Bioidentical Hormone Restoration Best Medical Practice

1. Bioidentical Hormone RestorationBest Medical Practice Relax: This presentation is available online.

2. Topics • Hormones are not Drugs • The Problem with Reference Ranges • Hormone Loss with Age • Hypometabolism: Cortisol and Thyroid • Estradiol and Progesterone for Menopause • Progesterone prevents Breast Cancer • Pharmaceutical Hormone Substitution • Testosterone for Women and Men • Compounding Pharmacies • Practical Issues

3. Hormones • Parts of our integrated neuro-endocrine-immune system • Travel via blood to all cells • Control cells’proliferation, differentiation, protein synthesis, metabolic rate, etc. • The most powerful molecules in biology • Optimallevels and effects are essential for health and quality of life

4. Central Control Master Gland TSH T3, T4 ACTH Cortisol, DHEA Aldosterone LH/FSH Epinephrine Norepinephrine Estradiol, Progesterone Testosterone Testosterone

5. Human Steroid Hormones Estradiol Testosterone DHEA Progesterone Aldosterone Cortisol Drug companies have patented ~5 to 200 variations of each molecule.

6. Bioidentical Hormones are not Drugs • Correct molecular structure—same action at receptors, same metabolism and elimination. • Dose can be adjusted by blood testing. • Non-toxic: • No side effects, only effects • Nointeractionswith drugs • No allergic reactions • Safe in youthful physiological levels/balance • Negative effects??Only with excessivedose,wrong delivery method,or imbalancewith other hormones

7. Where Do They Come From? • All bioidentical steroid hormones (and substitutes too) are chemically synthesized from diosgenin (from wild Mexican yams and soy). Avoid “natural”, “synthetic”—ambiguous terms.

8. Bioidentical Hormone Restoration is Best Medical Practice • If a hormone is missing, replace it!; if present but deficient, optimize it! • Type 1 Diabetes: bioidentical insulin • Hypothyroidism: bioidentical T4 • Growth hormone def.: bioidentical GH • Adrenal insufficiency: bioidentical cortisol • The Controversies: • How do we diagnosedeficiency? • How do we decide what dose is right? • What do we do about hormones lost due toaging?

9. Adrenopause DHEA  DHEA-S J Clin Endocrinol Metab. 1997 Aug;82(8):2396-402

10. Thyropause Endocr Rev. 1995 Dec;16(6):686-715 TSH response to low T4 (2.7-3.2g/dL) 80% decline Carle, Thyroid. 2007 Feb;17(2):139-44

11. Somatopause Growth Hormone (GH) Clinical Chemistry 48, No. 12, 2002

12. Andropause Testosterone in Men Baltimore Longitudinal Study of Aging (BLSA). Harman et al., 2001

13. Steroid Loss in Women>>Men Men Women Progesterone average Testosterone 50% loss pg/ml 90% Loss Less estrogen than old men! ♂ ♀ ♀ ♂ DHEA-S 5,000,000pg/ml Cortisol 100,000 pg/ml

14. Common View • Persistence of youthful levels of hormones would cause more heart attacks and cancers as we age (?) • The loss of hormones is adaptive–helps us to live longer (?) • Fits the Pharmaceutical Agenda:Takedrugs for every symptom and disorder caused by hormone loss (!?!)

15. Against the Common View • Aging is a natural self-destruct programthat kicks in around age 25in humans • Obesity, high blood pressure, diabetes, heart attacks, autoimmune diseases, and many cancers increaseyears after hormone deficiencies set in and occur moreoften in those with lower levels! • Studies of balanced hormone restoration show the expected youthful benefits and improvements in these disorders--and no proof of harm!!

