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- Alvin M. Yee, M.D.
- Griffin Medical Group, A Center for Anti-Aging Medicine
- Member, American Academy of Anti-Aging Medicine
- Graduate, USC School of Medicine
- General and Occupational Medicine
- http://www.griffinmedical.com
- Dr.yee@griffinmedical.com
- (714) 549-6500 ext. 550
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- “All of the hormones in your body are designed to work together. This is God’s plan. Therefore, if one is altered, or
deficient, it will affect the actions of all of the other hormones in
your body.”
- - Pamela W. Smith, M.D., MPH
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- -- David Brownstein, M.D.
- The Miracle of Natural Hormones
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- Traditional medicine combined with the latest in medical advances and
technologies
- Evidence-based medicine based on the latest scientific data published in
medical / scientific journals
- Treating the patient (& treating the cause of the pt’s symptoms) --
not just treating the patient’s laboratory values
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- A medical specialty found on the application of advanced scientific and
medical technologies for the early detection, prevention, treatment, and
reversal of age-related dysfunction, disorders, and diseases
- Following an optimal lifestyle documented by medical data
- Based on principles of sound and responsible medical that are consistent
with those applied in other preventive health specialties
- Well Documented by reputable peer
- reviewed journals: JAMA, NEJM,
- Annals of Internal Medicine,
- Journal of Endocrinology, etc.
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- Aging is a normal process
- Declining hormones are natural expected consequences of aging (and
should not be altered)
- Diseases such as osteoarthritis, cardiovascular disease, cancer,
diabetes mellitus, etc. are inevitable as we age
- Declining health and increasing pain (nagging aching and joint pain) are
similarly inevitable
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- Who says so? (why are our expectations so low?)
- There is now more than enough adequate scientific data to show that the
reason we age is because of our declining hormones
- Aging is a disease which can be prevented, delayed, or reversed
- We are not prisoners of our genetic destiny
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- Forms age spots
- Damages DNA
- Crosslinks in some molecules implicated in the formation of the neuritic
plaques in Alzheimer’s Disease
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- Secondary disease implicated in
- Atherosclerosis - Franconi’s anemia
- Cancer - Bloom syndrome
- Alzheimer’s - Amyloidosis
- Parkinson’s Dz - Lannec’s cirrohosis
- Essential HTN - Amyotrophic lateral
- Diabetes Mellitus sclerosis
- Cataracts
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- Cannot be prevented by the body as superoxide radicals and hydrogen
peroxide by-products are normally produced during mitochondrial
production of energy
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- The cumulative effect of multiple insults of Free Radical Damage to the
cells of our body over an extended period of time = Chronic Inflammation
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- Chronic Inflammation is the cause and the effect of the diseases of
aging
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- We age because our hormones decline, our hormones don’t decline because
we age
- Growth hormone (GH) is necessary for healthy adult life and GH
Replacement Therapy can prevent, delay or even reverse some aspects of
aging
- Testosterone replacement therapy is safe and provides dramatic benefits
in men and women
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- Traditional medicine
- We can treat the
- outcomes of aging
- Anti-aging medicine
- We can change the
- process of aging in the
- first place
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- Diagnosing and treating the cause of conditions before full-blown
disease manifests
- Restoration of optimal health and human physiologic function
- Increasing one’s quality of life and possibly quantity of life
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- coronary heart disease
- cancer
- dementia
- insulin resistance (type II diabetes)
- degenerative arthritis
- degenerating body composition
- osteoporosis
- immune system decline
- loss of libido and sexual function
- Why not treat the cause?
- Could there be one unifying cause?
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- Chronic Inflammation is the cause and the effect of illness and the
diseases of aging
- Anti-inflammation = Wellness
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- Lab tests: CRP, IL-6, TNFa
- Atherosclerosis, Heart Disease, Stroke
- Alzheimer's
- Cancer
- Lupus, Autoimmune disease
- Obesity, Lack of Exercise,
- Decreased Omega 3 and Increased Omega 6
- Diabetes, Insulin Resistance, Metabolic Syndrome, Syndrome X
- Stress (Psychological or Physical)
- Declining Hormones
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- “Low-level chronic inflammation is associated with all the classic
diseases of old age, including Alzheimer's"
- Decline in muscle mass and muscle strength characterizes normal aging -
sarcopenia
- Higher plasma concentrations of IL-6 and TNF-alpha are associated with
lower muscle mass and lower muscle strength in well-functioning older
men and women.
- Visser M et al. Relationship of interleukin-6 and tumor necrosis
factor-alpha with muscle mass and muscle strength in elderly men and
women: the Health ABC Study.
J Gerontol A Biol Sci Med Sci. 2002 May;57(5):M326-32.
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- Risk factor for illness
- Produced in liver in response to inflammatory cytokines
- Can rise 1000 x with acute inflammation
- IL-6
- TNFa
- Others
- What is your CRP?
