CONUNDRUMS IN BIO-IDENTICAL HRT

Lisa EverettBSPharm, FACA

Board Certified Clinical Nutritionist

HORMONES…

Who needs them, anyway?

PSYCHONEUROIMMUNOENDOCRINOLOGY

The study of the connectedness of mind, body, emotions and spirit.

The expansion of current concepts to include the human energy field.

The basis of Chinese, Indian, Hebrew and other world medicine systems.

The human energy field interacts with all the energy fields, beginning with the pineal gland.

Quantum physics is the basis of this study.

WHERE HAVE ALL THE HORMONES GONE?

Dec. by OC’s

Dec by tubal ligation

Dec by hysterectomy

Dec by oophorectomy

Dec by vasectomy

Dec by multiple pregnancies

Dec by harmful EMF exposure

Menopause & andropause

Dec by miscarriages & terminated pregnancies

Dec by stress adaptation Dec by medications Dec by physical anomalies Dec by lack of exercise Dec by nutritional

deficiencies

Dec by xenobiotics

CONCERNS IN TODAY’S WORLD OF HRT

Media reported over & over on 3 studies done on foreign substances, Premarin & Provera

This is not new information

Used term “estrogen”---a class of related analogues not a single substance

Unnecessary step back in time

Negative press does not negate cellular & biological studies from the early 1900’s on the roles of endocrine molecules in human physiology or cat physiology or cantaloupe physiology!

HEALTH AND HORMONES Hormones as they relate to whole body functioning

Misinterpretations of literature by media & health care professionals

The need for HRT created by the effects of xenobiotics

The difference of impact of bio-identical endocrine molecules and synthetic analogs on physiology

Righting the mistakes in HRT over the years

Appropriate monitoring

FUNCTIONS OF BIO-IDENTICAL PROGESTERONE

Antioxidant

Prepares breast for lactation

Prepares uterus for implantation

Saves pregnancies

Natural Anti-depressant

Decreases number of estrogen receptor sites

Non Carcinogenic, induces apoptosis of cells

Inhibits human cancer cell growth & invasiveness

Increases libido Diuretic -Tells the kidney

to rid body of excess sodium and water

Prevents & reverses fibrocystic breast disease

Helps regulate blood sugar levels

Anti-convulsive Thermogenic Thickens vag secretions

FUNCTIONS OFPROGESTERONE, (CON’T)

Normalizes zinc & copper levels

Escorts T 3 across mitochondrial membrane

Increases SHBG levels

Skeletal Muscle Relaxant

REM Sleep

Vasodilation via inc. Nitrous Oxide release

Adds to estrogen protection of glutamate toxicity

Normalizes blood clotting Lowers blood pressure Decreases Vascular

Proliferative and Inflammatory Responses

Decreases Sympathetic Activity

Immunosuppressant

Functions of Progesterone, (con’t)

– Helps the lining of the uterus mature in the second half of the cycle– Modulates estrogen distribution across the tissues– GABA receptor agonist (neuroinhibitory)– Stimulates osteoblastic and inhibits osteoclastic function (bone trophic)

Seifert-Klauss et al. Progesterone and bone: actions promoting bone health in women. J Osteoporos. 2010 Oct 31;2010:845180.

Finocchi et al. Female reproductive steroids and neuronal excitability. Neurol Sci. 2011 May;32 Suppl 1:S31-5.

Functions of Progesterone, (con’t)

– protects arterial linings

– Protects hippocampusJiang R et al. Progesterone Increases Circulating Endothelial Progenitor Cells and Induces Neural Regeneration after Traumatic Brain Injury in Aged Rats. J Neurotrauma. 2011 May 2.

Progesterone: Indications

PMS

Peri-menopause

Preeclampsia / Toxemia

Migraine Headaches

Hysterectomy

Luteal phase defect

Multiple Sclerosis

Progesterone: Indications, (con’t)

Anxiety Disorders (especially cyclic)

Adrenal insufficiency

Euthyroid Disorders

PCOS

Libido

Infertility

Mood disorders

Premature ovarian failure

Seizures

FUNCTIONS OF BIO-IDENTICAL E1,E2,E3

Sex Characteristics

Proliferates endometrium

Thins cervical mucus

Prevents & treats cervical dysplasia

Libido and Orgasm

Primes testosterone receptor site

Dec. risk of CVD

Promotes normal Heart rhythms

Dec plasma renin substrate

Improves lipid profile

Dec triglycerides

Stimulates reverse cholesterol transport

Lowers blood pressure

Normalizes blood clotting

Strengthens heart valves and venous valves

Inc. stroke volume

Inc flow acceleration

Dzugan SA et al. Correction of steroidopenia as a new method of hypercholesterolemia treatment. Neuro

Endocrinol Lett. 2011 Feb 21;32(1):77-81.

FXNS IN CARDIOVASCULAR HEALTH

ERα and ERβ (estrogen receptors) influence cytosolic signaling

Anti-athrogenic (1)

GPR30 or GPER1 mediates estrogenic response to cardiovascular and metabolic regulation

Vasorelaxation (1)

Smooth muscle cell proliferation (1)

Protection of myocardium against ischemia (1)

Estrogen impacts intracellular calcium to lower blood pressure (1)

Nilsson BO, Olde B, Leeb-Lundberg LM. G protein-coupled Estrogen Receptor 1 (GPER1)/GPR30: A New Player in Cardiovascular and Metabolic Estrogenic Signaling. Br J Pharmacol. 2011 Jan 21. doi: 10.1111/j.1476-5381.2011.01235.x

MORE FUNCTIONS OF E1,E2,E3

Promotes neural cell growth

Improves cerebral glucose utilization

Improves synaptic activity

Improves cerebral blood flow

Protects brain from glutamate toxicity

Improves cognitive function

Reduces risk of senility/Alzheimer’s

Natural antidepressant

Maintains REM sleep

Decrease in symptoms of Parkinson’s Disease

Promotes emotional stability

Increases desire to compete in life

Prevents morbidity

Protects the pancreas

•Patch, RJ et al. Identification of Diaryl Ether-Based Ligands for Estrogen- Related Receptor α as Potential

Antidiabetic Agents. J Med Chem. 2011 Jan 10.

Alzheimer’s Disease

Folding of amyloid beta protein is the pathogenic event in Alzheimer’s

Estrogens inhibit the oligomer formation, with estriol being the strongest inhibitor

Physiologic levels of hormones delay progression of disease

Morinaga A, et al. Effects of sex hormones on Alzheimer's disease-associated β-amyloid oligomer formation in vitro. Exp Neurol. 2011 Jan 31.