16. Why Docs Don’t Get It: Reference Range Endocrinology • “Normal” ranges on reports are misunderstood: • 2 standard deviations from the mean~95% of all persons tested (only 2.5% low) • or 95% of tested persons of same age • or adjudicated optimals (glucose, cholesterol) • Docs assume that all ranges are optimals! • Male free testosterone: 35-1555x! • Female free testosterone: 0.0-2.2! • Thyroid - Free T4: 0.6-1.83x! • Ranges far too broad to be optimal levels! • “Normal” resultno hormonal dx/rxdrugs May mean

17. Reference Range Endocrinology 95% population range “Everything is Normal” Hormone Effect “No Thyroid Disease” Too much Disease Too Little Disease But Hormone Effects vary continuously with concentration! 0 0.6 1 1.8 2 FT4 ng/dL Hormone Level

18. Restorative Endocrinology Tighter range based on young healthy persons and on physiological research Individualized Diagnosis and Treatment Hormone Effect Optimal?? 0 1 1.6 1.3 2 FT4 ng/dL Hormone Level

19. New Paradigm: Restorative Endocrinology • Endocrine glands and their feedback control systems deteriorate with age. • Our bodies cease to regulate our hormones for optimal health. • Partial hormone deficiencies are harmful. • The restoration of youthful/optimal nutrient and hormone levels is: • Essential to preventative medicine • Essential to the treatmentof disease • Essential to our quality of Life!

20. Hypometabolism: Thyroid and Cortisol Insufficiency • Thyroid sets throttle, cortisol delivers the fuel • Our health and quality of life require optimal levels of both hormones! • Deficiencyreduced metabolic ratefatigue, brain dysfunction, depression, pain • Conventional tests insensitive to moderate deficiencies • Irrational fear ofthyroidandcortisol supplementation • Underdiagnosed, undertreated—Docs prescribe pharmaceuticals instead(SSRIs, amphetamines, anti-seizure drugs, anti-psychotics, sedatives, etc.)

21. Glucocorticoids (“Steroids”) Cortisol (hydrocortisone) Methylprednisolone (5x) Medrol® Dexamethasone (70x) Decadron® Prednisone (4x)

22. Cortisol • Made in the adrenal glands • Maintains blood sugar (delivers the fuel) • Modulates the immune system • We needhigher levels with stress, disease • ToomuchDiabetes, HTN, osteoporosis (Cushing’s) • Women have lowercortisol levels/effects than men, much greater incidence of cortisol insufficiency.

23. Cortisol Insufficiency Fatigue Depression Irritability, anxiety Aches & pains Hot flashes, palpitations Hypoglycemia Insomnia Autoimmune diseases Allergies Variability: good days, bad days

24. ModerateCortisol Insufficiency • Common cause of chronic fatigue, pain, depression • Common cause of thyroid hormone intolerance • Clues: Feels much better on prednisone, often needs steroids for allergies, illnesses, etc. • Diagnosis: saliva cortisol profile: Serum cortisol and ACTH stimulation tests are insensitive. • Unrecognized: Docs taught to recognize only Addison’s Disease(total adrenal gland failure)

25. Normal Saliva Cortisol Profile

26. Cortisol Deficiency

27. Cortisol Restoration • Mild deficiency can resolve with stress, rest, vitamin/mineral supplements • Moderate-to-severe deficiency—needs cortisol restoration • Physiological doses do not cause hypertension, osteoporosis, diabetes • Doctors fear of low-dose cortisolunfounded • See Dr. William Jeffries’ Safe Uses of Cortisol

28. DHEA • Most abundant steroid hormone; yet ignored • Cells make testosterone and estradiol with it • Anabolic—builds tissues, improves immunity • Counteracts cortisol, the two must be in balance • Reduces intra-abdominal fat • Reducespain—restores natural endorphins • Reducesinflammation (IL-6, TNF-, IL-2) • Improves immunity—increases natural killer cells • Anti-cancer effect in animal, in vitro studies

29. Hypothyroidism • Mental fog, poor concentration • Depression • Fatigue, need for excessive sleep • Cold extremities • Aches and pains • Thinning scalp hair • Weight gain • Constipation • Ankle swelling, puffy face

30. Thyroid Testing • Doctors often order only a TSH test--Inadequate • Thyroid stimulating hormone (TSH) is NOT a thyroid hormone, it is an indirect and fallible indicator of thyroid hormone levels. • Must measure free T4 and free T3 levels—for both diagnosis and monitoring therapy. • Hypothyroidism: symptoms plus one or both hormone levels below middle of population ranges • Severe hypothyroidism: signs and symptoms plus both hormones in lower third of ranges.