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- Ridker PM et al. Comparison of C-reactive protein and low-density
lipoprotein cholesterol levels in the prediction of first cardiovascular
events. New England Journal of
Medicine 2002 Nov 14;347(20):1557-65
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- Relative risk
- Low < 1.0
- Medium 1.0-3.0
- High > 3.0
- Jialal I et al. C-Reactive protein:
Risk Marker or Mediator in Atherothrombosis? Hypertension. 2004;44:6.
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- Moderate exercise
- Nutraceutical / multivitamins
- High Omega 3’s
- Better cancer survival
- GH sufficiency
- Adequate Thyroid
- Non-obese habitus
- Testosterone sufficiency
- Less atherosclerosis
- Less inflammation
- Sedentary lifestyle
- No nutraceuticals
- Oral estrogens (BCPs & Premarin/Prempro)
- Low Omega 3’s
- Poorer cancer survival
- GH deficiency
- Low Thyroid status
- Obesity
- Low Total and Free Testosterone
- Metabolic Syndrome
- More atherosclerosis
- More inflammation
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- Church TS et al. Reduction of C-reactive protein levels through use of a
multivitamin.
Am J Med. 2003 Dec
15;115(9):702-7.
- Church TS et al Associations between cardiorespiratory fitness and
C-reactive protein in men. Arterioscler Thromb Vasc Biol 2002 Nov
1;22(11):1869-76
- McMillan DC et al. Systemic inflammatory response predicts survival
following curative resection of colorectal cancer. Br J Surg 2003
Feb;90(2):215-9
- Madsen T et al. C-reactive
protein, dietary n-3 fatty acids, and the extent of coronary artery
disease.
Am J Cardiol 2001 Nov 15;88(10):1139-42
- Visser M et al. Elevated
C-reactive protein levels in overweight and obese adults.
JAMA 1999 Dec 8;282(22):2131-5
- Laaksonen DE et al. Sex hormones,
inflammation and the metabolic syndrome: a population-based study. Eur J
Endocrinol. 2003 Dec;149(6):601-8.
1896 non-diabetic Finnish men
p < .001
- Laaksonen DE et al. Testosterone and Sex Hormone-Binding Globulin
Predict the Metabolic Syndrome and Diabetes in Middle-Aged Men. Diabetes
Care. 2004 May;27(5):1036-1041.
- 796 Finnish men with 11 year
follow up
- Jublanc C et al. Relationship of circulating C-reactive protein levels
to thyroid status and cardiovascular risk in hyperlipidemic euthyroid
subjects: low free thyroxine is associated with elevated hsCRP.
Atherosclerosis. 2004 Jan;172(1):7-11.
- Decensi A et al. Effect of
transdermal estradiol and oral conjugated estrogen on C-reactive protein
in retinoid-placebo trial in healthy women Circulation 2002 Sep
3;106(10):1224-8
- Sesmilo G et al. Inflammatory cardiovascular risk markers in women with
hypopituitarism.
J Clin Endocrinol Metab. 2001 Dec;86(12):5774-81.
- Leonsson M et al. Increased
Interleukin-6 levels in pituitary-deficient patients are independently
related to their carotid intima-media thickness.
Clin Endocrinol (Oxf). 2003 Aug;59(2):242-50.
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- Anti-Aging Lifestyle changes:
- Proper hormonally balanced diet
- Adequate Nutraceutical supplementation (anti-oxidants, vitamins, long
chain Omega-3 fatty acid/ fish oils )
- Adequate exercise / combination of aerobic and weight resistance
training
- Bio-Identical Hormone Replacement
- Identical molecular structure to hormones produced by human female or
male.
- Not xeno hormones or horse hormones
- Balanced hormone optimization to levels of 25-30 years of age and
monitored by regular levels – serum, urine, saliva
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- Advantages vs. synthetic
- More physiologic
- Less production of toxic metabolites and unintended side effects
- Better relief of symptoms
- Pronounced well known anti-oxidant and anti-inflammatory
characteristics
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- Growth Hormone
- Testosterone for men and women
- DHEA, Pregnenolone, Melatonin
- Estrogens only transdermally, bioidentical forms I.e. Estradiol, Estriol
(Not Premarin or Prempro)
- Progesterone – only bioidentical
- Thyroid (T3 and T4, not just T4)
- Cortisol
- Optimal replacement considers levels, but more importantly, “How do you
feel and are your symptoms resolving?”
