Bioidentical Hormone Restoration Best Medical Practice

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

2. Topics • Introduction • The Problem with Reference Ranges • Hypometabolism: Cortisol and Thyroid • Hormone Loss with Age • 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 Cortisol, DHEA Aldosterone ACTH LH/FSH Estradiol, Progesterone Testosterone Testosterone

5. Human Steroid HormonesBioidentical Molecules 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 • Non-toxic: • No side effects, only effects • Nointeractionswith drugs • No allergic reactions • Safe in youthful physiological levels/balance • Negative effects:Due to excessivedose,wrong delivery method,or imbalancewith other hormones

7. Bioidentical Hormone Restoration is Good 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 diagnose deficiency? • How do we decide which dose is right? • What do we do about deficiencies due toaging?

8. Why Docs Don’t Get It: Reference Range Endocrinology • “Normal” ranges on reports are misunderstood: • 95% of all persons tested (only 2.5% low) • or 95% of tested persons of same age • or Optimal values (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! • AM serum cortisol 5-255x! • “Normal” resultno hormonal dx/rxdrugs May mean

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

10. Intelligent 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

11. 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 are insensitive to most deficiencies • Irrational fear ofthyroidandcortisol supplementation • Underdiagnosed, undertreated—Docs prescribe pharmaceuticals instead(SSRIs, amphetamines, anti-seizure drugs, anti-psychotics, sedatives, etc.)

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

13. 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 • Too littlefatigue, depression, aches & pains, anxiety, hypoglycemia, autoimmune diseases, allergies • Women have lowercortisol levels/effects than men, much greater incidence of cortisol insufficiency.

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

15. Normal Saliva Cortisol Profile

16. Cortisol Deficiency

17. Cortisol Restoration • Mild deficiency can resolve with stress, rest, adrenal supplements • Moderate-to-severe deficiency—needs cortisol restoration • Physiological doses of 15-40mg dailydo not cause hypertension, osteoporosis, diabetes • Doctors fear of low-dose cortisolunfounded • See Dr. William Jeffries’ Safe Uses of Cortisol

18. DHEA • Most abundant steroid hormone; yet ignored • Cells make testosterone and estradiol with it • Counteracts cortisol, the two must be in balance • Cortisol supplementation lowers DHEA, must replace • Anabolic—builds tissues, improves immunity • Reduces intra-abdominal fat • Reduces pain—restores natural endorphins • Reduces inflammation (IL-6, TNF-, IL-2) • Anti-cancer effect in animal, in vitro studies

19. Bioidentical Hormones, Reference Ranges, Cortisol and DHEA Any Questions?

20. 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

21. Thyroid Testing • Doctors often order only a TSH test--Inadequate • Thyroid stimulating hormone (TSH) is a pituitary hormone. It is NOT a thyroid hormone, it is not a measure of thyroid hormone levels. • Must test free T4 and free T3 levels • Hypothyroidism: symptoms plus one or both hormone levels below middle of reference ranges • Severe hypothyroidism: signs and symptoms plus both hormones in lower third of ranges.

22. We Need OptimalT3Levels • Incidence of severe atherosclerosis doubled with lower T3 levels within the reference range Clin Cardiol. 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 • Prevents weight gain

23. Fatigue, Fibromyalgia and DepressionEpidemic • Fatigue, fibromyalgia, and depression are due to 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

24. Rational Thyroid Restoration • If sign/symptoms of hypothyroidism: Restore! • 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+T4) • Adjust dose according to symptoms and free hormone levels • Safe: • No bone loss if Vit. D and hormones are restored • No cardiac abnormalities J Clin Endo Metab. 2000 Jan;85(1):159-64 • No muscle wasting Am J Phys Endol Metab. 2005 Jun;288(6):E1067-73

25. Thyroid Restoration Any Questions?

26. What should we do about hormones that are lost to normal aging?

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

28. 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

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

30. Andropause Testosterone in Men

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

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

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

34. 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!

35. Aging and Hormones Any Questions?

36. 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)

37. Women Killers and Hormones • Cardiovascular disease (CVD), osteoporosis, andbreast cancer are all rare before menopause. • All three diseases are clearly related to hormone deficiency or imbalance. • Youthful estradiol/progesterone/testosterone hormonal milieu protects women from these diseases.

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

39. 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 less increase in carotid intimal thickness with CEE vs. placebo. • But there is a problem with oral estrogens…

40. 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.

41. 30 Speroff L, Fritz M Clinical Gynecologic Endocrinology and Fertility, 7th Ed.

42. 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.

43. 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 • Hormone restorationincluding Vit. D increases bone densitybetter than bisphosphonates and preserves normal bone remodeling • 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”.

44. 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.

45. Estradiol—Progesterone Complementarity • Estradiol (human estrogen) promotes breast/uterine proliferation and growth. • Progesterone stops proliferationand promotes maturation and differentiation. • Differentiated cells can’t become cancers. • Progesterone withdrawalsloughing and necrosis of uterine lining and breast duct epithelium.Longacre TA, Am J Surg Pathol. 1986 Jun;10(6):382-93 • High progesterone/estradiol ratio suppresses proliferation and prevents cancers • Estradiol is safe if opposed by progesterone.

46. Progesterone’s Anti-Estrogenic Actions in Uterus and Breast • Decreases synthesis of estradiol receptors • Increases conversion of estradiol to estrone (weak estrogen) by inducing 17β-hydroxysteroid dehydrogenase Type 2 • Reduces conversion of estrone to estradiol by inhibiting 17β-HSD Type 1 • Increases sulfation (inactivation) of estrogens Williams Text. of Endocrinology, 10th Ed., p. 612

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

48. 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

49. Normal Progesterone Dominance Ovulation Ovulation Menstrual Cycle

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