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SEXY! Part 3 of 3, plus…
       21 Century Medicine
         st
Louis B. Cady, MD – CEO & Founder – Cady Wellness Institute
        Adjunct Professor – University of Southern Indiana
    Adjunct Professor – Indiana University School of Medicine
     With Whitney W. Gabhart, ND - Cady Wellness Institute
             Newburgh Public Library July 11, 2012
What we do NOT want to see happen:
CURRENT PRACTICE OF MEDICINE:
What a patient had to say about her “specialists”:




“They just monitor my
    degeneration.”
"Sexy" - part 3 of the CWI Lecture Series - June 2012f sss lectures series for slide share - june july 2012.pt
Cady Wellness Institute – July 2005
                The Reasons:
•   Conventional medical practice had failed me twice.
•   A lot of “psychiatric cases” WEREN’T “psychiatric.”
•   Nobody was integrated.
•   Nobody was looking at ALL of the peer-reviewed
    literature.
Orientation to this talk
• Review the fundamental differences
  between “wnl” and OPTIMAL
• Quick review of hormones having to do with
  with “slim and sane” sections of this series
  – Thyroid
  – DHEA
  – estradiol/progesterone
  – IGF-1 (“food soldier” of growth hormone)
  – Integration of testosterone
• Exposure to current “state of the art”
American Journal of Health Promotion;
                 November/December, 2002

                                    66%                 19% of those
          18.8%
                            “Incompletely healthy”     surveyed were
        completely
                                                         completely
         unhealthy,
                                                         healthy with
          defined as
                                                        high levels of
          having low
                                                        both physical
       levels of health
                                                          and mental
           with high        Two-thirds of the adults     health and a
           levels of            reported some             low level of
            illness.         degree of mental
                                                            illness.
                                 or physical
                            illness that kept them
                             from being completely
                                    healthy.




                                                                    OPTIMAL
                            “Incompletely healthy.”
DEAD




                          HEALTH continuum
Critical area of concern for men &
    women. Things that will make them:
•   Tired &/or depressed
•   Unable to cope
•   “Mean”
•   Stressed
•   Demented
•   Deficient in libido or in the bedroom
How would you take care of a classic?
“Age management”           “Conventional practice”
There are fuel additives    No fuel additives should
we can use to keep our      be used. They are
cars burning cleaner and    unnatural. Gas is all that
preserve engines.           is required.
We should use optimal       The quality of the gas is
quality of gas. Cheap gas   irrelevant. Anything that
causes “pinging” which is   the motor will burn is
hard on the engine.         adequate.
We should take our car in   Preventive maintenance? This
for preventive              is silly! Wait until something
                            breaks, then have the car
maintenance before
                            towed in so the mechanic can
anything breaks.
                            really tell what is wrong.
And if you’re just a tired
ol weenie (or weenette),
you will definitely note
be feeling SEXY.
Toward an INTEGRATED approach:
   Traditional     INTEGRATED




                                                                      Optimal Health
                            No Disease = Health
    Medicine          Medicine
                                                     Forestall and
        Diagnose and                              PREVENT Disease –
        Treat Disease                              Optimize Mood &
Death



                                                       Function

        New Drugs                                   Functional
        New Surgical                                & Informed
         Techniques                                 Lab Testing


             Vitamins, HRT, Nutrition, Exercise
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
"Sexy" - part 3 of the CWI Lecture Series - June 2012f sss lectures series for slide share - june july 2012.pt
"Sexy" - part 3 of the CWI Lecture Series - June 2012f sss lectures series for slide share - june july 2012.pt
Modern Medicine’s Paradigm:
Two Standard Deviations – “if you are not
     sick, then you must be well.”