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- Increased fat mass
- Decreased lean body mass
- Impaired physical performance
- Thinning skin
- Decreased bone mass
- Atherogenic lipid profile
- Increased cardiovascular risk
- Chronic fatigue, depression
- Reduced energy and vitality
- Decreased memory and quality of sleep
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- Major symptoms
- Reduced exercise capcity / increased recovery time
- Fatigue/exhaustion
- Inability to lose weight with diet and exercise
- Minor symptoms
- Loss of concentration
- Loss of self confidence / self esteem
- Tends to isolate self
- Decreased in quality of sleep
- Major physical signs
- General muscle loss
- “Pot belly”
- Sagging cheeks
- Thinning lips
- Deep forehead lines
- Decreased facial tone
- Flabby muscles
- Minor physical signs
- Older than stated age
- Thinning hair
- Thinning skin
- Receding gums
- Atrophied jaw angle
- Tension in upper back / kyphosis
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- Improves
- Cognitive Ability
- Memory
- Concentration
- Alertness
- Motivation, Work Capacity
- • Nyberg F. Growth Hormone in the
Brain: Characteristics of Specific Brain Targets for the Hormone and
Their Functional Significance.
Front Neuroendocrinol 2000 Oct;21(4):330-348
- GH Replacement Therapy
- Increased lean body and muscle mass
- Increases CV function
- Less atherogenic lipid profile
- Reverses atherosclerosis
- Reduced carotid intima media thickness
- Improves dilated cardiomyopathy
- Improved sense of well being
- Improved quality of life
- Gibney J et al. The effects of 10
years of GH in adult GH deficient adults. J Endocrin Metab August 1, 1999;
84(8):2596-2602
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- Sustained increase in lean body mass and a decrease in body fat observed
- Bone mineral density in lumbar spine and femur neck were increased
- Total cholesterol and LDL cholesterol decreased, with HDL increased
- Triglycerides and HbA1c reduced compared with baseline values
- Conclusion:
- 5 years of GH substitution in GHD adults is safe and well tolerated
- Effects on body composition, bone mass and metabolic indices were
sustained
- Götherström G. J Clin Endocrinol Metab. Oct 1, 2001; 86(10):4657-65
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- “There does not appear to be an increase in rates of cancer in adult
patients who have received GH Therapy”
- Isley WL. Ann Intern Med. 6-Aug-2002; 183(3): 190-6
- “No evidence that GH replacement therapy affects the risk of cancer or
cardiovascular disease”
- Vance L. et al. GH Therapy in Adults and Children. NEJM October 14,
1999.
- “More than 100,000 patients worldwide have received hGH therapy…Data to
date does not suggest that hGH therapy of adults with GH Deficiency
increases the risk of cancer, provided that IGF-1 levels remain with the
normal range”
- Janssen JA Ned Tijschr Geneeskd. 2004 Jul 24;148(30);1486-9.
- “Although there has been some concern about an increased risk of cancer,
reviews of existing, well-maintained databases of treated patients have
shown this theoretical risk to be nonexistent”
- Molitch ME. Diagnosis of GH
deficiency in adults – how good do the criteria need to be? J Clin
Endocrinol Metab 2002 Feb;87(2):473-6
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- Increases sexual interest / libido / erectile function
- Increases sense of emotional well-being, self-confidence, and motivation
- Increases muscle mass and strength
- Increases muscle tone so your skin does not sag
- Decreases excess body fat
- Decreases bone deterioration and helps maintain bone strength / reversal
of osteoporosis
- Has an anti-depressant effect due to elevation of norepinephrine in the
brain
- Neuroprotective effects with Alzheimer’s prevention
- Reverses insulin resistance and Type II Diabetes
- Anti-inflammatory effects results in less pain and inflammation (as seen
in OA and RA) via decrease in inflammatory cytokines (CRP, IL-6, TNFα,
etc.)
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- Does not increase the risk of clinical prostate CA or BPH
- Does NOT increase the risk of atherosclerosis or heart disease, in fact
causes the opposite to occur:
- Dilates coronary arteries
- Reverses angina
- Prevents plaque rupture
- Reverses atherosclerosis
- Protects against atherosclerosis and plaque rupture by limiting
inflammation
- Malkin CJ Testosterone as a
protective factor against atherosclerosis--immunomodulation and
influence upon plaque development and stability.
- Endocrinol. 2003
Sep;178(3):373-80.
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- “There is no clinical evidence that the risk of either prostate cancer
or BPH increases with Testosterone therapy”
- Morley JE Testosterone replacement and the physiologic aspects of aging
in men. Mayo Clin Proc. 2000;75 Suppl:S83-7
- “No compelling evidence at present (exists) to suggest that men with
higher testosterone levels are at greater risk of prostate cancer or
that treating men who have hypogonadism with exogenous androgens
increases this risk. In fact, it
should be recognized that prostate cancer becomes more prevalent exactly
at the time of a man’s life when testosterone levels decline.” Rhoden
NEJM 2004
- “To date there is no evidence that exogenous androgens promote
development of Prostate Cancer”
- Morales, A. Androgen replacement therapy and prostate safety. Eur Urol
2002 Feb;41(2):113-20
- The incidence of prostate cancer is not increased by testosterone
administration
- Basaria. Anabolic-Androgenic Steroid Therapy in the Treatment of
Chronic Diseases. J Clin Endocrinol & Metab 2001; 86(11); 5108-17
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- Bhasin, S. The dose-dependent effects of testosterone on sexual function
and on muscle mass and function.
