Generative AI in Health Care a scoping review and a persoanl experience.
Hormones, Cognition, and Mood Changes in Older Adults
1. Hormones, Cognitive Dysfunction &
Depression in Older Adults
Louis B. Cady, MD – CEO & Founder – Cady Wellness Institute
Adjunct Asst. Prof of Psychiatry – Indiana University School of Medicine
Department of Psychiatry
Child, Adolescent, Adult, Functional Neuropsychiatry – Evansville, Indiana
AMMG Fall Conference – Nov. 2, 2012 – General
Session Curriculum 2:00 – 2:45 pm Las Vegas, NV - USA
2. “There are two objects of medical education: to heal
the 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. 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
9. 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
11. • “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
12. FEEDBACK
INHIBITION
Selenium CORTISOL
required!
“the foot soldier” “the evil twin”
13. % Mineral depletion from the soil
during 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
14. Jrnl of Amer. College of Nutrition Vol 23, No.
6, 669-682 (2004).
Objective: evaluate possible changes in USDA nutrient content data for
43 crops between 1950 – 1999; consider potential causes
Methods: ratios calculated for “R” 1999/1950
Results: as a group, the 43 foods showed apparently, statistically reliable
declines for 6 nutrients: protein, Ca, P, Fe, riboflavin, and ascorbic acid.
- 6% decrease in protein
- 38% decrease in riboflavin
CONCLUSIONS: trade off between yield and nutrient content
15. 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
18. • 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)
20. 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 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.
21. Modern Medicine’s Paradigm:
Two Standard Deviations – “if you are not
sick, then you must be well.”
“NORMAL”
OPTIMAL?
OPTIMAL
22. 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?
23. Serum concentrations of Free T3, Free T4, morning cortisol,
afternoon cortisol and change in cortisol concentrations.
Adjustments for: age, sex, body mass index, hypertension, previous
MI, heart failure, diabetes, NY Heart Assn. functional class,
depressive symptoms and anxiety symptoms.
Lower Free T3 = more physical fatigue
Lower Free T4 = more exertional fatigue
Lower morning cortisol and change in cortisol concentration = more
mental fatigue.
24. Aim: evaluate biological factors assoc. with suicide attempts in
naturalistic sample
439 patients with major depression, bipolar and psychotic
disorders consecutively assessed in the ER of an Italian Hospital
(Jan 2008-Dec 2009)
Suicide attempters were 2.27 times less likely to have higher Free
T3 values than non-attempters (odds ratio = 0.44; 95% CI; p=0.01)
(prolactin level differences failed to reach significance)
25. Treatment resistant depression is a common challenge.
Best augmenting strategies available:
-Lithium
-Thyroid hormone
-Anti-anxiety medications
-Atypical antipsychotics.
26. 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
27. 63 patients with “subclinical hypothyroidism”
HAM-D and MADRS scales with serum TSH Free T4, free T3
TPO 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?
28. Aim: Evaluate relationship of subclinical hypothyroidism and
cognition in the elderly.
- 337 outpatients; {177 = men; 160 = women}
MMSE scores were SIGNIFICANTLY lower in
subclinical hypothyroid patients compared to
euthyroid (p<0.03)
“Patients with subclinical hypothyroidism had a
probability about 2 times greater (RR = 2.028, p<0.05) of
developing cognitive impairment.”
29. 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}
30. 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”
31. G.G. – labs before and after
4/11/11 interventions 7/11/11 changes
TSH 3.84 Raise T4 from 0.01 (L) none
50 – 75 ug
FT4 1.16 “ 1.24 “
FT3 2.8 “ 3.3 “
Progesterone <0.2 100mg topical 0.9 None
HS
Testosterone 11 4mg topical 15 4 mg LABIAL
DHEA-S 25 25 mg SR n/a continue
32. 24 post-menopausal women with intact uterus. Neuropsych
testing. No hormone therapy used in the past. Recruited by
newspaper ads.
Randomized to CEE + PL, CEE + MPA, CEE +
MP (Micronized progesterone)
Mood improved in all groups.
CEE + MP performed significantly better on a test of
working memory than the other two groups.
33. 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.
34. The glamorous grandmother – post tune-up:
DHEA, thyroid, testosterone, progesterone
Photos removed for internet slideshare
and .pdf postings
9/28/2011 (permission granted to use photos & data) 01/26/2012
35. Photos removed for internet slideshare
and .pdf postings
October 12, 2012 – used with permission
36. 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.