NEUROPROTECTIVE

Estradiol, progesterone, and androgens

– Estrogen• Activation of signaling molecules and interactions with growth factors• Effects dopamine signaling pathway– Women with low estrogen often have low dopamine and serotonin levels when urine is tested

Telomeres

Biomarkers for cellular aging – Telomere length– Telomerase activity– HRT for 1 year or longer

– Longer endogenous exposure associated with greater telomere length and lower telomerase activityLin J, et al. Greater endogenous estrogen exposure is associated with longer telomeres in postmenopausal women at risk for cognitive decline. Brain Res. 2010 Oct 18.

EVEN MORE FUNCTIONS OF E1,E2,E3

Antioxidant

Increases energy production

Blocks receptor sites from Xenoestrogens Dec. risk of colon cancer

Slows calcium loss from bones

Prevents macular degeneration, dry eye syndrome, cataracts, & most ocular diseases

Improves fat to muscle ratio

Sivritas D emediated by Kruppel-like factor-4 and manganese superoxide dismutase. Basic Res Cardiol. 2011 Apr 12.

Maiti K et al. G-1-Activated Membrane Estrogen Receptors Mediate Increased Contractility of the Human Myometrium.

Endocrinology. 2011 Mar 22.

Diabetes

ERRα– Improves insulin sensitivity

• Newest evidence that estrogen is functional metabolicallyPatch, RJ et al. Identification of Diaryl Ether-Based Ligands for Estrogen-Related Receptor α as Potential Antidiabetic Agents. J Med Chem. 2011 Jan 10.

Pancreas

Stabilizes blood glucose

Supports survival of pancreatic B cells– Stimulates insulin release– Protects against pancreatic B cell apoptosis

Nilsson BO, Olde B, Leeb-Lundberg LM. G protein-coupled Estrogen Receptor 1 (GPER1)/GPR30: A New Player in Cardiovascular and Metabolic Estrogenic Signaling. Br J Pharmacol. 2011 Jan 21. doi: 10.1111/j.1476-5381.2011.01235.x

Metabolic

Perimenopause– Increased abdominal fat – Loss of skeletal muscle

• HRT reverses or reduces menopausal changes in body compositionSørensen MB. Changes in body composition at menopause--age, lifestyle or hormone deficiency? J Br Menopause Soc. 2002 Dec;8(4):137-40.

ENDOTHELIAL FUNCTION• Endothelial dysfunction

o Aging causes decreased Endothelium dependent dilation in response to stimuli

o Reduced bioavailability of NO as a result of oxidative stress

o Aging leads to increased oxidative stress without increase in antioxidant status

o Increased activity of endothelin 1 reduces productions of dilatory prostaglandins

Development of vascular inflammation

Formation of advanced glycation end products

Increased endothelial apoptosis

Reduced expression of estrogen receptor alpha

Impaired endothelium dependent dilation

ENDOTHELIAL FUNCTION• Moderation of vascular endothelial

functionoBody weight

oVitamin D status

oEstrogen status

oExercise

oDiet high in antioxidants

THE ROLE OF E1, E2, AND E3 IN HEALING

Increases energy production

Decreases osteooblastic function

Increases osteoclastic function

Necessary for rapid bone turnover, but not great for rebuilding lost bones

Slows bone loss by mediating mineral content of the bone, both in bone matrix & kidneys

Increases collagen mass-ligaments, tendons, muscle, connective tissue

Normalizes blood clotting

Maintains REM Sleep/reduces stress

Helps with osteocalcin formation

Inc. stroke volume

Inc. strength of cardiac valves & muscle

Promotes neural cell growth

Improves cerebral & other tissue glucose utilization

Improves synaptic activity

Increases cerebral and total body blood flow

Protects from glutamate toxicity

Lowers blood pressure

Improves lipid profile

ESTRIOLHas been used successfully in western Europe for over 60 years

80 times weaker than beta-17 estradiol

Is not metabolized backwards to estrone or estradiol

Is an adaptogen

Prevents bone loss in post menopausal women

Oral use was not associated with a risk of breast cancer

Is safe for use in post menopausal women previously treated for breast cancer

ESTRIOL

At 10 times the concentration of estradiol it is antagonistic to the effects of E2

Effective in the treatment of MS

Is useful as alternative in post menopausal women with UG tract disturbance

Decreases total cholesterol and LDL’s

Up-regulates LDL receptor activity

Raises HDL’s

The Structure of Hormones

Cholesterol

Progesterone

Testosterone

Estrogen

Cortisone

13 17

103

Natural(bio-identical)

vs.Synthetic

SIDE EFFECTS OF PROGESTINS

Increases sodium and water retention

Causes depression

Cannot maintain pregnancy

Increases appetite and weight gain

Carcinogenic

Blood clots lungs, periphery, brain

Hair loss

Masculinizes the female fetus

Can be estrogenic or androgenic

Cannot be synthesized into other

compounds

Cannot raise basal temperature

Acne & facial hair growth

Impaired glucose tolerance

MORE SIDE EFFECTS OF PROGESTINS

Breakthrough bleeding

Fibrocystic breasts

Headaches & migraines

Cardiac arrest

Nausea

Cholestatic jaundice

Diarrhea

Irritability/moodiness

Seizures

Lethargy

Anxiety/panic/ anger

Insomnia

Dysrhythmias

Poor lipid profile

Elevated BP

Skeletal muscle spasms overall tightness

Dec immune function & stress adaptation

ADDITIONAL OBSERVATIONS IN OC USERS

Altered Immune Factors

Altered Inflammatory Factors

Vitamin Deficiency

Magnesium, Folic Acid, B2, B6, B12, Vitamin C and Zinc

Blum M, Kitai E, Ariel Y, Schneierer M, Bograd H. Oral contraceptive lowers

serum magnesium. Harefuhah. 1991;121(10): 363-4.

Pelton R, LaValle JB, Hawkins EB, Krisky DL. Drug-induced Nutrient Handbook.