Mayo Clin Proc. 2000 Jan;75 Suppl:S70-5
- Malkin CJ et al. The effect of testosterone replacement on endogenous
inflammatory cytokines and lipid profiles in hypogonadal men J Clin
Endocrinol Metab. 2004 Jul; 89(7):33113-8.
- Boyanov MA et al. Testosterone supplementation in men with type 2
diabetes, visceral obesity and partial androgen deficiency. Aging Male. 2003 Mar;6(1):1-7.
- Barrett-Connor E et al. Endogeneous sex hormones and cognitive function
in older men. J Clin Endocrinol
Metab 1999 Oct; 84(10): 3681-5
- Gouras GK etal. Proc Natl Acad Sci USA 2000 Feb 1;97(3):1202-5
Testosterone reduces neuronal secretion of Alzheimer’s beta-amyloid
peptides.
- Tan RS A pilot study on the effects of testosterone in hypogonadal aging
male patients with Alzheimer’s disease. Aging Male. 2003 Mar;6(1): 13-17
- Muller M Et al. Endogenous sex hormones and progression of carotid
atherosclerosis in elderly men.
Circulation. 2004 May 4; 109(17):2074-9. Epub 2004 Apr 19.
- English KM et al. Low-dose transdermal testosterone therapy improves
angina threshold in men with chronic stable angina: A randomized,
double-blind, placebo-controlled study.
Circulation 2000 Oct 17;102(16):1906-11
- Hoffman MA. Is low serum free testosterone a marker for high grade
prostate cancer? J Urol 2000 Mar;163(3):824-7
- Prehn RT. On the prevention and therapy of prostate cancer by androgen
administration. Cancer Res 1999
Sep 1;59(17):4161-4
- Stattin P et al. High levels of circulating testosterone are not
associated with increased prostate cancer risk: a pooled prospective
study. Int J Cancer. 2004 Jan 20;
108(3):418-24.
- Gunawarden, K etal. Testosterone is a potential augmentor of antioxidant
induced apoptosis in human prostate cancer cells. Cancer Detect Prev.
2002;26(2):105-13.
- Morales, A. Monitoring androgen replacement therapy; testosterone and
prostate safety. J Endocrinol Invest. 2005;28(3 Suppl):122-7
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- Regulates metabolic rate, energy, temperature
- Increases protein synthesis, ¯s
cholesterol
- Necessary for sub-q fat breakdown (NE stimulated lipolysis) Haluzik M et
al. Effects of hypo- and hyperthyroidism on noradrenergic activity and
glycerol concentrations in human subcutaneous abdominal adipose tissue
assessed with microdialysis. J Clin Endocrinol Metab. 2003 Dec;
88(12):5605-8
- Improves cognition, memory
- Stimulates the heart via coronary artery vasodilation
- Latest indication for replacement therapy is TSH ³ 2.0 mu/l. Suggested
new normal TSH range is 0.5 – 2.0
- J Clin Endocrinl Metab 2002
87(2) 489-499.
- Wartofsky Land Dickey RA. The evidence for a narrower
thyrotropin reference range is compelling. J Clin Endocrinol Metab. 2005
Sep;90(9):5483-8
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- Lowers CRP, homocysteine
- Subclinical (mild) hypothyroidism associated with atherosclerosis and MI
- T3 IV improves advanced CHF
- T3 dilates coronary arteries
- Low fT3 predicts post-op AF s/p CABG
- Low fT3 strongest predictor of death in cardiac patients
- rT3 best predictor of mortality in AMI
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- Nedrebo BG et al. Plasma total homocysteine levels in hyperthyroid and
hypothyroid patients. Metabolism. 1998 Jan;47(1):89-93.
- Christ-Crain M et al. Elevated C-reactive protein and homocysteine
values: cardiovascular risk factors in hypothyroidism? A cross-sectional
and a double-blind, placebo-controlled trial. Atherosclerosis 2003
Feb;166(2):379-86
- Hak AE et al. Subclinical hypothyroidism is an independent risk factor
for atherosclerosis and myocardial infarction in elderly women: the
Rotterdam Study Ann Intern Med 2000 Feb 15;132(4):270-8
- Hamilton MA Safety and hemodynamic effects of intravenous
triiodothyronine in advanced congestive heart failure. Am J Cardiol 1998
Feb 15;81(4):443-7
- Hamilton MA Thyroid hormone abnormalities in heart failure:
possibilities for therapy Thyroid 1996 Oct;6(5):527-9
- Yoneda K et al. Direct effects of thyroid hormones on rat coronary
artery: nongenomic effects of triiodothyronine and thyroxine. Thyroid
1998 Jul;8(7):609-13
- Shimoyama N et al. Serum thyroid hormone levels correlate with cardiac
function and ventricular tachyarrhythmia in patients with chronic heart
failure. J Cardiol 1993;23(2):205-13
- Cerillo AG et al. Free Triiodothyronine: a novel predictor of
postoperative atrial fibrillation. Eur J. Cardiothorac Surg 2003 Oct,
24(4) 487-92
- Iervasi, G et al. Low-T3 Syndrome, A Strong Prognostic Predictor of
Death in Patients With Heart Disease Circulation. 2003;107:708
- Friberg L et al. Association between increased levels of reverse
triiodothyronine and mortality after acute myocardial infarction.