                               “NORMAL”


                              OPTIMAL
What are We Trying
    to Accomplish?
The Laboratory midrange
of the 30 y/o is the same
as the upper quartile of
the 70 y/o.
                     Miami - 2002 - 17
4
•   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.”
Selenium, the Thyroid, and You
              • “T3” is the ACTIVE
                form of thyroid
              • Conversion of T4
                to T3 is selenium
                dependent
              • LP Nano has
                200% of RDA of
        Se+
                selenium
    
"Sexy" - part 3 of the CWI Lecture Series - June 2012f sss lectures series for slide share - june july 2012.pt
"Sexy" - part 3 of the CWI Lecture Series - June 2012f sss lectures series for slide share - june july 2012.pt
“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
Rev T3




   Se
                        CORTISOL



“the foot soldier” “the evil twin”
"Sexy" - part 3 of the CWI Lecture Series - June 2012f sss lectures series for slide share - june july 2012.pt
Case report:
• 55 year old male entrepreneur
• Runs company with 200 employees – multi
  hundred million dollar budget
• Stressed with economy
• Very tired in the a.m.
• “Crashes” at night.
• Still golfing, exercising.
• Looks marvelous.
334 citations on “DHEA with energy” – as of
                07 29 2011
Why isn’t adrenal fatigue diagnosed?
• Not a medical emergency.
• Patient is blamed”
  – “just neurotic”
  – “avoidant”
• “Functional medicine” testing not
  typically done (& rarely is DHEA-S
  checked)
• Modern medicine focuses on
  NORMAL, rather than OPTIMAL.
  function.
• “Bell Curve” paradigm
SEXY!!
 “Women’s issues”
One destigmatizing notion:
            Estrogen as MAOI
• Estrogen & Testosterone (!) decrease
  MAO
  – Luin, VN. 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
Psychoactive Progesterone*
 Increases energy and libido
 Has a calming effect, acting like a
  benzodiazepine to the brain (HS dosing)
 Enhances mood
   Balances blood sugar (appetite)
   Regulates fluid balance, sodium mineral balance
   Necessary for fertility
   Helps relieve menopausal symptoms
   Decreases risk of endometrial cancer and may help protect
    against breast cancer, fibrocystic breasts, and
    osteoporosis            * Adapted from Whitney Gabhart, N.D.
Testosterone: The “sexist” bias
            against women
• 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.
Brief Description of Hormone
Function (Men AND Women)
        Testosterone
          – Enhances sex drive
          – Builds muscle & decreases
            fat
          – Elevates mood
          – Prevents osteoporosis
          – Improves memory
          – Lowers cholesterol
          – Protects against heart
            disease
We use Bio-identical “HRT” at CWI:

• Synthetic means that the molecule is not
 natural to the human body.

• Bio-identical hormone is one whose
 molecule is identical to that made by a
 human organ.


                                       SV2003- 34
50’ish 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.”
"Sexy" - part 3 of the CWI Lecture Series - June 2012f sss lectures series for slide share - june july 2012.pt
"Sexy" - part 3 of the CWI Lecture Series - June 2012f sss lectures series for slide share - june july 2012.pt
"Sexy" - part 3 of the CWI Lecture Series - June 2012f sss lectures series for slide share - june july 2012.pt
"Sexy" - part 3 of the CWI Lecture Series - June 2012f sss lectures series for slide share - june july 2012.pt
Treatment for this “normal” patient
1. Armour thyroid – 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)
"Sexy" - part 3 of the CWI Lecture Series - June 2012f sss lectures series for slide share - june july 2012.pt
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.”
The Case of the Crying Cleaner
                                    • 1/11/12 - Symptoms:
                                      – Crying/depressed = on
                                        Citalopram
                                      – Hot flashes
                                      – Night sweats
                                    • RX:
                                      – Estradiol – 2 mg @HS
                                      – Prometrium – 100 mg
                                        @HS
                                      – (continue citalopram)
                                    • 1/15/12 – RESOLVED
                                    • IN 2 WEEKS!!!.
Photo & data used with permission
"Sexy" - part 3 of the CWI Lecture Series - June 2012f sss lectures series for slide share - june july 2012.pt
"Sexy" - part 3 of the CWI Lecture Series - June 2012f sss lectures series for slide share - june july 2012.pt
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 to
be attributable to observed changes in explanatory
factors, including lifestyle characteristics such as
smoking and obesity.”
“Recent years have seen a SUBSTANTIAL, and as
yet UNRECOGNIZED age-independent population-
            November 2009
level decrease in T in American men.”
                “Alpha Male” issue
Travison, Araujo, et al. Jrnl of Clin. Endocrinol & Metabol 92:1; 196-202.
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
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
Testosterone functions (Men AND
Women)
         • Enhances sex drive
         • Builds muscle & decreases
           fat
         • Elevates mood
         • Prevents osteoporosis
         • Improves memory
         • Lowers cholesterol
         • Protects against heart
           disease
Physiology of testosterone