2 ed Lexi-Comp

Webb JL. Nutritional effects of oral contraceptive use: A review. Journ Reprod

ADDITIONAL OBSERVATIONS IN OC

Increased Insulin resistance and Glucose Intolerance

Elevated Cholesterol and Triglycerides

Increased C-Reactive Protein

3-6 fold increase risk of venus thrombosis

2-5 fold increase of Mi’s and Stroke

Increased Hepatocytes CRP synthesis

REFERENCES FOR PREVIOUS SLIDE

Tanis BC, Rosendaal FR, Venous and Arterial thrombosis during oral contraceptive use: risks and risk factors SeminVasc Med. 2003;3(1):69-84

Frempong BA, Ricks M, Sen S, Sumner AE. Effect of low dose oral conracptives on metabolic risk factors in African American women. J Clin Edocrin Metab 2008;93(6);2097-103

Kluft C, Leuven JA, Helmenhorst FM, Krans HM, Pro-inflammatory effects of oestrogens during use of oral contraceptives and hormone replacement treatment. Vasc Pharmacol. 2002;93(3):149-54

Fisch IR, Freedman SH. Smoking, oral contraceptives and obesity. Effects on white blood cell count. JAMA 1975 ;234(5);500-6

ORAL CONTRACEPTIVES

The presence of serum immune complexes such as antiethinylestradiol and anti progestogen antibodies cause vascular lesions and other inflammatory cytotoxic conditions including thrombosis. These form in as little as 3 weeks

Researchers confirmed that the immune complexes are not formed against non synthetic hormones

REFERENCES FOR PREVIOUS SLIDE

World Health Organization. Improving access to quality care in family planning. Published 1996. Revised 2001

Beaumont V, Beaumont JL Vascular thrombosis in synthetic estrogen-progestogen users: an immune mechanism. Nouv Press Med. 1981;10(7):503-7

Beaumont V, Delplanque B, Lemort N, Beaumont JL, Mann Jl. Blood changes in sex steroid hormone users. Circulating immune complexes induced by estrogens and progestogens and their relation to vascular thrombosis. Athersclerosis 1982;44(3):343-53

ORAL CONTRACEPTIVES

Increased risk of lupus, Rheumatoid Arthritis, Crohn’s and Ulcerative Colitis

increased incidence of severe periodontitis, periodontal pockets and gingival inflammation

Increased inflammatory immune cytokines

Cutolo M, Sulli A, Capellino S, et al. Sex hormones influence on the immune system:basic and clinical aspects of autoimmunity. Lupus 2004;13(9):635-8

Cutolo M, Capellino S, Straub RH. Oestrogens in rheumatic diseases: friend or foe? Rheumatology. 2008;47(Suppl3):iii2-5

Cutolo, M, Seriolo B, Villaggio B,Pizzorni C, Craviotto C, Sulli A, Androgens and estrogens modulate the immune and inflammatory responses in rheumatoid arthritis. Ann N Y Acad Sci.2010;1193(1):36-42

Boyko EJ, Theis MK, Vaughan TL, Nicol-Blades B. Increased risk of inflammatory bowel disease associated with oral contraceptive use. Am J Epidemiol. 1994;140(3):268-78

Brusca MI, Rosa A, Albaina O, Moragues MD, Verdugo F, Ponton J,. The impact of oral contraceptives on women;s periodontal health and the subgingival occurrence of aggressive periodontaopathogens and candida species. J Periodontal. 2010;81(7):1010-8

ORAL CONTRACEPTIVES

Elevated WBC’ s in OC users

Increased hospitalization for inflammatory diseases of the respiratory, digestive, urogenital and musculoskeletal system of women under age 40 that use OC’s

Swan SH, Inflammatory disease associated with oral contraceptive use. Lancet 1981;10:2(8250):809

ESTROGEN DISTRIBUTION (ENDOGENOUS)

Secreted directly to the blood stream

Travels directly to tissues via the inferior venacava

Returned to the liver after exerting its affect on tissue receptor sites for methylation and conjugation

ESTROGEN DISTRIBUTION (TRANSDERMAL/ TRANSMUCOSAL)

Transmucosal- Same as exogenous

Transdermal- Same as exogenous except when applied to abdominal skin

Transformation in subcutaneous adipose to other molecules

Subcutaneous adipose deposition for later release

TD/TmM does not have the same impact on liver, clotting factors

Ref 17-19

ESTROGEN DISTRIBUTION(ORAL)

Significant processing through gut lumen and in gut endothelial cells

Travels to the portal circulation

Liver transformation and metabolism

Only 10% of dose is bio-available

90% is converted in to bioactive, untoward metabolites before absorption

Ref - #6 and 7

METABOLISM OF ESTROGENS

After oral and intravenous administration of E2 - 50% is converted to E1

CYP450 phase 1 oxidation - 16-alpha hydroxylation (estrogen dependant diseases- lupus and breast cancer), 2 - alpha hydroxylation, (protective) 4 hydroxylation- (DNA damaging quinone)

Phase 2 conjugation - sulfation, methylation,glucuronidation of 2-,4-,16-hydroxylated compounds

phase 3 excretion in bile or urine

Cavalieri E, Frenkel K, Liehr JG, Rogan E, Roy D, Estrogens as endogenous genotoxic agents-DNA adducts and mutations. J Natl Cancer Inst Monogr 2000;(27):75-93Review

Yager JD, Endogenous estrogens as carcinogens through metabolic activation. J Natl Cancer Inst Monogr.2000;(27):67-73

SIDE EFFECTS OF ORALLY ADMINISTERED ESTROGEN

Migraine headaches

Increases Estrone, not Estradiol levels

Increases triglycerides

Increases blood pressure

Carcinogenic

Cholelithiasis

Sat of Cytochrome P450

Gallbladder Disease

Bloating

Depression

Thromboembolism

Increase in Fibrocystic Breast Disease

Competes with hepatic conversion of HGH to IGF-1 (Dec 1GF-1)

CHANGES IN HEPATIC PROTEIN SYNTHESIS WITH ORAL ESTROGENS

Prothrombotic

Inc fibrinogen I&II

Dec TFPI (Tissue Factor Pathway Inhibitor)

Inc CRP( X2)

Inc Factor VII

Inc D-Dimer

Dec Plasminogen Activator Inhibitor Type I

Dec circulating Antithrombin III

Inc Renin

Inc IGF-1 clearance & induction of GH resistance

Promotes insulin resistance

16-alpha hydroxyestrone & other psycho hormones

Inc triglycerides

Inc lipid per oxidation, inc fat mass

IS THERE SAFE & EFFECTIVE ENDOCRINE

SUPPLEMENTATION ?