Am J Med. 2001 Dec 15;111(9):699-703.
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- Decreases cholesterol
- Decreases formation of fatty deposits
- Prevents blood clots
- Increases bone growth
- Increases brain function
- Increases sense of well being
- Helps you deal with stress
- Supports your immune system
- Helps your body repair itself and maintain tissues
- Decreases allergic reactions
- References: Alhgrimm, M., The
HRT Solution, 1999; New York:
Avery Publishing, p. 22, 28, 35, 43, 55, 55, 55, 98, 113, 113.
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- Anti-Aging steroid
- Based on both in vitro and in vivo studies
- Stimulatory effect of immune system
- Anti-diabetes mellitus
- Anti-atherosclerosis
- Anti-dementia (neurosteroid)
- Anti-obesity
- Anti-osterporosis
- Anti-cancer
- References: Nawata H et al., Mechanism
of action of anti-aging DHEA-S and the replacement of DHEA-S. Mech Aging
Dev 2002 Apr 30;123(8):1101-6.
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- Thinner skin
- More wrinkles/aging skin
- Decrease in breast size
- Stress incontinence
- Oily skin
- Acne
- Decreased sex drive
- Decreased dexterity
- Increase in insulin resistance and possible diabetes
- Vaginal dryness
- Decreased memory
- Osteoporosis
- UTIs
- cholesterol
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- Prevention of Alzheimer’s disease
- Increases metabolic rate
- Prevents muscle damage and maintains muscle
- Helps you sleep deeply
- Helps maintain the elasticity of your arteries
- Maintains the amount of collagen in your skin
- Decreases blood pressure
- Decreases LDL and prevents its oxidation
- Increases HDL by 10-15%
- Helps maintain your memory
- Protects against macular degeneration and cataracts
- Increases the water content of your skin and is responsible for its
thickness and softness
- Decreases wrinkles
- Reduces the overall risk of heart disease by 40-50%
- Enhances energy
- Improves your mood
- Increases concentration
- Maintains bone density
- Increases sexual interest
- Reduces homocysteine (a risk factor for heart disease)
- Decreases risk of colon cancer
- Helps prevent tooth loss
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- Enhances the production of nerve-growth factor
- Increases reasoning and new ideas
- Helps with fine motor skills
- Aids in the formation of neurotransmitters in your brain such as
serotonin which decreases depression, irritability, anxiety, and pain
sensitivity
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- Estrogen given by mouth can:
- Increase blood pressure
- Increase triglycerides
- Cause gallstones
- Elevate liver enzymes
- Decrease growth hormone
- Increase carbohydrate cravings
- Increase weight gain
- Interrupt tryptophan & serotonin metabolism
- Sinatra, S., Heart Sense for Women, Washington D.C.: Lifeline press,
2000, p. 210
- Pansini, F., et al., “Control of carbohydrate metabolism in menopausal
women receiving transdermal estrogen therapy,” Ann NY Acad Sci 1990;
592:460-462.
- Vliet, E., et al., “New insights on hormones and mood,” Menopause
Management 1993; June/July: p. 224
- Hypertension and CV disease increases dramatically after menopause
implicating E as having protective role
- Discrepancy in large clinical trials
- Negative results may be from study designs
- Oral E produces high concentrations in liver sinusoids (5x)
- Hepatic derived proteins changed (Acute phase proteins)
- Transdermal E – no first pass effect
- Menon DV et al. Effects of transdermal estrogen replacement therapy on
cardiovascular risk factors.