31. We Need OptimalT4/T3Levels • Incidence of severe atherosclerosis cut in half with higher T3 levels within the laboratory rangeClinCardiol. 2003 Dec;26(12):569-73 • Lowers cardiac risk factors: cholesterol, triglycerides, C-reactive protein, homocysteine and lipoprotein(a) • Lowers blood pressure, dilates arteries • Reduces tendency to form blood clots • Helps prevent weight gain

32. Fatigue, Fibromyalgia and DepressionEpidemic • Chronic fatigue, fibromyalgia, and depression: low cortisol and/or low thyroid until proven otherwise • Pre-1970s: Treat the patient’s signs and symptoms with T4andT3(desiccated thyroid--Armour ) • Post-1970s: Treat TSH test using T4 only! • Doctors often lowered doses by 30-50%! • TSH-normalizing T4dose oftenlower free T3 levels weight gain, persistence of symptoms • Thyroid optimizationhelps most patients with symptoms and “low-normal” thyroid levels.

33. Restorative Thyroidology • Do Not Rely on TSH test for diagnosis or treatment Fraser WD, Are biochemical tests of thyroid function of any value in monitoring patients receiving thyroxine replacement? Br Med J (Clin Res Ed). 1986 Sep 27;293(6550):808-10 • Give T4 plus T3 (Armour, Cytomel+levothyroxine) • Adjust dose according to symptoms and free T4 and free T3 levels • Optimizing hormone levels within physiological ranges is safe: • No bone loss if Vit. D and hormones are restored • No cardiac dysfunction J Clin Endo Metab. 2000 Jan;85(1):159-64 • No muscle wasting Am J Phys EndolMetab. 2005 Jun;288(6):E1067-73

34. Not Just “Sex Hormones” Estradiol, progesterone, testosteroneandDHEA arerequired for the function, growth, and maintenance, of alltissues in both sexes! • Maintainbrain function and health—neurosteroids affect mood, cognition, memory, pain, etc. • Maintain the immune system—progesteroneand testosteroneare mild immunosuppressants • Maintainconnective tissue: skin, hair, bone, muscle • Improve insulin sensitivity: prevent diabetes, fatty liver • Reduce blood pressure—improve endothelial function • Prevent atherosclerosis(plaques in arteries)

35. Female Endocrinology • Nature makes special demands on the female body for reproduction. • Much more complex hormonal system than men • Breast, uterine and ovarian tissues undergo a monthly cycle of proliferation, differentiation, and breakdown • Defects in this cycle can lead to cancers in female organs and to many medical disorders.

36. Aging Ovaries • Females born with a fixed no. of oocytes which are continually lost • With aging, fewer oocytes of lower quality are leftreduced estradiol andprogesterone production beginning as early as age 30 • Lower progesteroneestrogen dominance • No ovulation=noprogesterone

37. Normal Progesterone Dominance Ovulation Ovulation Menstrual Cycle

38. Perimenopause Luteal Insufficiency=Estrogen Dominance Inadequate Luteal Phase shorter periods, early spotting ’d risk of breast cancer Ovulation Menstrual Cycle