• T regulates
  – Nitric oxide (NO)
  – Phosphodiesterase type 5 (PDE-5)
  – Both critical for initiation & maintenance of
    erectile function
• T maintains
  – Penile structural integrity
  – Functional integrity



              Wang C, J Clin Endocrinol Metab. 89(2004):2085-98
“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…”
“…both estrogencs and androgens can play a
protective role against AD related
neurodegeneration.”
“Hypogonadal in later life” = “problems with memory”
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
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!
• (Hubby reference: www.isitlowt.com)
                Charlton R. JMHG. 1(2004): 55-9
           Kaufman JM. Endocrine Reviews. 26(2005):833-76
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
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
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 of Androgel per day 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.
Treatment options – not just
       “the needle”
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
Treatment options – the needle
HCG – human chorionic gonadotropin -1250 – 2500 x/wk
(tiny needle; “off-label”, doesn’t work in much older men)
Testosterone cypionate – 200mg/cc – dosing determined by
size – administered IM – one to two X per week– (bigger
needle; on-label per FDA, works in everyone, shrinks
testicles).
"Sexy" - part 3 of the CWI Lecture Series - June 2012f sss lectures series for slide share - june july 2012.pt
"Sexy" - part 3 of the CWI Lecture Series - June 2012f sss lectures series for slide share - june july 2012.pt
"Sexy" - part 3 of the CWI Lecture Series - June 2012f sss lectures series for slide share - june july 2012.pt
Evansville Courier & Press: May 29,
2006
What is Raman Spectroscopy?
           Monochromatic photons interact with molecules that have
           vibrational energy (e.g., carotenoids), and gets scattered at
           a higher wavelength. Sir C. V. Raman, Nobel Prize in
           Physics, 1930




Carotenoid molecules shift blue laser light color to green:
                  473 nm to 510 nm
"Sexy" - part 3 of the CWI Lecture Series - June 2012f sss lectures series for slide share - june july 2012.pt
Where to read more…
“Pending strong evidence …from randomized trials, it
appears prudent for all adults to take vitamin
supplements.” Fletcher & Fairfield, JAMA 2002
“The Complete Idiot’s Guide to the
          “Cady White Paper”

• Pp 1-3 Patent claim synthesis: assessing
  the overall antioxidant status in human
  tissue via Raman spectroscopy via
  measuring carotenoids
  – Carotenoids are antioxidants
     • Identified in 1992
     • Potent antioxidants
     • Lycopenes and carotenoids appear to diminish risk of
       prostate CA.
• P 4 Further discussion of prostate CA
Lipid peroxidation, antioxidant status
& survival in institutionalized elderly
• Plasma MDA
  predicted mortality
  independently of all
  other variables.
• B-carotene and
  alpha tocopherol
  were independently
  association with
  survival.          Huerta JM et al.   Free Radical Research
                       2006, vol 40, no 6. pp 571-578.
Epidemiology of Vascular Aging (EVA)
• Study population:
  – N=1,389; age range {59-71 yoa}
  – 9 year study
• Relative risks:
  – all cause mortality at 2.94X in men in lowest
    quintile (95% CI, P=0.03)
  – cancer 1.72X in men (95% CI, P=0.01
• “Total plasma carotenoids levels
  were independently associated
  with mortality risk in men.”
Antioxidants and brain tumors?


