011 Nov 2011 Dec 29, 2012Interventions 100 mg DHEA SR 100 mg DHEA SR ½ grain Armour ½ grain Armour 1 pump T to each inner thighTSH 1.2 0.86 0.93Free T4 1.7 1.5 1.3Free T3 303 373 361Rev T3 44 (H) 57 (H) 39 (H)DHEA-S 128 472 (“H”) 306 (“H”)IGF-1 81 106 120Total testosterone 820 913 969Free Testosterone 87.7 131.5 100.8
    45. 45. Other than fatigue, what’s the relevance?• Excess corticosteroid = catabolic consequences and “breakdown of vital functions.”• Review of classical depression = hypercortisolism• “Atypical depression” – hypocortisolism• Association of high cortisol and psychotic depression DeKloet.Anna NY Acad. Sci. 1018:1-15(2004)http://www.people.vcu.edu/~mreimers/SysNeuro/de%20Kloet%20-%20HPA%20review.pdf
    46. 46. Saliva or blood?• Saliva: • Blood testing: – 4 cortisols give rhythm, plus: – More published literature • Average x 4 of: targeting specific blood levels of – DHEA, testosterone, estradiol, sex hormones and DHEA (S) and progesterone – More predictable dosing of – Much easier to obtain hormones with assiduous blood – Early a.m. cortisol arguably monitoring. more accurate. – 4 lab values in a day averaged • Downsides – woefully arguably more accurate – Cheaper if cash pay skewed a.m. cortisol – Less likely to get 4 cortisols – Perfectly acceptable as a screening tool. Downside: Apparent “disconnect” between post-treatment levels and salivary measurements
    47. 47. One destigmatizing notion: Estrogen as MAOI• Estrogen & Testosterone (!) decrease MAO – Luin, VN. Effect of gonadal steroids on activities of MAO and choline acetylase in rat brain. Brain Res. 1975;86:273-306• Platelet MAO levels inversely correlated to estradiol levels – Klaiber EL et al. Psychoneuroendo- crinology. 1997 Oct;22(7):549-58.• Estrogen decreases MAO-A & MAO-B – Holschneider DP et al. Life Sci. 1998;63(3):155-60
    48. 48. Estrogen: Good For Your Brain• Estradiol influences performances of learning and memory tasks as well as increase working memory – Sub-point – women are living three decades longer; hence they are spending more time hypoestrogenic – Pompilli A et al. Estrogens and memory in physiological and neuropathological conditions. Psychoneuroendocrinology. 2012 Sept; 37 (9):1379-96• Estradiol = protective against schizophrenia. – Kulkarni J, et al. Hormones and Schizophrenia. Curr Opin Psychiatry. 2012 Mar;25(2):89-95
    49. 49. Testosterone: The “sexist” bias against women (e.g., “your loss of sex drive is just natural for your age.”)• Fall in the circulating testosterone and the adrenal preandrogens most closely parallel increasing age.• Accelerated decrease occurs in the years preceding menopause (like estrogen).• Their loss affects: libido, vasomotor symptoms (hot flashes), mood, well-being, bone structure, and muscle mass. – Burd, Bachmann. Androgen replacement in menopause. Curr Womens Health Rep. 2001 Dec; 1(3):202-5.
    50. 50. Estrogen-related mood disorders – reproductive life cycle factors. Douma SL et al. Adv. Nursing Sci. 2005. 28 (4):364-375• “Clinical recovery from depression postpartum, perimenopause, and postmenopause through restoration of stable/optimal levels of estrogen has been noted.”
    51. 51. The Case of the Crying Cleaner • 1/11/12 - Symptoms: – Crying/depressed = on Citalopram – Hot flashes Photo removed for internet slideshare and .pdf postings – Night sweats • RX: – Estradiol – 2 mg @HS – Prometrium – 100 mg @HS – (continue citalopram) • 1/15/12 – RESOLVED • In 4 days!Photo & data used with permission
    52. 52. Testosterone (Men) • 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
    53. 53. Observational study of randomly selected men –Boston3 cohorts of men: 1987-1989; 1995-1997; 2002-2004.1374, 906, and 489 men, respectively.“Age independent decline in T that does not appear tobe attributable to observed changes in explanatoryfactors, including lifestyle characteristics such assmoking and obesity.”“Recent years have seen a SUBSTANTIAL, and asyet UNRECOGNIZED age-independent population- November 2009level decrease in T in American men.” “Alpha Male” issueTravison, Araujo, et al. Jrnl of Clin. Endocrinol & Metabol 92:1; 196-202.
    54. 54. 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
    55. 55. Prevalence of Low Total Testosterone• 12% for men in 50s• 19% for men in 60’s• 28% for men 70s• 49% for men >80Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR. Longitudinal effects of ageing on serumtotal and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. J ClinEndocrinol Metab 2001; 86(2): 724-31.
    56. 56. T vs Cognitive Function Rosario ER. Age-related testosterone depletion and thedevelopment of Alzhiemer disease. JAMA. 292(2004):1431-2
    57. 57. 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, et al. Neurology. 2005 Mar;64(5): 866-71
    58. 58. 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
    59. 59. Testosterone appears to be good for guys.• Serum T, DHT and E(2) displayed no decrease associated with age among men over 40 years of age who self-report very good or excellent health – Sartorius G, et al. Serum testosterone, dihydrotestosterone and estradiol concentrations in older men self-reporting very good health: the healthy man study. Clin Endocrinol (Oxf). 2012 Nov; 77(5):755-63
    60. 60. T vs. Heart Disease• Men with CAD have significantly LOWER levels of androgens than normal controls. – English, KM et al. Men with coronary artery disease have lower levels of androgens than men with normal coronary angiograms. Eur Heart J. 2000 June; 21(11):890-4.• “There is early evidence from non-randomized studies that physiological testosterone replacement is extremely safe and may reduce cardiovascular mortality.” – Hackett G. Testosterone and the heart. Int J Clin Pract. 2012 July;66(7):648-55.