39. Anovulation=Estrogen Dominance ’d risk of breast and uterine cancers Menstrual Cycle

40. Allergies Autoimmune diseases Anxiety, moodiness Insomnia Decreased sex drive Depression Bloating and edema Fibrocystic breasts Uterine fibroids Heavy periods Endometriosis Breast cancer Ovarian cancer Uterine cancer Thyroid dysfunction Gallbladder disease Migraines Seizures Progesterone Deficiency Estrogen Dominance Progesteronerestoration is the only effective treatment for estrogen dominance

41. Menopause Estradiol and Progesterone Deficiency

42. Estradiol Deficiency • Hot flashes • Irritability, insomnia, depression • Fatigue, aches and pains • Poor memory, ’d risk of Alzheimer’sdementia • Osteoporosisspine and hip fractures, loss of teeth • Genital atrophy, vaginal dryness • Atrophy of skin and connective tissue • Endothelial dysfunction, blood pressure • Increased blood sugar • Atherosclerosis, heart disease

43. Women Killers and Hormones • Cardiovascular disease (CVD), osteoporosis, dementia andbreast cancer are all rare before menopause. • The first 3 diseases are clearly related to estradiol deficiency ; breast cancer is related to progesterone deficiency. • Early removal of ovaries increases risk of heart disease, osteoporosis, and dementia. Parker WH, Effect of bilateral oophorectomy on women's long-term health. Womens Health (LondEngl). 2009 Sep;5(5):565-76. • Youthful estradiol/progesterone/testosterone hormonal milieu protects women from these diseases.

44. Coronary Heart Disease vs. Age AIHW Heart, stroke and vascular diseases - Australian facts 2004. Female Menopause

45. Estrogen Replacement and CADPrior to WHI Study • Oral conjugated equine estrogens (CEE) shown to reduce risk of heart disease in 40 observational and case-control studies, and one randomized study • Four angiographic studies: Estrogen reduced atherosclerosis 50-80%. • EPAT: RPC trial showed much less increase in carotid intimal thickness with CEE vs. placebo. • But there is a problem with oral estrogens…

46. Estrogen Replacement PreventsAlzheimer’s Disease Longer Estrogen Use Women without Estrogen Men 72% used Premarin only Zandi PP, et al., Cache County Study. JAMA. 2002 Nov 6;288(17):2123-9. RR 0.46 in Kawas C, The Baltimore Longitudinal Study of Aging. Neurology 1997;48:1517-1521 RR 0.65 Paganini-Hill A, Arch Intern Med 1996;156:2213-2217. RR 0.4, Tang M-X, Lancet 1996;348:429-432.

47. Breast Cancer Rate vs. Age Loss of ovarian functionhigher risk of breast cancer Menopause Ovarian function National Cancer Institute. SEER cancer statistics review 1975-2002. Table IV-3.

48. 30 Speroff L, Fritz M Clinical Gynecologic Endocrinology and Fertility, 7th Ed.

49. Osteoporosis • In menopause 5% bone loss each year for first 5 years=25%—due to loss of estrogen! • 20 yrs. post menopause—50% reduction in trabecular bone, 30% in cortical bone • 50% of women >65 yrs. old have spinal compression fractures • 14% lifetime risk of hip fracture for 50 yr.old woman, 30% for 80 yr. old. Speroff L, Fritz M Clinical Gynecologic Endocrinology and Fertility, 7th Ed.

50. OsteoporosisPrevention and Treatment • A hormone deficiency disease—the proper prevention and treatment is hormone restoration. • Estradiol prevents resorption of old bone while testosterone, progesterone, DHEA and GH build new bone. Raisz LG, J Clin Endo Metab. 1996; 81:37-43 Barrett-Connor E, J Reprod Med. 1999 Dec;44(12):1012-20 • Bisphosphonate drugs cause Ca++, esophageal inflammation and cancer, pain, and suppression of normal bone formationpoor fracture healing, late non-traumatic fractures, and “rotting jaw”. • Hormone restorationincluding Vit. D increases bone densitybetter than bisphosphonatesand preserves normal bone remodeling