I believe there is if we learn from our mistakes and follow a few integral principles…

PRINCIPLES OF NATURAL HORMONE REPLACEMENT

Use only bio-identical hormones (natural human hormones)

Use the safest route of administration ( buccal)

Preserve the delicate balance

Individualize the dose

Eat a Diet void of Xenobiotics & rich in fruits and vegetables

Supplement with MVM, antioxidants, EFA’s

TESTOSTERONE

Necessary for emotions of confidence, joy, affection, friendliness

Is lowered by OC’s

Is protective of autoimmune diseases

Is inc’d by weight training & exercise

Is dec’d by menopause & oophorectomies

Restores ability to achieve & sustain erections

Prevents platelet aggregation

Lowers blood pressure Is lower in Andropause

and BPH Lowered by

environmental toxicities Physiologic levels protect

against prostatic hyperplasia

Raynaud JP, Prostate cancer risk in testosterone treated men. Steroid Biochem Mol Biol. 2006Dec;102(1-5):261-6

FUNCTIONS OF TESTOSTERONE

Produced in adrenals and testicles in men

Produced in adrenals, skin, adipose tissue, muscles, brain, and ovaries in women

Male secondary sex characteristics

Anabolic: increases MM and bone mass and all collagen

Increases libido in both men and women

Improves memory and cognitive function

Reduces body fat Desire to compete in game

of life Necessary for energy and

sense of well-being Antidepressant Decreases drinking

FUNCTIONS OF TESTOSTERONE

Antioxidant

Necessary for collagen formation

Improves neural cell formation

Positive lipid profile, stroke prevention

Required for optimal transport of excess cholesterol from tissues and blood vessels back to the liver

Enhances HDL -induced reverse cholesterol transport from arterial walls

Decreases platelet aggregation

Improves all tissue stamina

Decreases SHBG

Levels are decreased by 250 drugs

Elevates hepatic lypase necessary for the liver to safely

clear the body of excess

cholesterol

HORMONE STATUS

High levels of DHEA, testosterone, and IGF-1

Deficiency in one hormone (DHEA, testosterone, or IGF-1)

Deficiency in two hormones(DHEA, testosterone, or IGF-1)

Deficiency in all three hormones(DHEA, testosterone, or IGF-1)

Three-Year Survival Rate

74%

55%

27%

Jankowska EA, Biel B, Majda J, et al. Anabolic deficiency in men with chronic heart failure: prevalence and detrimental impact on survival. Circulation. 2006 Oct 24;114(17):

1829-37

83%

TESTOSTERONE BLOOD LEVELS AND SUBSEQUENT INCIDENCES OF DISEASE AND DEATH

Khaw KT, Dowsett M, Folkerd E, et al. Endogenous testosterone and mortality due to all

causes , cardivascular disease, and cancer in men: European prospetive investigation into

cancer in Norfolk(EPIC-Norfolk) Prospective Population Study. Circulation. 2007 Dec 4;116-

(23):2694-701

Highest Testosterone

Next to Highest

Testosterone

Next to Lowest

TestosteroneLowest

Testosterone

All-Cause Mortality

41% Reduction

38% Reduction

25% Reduction

Highest rate of Death

Coronary Heart

Disease48%

Reduction41%

Reduction29%

ReductionHighest rate of Death

Cancer29%

Reduction23%

Reduction26%

ReductionHighest rate of Death

DOSAGE FORMS

Orally Ingested

In Oil Suspension

Sustained-Release

Rectal/Vaginal

Suppositories

Pessaries

Emulsions

Implants

DOSAGE FORMS (CONT’D)

Injectable

Topical

Enhanced Absorption Bases

Hydrophilic Creams

Ointments

Buccal

Troches

Sprays

Drops

Evaluation of Patients

Laboratory Studies– Saliva testing– Blood testing– Timing of the testing– Testing with creams vs.troches

HORMONAL MONITORING

Serum - bound fractions:

Total estrogens, E2, DHEA, DHEA-S, Testosterone, etc.

Expensive, but insurance usually covers

Most accurate

Saliva - unbound (free-floating) fractions:

Full panel of sex hormones, adrenal steroids

Least expensive

Least accurate

Urine - conjugated forms:

E1, E2, E3, and other steroids; useful for metabolic errors

Most expensive

163

HORMONE DOSING AND MONITORING (PROGESTERONE)

Luteal PhaseLuteal Phase

Saliva 0.1-0.3ng/ml

Luteal Phase Serum

12-32ng/ml

Luteal Phase- Capillary

12-32ng/ml

Buccal Troche 100mg

Troche Saliva1000 -3000ng/ml

Troche Serum 27-30ng/ml

Troche Capillary 270-300ng/ml

Transdermal Progesterone

20-30mg

Transdermal Saliva

10-30ng/ml

Transdermal Serum

2-3ng/ml

Transdermal Capillary

20-30ng/ml

Capsules 100mg Capsule Saliva0.02-0.04ng/ml

Capsule Serum 2-4 ng/ml

Capsule Capillary 2.4ng/ml

OC REFERENCES

Miller A, Raison C. Immune system contributions to the pathophysiology of depression. Jour Am Psych Assoc. 2008;6:36-45

Illman J, Corringham R, Robinson D Jr. Are inflammatory cytokines the common link between cancer-associated cachexia and depression? Jour Support Oncol. 2005;3(1):37-50

Dantzer R, Kelley KW, Twenty years of research on cytokine-induced sickness behavior, Brain Behav Immun. 2007;21(2):153-60

Dantzer R. Cytokine induced sickness behavior: where do we stand? Brain Behav Immun. 2001;15(1):7-24

Trussell, James. Contraceptive Efficacy. IN Hatcher Robert A, et al. Contraceptive Technology 19 ed New York: Ardent Media; 2007

REFERENCES Natural Hormone Replacement for Women Over 45, Johnathan Wright, M.D.

Women’s Bodies, Women’s Wisdom, Christiane Northrup, M.D.

Smart Medicine for Menopause, Sandra Cabot, M.D.

Once A Month, Katharina Dalton, M.D.

Screaming to be Heard, Elizabeth Vliet, M.D.

The Hormone of Desire, Susan Rako, M.D.

What your Dr. may not tell you about Menopause, John R. Lee, M.D.

Preventing and Reversing Osteoporosis, Alan Gaby, M.D.

The Formula, Vernon Sylvest, M.D.

The Power of the Mind to Heal, Joan Borysenko, Ph.D.

Minding the Body, Mending the Mind, Joan Borysenko, Ph.D.

Healing Words: The Power of Prayer and the Practice of Medicine, Larry Dossey, M.D.

The Molecules of Emotion, Candace Pert, Ph.D.