    61. 61. Relevance of testosterone (and DHEA + Thyroid) Photos removed for internet slideshare and .pdf postingsRX: dairy free diet (+IgG test); D3 5000 IU/d; Armour thyroid,Testosterone cypionate 100 mg IM q wk, MVI, Zinc, DHEA 50 mgSR, CoQ10 400mg (permission granted to use photos & data)
    62. 62. Testosterone appears to be seriously good for guys’ brains• “Results from cell culture and animal studies provide convincing evidence that testosterone could have protective effects on brain function.”• “Testosterone levels are lower in Alzheimer’s cases compared to controls, and some studies have suggested that low free testosterone (FT) may precede AD onset.”• “Positive associations have been found between testosterone levels and global cognition, memory, executive functions and spatial performance in observational studies.” Holland J, et al. Testosterone levels and cognition in elderly men: a review. Maturitas. 2011 Aug; 69(4):322-37.
    63. 63. 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
    64. 64. Benefits (and minimal risk) of testosterone – J Sex Med Sep 2012Risks of Low T: Risks of TX:•Reduced longevity •“There is no compelling evidence•Fatal Cardiovascular events Testosterone therapy causes that•Obesity prostate cancer or its progression in men.”•Sarcopenia•Mobility limits Conclusions: men with sexual•Osteoporosis dysfunction, visceral obesity, and•Frailty metabolic diseases should be•Cognitive impairment screened for testosterone deficiency and treated. Young men•Depression with TD should also be treated.•Sleep Apnea Syndrome Buvat J et al. Testosterone deficiency in men: Systematic Review. J Sex Med. 2012 Sep 12
    65. 65. The Case of the Mismanaged Executive - summary• 42 year old male ADHD CEO. Background in psychology. Now EXTREMELY stressed.• “So tired I feel like I’m dying.” “Depressed.”• Lab findings – low testosterone, despite multiple pumps daily of low potency FDA-approved “BigPharma” transdermal testosterone gel managed by endocrinologist• Low thyroid. Low DHEA.• RX: Testosterone cypionate IM – 60 mg twice weekly. DHEA – 50 mg SR. Armour thyroid – ½ grain.• Clinical status: total resolution of symptoms in 3- 4 weeks. No antidepressant used.
    66. 66. What if we could just look at neurotransmitters like they would on Star Trek ? Cell rate 
    67. 67. Low estrogen, DHEA, cortisol, and low NT’s – putting it all together 52 yo woman, s/p TAH with fatigue and depressionHormone Value normsCortisols All barely various above pathologicalDHEA 47.66 {106-300}Estradiol (E2) <1.00 {1.0 – 3.2 = post menopausal}Testosterone 8.44 {6.1 – 49 – female}
    68. 68. REFERENCES: Hormones in the body;neurotransmitters in the head – & pee• Evaluation of a novel ELISA for serotonin: urinary serotonin as a potential biomarker for depression. – Nichkova MI et al. Anal Bioanal Chem. 2012 Feb;402(4):1593-600.• Neurotransmitters excreted in the urine as biomarkers of nervous system activity: validity and clinical applicability. – Marc DT et al. Neurosci Biobehav Rev. 2011 Jan;35(3):635-44.• Novel ELISAs for screening of the biogenic amines GABA, glycine, beta-phenylethylamine, agmatine, and taurine using one derivatization procedure of whole urine samples. – Hulsman H et al. Anal Chem. 2010 Aug 1;82(15):6526-33.• Not a new technology. Already used for diphenhydramine, zolpidem, nicotine, amphetamines, methamphetamine, 5HIAA, prostaglandin E2, numerous others.
    69. 69. “It’s really not thatSo what the heck am I complicated!”supposed to do with thisstuff?
    70. 70. Behaviors/status Interventionsstress Job/life stress Meditation, spiritual practice, T’ai chi, Qigong, make needed life changesAbnormal Presumptively low or Get levels – saliva or blood (pre-treatment)hormones unknown Check Neurotransmitters (urine ELISA) Thyroid DHEAInterventions Optimize/support cortisol Testosterone, Estradiol & Progesterone Growth hormone? Amino acid precursor loading for NT’s? Prescriptive agents – e.g., anti- depressants, neurostimulants, etc.
    71. 71. How obvious does it have to be?LET’S START CHECKING THOSE LEVELS! Ron Hunt lost an eye but suffered no brain damage after a freak accident with a large drill bit. (ABCNEWS.com)
    72. 72. Contact information: Louis B. Cady, M.D. www.cadywellness.comOnce more….  www.facebook.com/cadywellnessWhere to “get the slides” - www.indianaTMS-cadywellness.comwww.slideshare.net/lcadymd Office: 812-429-0772 E-mail: lcady@cadywellness.com 4727 Rosebud Lane – Suite F Interstate Office Parkwww.cadywellness.com/ammg/ Newburgh, IN 47630 (USA)hormones.ppt @LouisCadyMD @TMS4depression
    73. 73. “Sit down before fact asa little child,be prepared to give upevery preconceivednotion,follow humbly wherever… nature leads, or you shall learnnothing.”- Thomas H. Huxley

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