Treat Endocrinol. 2006;5(1):37-51
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- Anxiety
- Depression
- Irritability
- Mood swings
- Insomnia
- Pain and inflammation
- Osteoporosis
- Decreased HDL
- Excessive menstruation
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- Helps balance estrogen
- Leaves your body quickly
- Helps you sleep
- Natural calming effect
- Lowers high BP
- Aids in use and elimination of fats
- Lowers cholesterol
- May protect against breast cancer
- Normalizes libido
- Has an antiproliferative effect (decreases the rate of cancer) on all
progesterone receptors, not just the ones in the uterus)
- Does not change the good affect estrogen has on blood flow
- Increases metabolic rate
- Natural diuretic
- Natural antidepressant
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- Builds bone
- Helps thyroid hormone function
- Protects against fibrocystic breast disease
- Protects against endometrial cancer
- Normalizes zinc and copper levels
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- Wrong Estrogen
- Premarin is not a human hormone
- Mostly Equillin
- Low Estradiol (E2)
- No Estriol (E3)
- Wrong “Progesterone”
- Provera blocks progesterone receptors and is not a human hormone
- Wrong route
- Oral Estrogens increase inflammation
- Wrong women
- Older with established CV disease
- Women Ages 50-79 years, mean 63.2 years
- Predisposed to coronary and cerebral atherosclerosis
- Untested regimen of CEE and MPA
- Major design flaws
- Breast cancer takes 7-10 years to develop
- Many patients already had Subclinical breast cancer
- Most studies show all cause mortality lower on women on HRT
- Klaiber EL, Vogel W, Rako S A critique of the Women's Health Initiative
hormone therapy study. Fertil Steril. 2005 Dec;84(6):1589-601.
- Grodstein F, Manson JE, Stampfer
MJ J Hormone Therapy and Coronary Heart Disease: The Role of Time since
Menopause and Age at Hormone Initiation.
Womens Health (Larchmt). 2006 January/February;15(1):
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- “Obtained exclusively from natural sources
- Blended to represent the average composition of material derived from
pregnant mares urine.
- estrone
- equillin
- 17 alpha-estradiol
- equilenin
- 17 alphadihydroequilenin”
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- Observational Studies – Menopausal Hormone Therapy prevents CV disease
- 30-50% decrease in CV and all cause mortality
- Even if slight increase in breast cancer this morbidity and mortality would be canceled by
fewer hip fx
- Confounding socio-economic factors
- Grodstein F et al. Postmenopausal hormone therapy and mortality.
N Engl J Med. 1997 Jun 19;336(25):1769-75
- Current hormone users had a lower risk of death (relative risk, 0.63)
than subjects who had never taken hormones
- Current hormone users with coronary risk factors (69 percent of the
women) had the largest reduction in mortality
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- Mortality reduced in breast cancer with HRT exposure
- Endometrial cancer counteracted by progesterone
- Reduced risk of colorectal cancer with HRT
- Schneider HP. HRT and cancer risks. Maturitas. 2002 Aug 30;43 Suppl
1:S35-52.
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- Fournier A et al. Breast cancer risk in relation to different types of
hormone replacement therapy in the E3N-EPIC cohort.
Int J Cancer. 2005 Apr 10;114(3):448-54.
- The risk was significantly greater (p <0.001) with HRT containing
synthetic progestins than with HRT containing micronized progesterone,
the RRs being 1.4 and 0.9 respectively.
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- Sleep
- Mood
- Stress response
- Immune function
- Release of sex hormones
- Antioxidant activity (more potent than Vitamin C or E)
- Helps to prevent cancer
- Blocks estrogen from binding to estrogen receptors
- Stimulates the parathyroid gland which regulates bone formation
- Stimuates the production of growth hormone
- Decreases cortisol
- Increases the action of benzodiazepine medications
- Reverses osteoporosis
- Improves deep sleep and GH release
- Cardinali DP et al. Melatonin
effects on bone: experimental facts and clinical perspectives.
J Pineal Res 2003 Mar;34(2):81-7
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- Most effective free radical scavenger of hydroxyl radical known
- More than Glutathione or Vitamin E
- Hydroxyl radical damages mitochondria
- Protects DNA from Injury
- Especially in Pharmacologic concentrations
- Protects against pro-oxidation effect of Fe
- Herrera J Melatonin prevents oxidative stress resulting from iron and
erythropoietin administration Am J Kidney Dis 2001 Apr;37(4):750-7
- Protects lipids, proteins, DNA
- Stimulates glutathione
- Protects mitochondria
- Protects against ischemia-reperfusion injury
- Protects against ionizing radiation
- Reiter RJ et al. Pharmacological utility of melatonin in reducing
oxidative cellular and molecular damage. Pol J Pharmacol. 2004
Mar-Apr;56(2):159-70.
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- Enhanced immune function
- Nelson RJ Melatonin mediates seasonal changes in immune function Ann N
Y Acad Sci 2000;917:404-15
- Kriegsfeld LJ In vitro melatonin treatment enhances cell-mediated
immune function in male prairie voles J Pineal Res 2001 May;30(4):193-8
- Suppression of insulin and visceral fat; perhaps the most powerful
anti-aging intervention
- Wolden-Hanson T Daily melatonin administration to middle-aged male rats
suppresses body weight, intraabdominal adiposity, and plasma leptin and
insulin independent of food intake and total body fat Endocrinology 2000
Feb;141(2):487-97
- Prolongation of lifespan (as seen in rats)
- Dilman VM, Increase in the lifespan of rats following polypeptide
pineal extract. Exp Pathol 1979;17:539-45. 78.