• “free radicals are another etiological factor
  of brain tumor and are removed by cellular
  antioxidants in the human body.”
• Inverse correlation between:
  – antioxidant levels and oxidative DNA damage
  – Grades of malignancy
• Decrease in antioxidants are associated
  with severity of malignancy
A quick look back in history




The Interpretation of   Ugo Cerletti 1935
                                            Prozac - 1987
Dreams – 1885 - 1890
The Therapeutic Trifecta of Psychiatry:
             Shrinking
             Shocking
            or Drugging
        [Supposedly] the only three
     things you could do to a patient’s
                 brain…]
Faraday’s Law of Induction

      TMS     Induced neuronal
     Magnetic      current
      field
"Sexy" - part 3 of the CWI Lecture Series - June 2012f sss lectures series for slide share - june july 2012.pt
From electricity to
    magnetism
• Bartholow, R (1874)
   – Stimulation of human brain
     (exposed cortex) of patient with
     cranial defect.

• d’Arsonval – “Phosphenes
  and vertigo” induced inside
  powerful magnetic coil

• Silvanus P. Thomson, Ph.D.
  – new type of magnetic     Thompson, SP. “A Physiological
                             Effect of an Alternating Magnetic
  stimulation (1910)         Field.” Proceedings of the Royal
                                        Society of London B82:396-399, 1910
NeuroStar Directly Depolarizes Cortical
              Neurons



                   Neuron    Pulsed magnetic fields
                             from NeuroStar:
                             •induce a local electric
                             current in the cortex which
                             depolarizes neurons
          Neurons are        •eliciting action potentials
       “electrochemical      •causing the release of
     cells” and respond to   chemical
      either electrical or   neurotransmitters
     chemical stimulation
"Sexy" - part 3 of the CWI Lecture Series - June 2012f sss lectures series for slide share - june july 2012.pt
"Sexy" - part 3 of the CWI Lecture Series - June 2012f sss lectures series for slide share - june july 2012.pt
Does it work?
• Original registration trial
  – 307 major depressed patients
     • 67% women
     • 93% recurrent depressives
     • 43% had been hospitalized already
  – 42 sites
  – Treatment per label
• Results: ½ patients responded; 1/3 of
  patients remitted.
• 80% patients completed the treatment.
Who Was Studied?
    • Primary diagnosis: DSM-IV Major Depressive
      Disorder
           – Unipolar type, non-psychotic
           – Moderate to severe symptoms at baseline
           – Approximately one-third of patients had a co-morbid anxiety
             disorder (OCD excluded)
    • Antidepressant Treatment History:
           – Average number of antidepressant medication trials in current
             episode = 4 (range: 1 to 23 attempts)
                   • Majority of treatment attempts were unable to achieve adequate
                     dose and duration of treatment due to intolerance
           – In the indicated patient population, all patients failed to
             achieve satisfactory benefit from one antidepressant
             medication at an adequate dose and duration in current
             episode
                                               82
Demitrack and Thase (2009) Psychopharm
     Bulletin
"Sexy" - part 3 of the CWI Lecture Series - June 2012f sss lectures series for slide share - june july 2012.pt
"Sexy" - part 3 of the CWI Lecture Series - June 2012f sss lectures series for slide share - june july 2012.pt
H - 85
www.drlife.com
“But my patients don’t know about
  this and aren’t asking for it….”
                  “It’s not the
                  consumers’
                  job to know
                  what they
                  want.”
                  - Steve Jobs
Perhaps the ability not only to acquire
the confidence of the patient, but to
deserve it, to see what the patient
desires and needs, comes through the
sixth sense we call intuition, which in
turn comes from wide experience and
deep sympathy for and devotion to
the patient, giving to the possessor
remarkable ability to achieve results.
           ...William J. Mayo, 1935

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"Sexy" - part 3 of the CWI Lecture Series - June 2012f sss lectures series for slide share - june july 2012.pt

