Bioidentical Hormone Restoration Best Medical Practice

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

2. Topics • Introduction • Reference Range Endocrinology • Hormone Loss with Age • Hypometabolism: Thyroid and Cortisol Deficiency • Steroidsand DHEA in Rheumatic Diseases • Vitamin D and Fish oil • Sex hormone replacement for Women and Men

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 Hormones Bioidentical 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. Pharmaceutical Model Funding all schools, journals, organizations, research Naturally-occurring molecules cannot be patented FDA-approve s any drug that works better than placebo in two short-term trials. Symptoms labeled as syndromes, treated with drugs (depression, fatigue, fibromyalgia, anxiety, etc.) Misinformation about hormones is rampant. Hormone and nutrient deficiencies underdiagnosed and undertreated.

8. 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?

9. Why Docs Don’t Get It: Reference Range Endocrinology • “Normal” ranges on reports are misunderstood: • 95% of all persons tested (only 2.5% low) • 95% of tested persons of same age • adjudicated diagnostic values (glucose, cholesterol) • Docs assume that all ranges are diagnostic! • 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

10. Reference Range Endocrinology One size fits all 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 Thyroid Free T4 ng/dL Hormone Level

11. Intelligent Endocrinology Tighter range based on healthy persons and on physiological research Individualized Diagnosis and Treatment Hormone Effect Optimal?? 0 1 0.6 1.6 1.3 2 FT4 ng/dL Hormone Level

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

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

14. 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

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

16. Andropause Testosterone in Men

17. 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

18. 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 (!?!)

19. 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 deficienciesset in, and occur moreoften in those with lower hormone levels! • Studies of balanced hormone restoration show the expected benefits and no proof of harm!!

20. 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!

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

22. 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

23. 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.

24. 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

25. Fatigue, Fibromyalgia and DepressionEpidemic • Chronic fatigue, fibromyalgia, and depression: low thyroid and/or low cortisol 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.

26. 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 Endo Metab. 2005 Jun;288(6):E1067-73

27. Cortisol • Made in the adrenal glands • The body’s natural “steroid”--↑’d levels needed in stress, inflammation • Maintains blood sugar (delivers the fuel) • ToomuchDiabetes, HTN, belly fat, osteoporosis • Too littlefatigue, depression, aches & pains, anxiety, hypoglycemia, insomnia, inflammation • Modulates the immune system—prevents and treats allergies and autoimmune diseases • We needhigher levels with stress and disease

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

29. Mild-to-ModerateCortisol Insufficiency • Common cause of chronic fatigue, pain • Common cause of thyroid hormone intolerance • Unrecognized: Docs taught to recognize only Addison’s Disease(total adrenal gland failure) • Serum cortisol and ACTH stimulation tests are insensitive Reimondo G, Pituitary. 2008;11(2):147-54. Streeten DH, J ClinEndocrinolMetab. 1996 Jan;81(1):285-90. • Best test is saliva cortisol levels throughout day. Gozansky WS, ClinEndocrinol (Oxf). 2005 Sep;63(3):336-41. • Clues:Feels much better on prednisone, often needs steroids for allergies, illnesses, etc.

30. Normal Saliva Cortisol Profile

31. Cortisol Deficiency

32. Cortisol Restoration • Mild deficiency will improve with stress, rest, adrenal supplements, licorice root • Moderate-to-severe deficiency—needs cortisol restoration • Physiological doses of 15-30mg dailydo not cause hypertension, osteoporosis, diabetes • Taking cortisol or any glucocorticoid depresses DHEA, must replace. • Doctors fear of low-dose cortisol therapy is unfounded Dr. William Jeffries’ Safe Uses of Cortisol

33. Adrenal Hormones and Rheumatic Diseases Rheumatic diseases assoc. with ↓HPA activity, lower cortisol levels, and relative adrenal insufficiency Johnson EO, Ann N Y Acad Sci. 2006 Nov;1088:41-51. Demir H, Scand J Rheumatol. 2006 May-Jun;35(3):217-23. Chikanza IC, Arthritis Rheum. 1992 Nov;35(11):1281-8. CutoloM, J Endo Invest. 2002;25(10 Suppl):19-23. Ann N Y Acad Sci. 2006 Jun;1069:289-99. Gudbjornsson B, J Rheumatol. 1996 Apr;23(4):596-602. Mastorakos G, Z Rheum.2000;59 Suppl2:II/75-9. KebapcilarL, J Endocrinol Invest. 2009 Jul 20. Shah D, Kathmandu Univ Med J (KUMJ). 2009 Jul-Sep;7(27):213-9. Cortisol receptor isoforms and polymorphisms assoc. with autoimmune disease. TaitAS J Leukoc Biol. 2008 Oct;84(4):924-31. Low DHEAS found years before onset of RA, and in all rheumatic diseases. Masi AT, Ann N Y Acad Sci. 1999 Jun 22;876:53-62; disc.62-3. Stress is a trigger of autoimmune disease. Stojanovich L, Autoimmun Rev. 2008 Jan;7(3):209-13. Low cortisol levels in fibromyalgia , chronic pain. Gur A, Ann Rheum Dis. 2004 Nov;63(11):1504-6. McBeth J, Arthritis Res Ther. 2005;7(5):R992-R1000.

