Thyroid, Adrenals & Sex Hormones: A Balancing Act

Louis B. Cady, MD – CEO & Founder – Cady Louis B. Cady, MD – CEO & Founder – Cady Wellness Institute Wellness Institute Adjunct Professor – University of

Southern IndianaAdjunct Professor – Indiana University School of

MedicineIntegrative Medicine for Mental Health Conference

Sedona, ArizonaSeptember 17-18, 2011

Framework for this presentation:

“Slumber not in the tents of your fathers. The world is advancing. Advance with it.” - Giuseppe Mazzine

Orientation to this talk• Sketch in the fundamental differences

between “wnl” and OPTIMAL

• Quick review of hormones having to do with FATIGUE and DEPRESSION:– Thyroid– DHEA– Testosterone/estradiol/progesterone– IGF-1 (“food soldier” of growth hormone)

• Exposure to the literature/stimulation

American Journal of Health Promotion; November/December, 2002

19% of those surveyed

were completely healthy with high levels of both physical

and mental health and a low level of

illness.

18.8% completely unhealthy, defined as having low

levels of health with high levels of illness.

Two-thirds of the adults reported some

degree of mental or physical illness that kept them from being completely healthy.

“Incompletely healthy.”

HEALTH continuum

DE

AD

OP

TIM

AL

66%“Incompletely healthy”

VISION: “We dramatically transform the lives of our patients and clients to levels of peak physical and mental health, supporting a lifetime of maximum performance and happiness.”

BODY

MIN

D

ACTIO

NS

Critical area of concern for men & women. Things that will make them:

• Tired &/or depressed

• Unable to cope

• “Mean”

• Stressed

• Deficient in libido or in the bedroom

• Demented

How would you take care of a classic?

There are fuel additives we can use to keep our cars burning cleaner and preserve engines.

No fuel additives should be used. They are unnatural. Gas is all that is required.

We should use optimal quality of gas. Cheap gas causes “pinging” which is hard on the engine.

The quality of the gas is irrelevant. Anything that the motor will burn is adequate.

We should take our car in for preventive maintenance before anything breaks.

Preventive maintenance? This is silly! Wait until something breaks, then have the car towed in so the mechanic can really tell what is wrong.

“Age management” “Conventional practice”

A Shrink meets the “anti-aging” crowd

• Patient “complaints”• Loss of energy• Loss of stamina• Loss of libido• Weight gain• Loss of zest for life• Loss of interest in career• “I’ve felt like I’ve been

aging since I was 35.”

• Personal experience• Previous state:

“energy to burn”• “Snooze bar

syndrome”• “Piles syndrome”• “Why can’t I make

myself exercise?”

• Car wash MSE!

Depression & Anxiety Dx in 1 Easy Lesson

DEPRESSIONSIG: E- CAPS!

• Sleep• Sadness • Interest loss• Guilt• *Energy• Concentration• Appetite• Psychomotor Sx• Suicidal thinking

Gen. ANXIETY D.O.•Somatic Sx (“energy”,etc.)•WORRY•Irritability•Concentration•Keyed up•Insomnia (“sleep”)•Restlessness

SWICKIR is Quicker:

Worry + 3 = GAD (Baughman)5of 9 with 1 of 2 x 2 weeks

*MUST MUST MUST exclude “mood disorder due to a general medical condition”

Depressed mood 100%

Reduced energy: 97%3

Fatigue or loss of energy: 94%2 Impaired concentration: 84%3

Tiredness: 73%1

Hypersomnia: 10%–16%4 (Insomnia)

Useful Target Symptoms in MDDUseful Target Symptoms in MDD

1. Tylee et al. Int Clin Psychopharmacol 1999;14:139-151. 2. Maurice-Tison et al. Br J Gen Pract 1998;48:1245-1246. 3. Baker et al. Comp Psychiatry 1971;12:354-65. 4. Horwath et al. J Affect Disord 1992;26:117-25. 5. Reynolds and Kupfer. Sleep 1987;10:199-215.

Stahl, SM. Symptoms & Criuits, Part 1 Major Depressive Disorder. “Brainstorms.” J Clin Psych 64:11, Nov 2003:1282-1283.

“Each symptom may be mediated by separate and distinct neuronal [AND PHYSIOLOGICAL – (Cady)] circuits.”

Death

Optimal Health

TraditionalMedicine

Functional & Informed Lab Testing

No

Dis

ease

= H

ealth

Vitamins, HRT, Nutrition, Exercise

INTEGRATED Medicine

Diagnose andTreat Disease

New DrugsNew Drugs New Surgical New Surgical TechniquesTechniques

Forestall and PREVENT Disease –

Optimize Mood & Function

Toward an INTEGRATED approach:

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

Modern Medicine’s Paradigm: Two Standard Deviations – “if you are not

sick, then you must be well.”