  • 1. SEXY! Part 3 of 3, plus… 21 Century Medicine st Louis B. Cady, MD – CEO & Founder – Cady Wellness Institute Adjunct Professor – University of Southern Indiana Adjunct Professor – Indiana University School of Medicine With Whitney W. Gabhart, ND - Cady Wellness Institute Newburgh Public Library July 11, 2012
  • 2. What we do NOT want to see happen:
  • 3. CURRENT PRACTICE OF MEDICINE: What a patient had to say about her “specialists”: “They just monitor my degeneration.”
  • 5. Cady Wellness Institute – July 2005 The Reasons: • Conventional medical practice had failed me twice. • A lot of “psychiatric cases” WEREN’T “psychiatric.” • Nobody was integrated. • Nobody was looking at ALL of the peer-reviewed literature.
  • 6. Orientation to this talk • Review the fundamental differences between “wnl” and OPTIMAL • Quick review of hormones having to do with with “slim and sane” sections of this series – Thyroid – DHEA – estradiol/progesterone – IGF-1 (“food soldier” of growth hormone) – Integration of testosterone • Exposure to current “state of the art”
  • 7. American Journal of Health Promotion; November/December, 2002 66% 19% of those 18.8% “Incompletely healthy” surveyed were completely completely unhealthy, healthy with defined as high levels of having low both physical levels of health and mental with high Two-thirds of the adults health and a levels of reported some low level of illness. degree of mental illness. or physical illness that kept them from being completely healthy. OPTIMAL “Incompletely healthy.” DEAD HEALTH continuum
  • 8. Critical area of concern for men & women. Things that will make them: • Tired &/or depressed • Unable to cope • “Mean” • Stressed • Demented • Deficient in libido or in the bedroom
  • 9. How would you take care of a classic?
  • 10. “Age management” “Conventional practice” There are fuel additives No fuel additives should we can use to keep our be used. They are cars burning cleaner and unnatural. Gas is all that preserve engines. is required. We should use optimal The quality of the gas is quality of gas. Cheap gas irrelevant. Anything that causes “pinging” which is the motor will burn is hard on the engine. adequate. We should take our car in Preventive maintenance? This for preventive is silly! Wait until something breaks, then have the car maintenance before towed in so the mechanic can anything breaks. really tell what is wrong.
  • 11. And if you’re just a tired ol weenie (or weenette), you will definitely note be feeling SEXY.
  • 12. Toward an INTEGRATED approach: Traditional INTEGRATED Optimal Health No Disease = Health Medicine Medicine Forestall and Diagnose and PREVENT Disease – Treat Disease Optimize Mood & Death Function New Drugs Functional New Surgical & Informed Techniques Lab Testing Vitamins, HRT, Nutrition, Exercise
  • 13. 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. Modern Medicine’s Paradigm: Two Standard Deviations – “if you are not sick, then you must be well.” “NORMAL” OPTIMAL
  • 17. What are We Trying to Accomplish? The Laboratory midrange of the 30 y/o is the same as the upper quartile of the 70 y/o. Miami - 2002 - 17
  • 18. 4
  • 19. 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.”
  • 20. Selenium, the Thyroid, and You • “T3” is the ACTIVE form of thyroid • Conversion of T4 to T3 is selenium dependent • LP Nano has 200% of RDA of Se+ selenium 
  • 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 Accessed: 9/5/2011
  • 24. Rev T3 Se CORTISOL “the foot soldier” “the evil twin”
  • 26. Case report: • 55 year old male entrepreneur • Runs company with 200 employees – multi hundred million dollar budget • Stressed with economy • Very tired in the a.m. • “Crashes” at night. • Still golfing, exercising. • Looks marvelous.
  • 27. 334 citations on “DHEA with energy” – as of 07 29 2011
  • 28. Why isn’t adrenal fatigue diagnosed? • Not a medical emergency. • Patient is blamed” – “just neurotic” – “avoidant” • “Functional medicine” testing not typically done (& rarely is DHEA-S checked) • Modern medicine focuses on NORMAL, rather than OPTIMAL. function. • “Bell Curve” paradigm