Love, Medicine, and Miracles: Lessons Learned, Bernie Siegel

Reprogramming Pain, Barry Bittman, M.D.

Getting Well Again, Carl Simonton, M.D., et.al.

The Healing Journey, Carl Simonton, M.D., et.al.

The Anatomy of the Spirit, Caroline Myss, Ph.D.

Why People Don’t Heal, and How They Can, Caroline Myss, Ph.D.

DHEA REFERENCES

Kocis, P. Prasterone. Am J Health Syst Pharm. 2006 Nov15;63(22):2201-10

Mease PJ, Ginzler EM, Gluck OS, et al. Effects of prasterone on bone mineral density in women with systemic lupus erythematosus receiving chronic glucocorticoid therapy. J Rheumatol. 2005 Apr;32(4):616-21

Petri MA, Lahita RG, van Vollenhoven RF, et al. Effects of prasterone on corticosteroid requirements odf women with systemic lupus erythematosus: a double-blind randomized, placebo-controlled trial. Arthritis Rheum. 2002 Jul;46(7): 1820-9

vanVollenhoven RF, Engelman EG, McGuire JL, Dehydroepiandrosterone in systemic lupus erythematosus. Results of a double-blind, placebo-controlled, randomized clinical trial. Arthritis Rheum. 1995 Dec;38(12):1826-31

ESTRIOL REFERENCES

Lyytinen H, Pukkala E, Ylikorkala O. Breast Cancer Risk in Postmenopausal Women Using Estrogen- Only Therapy. Obstetrics and Gynocology 2006 Dec;108(6): 1354-60

Terauchi M, Obayashi S, Aso T. Estriol, Conjugated equine estrogens, and alendronate therapy for osteoporosis. Int J Gynaecol Obstet. 2006;92:141-2

Fournier A, Berrino F, Riboli E, Avenel V, Clavel-Chapelon F. 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

Dessole S, Rubattu G, Ambrosini G, et al. Efficacy of low dose intravaginal estriol on urogenital aging in postmenopausal women. Menopause 2004;11(1):49-56

Drew JEm Wren BG, Edne JA. A cohort study of topical vaginal estrogen therapy in women previously treated for breast cancer. Climacteric 2003;6:45-52

REFERENCESBruch HR, Wolf L, Budde R, Romalo G, Schweikert HU. Androstenedione metabolism cultured human osteoblast-like cells. J Clin Endocrinol Metab. 1992 Jul; 75(1):101-105.

Hecter O, Grossman A, Chatterton RT. Relationship of Dehydroepiandrosterone and Cortisol in Disease. Medical Hypothesis. 1997, 49:85-91.

Phillips GB, et.al. The Association of Hypotestosteronemia with Coronary Artery Disease in Men. Arterioscler. Thromb., May 1994; 14(5):701-6.

Tenover J. Effects of Testosterone Supplementation in the Aging Male. Journal of Clinical Endocrinology and Metabolism, 1992: 1092-98.

Vermeulen A. Plasma Levels and Secretion Rate of Steroids with Anabolic Activity in Man. Environ Qual Safety Suppl. 1976; 5:471-80

Organochlorines and Breast Cancer. Alternatives for the Health Conscious Individual. 1998; 7(13).

Endocrinology, 3rd ed. DeGroot LJ (ed.), 1995.

Williams Textbook of Endocrinology, 8th ed. Wilson JD and Foster DW (eds.). 1992.

Endocrine Physiology, Constance R. Martin, Ph.D., 1985.

DHEA, A Practical Guide, Ray Sahelian, M.D.

Hormonal Health, Michael Colgan, M.D.

The Doctor’s Case Against the Pill, Barbara Seaman

Washington Toxics Coalition. Fall 1995, 14(3).

National Coalition Against the Misuse of Pesticides. Washington D.C. 20003

REFERENCESBoyd, D.A. (1942). Ameri. J. Obstet. Gynec.; 149-163.

Dalton K. (1971). Brit. J. Psychiat.; 118, 547.

Dalton K. (1971). Proc. Roy. Soc., Med.; 64, 12, 1249-1252.

Dalton K. (1980). Depression After Childbirth, Oxford University Press, Oxford.

Foundeur M., Fixsen C., Triebel W.A., White M.A. (1957). Arch. Neurol. Psychiat.;77, 503-512.

Hegarty A.B. (1955). Brit. Med. J.; 1, 637.

Hoffman, F., v Lam. L. (1948); Zbl. Gynak; 70, 1177.

Malleson J. (1963). Brit. Med. J.; 2, 158.

Pitt B. (1968). Brit. J. Psychiat.; 114, 1325-1335.

Pitt B. (1973). ibid; 122, 431-443.

Ryle A. (1961). J. Ment. Sci.;107, 279-286.

Schmidt H.J. (1943). J. Med. Ass.; 190-192.

Soltau D.H.K., Taylor N.H. (1982). Brit. Med. J.;284, 981.

Tod E.D.M. (1964). Lancet; ii, 264.

Yalom I.D., Lunde D.T., Moss R.H., Hamburg D.A. (1968). Arch. Gen Psychiat.; 18, 16.

REFERENCES (CONT’D)

Swyer GIM, Daley D. (1953). Brit.Med. J.;1,1073

Bishop PMF, Richards NA. (1952). Brit.Med. J.;1,1244.

Bishop PMF, Richards NA, Doll R. (1956). Brit.Med. J.;2,130.

Csapa A,Pahanka O, Kaihola LH. (1973). Lancet; ii, 1097.

Dalton K. (1969) The Menstrual Cycle, Penguin Books Ltd, London

Johansson EDB. (1969). Acta Endocrin., Copenh.; 61,607.

Jones SB. (1973). Obstet. Gynec.; 26-34

Jones SB. (1983). Progesterone and Progestins, Ed.Barin CW, Milgram E, Mauvais-Jarvis P, Raven Press,New York, 189-202

REFERENCES

Stanworth RD et al. Dyslipidaemia is associated with testosterone, oestradiol and androgen receptor CAG repeat polymorphism in men with type 2 diabetes. Clin Endocrinol (Oxf). 2011 May;74(5):624-30. doi: 10.1111/j.1365-2265.2011.03969.x.

Borst SE et al. Testostserone administration induces protection against global myocardial ischemia. Horm Metab Res. 2010 Feb;42(2):122-9. Epub 2009 Oct 27.

Wainwright SR et al. Hypogonadism predisposes males to the development of behavioural and neuroplastic depressive phenotypes. Psychoneuroendocrinology. 2011 Apr 9.