“NORMAL”

OPTIMAL

4

Releasing Factors

Releasing Factors

AdrenalGland

AdrenalGland OvariesOvariesTesticlesTesticles ThyroidThyroidLiverLiver

Testosterone EstrogenCortisolDHEA Progesterone

T3 & T4

GHLH & FSH TSH ProlactinACTH

IGF-1

Pituitary

BrainBrain

HypothalamusHypothalamusDHEA

“But the doctor told me my thyroid was fine.”

• Can be “wnl” but suboptimal.• TSH frequently only thing checked.• Nothing known about Free T4 or Free T3.• Free T4 can be converted to Reverse T3 under

stress (cortisol)• Free T4 can be underconverted to T3.• Can have normal levels (or slightly elevated

levels) of everything and have auto-immune thyroid disease.

“the foot soldier” “the evil twin”

“Thyrotropin (Thyroid-Stimulating Hormone or TSH). Measuring TSH is the most sensitive indicator of hypothyroidism.” (hunh?!)

http://www.umm.edu/patiented/articles/how_serious_hypothyroidism_000038_6.htmAccessed: 9/5/2011

“the foot soldier” “the evil twin”

CORTISOLSe

Yes, T-3 DOES get into the brain (Transthyretin = carrier protein)

• Terasaki, T. and Pardridge, W.M.: Stereospecificity of triiodothyronine transport into brain, liver, and salivary gland: role of carrier- and plasma protein-mediated transport. Endocrinology, 121(3):1185-1191, 1987.

• http://www.kingpharm.com/uploads/pdf_inserts/Cytomel_PI.pdf.• Mooradian, A.D.: Blood-brain transport of triiodothyronine is reduced in

aged rats. Mech. Ageing Dev., 52(2-3):141-147, 1990.• Cheng, L.Y., Outterbridge, L.V., Covatta, N.D., et al.: Film

autoradiography identifies unique features of [125I]3,3'5'-(reverse) triiodothyronine transport from blood to brain. J. Neurophysiol., 72(1):380-391, 1994.

• Rudas, P. and Bartha, T.: Thyroxine and triiodothyronine uptake by the brain of chickens. Acta Vet. Hung, 41(3-4):395-408, 1993.

Or: The idiocy of T4 only thyroid treatment…

Transthyretin (a systemic amyloid precursor) may be protective for Alzheimer’s (Why?)

Li X et al. J Neurosci 2011 Aug 31;31(55):12483-90

Per HRSD – 17, remission in:15.9% on Li24.7% on T3

Per QIDS-SR16, remission in:13.2% on Li24.7% for T3 *

* Fava & Covino: Augmentation/Combination Therapy in STAR*D Trial, Medscape Psychiatry

LEVEL III RESULTS:

“No duh” obvious thyroid teaching points:

• You must check the thyroid and you must check ALL OF IT (not just “TSH.”)

• Stress and/or selenium deficiency can PROFOUNDLY alter it.

• Do you want “normal” or “optimal”?

Fatigue from Adrenal Dysfunction - The Worst Case Scensario:

Addison’s Disease

Signs & Symptoms of Adrenal FATIGUE• Difficulty getting up in a.m.• Ongoing lethargy during the day.• Continued fatigue not relieved by sleep.• Craving for salt or salty foods.• Increased effort to do daily tasks• LESS PRODUCTIVE• Decreased sex drive• Decreased ability to handle stress.• Light-headed when standing up quickly• Increased recovery time for illness• Generally less happy about life.

“Hypoadrenia”: The Adrenal Problem that most conventionally trained physicians don’t know about.• Non-Addison’s hypoadrenia• Subclinical hypoadrenia• Neurasthenia• Adrenal neurasthenia• Adrenal apathy• Adrenal fatigue• “Adrenal burnout”• “Chronic fatigue syndrome”?!!

The state of adrenal exhaustion can be determined

Early-stage Chronic Stress Response

Mid-stage Chronic Stress Response

End-stage (exhausted) Chronic Stress

Response

DHEA – the critical hormone most doctors never check

• Produced in the adrenal cortex– Humans and primates are unique in secreting large

amounts

• Immune system booster• Insulin regulator• Energy increase – remarkable• Boosts growth hormone

– 20% in men; 30% in women in one study• [Yen, Morales Khorram – one year double-blind placebo

controlled crossover experiment – with 100mg DHEA]

334 citations on “DHEA with energy” – as of 07 29 2011

Why isn’t adrenal fatigue diagnosed?