  • 30. One destigmatizing notion: Estrogen as MAOI • Estrogen & Testosterone (!) decrease MAO – Luin, VN. 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
  • 31. Psychoactive Progesterone*  Increases energy and libido  Has a calming effect, acting like a benzodiazepine to the brain (HS dosing)  Enhances mood  Balances blood sugar (appetite)  Regulates fluid balance, sodium mineral balance  Necessary for fertility  Helps relieve menopausal symptoms  Decreases risk of endometrial cancer and may help protect against breast cancer, fibrocystic breasts, and osteoporosis * Adapted from Whitney Gabhart, N.D.
  • 32. Testosterone: The “sexist” bias against women • 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.
  • 33. Brief Description of Hormone Function (Men AND Women) Testosterone – Enhances sex drive – Builds muscle & decreases fat – Elevates mood – Prevents osteoporosis – Improves memory – Lowers cholesterol – Protects against heart disease
  • 34. We use Bio-identical “HRT” at CWI: • Synthetic means that the molecule is not natural to the human body. • Bio-identical hormone is one whose molecule is identical to that made by a human organ. SV2003- 34
  • 35. 50’ish 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.”
  • 40. Treatment for this “normal” patient 1. Armour thyroid – 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)
  • 42. 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.”
  • 43. The Case of the Crying Cleaner • 1/11/12 - Symptoms: – Crying/depressed = on Citalopram – Hot flashes – Night sweats • RX: – Estradiol – 2 mg @HS – Prometrium – 100 mg @HS – (continue citalopram) • 1/15/12 – RESOLVED • IN 2 WEEKS!!!. Photo & data used with permission
  • 46. 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 to be attributable to observed changes in explanatory factors, including lifestyle characteristics such as smoking and obesity.” “Recent years have seen a SUBSTANTIAL, and as yet UNRECOGNIZED age-independent population- November 2009 level decrease in T in American men.” “Alpha Male” issue Travison, Araujo, et al. Jrnl of Clin. Endocrinol & Metabol 92:1; 196-202.
  • 47. 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
  • 48. 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
  • 49. Testosterone functions (Men AND Women) • Enhances sex drive • Builds muscle & decreases fat • Elevates mood • Prevents osteoporosis • Improves memory • Lowers cholesterol • Protects against heart disease
  • 50. Physiology of testosterone • T regulates – Nitric oxide (NO) – Phosphodiesterase type 5 (PDE-5) – Both critical for initiation & maintenance of erectile function • T maintains – Penile structural integrity – Functional integrity Wang C, J Clin Endocrinol Metab. 89(2004):2085-98
  • 51. “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…”
  • 52. “…both estrogencs and androgens can play a protective role against AD related neurodegeneration.” “Hypogonadal in later life” = “problems with memory”
  • 53. 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
  • 54. 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! • (Hubby reference: www.isitlowt.com) Charlton R. JMHG. 1(2004): 55-9 Kaufman JM. Endocrine Reviews. 26(2005):833-76
  • 55. 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
  • 56. 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
  • 57. 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 of Androgel per day 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.
  • 58. Treatment options – not just “the needle”
  • 59. 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
  • 60. Treatment options – the needle HCG – human chorionic gonadotropin -1250 – 2500 x/wk (tiny needle; “off-label”, doesn’t work in much older men) Testosterone cypionate – 200mg/cc – dosing determined by size – administered IM – one to two X per week– (bigger needle; on-label per FDA, works in everyone, shrinks testicles).
  • 64. Evansville Courier & Press: May 29, 2006
  • 65. What is Raman Spectroscopy? Monochromatic photons interact with molecules that have vibrational energy (e.g., carotenoids), and gets scattered at a higher wavelength. Sir C. V. Raman, Nobel Prize in Physics, 1930 Carotenoid molecules shift blue laser light color to green: 473 nm to 510 nm