REFERENCES

Schulz K, Korz V. Hippocampal testosterone relates to reference memory performance and synaptic plasticity in male rats. Front Behav Neurosci. 2010 Dec 17;4:187.

Isbarn H et al. Testosterone and prostate cancer: revisiting old paradigms. Eur Urol. 2009 Jul;56(1):48- 56. Epub 2009 Apr 8.

Morgentaler A. Turning conventional wisdom upside-down: Low Serum testosterone and high-risk prostate cancer. Cancer. 2011 Mar 1. doi: 10.1002/cncr.25975.

References

Howell A, Evans GD. Hormone replacement therapy and breast cancer. Recent Results Cancer Res. 2011;188:115-24.

• Nilsson BO, Olde B, Leeb-Lundberg LM. [G protein-coupled Estrogen Receptor 1 (GPER1)/GPR30: A New Player in Cardiovascular and Metabolic Estrogenic Signaling. Br J Pharmacol. 2011 Jan 21. doi: 10.1111/j.1476-5381.2011.01235.x.• Seals DR, Jablonski KL, Donato AJ. Aging and vascular endothelial function in humans. Clin Sci (Lond). 2011 May;120(9):357-75.

References

Bourque M, Dluzen DE, Di Paolo T.

Neuroprotective actions of sex steroids in Parkinson's disease. Front Neuroendocrinol. 2009 Jul;30(2):142-57. Epub 2009 May 3.• Morinaga A, Ono K, Takasaki J, Ikeda T, Hirohata M, Yamada M. Morinaga A, Ono K, Effects of sex hormones on Alzheimer's disease-associated β-amyloid oligomer formation in vitro. Exp Neurol. 2011 Jan 31.

ReferencesLin J, Kroenke CH, Epel E, Kenna HA, Wolkowitz OM, Blackburn E, Rasgon NL. Greater endogenous estrogen exposure is associated with longer telomeres in postmenopausal women at risk for cognitive decline. Brain Res. 2010 Oct 18.

• RJ, Searle LL, Kim AJ, De D, Zhu X, Askari HB, O’Neill JC, Abad MC, Rentzeperis D, Liu J, Kemmerer M, Lin L, Kasturi J, Geisler JG, Lenhard JM, Player MR, Gaul MD. Identification of Diaryl Ether-Based Ligands for Estrogen-Related Receptor α as Potential Antidiabetic Agents. J Med Chem. 2011 Jan 10. • Nilsson BO, Olde B, Leeb-Lundberg LM. G protein-coupled Estrogen Receptor 1 (GPER1)/GPR30: A New Player in Cardiovascular and Metabolic Estrogenic Signaling. Br J Pharmacol. 2011 Jan 21. doi: 10.1111/j.1476-5381.2011.01235.x

ReferencesSørensenMB.Changesinbodycompositionat menopause--age, lifestyle or hormone deficiency? J Br Menopause Soc. 2002 Dec;8(4):137-40.

• Seifert-Klauss V, Prior JC. Progesterone and bone: actions promoting bone health in women. J Osteoporos. 2010 Oct 31;2010:845180.

• Maiti K, Paul JW, Read M, Chan EC, Riley SC, Nahar P, Smith R. G-1-Activated Membrane Estrogen Receptors Mediate Increased Contractility of the Human Myometrium. Endocrinology. 2011 Mar 22.

References

Stanworth RD, Kapoor D, Channer KS, Jones TH.

Dyslipidaemia is associated with testosterone, oestradiol and androgen receptor CAG repeat polymorphism in men with type 2 diabetes. Clin Endocrinol (Oxf). 2011 May;74(5):624-30. doi: 10.1111/j.1365-2265.2011.03969.x.• Borst SE, Quindry JC, Yarrow JF, Conover CF, Powers SK. Testosterone administration induces protection against global myocardial ischemia. Horm Metab Res. 2010 Feb;42(2):122-9. Epub 2009 Oct 27

REFERENCESTarasoy IuA, Sheibak VM, Mioseenok AG. Adrenal cortex functional activity in pantothenate deficiency and the administration of the vitamin or its derivatives]. Vopr Pitan. 1985 Jul-Aug; (4):51-4.

Haililoglu S, Frdem H, Sernek B, Tekeli T, Rulut Z. The relationship among vitamin C, beta- carotene, vitamin A, progesterone and oestradiol 17-beta concentrations in plasma and cyst fluid of Holstein cows with ovarian cyst. Reprod Domest Anim. 2008 Oct;43(5):573-7. Epub 2008 Mar 23.

References

Camporez JP, Akamine EH, Davel AP, Franci CR, Rossoni LV, de Oliveria Carvela CR.

Dehydroepiandrosterone protects against oxidative stress-induced endothelial dysfunction in ovariectomized rats. J Physiol. 2011 May 15;589(Pt 10):2585-96. Epub 2011 Mar 14.• Tellez N, Comabella M, Julia E, Rio J, Tintore M, Brieva L, Nos C, Montalban X. Fatigue in progressive multiple sclerosis is associated with low levels of dehydroepiandrosterone. Mult Scler. 2006 Aug;12(4):487-94.

References

Sivritas D, Becher MU, Ebrahimian T, Arfa O, Rapp S, Bohner A, Mueller CF, Umemura T, Wassmann k.

Antiproliferative effect of estrogen in vascular smooth muscle cells is mediated by Kruppel-like factor-4 and manganese superoxide dismutase. Basic Res Cardiol. 2011 Apr 12.• SA, Rozakis GW, Dzugan KS, Emhof L, Dzugan SS, Xydas C, Michaelides C, Chene J, Medvedovsky M.Correction of steroidopenia as a new method of hypercholesterolemia treatment. Neuro Endocrinol Lett. 2011 Feb 21;32(1):77-81.

ReferencesFinocchi C, Ferrari M. Female reproductive steroids and

neuronal excitability. Neurol Sci. 2011 May;32 Suppl 1:S31-5.

• Jiang R, Chen J. Progesterone Increases Circulating Endothelial Progenitor Cells and Induces Neural Regeneration after Traumatic Brain Injury in Aged Rats. J Neurotrauma. 2011 May 2.

• Ahlem CN, Auci DL, Nicoletti F, Pieters R, Kennedy MR, Page TM, Reading CL, Enioutina EY, Frincke JM. Pharmacology and immune modulating properties of 5-androstene-3β,7β,17β-triol, a DHEA metabolite in the human metabolome. J Steroid Biochem Mol Biol. 2011 May 5.