• Not severe enough to be an emergency• Symptoms can be attributed to other

things, including “just neurotic” or “avoidant”

• “Functional medicine” testing not typically done (& rarely is DHEA-S checked)

• Modern medicine focuses on the treatment of sickness, not “less than optimal” function.

• “Bell Curve” paradigm

Modern Medicine’s Paradigm: 2 Standard Deviations – a model

“NORMAL”

OPTIMAL

432 citations on DHEA with depression as of 9/5/2011

“Neuroeconomic paramaters predicted to be related to suicidal behavior.” DHEA is related to these, acting in amygdala.

Low levels of DHEA/DHEA-S assoc. with depression, as per Western studies. “DHEA was significantly assoc. w/ [Chinese] Geriatric Depression Scale (GDS).”

Neurobiological & neuropsychiatric effects of DHEA & DHEAS [Maninger N et al. Front

Neuroendocrinology 2009]

• DHEA & DHEAS synthesized in adrenals AND BRAIN.

• Biological actions of DHEA/DHEA-S:– Neuroprotection– Neurite growth– Antagonistic effects on oxidants & glucocorticoids

• “accumulating data suggest abnormal DHEA (S) concentrations in several neuropsychiatric conditions.”

Source: Maninger, N et al : Front Neuroendocrinol. 2009 Jan;30(1):65-91. Epub 2008 Dec 3.

“Women’s issues”

One destigmatizing notion:Estrogen as MAOI

• 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

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.”

Symptoms of estrogen imbalances*: Hot flushes or flashes; night sweats Mood swings DEPRESSION, and/or anxiety, panic attacks “Concentration” issues: Memory, communication, and

attention span loss, “brain fog.” (Think: “MORE MAO.”)

Insomnia Weight gain – “appetite changes” SOMATIC symptoms : aches and pain General deterioration: Incontinence, digestive disturbances,

sensory function loss, aging skin . . . thinning, wrinkles, sagging

* Adapted from Whitney Gabhart, N.D.

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.

Traditional vs. Bio-identical “HRT”:

• 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. 

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Women’s Health Initiative Study•Flawed study - it was designed as a “Premarin & Provera” study, not a bioidentical estrogen study.

•Premarin is a non-bio-identical substance

•Provera is a non-bio-identical substance

•Premarin is an equine derived array of 30+ female horse hormones.

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Women’s Health Initiative Study

•The results presented did not justify their overall broad conclusion:

• “Premarin & Provera yielded these findings; therefore, Hormone Replacement Therapy is not appropriate for women.”

Women’s Health Initiative Study

THE PARTICIPANTS:• 2/3 of the women in the study were older than

sixty• Of these women, most were first-time users of

HRT.• Had already experienced cessation of

endogenous hormone production (for a DECADE!!!), therefore, at risk for:– Heart attacks, strokes, clots, cancer

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Women’s Health Initiative StudyFacts You Should Know

• In the first 1-3 years there was a higher incidence of M.I.’s.

• Patients who stayed on that program beyond the 8th year started to actually outperform women on placebo.

• WHY????

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Women’s Health Initiative Study Facts You Should Know

•When the W.H.I. Study was organized, the subjects were not prescreened for heart disease.

•Without prescreening, a group of women was included with pre-existing heart disease.

•

Hx of Baseline Health Characteristics (total # of participants 16,608)

Disease HRT PlaceboHypertension 3039 2949High Cholesterol 944 962Myocardial Infarction 139 157Angina 288 234Stroke 61 77Embolism 79 62Family Breast Cancer 1286 1175Diabetes 374 360Fracture 1031 1029

37%

11%2%

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Traditional vs. Bio-identical “HRT”:

•Premarin raises C-reactive protein significantly.

•CRP is an inflammation marker.•Inflammation is either the root cause (e.g., rupturing plaque), or a strongly contributing cause, of both Cancer & Heart Disease.

Some of the “10 reasons” to be happy [Studd J. Menopause Int. 2010 Mar;16(1):44-6

• Trans-derm safer than oral– Coag factors not induced in

liver

• Safe for tx of flushes, sweats, vaginal dryness

• Estrogens prevent osteoporotic fracutres – should be FIRST CHOICE rather bisphosphonates

• HRT protects intervertebral discs

• Est + T helps “reproductive depression”

• Improves energy & libido• Reduces incidence of heart

attakcs.• Beneficial effects on collagen• Note 1 % increased lifetime

risk of breast cancer

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.”

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)

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.”