37. 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.”
39. 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
42. 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
survival
Manninger, N et al. Neurobiological & neuropsychiatric effects of DHEA and DHEA
43. DHEA has been correlated with lower susceptibility to anxiety
and mood disturbance.
Behavioral task – series of anagram puzzles
from possible to IMPOSSIBLE.
Other indices: ACT scores, # of college classes dropped
or failed, current GPA
Higher DHEA: cortisol ratio associated with
“lowest probability of failing the task.”
44. 91 students ½ male, ½ female – taking Organic
Chemistry in the USA.
Displacement activities (DA’s) screened for by video
recording during tests.
A logistical model built on GPA, DA’s, and
salivary hormone levels of cortisol and
DHEA correctly predicted 90% of the
students who passed the class.
45. 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.
46. 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”
47. July 2011 Nov 2011 Dec 29, 2012
Interventions 100 mg DHEA SR 100 mg DHEA SR
½ grain Armour ½ grain Armour
1 pump T to each
inner thigh
TSH 1.2 0.86 0.93
Free T4 1.7 1.5 1.3
Free T3 303 373 361
Rev T3 44 (H) 57 (H) 39 (H)
DHEA-S 128 472 (“H”) 306 (“H”)
IGF-1 81 106 120
Total testosterone 820 913 969
Free Testosterone 87.7 131.5 100.8
48. 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
49. 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
50. 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
51. 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
52. 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.
54. 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.”
55. 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
56. 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
57. 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.
58. 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
59. Prevalence of Low Total Testosterone
• 12% for men in 50s
• 19% for men in 60’s
• 28% for men 70s
• 49% for men >80
Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR. Longitudinal effects of ageing on serum
total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. J Clin
Endocrinol Metab 2001; 86(2): 724-31.
60. T vs Cognitive Function
Rosario ER. Age-related testosterone depletion and the
development of Alzhiemer disease. JAMA. 292(2004):1431-2
61. 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
62. 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
63. 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
64. 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.
65. Relevance of testosterone (and DHEA
+ Thyroid)
Photos removed for internet slideshare
and .pdf postings
RX: dairy free diet (+IgG test); D3 5000 IU/d; Armour thyroid,
Testosterone cypionate 100 mg IM q wk, MVI, Zinc, DHEA 50 mg
SR, CoQ10 400mg (permission granted to use photos & data)
66. 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.
67. 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
68. Benefits (and minimal risk) of testosterone –
J Sex Med Sep 2012
Risks 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
69. 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.
70. What if we could just look at neurotransmitters
like they would on Star Trek ?
Cell rate
71. Low estrogen, DHEA, cortisol, and low NT’s – putting it all together
52 yo woman, s/p TAH with fatigue and depression
Hormone Value norms
Cortisols All barely various
above
pathological
DHEA 47.66 {106-300}
Estradiol (E2) <1.00 {1.0 – 3.2 =
post
menopausal}
Testosterone 8.44 {6.1 – 49 –
female}
74. 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.
75. “It’s really not that
So what the heck am I complicated!”
supposed to do with this
stuff?
76. Behaviors/status Interventions
stress Job/life stress Meditation, spiritual practice, T’ai chi,
Qigong, make needed life changes
Abnormal Presumptively low or Get levels – saliva or blood (pre-treatment)
hormones unknown Check Neurotransmitters (urine ELISA)
Thyroid
DHEA
Interventions Optimize/support cortisol
Testosterone, Estradiol & Progesterone
Growth hormone?
Amino acid precursor loading for NT’s?
Prescriptive agents – e.g., anti-
depressants, neurostimulants, etc.
77. 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)
78. Contact information:
Louis B. Cady, M.D.
www.cadywellness.com
Once more…. www.facebook.com/cadywellness
Where to “get the slides” -
www.indianaTMS-cadywellness.com
www.slideshare.net/lcadymd Office: 812-429-0772
E-mail: lcady@cadywellness.com
4727 Rosebud Lane – Suite F
Interstate Office Park
www.cadywellness.com/ammg/ Newburgh, IN 47630 (USA)
hormones.ppt @LouisCadyMD
@TMS4depression
79. “Sit down before fact as
a little child,
be prepared to give up
every preconceived
notion,
follow humbly wherever
… nature leads,
or you shall learn
nothing.”
- Thomas H. Huxley
Notes de l'éditeur
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