• Wainwright SR, Lieblich SE, Galea LA, Hypogonadism predisposes males to the development of behavioural and neuroplastic depressive phenotypes. Psychoneuroendocrinology. 2011 Apr 9.

ReferencesIsbarn H, Pinthus JH, Marks LS, Montorsi F, Morales A, Morentaler A, Schulman C.

Testosterone and prostate cancer: revisiting old paradigms. Eur Urol. 2009 Jul;56(1):48-56. Epub 2009 Apr 8.• Morgentaler A. Turning conventional wisdom upside-down: Low Serum testosterone and high-risk prostate cancer.Cancer. 2011 Mar 1. doi: 10.1002/cncr.25975.

ReferencesLiu RZ, Graham K, Glubrecht DD, Germain DR, Mackey JR, Godbout R. Association of FABP5 expression with poor survival in triple-negative breast cancer: implication for retinoic acid therapy. Am J Pathol. 2011 Mar;178(3):997-1008.

Tarasoy IuA, Sheibak VM, Mioseenok AG. Adrenal cortex functional activity in pantothenate deficiency and the administration of the vitamin or its derivatives]. Vopr Pitan. 1985 Jul-Aug;(4):51-4.

Haililoglu S, Frdem H, Sernek B, Tekeli T, Rulut Z. The relationship among vitamin C, beta-carotene, vitamin A, progesterone and oestradiol 17-beta concentrations in plasma and cyst fluid of Holstein cows with ovarian cyst. Reprod Domest Anim. 2008 Oct;43(5):573-7. Epub 2008 Mar 23.

REFERENCES

Kansas City Endometriosis Chapter. “The Milk Controversy” July/August 2000

Campbell, Colin T. “Milk Shouldn’t be Considered Healthy.” Ithacajournal.com. 26 July 2008.

Lara-Villoslada F, Olivares M, Xaus J. “The Balance between Caseins and Whey Proteins in Cow’s milk determines its Allergenicity” J Dairy Sci. 2005 May; 88 (5):1654-60.

Outwater, J.L., Nicholson, A., Bernard, N. Dairy Products and Breast Cancer: The IGF -1, estrogen, and bGH hypothesis. Med Hypothesis 48:453-461, 1997

REFERENCES

Nahoul K, Dehennin L, Jondet M et al. The metabolism of estradiol: Oral compared to intravenous administration. J Steroid Biochem 1985;23:1065-1070

Komesaroff PA, Black CV, Westerman RA. A novel, nongeonomic action of estrogen on the cardiovascular system, J Clin Endocrinol Metab 1998;83:2313-2316

Vongpatanasin W, Tuncel M, Mansour et al. Transdermal estrogen replacement therapy decreases sympathetic activity in postmenopausal women. Circulation 2001; 103:2903-2908

Dubey RK, Jackson EK, Gillespie DG et al, Clinically used estrogens differentially inhibit human aortic smooth muscle cell growth and mitogen-activated protein kinase activity. Arterioscler Thromb Vasc Biol 2000;20:964-972

REFERENCES

Clarkson TB, Progestogens and cardiovascular disease. A critical review. J Reprod Med 1999;44(2 Suppl):180-184

Miyagawa K, Rosch J, Stanczyk F et al. Medroxyprogesterone interferes with ovarian steroid protection against coronary vasospasm. Nat Med 1997;3:324-327

Wakatasuki A, Okantani Y, Ikenoue N et al. Effect of medroxyprogesterone acetate on endothelium-dependent vasodilation in postmenopausal women receiving estrogen. Circulation 2001;104:1773-1778

Kojima K, Abe-Dohmae S, Arakawa R et al. Progesterone inhibits apolipoprotein-mediated cellular lipid release: A putative mechanism for the decrease of high density lipoprotein. Biochem Biophys Acta 2001:1532-:173-184

REFERENCES

The Writing Group for Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in post menopausal women. JAMA 1995;272:199-208

Adams MR, Kaplan JR, Manuck SB et al. Inhibition of coronary artery atherosclerosis by 17-beta estradiol in ovariectomized monkeys: Lack of an effect of added progesterone. Arteriosclerosis 1990;10:1051-1057

Adams M, Register T, Golden D et al. Medroxyprogesterone acetate antagonizes inhibitory effects of conjugated equine estrogens on coronary artery atherosclerosis. Atheroscler Thromb Vasc Biol 1997;17:217-221

REFERENCES

Rosano GM, Webb CM, Chierchia S et al. Natural progesterone, but not medroxyprogesterone acetate, enhances the beneficial effect of estrogen on exercise- induced myocardial ischemia in postmenopausal women. J Am Coll Cardiol 2000;36:2154-2159

Molinari C, Battaglia A, Grossini E et al. Effect of progesterone on peripheral blood flow in prepubertal female anesthetized pigs. J Vasc Res 2001;38:569-577

Williams JK, Honore EK, Washburn SA et al. Effects of hormone replacement therapy on reactivity of atherosclerotic coronary arteries in cynomolgus monkeys. J Am Coll Cardiol 1994;224:1757-1761

REFERENCES

Godsland IF. Effects of postmenopausal hormone replacement therapy on lipid, lipoprotein, and apolipoprotein (a) concentrations: Analysis of studies published from 1974-2000. Fertil Steril 2001;75:898-915

Levine H, Watson N. Comparison of the pharmacokinetics of crinone 8% administered vaginally versus prometrium administered orally in postmenopausal women. Fertil Stril 2000;73:516-521

Arafat ES, Hargrove JT, Maxson WW et al. Sedative and hypnotic effects of oral administration of micronized progesterone may be mediated through its metabolites. Am J Obstet Gynecol 1988;159:1203-1209

REFERENCES

Freeman EW, Purdy RH, Coutifaris C et al. Anxiolytic metabolites of progesterone: Correlation with mood and performance measures fallowing oral progesterone administration to healthy female volunteers. Neuroendocrinology 1993;58:478-484

Ottoson UB, Carlstrom K, Damber JE et al. Serum levels of progesterone and some of its metabolites including deoxycorticosterone after oral and parenteral administration. Br J Obstet Gynecol 1984;91:1111-1119

Cicinelli E, Cignarelli M, Resta L et al. Effects on the repetitive administration of progesterone by nasal spray in postmenopausal women. Fertil Steril 1993; 60:1020-1024

REFERENCES

Franchin R DeZiegler D, Bergeron C et al. Transvaginal administration of progesterone. Obstet Gynecol 1997;90:396-401