  • 67. Where to read more…
  • 68. “Pending strong evidence …from randomized trials, it appears prudent for all adults to take vitamin supplements.” Fletcher & Fairfield, JAMA 2002
  • 69. “The Complete Idiot’s Guide to the “Cady White Paper” • Pp 1-3 Patent claim synthesis: assessing the overall antioxidant status in human tissue via Raman spectroscopy via measuring carotenoids – Carotenoids are antioxidants • Identified in 1992 • Potent antioxidants • Lycopenes and carotenoids appear to diminish risk of prostate CA. • P 4 Further discussion of prostate CA
  • 70. Lipid peroxidation, antioxidant status & survival in institutionalized elderly • Plasma MDA predicted mortality independently of all other variables. • B-carotene and alpha tocopherol were independently association with survival. Huerta JM et al. Free Radical Research 2006, vol 40, no 6. pp 571-578.
  • 71. Epidemiology of Vascular Aging (EVA) • Study population: – N=1,389; age range {59-71 yoa} – 9 year study • Relative risks: – all cause mortality at 2.94X in men in lowest quintile (95% CI, P=0.03) – cancer 1.72X in men (95% CI, P=0.01 • “Total plasma carotenoids levels were independently associated with mortality risk in men.”
  • 72. Antioxidants and brain tumors? • “free radicals are another etiological factor of brain tumor and are removed by cellular antioxidants in the human body.” • Inverse correlation between: – antioxidant levels and oxidative DNA damage – Grades of malignancy • Decrease in antioxidants are associated with severity of malignancy
  • 73. A quick look back in history The Interpretation of Ugo Cerletti 1935 Prozac - 1987 Dreams – 1885 - 1890
  • 74. The Therapeutic Trifecta of Psychiatry: Shrinking Shocking or Drugging [Supposedly] the only three things you could do to a patient’s brain…]
  • 75. Faraday’s Law of Induction TMS Induced neuronal Magnetic current field
  • 77. From electricity to magnetism • Bartholow, R (1874) – Stimulation of human brain (exposed cortex) of patient with cranial defect. • d’Arsonval – “Phosphenes and vertigo” induced inside powerful magnetic coil • Silvanus P. Thomson, Ph.D. – new type of magnetic Thompson, SP. “A Physiological Effect of an Alternating Magnetic stimulation (1910) Field.” Proceedings of the Royal Society of London B82:396-399, 1910
  • 78. NeuroStar Directly Depolarizes Cortical Neurons Neuron Pulsed magnetic fields from NeuroStar: •induce a local electric current in the cortex which depolarizes neurons Neurons are •eliciting action potentials “electrochemical •causing the release of cells” and respond to chemical either electrical or neurotransmitters chemical stimulation
  • 81. Does it work? • Original registration trial – 307 major depressed patients • 67% women • 93% recurrent depressives • 43% had been hospitalized already – 42 sites – Treatment per label • Results: ½ patients responded; 1/3 of patients remitted. • 80% patients completed the treatment.
  • 82. Who Was Studied? • Primary diagnosis: DSM-IV Major Depressive Disorder – Unipolar type, non-psychotic – Moderate to severe symptoms at baseline – Approximately one-third of patients had a co-morbid anxiety disorder (OCD excluded) • Antidepressant Treatment History: – Average number of antidepressant medication trials in current episode = 4 (range: 1 to 23 attempts) • Majority of treatment attempts were unable to achieve adequate dose and duration of treatment due to intolerance – In the indicated patient population, all patients failed to achieve satisfactory benefit from one antidepressant medication at an adequate dose and duration in current episode 82 Demitrack and Thase (2009) Psychopharm Bulletin
  • 87. “But my patients don’t know about this and aren’t asking for it….” “It’s not the consumers’ job to know what they want.” - Steve Jobs
  • 88. Perhaps the ability not only to acquire the confidence of the patient, but to deserve it, to see what the patient desires and needs, comes through the sixth sense we call intuition, which in turn comes from wide experience and deep sympathy for and devotion to the patient, giving to the possessor remarkable ability to achieve results. ...William J. Mayo, 1935