November 2009 “Alpha Male” issue

Observational study of randomly selected men – Boston3 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-level decrease in T in American men.” 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 Disorders, 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

“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…”

• Decline in male sex steroids not as abrupt as menopause, but equally debilitating

–Between 40 – 70, average male loses:

• Nearly 2" of height

• 15% of bone density

• 10 – 20 pounds of muscle

•At 70 yoa, 15% completely impotent

Testosterone (Men)

Andropause: Characteristics of Change

• Insidious & unpredictable onset

• Slow progression

• Subtle & variable manifestations

• Cannot be linked directly to a decrease in the hormone testosterone

• Very different from menopause in women!

Charlton R. JMHG. 1(2004): 55-9 Kaufman JM. Endocrine Reviews. 26(2005):833-76

T vs Cognitive Function

Rosario ER. JAMA. 292(2004):1431-2

T vs Cognitive Function

Rosario ER. JAMA. 292(2004):1431-2

“Testosterone depletion likely precedes and thus may contribute to rather than result from the development of AD, since low brain testosterone is observed in men with early indications of AD neuropathology”

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

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

HOW OBVIOUS DOES IT HAVE TO BE? The Challenge of Empathic Listening

& CREATIVE THINKING

Ron Hunt lost an eye but suffered no brain damage after a freak accident with a large drill bit. (ABCNEWS.com)

Do you really want to try 100,000 miles without changing the oil?

Definition of ‘normal’ – “where your hormone levels are as lousy as

everyone else’s.” Neal Rouzier, MD

“NORMAL”

OPTIMAL

American Journal of Health Promotion; November/December, 2002

HEALTH continuum

DE

AD

OP

TIM

AL

66%“Incompletely

healthy”**“treatment resistant”?

“For me, the practice of medicine has opened the door to the greatest adventure in life. Medicine is like a hallway lined with doors, each door opening into a different room, and each room openinginto another hallway, again lined with doors. Medicine is always wonderful and never will be finished.”- Charles H. Mayo, M.D.

Extra slides for further background follow in notes

Contact info:Louis B. Cady, M.D.www.cadywellness.com Office: 812-429-0772

Health is a state of complete physical, mental and social well-being, and not merely the absence of disease or infirmity.  -  World Health Organization

Cady response to DHEA: March – May – 2 months…

• Dropped from 25.6% BF to 21.5% BF• Lost 3.3 inches off waist• Lost 8 pounds of fat• Gained 4 pounds of muscle

– March: 48,439 grams = 106.57 lbs of muscle

– May 50, 251 grams = 110.55 lbs of muscle

• Cybex: 47.724 sec down to 40.726 sec

The R-Factor Question*

If we were meeting here three years from today – and you were to look back over those three years all the way back to today – what has to have happened during that period …for you to feel happy about your progress and what you have accomplished and the changes made?*Adapted from The Dan Sullivan Question © Dan Sullivan

May 2010

Indole-3-Carbinol – good with or without HRT (for women AND men)

Estradiol

16 alpha-OH Estrone (Ca)

4-OH Estrone (B)

2-OH Estrone (B)

I3C

“I-3 C raises the 2:16-OH Estrogen ratio”N.B.: available from LabCorp

ADAM Questionnaire

• Do you have a decrease in libido (sex drive)?

• Do you have a lack of energy?

• Do you have a decrease in strength and/or endurance?

• Have you lost height?

• Have you noticed a decreased “enjoyment of life”?

Tancredi A. Eur J Endocrinol. 151(2004):355-60

ADAM Questionnaire

• Are you sad and/or grumpy?

• Are your erections less strong?

• Have you noted a recent deterioration in your ability to play sport?

• Are you falling asleep after dinner?

• Has there been a recent deterioration in your work performance?

Tancredi A. Eur J Endocrinol. 151(2004):355-60

ADAM Questionnaire

• Positive result if yes to– answer 1 or 7– any three other questions

• High sensitivity (~80%) to identifying aging males w/low free testosterone levels

• Low specificity (~20%)

• Validated in other languages

Tancredi A. Eur J Endocrinol. 151(2004):355-60

MENOPAUSE FACTS and hormonal optimization facts:

• 12 months of HRT increased skin elasticity by 5.2%

• Post menopause, women lose .55% skin elasticity each year.– Sumino H, et al. Effects of aging, menopause,

and HRT on forearm skin elasticity in women. J Am Geriatr Soc. 2004 June; 52(6):945-9

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Fatter upper body and decreased antioxidants in menopause

• Fat content increases in upper part of body (trunk and arms)

• Antioxidant status decreases. – Pansini F, et al. Oxidative stress, body fat

composition, and endocrine status in pre- and postmenopausal women. Menopause. 2008 Jan-Feb; 15(1):112-8.