- Pierpaoli W, Regelson W. Pineal control of aging: effect of melatonin
and pineal grafting on aging mice. Proc Natl Acad Sci U S A
1994;91:787-91.
- Major anti-cancer effects in humans
- Inhibits tumor growth in humans
- Improved outcome in glioblastoma, malignant melanoma, breast cancer
- Prevents and cures induced breast cancer in rats
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- Hill SM, Blask DE. Effects of the pineal hormone melatonin on the
proliferation and morphological characteristics of human breast cancer
cells (MCF-7) in culture. Cancer Res 1988;48:6121-6.
- Ying SW, Niles LP, Crocker C. Human malignant melanoma cells express
high-affinity receptors for melatonin: antiproliferative effects of
melatonin and 6-chloromelatonin. Eur J Pharmacol 1993;246:89-96.
- Molis TM, Spriggs LL, Hill SM. Modulation of estrogen receptor mRNA
expression by melatonin in MCF-7 human breast cancer cells. Mol
Endocrinol 1994;8:1681-90.
- Lissoni P, Meregalli S, Nosetto L, et al. Increased survival time in
brain glioblastomas by a radioneuroendocrine strategy with radiotherapy
plus melatonin compared to radiotherapy alone. Oncology 1996;53:43-6.
- Lissoni P, Barni S, Meregalli S, et al. Modulation of cancer endocrine
therapy by melatonin: a phase II study of tamoxifen alone. Br J Cancer
1995;71:854-6.
- Gonzalez R, Sanchez A, Ferguson JA, et al. Melatonin therapy of advanced
human malignant melanoma. Melanoma Res 1991;1:237-43.
- Lissoni P, Barni S, Ardizzoia A, Tancini G, Conti A, Maestroni GM. A
randomized study with the pineal hormone melatonin versus supportive
care alone in patients with brain metastases due to solid neoplasms. Cancer
1994;73:699-701.
- Cos S Direct antiproliferative effects of melatonin on two metastatic
cell sublines of mouse melanoma Melanoma Res 2001 Apr;11(2):197-201
- Lissoni P Anti-angiogenic activity of melatonin in advanced cancer
patients Neuroendocrinol Lett 2001;22(1):45-7
- Lenoir V et al. Preventive and curative effect of melatonin on mammary
carcinogenesis induced by dimethylbenz[a]anthracene in the female
Sprague-Dawley rat.
Breast Cancer Res. 2005;7(4):R470-6. Epub 2005 Apr 29.
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- Scavenges free radicals – protects DNA
- Inhibits tumor growth – augments immune response
- Regulates sleep, restores circadian rhythm, improves jet lag
- May protect against aging changes
- Protects against cancer
- But don’t use it………
- Amnon Brzezinski Mechanisms of Disease: Melatonin in Humans The New
England Journal of Medicine -- January 16, 1997 -- Vol. 336, No. 3
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- “Zone” type diet
- 40% carbohydrate
- 30% protein
- 30% fat
- Less insulin secretion / less insulin resistance
- Decreased fat storage
- Improved lipid profile
- Favorable Eicosanoid hormone balance
- Vasodilation vs. constriction
- Anti-inflammatory vs. inflammation
- Decreased: fat storage,
glycation, silent / chronic inflammation
- No carbohydrate cravings
- Add omega-3 high dose fish oil for Eicosanoid control
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- Diet implies “as a way of life” or lifestyle
- Hence, fad temporary diets do not work because of unsustainable nature
- Insulin resistance associated with diseases of aging
- Lab test: Fasting Insulin
- Ideal range <7.0
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- 5 smaller meals per day instead of 3 big meals – benefits include more
even energy / less highs and lows during the day
- High protein intake – approximately 1 gram / lb. of ideal body weight or
5 palm sized patties of meat per day
- “Zone” combination of protein, fats and favorable carbohydrates
- Lots of vegetables
- No Trans fats
- Minimal sodas, juices, aspartame, sucralose
- Minimal high glycemic foods
- Minimal arachidonic acid
- Minimal foods cooked at high temperatures
- Extra virgin olive oil for cooking
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- Concept: Glycemic index (GI)– the
amount of insulin secreted by your pancreas in response to the food you
ate
- High, moderate and low GI foods
- Too much secretion of insulin is proinflammatory and will cause
increased production of triglycerides and therefore storage of fat
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- Hamburger bun
- Shortbread
- Soft drinks
- Candy
- Croissant
- White potato
- Bagels
- Donuts
- Watermelon
- French fries
- Popcorn
- Cocoa puff cereal
- Rice
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- Macaroni
- Linguine
- Green peas
- Corn
- Chocolate
- Sweet potatoes
- Yams
- Banana
- Potato chips
- Special K cereal
- Orange juice
- Bran chex cereal
- Blueberry
- Pizza, cheese
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- Soybeans
- Cherries
- Kidney beans
- Peaches
- Lentils
- Green beans
- Rye rice
- Raspberries
- Strawberries
- Peppers
- Apples
- Pears
- Spaghetti, whole wheat
- Navy beans
- Tomatoes
- Grapes
- Celery
- Oranges
- Mushrooms
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- Essential for optimum wellness
- Dramatic recent data on prevention of sudden death from CV disease
- Essential for favorable eicosanoid hormone production
- Used to treat: Heart disease,
Cancer, Depression, ADD, MS, Alzheimer’s, Chronic pain, Osteoporosis,
Skin Disorders, Fertility, Fat Loss
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- Can be 10-20 years younger than biological age with regular exercise:
aerobic, anaerobic, flexibility
- Exercise promotes longevity and compression of disability into fewer
years (Vita, NEJM 1998 Apr)
- Increased production of GH
- Increased Sense of Well Being and cognition
- Decreases Inflammation, CRP
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- Wegge JK et al. Effect of diet and exercise intervention on inflammatory
and adhesion molecules in postmenopausal women on hormone replacement
therapy and at risk for coronary artery disease.