Editor's Notes

  1. These symptoms correlate to decrease in bioavailable testosterone
  2. 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
  3. Hypogonadal if TT &lt; 200ng/dL or FT &lt; 0.9ng/dL
  4. He discovered that if you shine a particular wave length of light on a substance it may give off another wave length of light. It will absorb one and give off another wave length of light. Today this is called the Raman Effect, or the substance that does this is “Raman Active.” And he discovered that based on the intensity of that light that is fed back into the spectrometer, we can quantify the exact amount of molecules in that substance. So what does that do for us, but to allow the measurement of the exact number of carotenoid molecules in someone’s tissue. The specific wavelength of light that we are looking for is a green wavelength of light. You’ve all see the blue light that comes out of the scanner. But did you know we are looking for a green light that is fed back into the scanner off of your palm. And based on the brightness of that light we can tell how many carotenoid molecules are in your tissue.
  5. In the following section of my talk, I ’d like to discuss TMS in more detail. I will review its mechanism of action, and then discuss some of the most recent randomized clinical trial evidence supporting its efficacy and safety. I will also discuss recent outcomes in real-world practice settings obtained from an ongoing large, prospective outcomes study.
  6. Capacitors of the day did not permit high intensity or rapid frequency use. The “ phosphenes ” were either generate from effects on the occipital cortex or directly on the retina of the eye. 1959 – Kolin et al – first to demonstrate magnetic field could stimulation a peripheral frog muscle preparation.
  7. The underlying rationale for the use of TMS exploits the fact that neurons are electrochemical cells. This means that neuronal activity can be affected either chemically, via the use of drugs, or electrically, via interventions like TMS.   Unlike drug action, whose effects tend to be anatomically diffuse, the effects of TMS are anatomically focused, and by design are non-invasive and non-systemic in action. Under normal conditions of use, TMS therefore incurs far fewer adverse events, and is devoid of undesired systemic adverse events commonly observed with antidepressant medications. The TMS device is a powerful electromagnet, which is turned on and off in a rapid fashion, producing a pattern of “pulsed” magnetic fields. When pulsed magnetic fields are positioned close to an electrical conductor, like neurons, a local electrical current is produced in that conductor. This electric current is powerful enough right under the magnetic coil to elicit action potentials, which then travel down the neuron, ultimately causing the release of neurotransmitters at the synapse (Post 2001, p. 193A) . References : Post A, Keck ME. Transcranial magnetic stimulation as a therapeutic tool in psychiatry: what do we know about the neurobiological mechanisms? J Psychiatric Research. 2001;35: 193-215.
  8. This slide describes some of the major demographic and clinical characteristics of the patients studied in the registration clinical trials that led to FDA clearance for the NeuroStar TMS Therapy system.   All patients had a diagnosis of unipolar, non-psychotic major depression, with moderate to severe symptoms at entry to the study. About a third of all patients had a concurrent secondary diagnosis of an anxiety disorder.   All patients received a rigorous characterization of their antidepressant medication treatment history in the current illness episode. Most patients had received numerous medication treatment attempts, with one of these treatment attempts being administered at an adequate daily dose and for at least four weeks without clinical benefit. The average number of overall treatment attempts (which includes all antidepressant medications administered in the current episode, regardless of whether they reached an adequate dose and duration) was 4, with a range across the study population from 1 to as many as 23 treatment attempts.   Consistent with the data that I reviewed earlier in this presentation, about 75% of the time, these antidepressant treatment attempts were unable to achieve this minimum level of exposure adequacy (usually because of treatment intolerance, or failure to adhere to the recommended treatment regimen).   References : Demitrack, MA , Thase, ME,. (2009) Clinical significance of transcranial magnetic stimulation (TMS) in the treatment of pharmacoresistant depression: synthesis of recent data. Psychopharm Bulletin 42(2) :5-38