Mircioiu C, Perju A, Griu E et al. Pharmacokinetics of progesterone in postmenopausal women: 2. Pharmacokinetics following percutaneous administration. Eur J Drug Metab Pharmacokinet 1998;23:397-402

Burry KA, Patton PE, Hermsmeyer K. Percutaneous absorption of progesterone in postmenopausal women treated with transdermal estrogen. Am J Obstet Gynocol 1999;180:1504-1511

REFERENCES

Longcope C, Gorbach S, Goldin B et al. The metabolism of estradiol; Oral compared to intravenous administration. J Steroid Biochem 1985;23:1065-1070

Nahoulk K, Dehennin L, Jondet M et al. Profiles of plasma estrogens, progesterone and their metabolites after oral or vaginal administration of estradiol or progesterone. Maturitas 1993;16:185-202

REFERENCES

Carey BJ, Carey AH, Patel S et al. A study to evaluate serum and urinary hormone levels following short and long term administration of two regimens of progesterone cream in postmenopausal women. BJOG 2000;107:722-726

Wren BG, McFarland K, Edwards L et al. Effect of sequential transdermal progesterone cream on endometrium, bleeding pattern, and plasma progesterone and salivary progesterone levels in postmenopausal women. Climacteric 2000;3:155-160

Anasti JN, Leonetti HB, Wilson KJ. Topical progesterone cream has antiproliferative effect on estrogen-stimulated endometrium. Obstet Gynecol 2001;97(Suppl1):S10

REFERENCES

Chang KJ, Lee TT, Linares-Cruz G et al. Influences of percutaneous administration of estradiol and progesterone on human breast epithelial cell cycle in vivo. Fertil Steril 1995;63:785-791

Lewis LG, McGill H, Patton VM et al. Caution on the use of saliva measurements to monitor absorption of progesterone from transdermal creams in postmenopausal women. Maturitas 2002;41:1-6

Lipworth L, Adami HO, Trichopoulos D et al. Serum steroid hormone levels, sex hormone-binding globulin, and body mass index in the etiology of postmenopausal breast cancer. Epidemiology 1996;7:96-100

REFERENCES

Koh KK, Mincemoyer R, Bui MN et al. Effects of hormone replacement therapy on fibrinolysis in postmenopausal women. N Engl J Med 1997;336:683-690

Luyer MD, Khosla S, Owen WG et al. Prospective randomized study of effects of unopposed estrogen replacement therapy on markers of coagulation and inflammation in postmenopausal women. J Clin Endocrinol Metab 2001;86:3629-3634

Vehkavaara S, Silveira A, Hakala-Ala-Pietila T et al. Effects of oral and transdermal estrogen replacement therapy on markers of coagulation, fibrinolysis, inflammation and serum lipids and lipoproteins in postmenopausal women. Thromb Haemost 2001;85:619-625

REFERENCES

Lobo RA, Bush T, Carr BR et al. Effects of lower doses of conjugated equine estrogens and medroxyprogesterone acetate on plasma lipids and lipoproteins, coagulation factors, and carbohydrate metabolism. Fertil Steril 2001;76:13-24

Chetkowski RJ, Meldrum DR, Steingold KA et al. Biologic effects of transdermal estradiol. N Engl J Med 1986;314:1615-1620

Crook D. The metabolic consequences of treating postmenopausal women with non oral hormone replacement therapy. Br J Obstet Gynaecol 1997;104(Suppl16):4-13

REFERENCES

Natchigall LE, Raju U, Banerjee S et al. Serum estradiol-binding profiles in postmenopausal women undergoing three common estrogen replacement therapies: Associations with with sex hormone-binding globulin, estradiol, estrone levels. Menopause 2000;7:243-250

Scarabin PY, Ahlene-Gelas M, Plu-Bureau G et al. Effects of oral and transdermal estrogen/progesterone regimens on blood coagulation and fibrinolysis in postmenopausal women. A randomized controlled trial. Arterioscler Thromb Vasc Biol 1997;17:3071-3078

Modena MG, Molinari R, Muia N et al. Double-blind randomized placebo controlled study of transdermal estrogen replacement therapy on hypertensive postmenopausal women. Am J Hypertens 1999:12:1000-1008

REFERENCES

Erenus M, Karakoc B, Gurler A. A comparison of effects of continuous combined transdermal with oral estrogen and oral progesterone replacement therapy on serum lipoproteins and compliance. Climacteric 2001;4:28-234

Greenblat RB, Natrajan PK, Aksu MF et al. The fate of large bolus of exogenous estrogen administered to postmenopausal women. Maturita 1979;2:29-35

Lundstrom E, Wilczek B, von Palffy Z et al. Mammographic breast density during hormone replacement therapy: Effects of continuous combination, unopposed transdermal and low potency estrogen regimens. Climacteric 2001;4:42-48

REFERENCES

Ettinger B, Genant H, Cann C, Late term estrogen replacement therapy prevents bone loss and fractures. Ann Intern Med 1985;102:319-324

Lindsay R, Tohme J. Estrogen treatment of patients with established postmenopausal osteoporosis. Obstet Gynocol 1990;76:290-295

Felson D, Zhang Y, Hannan M, et al. The effect of postmenopausal estrogen therapy on bone density in elderly women. N Engl J Med 1993;329:1141-1146

REFERENCES

Silva I, Mor G, Naftolin F. Estrogen and the aging brain. Maturitas 2001;38:95-100

Blanchet PJ, Fang J, Hyland K et al. Short term effects of high dose 17beta estradiol in postmenopausal PD patients: A crossover study. Neurology 1999;53:91-95

Saunders-Pullman R, Gordon- Elliott J, Parides M et al. The effect of estrogen replacement on early Parkinson’s disease, Neurology 1999;52:1417-1421

REFERENCES

Feskanich D, et al., “Milk, Dietary Calcium, and Bone Fractures in Women…”American Journal of Public Health 87 (1997):992-7.

Lloyd, T., “Adult Female Hip Bone Density Reflects Teenage Sports-Exercise Patterns, But not Teenage Calcium Intake,” Pediatrics 106:1 (July 2000):40-4

Clyne P.S., et al. Pediatrics 87:439-444, 1991

Childhood Dairy Intake and Adult Cancer Risk: 65-y follow up of the Boyd Orr cohort, Van Der Pols JC, Martin, RM, et al, Am J Clin Nutr, 2007; 86(6): 1722-1729