Metabolism. 2004 Mar;53(3):377-81.
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- Quench Free Radicals
- Decrease inflammation
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- Strenuous exercise increases inflammation and inflammatory markers, TNF-α
and IL-1β and IL-6
- Trained athletes have less inflammatory response
- Antioxidant treatment for 60 days eliminated increase in inflammatory
markers.
- Vassilakopoulos T et al. Antioxidants attenuate the plasma cytokine
response to exercise in humans J Appl Physiol. 2003 Mar;94(3):1025-32.
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- B vitamins
- B6, B12, Folic Acid
- Control homocysteine
- What is your homocysteine level?
- “Normal” < 12
- “Optimal” < 7
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- 4 x increase risk for men
- 2 x increase risk for women
- McLean R. et al. Homocysteine as
a Predictive Factor for Hip Fracture in Older Persons
NEJM Volume 350:2042-2049 May 13, 2004
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- “Inflammation plays a pivotal role in both atherosclerosis and
osteoporosis”
- McFarlane SI et al. Osteoporosis
and cardiovascular disease: brittle bones and boned arteries, is there a
link?
Endocrine. 2004 Feb;23(1):1-10.
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- Garcia Rodriguez et al. Inverse association between nonsteroidal
anti-inflammatory drugs and prostate cancer.
Cancer Epidemiol Biomarkers Prev. 2004 Apr;13(4):649-53.
- Slattery ML et al. Aspirin, NSAIDs, and colorectal cancer: possible
involvement in an insulin-related pathway.
Cancer Epidemiol Biomarkers Prev. 2004 Apr;13(4):538-45.
- “These data support the protective effect of aspirin and NSAIDs on
colorectal cancer risk”
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- We age because our hormones decline, our hormones don’t decline because
we age
- Declining hormones increase chronic inflammation
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- Evaluation day
- Blood tests of organ functions, hormone levels, risk factors
- Comprehensive medical history and physical exam by MD
- Comprehensive analysis of proper diet, diet patterns, exercise
recommendations, evaluation nutritional status and relative
cardiovascular / cancer risk, tailored nutraceutical / vitamin regimen
based on individual needs
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- General
- CBC
- Comprehensive Metabolic Panel
- Cardiac
- Lipid Profile
- Homocysteine
- C-Reactive Protein +
- Osteoporosis
- Glucose and Insulin
- Fasting Insulin
- Hemoglobin A1C
- IGF-1
- Testosterone
- Free Testosterone
- FSH, LH
- Estradiol
- DHEA Sulfate
- TSH, Free T3, Free T4
- Women: Progesterone
- Cancer screens:
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- Formulate an individualized, customized anti-aging program based on the
H&P, laboratory results
- Diet
- Supplements
- Exercise
- Stress Reduction
- Balanced Hormone Replacement
- Ongoing monitoring and medical supervision
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- Goal: Decrease Inflammation,
Increase Wellness
- Lab test: CRP, homocysteine
- Diet: Zone 40/30/30
- Lab test : Fasting Insulin
- Exercise – moderate 3x per week (30 minutes per session)
- Stress Reduction
- Eliminate infections
- Reduce oxidative stress
- Balanced antioxidants divided doses
- Coenzyme Q 10
- Reduce homocysteine
- B6, B12, Folic Acid
- Ideal < 7
- Daily NSAID
- Optimal Eicosanoid Omega 3 Fish Oil Dose
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- Youthful bio-identical hormones
- Treat a “deficiency disease”
- Improve Quality of Life
- Decrease Inflammation
- Do not increase cancer risk
- Do not increase heart disease risk
- Are a matter of personal choice
- Must be given by the correct route
- Are a “work in progress”
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- Control Inflam-aging
- Increased quality of life
- We all have to die sometime
- What will the journey be like?
- And if we delay, intervene and reverse the diseases of aging….
- Increased quantity of life as well
- Let the journey begin…
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Notes