34. The Female Dilemma Women make 1/2 as much cortisol as men. VierhapperH, Metabolism. 1998 Aug;47(8):974-6. Women release less cortisol under stressTakaiN, Ann N Y Acad Sci. 2007 Mar;1098:510-5. Estradiol lowers cortisol levels and opposes cortisol throughout the body. Kerdelhué B, NeuroEndocrinolLett. 2006 Oct;27(5):659-64. Ligeirode Oliveira AP, Neuroimmunomodulation. 2004;11(1):20-7 Anti-depressants increase cortisol levels and effects. SagudM, Neuropsychobiology. 2002;45(3):139-43 Female/Male ratios: Fibromyalgia 8:1, RA 3:1, SLE 9:1, PMR 2:1, Sjogrens 18:1, Chronic fatigue 4:1, Depression 2:1, Hashimotos /Graves thyroiditis 5:1, Anxiety 3:2, Mult. Sclerosis 3:1

35. DHEA • Most abundant steroid hormone; yet ignored • Cells make testosterone and estradiol with it • Anabolic—builds tissues, improves immunity • Reduces intra-abdominal fat Villareal DT, JAMA. 2004 Nov 10;292(18):2243-8. • Reduces inflammation • Anti-atherosclerotic effect • Anti-cancer effect in animal, in vitro studies • Low levels of DHEAS found in autoimmune diseases • Steroid therapy greatly reduces DHEA, must replace

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

37. DHEA Replacement • Improves blood sugar control, lowers insulin levels, and counteracts negative effects of diabetes Brignardello E, Diabetes Care. 2007 Nov;30(11):2922-7. Dhatariya K, Diabetes. 2005 Mar;54(3):765-9. Lasco A, Eur J Endocrinol. 2001 Oct;145(4):457-61. • 25mg/day improves mood, fatigue and joint pain in elderly men. Genazzani AR, Aging Male. 2004 Jun;7(2):133-43. • Improves fertility in older women Barad D, J Assist Reprod Genet. 2007 Dec;24(12):629-34, • Improves sexuality in postmenopausal women. Hackbert L, J Womens Health Gend Based Med. 2002 Mar;11(2):155-62. • Alleviates depression Bloch M, Biol Psychiatry. 1999 Jun 15;45(12):1533-41.Rabkin JG, Am J Psychiatry. 2006 Jan;163(1):59-66. Schmidt PJ, Arch Gen Psychiatry. 2005 Feb;62(2):154-62. • Reduces pain—restores natural endorphins Stomati M, GynecolEndocrinol. 1999 Feb;13(1):15-25.

38. DHEA Replacement • Improves mood and energy in patients on steroid replacement Hunt PJ, ClinEndocrinolMetab. 2000 Dec;85(12):4650-6 • Decreases platelet aggregation Jesse RL. Ann N Y AcadSci 1995 Dec 29;774:281-90 • Increases bioavailable IGF-1 Morales AJ, J ClinEndocrinolMetab. 1994 Jun;78(6):1360-7 • Counteracts high cortisol level/effects KrobothPD, J ClinPsychopharmacol. 2003 Feb;23(1):96-9 • Increasesnatural killer cell number and activity Casson, P Am J. ObstetGynecol 169: 1536-39 • Reducesinflammatory markers (IL-6, TNF-) DaynesRA, J Immunol 1993 Jun 15;150(12):5219-30 • Beneficial in ulcerative colitis and Crohn’s disease AndusT, Aliment PharmacolTher 2003 17:409-414

39. DHEA for SLE SLE patient have very low DHEAS levels Given by prescription as Prasterone Increases IL-2 and reduces SLE disease activity Petri MA, Arthritis Rheum. 2004 Sep;50(9):2858-68 Allows reduction in steroid dose. Petri MA, Arthritis Rheum. 2002 Jul;46(7):1820-9. Suppresses IL-10, a cytokine that increases autoantibody production in Lupus Chang DM, Ann Rheum Dis. 2004 Dec;63(12):1623-6. Improves well-being, sexuality, and cognition in women with Lupus or adrenal insufficiency Arlt W, Endocr Res. 2000 Nov;26(4):505-11. Nordmark G, Autoimmunity. 2005 Nov;38(7):531-40.

40. TNF-α and Adrenal Hormones TNF-α is an inflammatory cytokine that is elevated in autoimmune diseases. Better cortisol and DHEAS levels suppress TNF-α levels. TNF-α suppresses cortisol and DHEAS production→more inflammation, vicious cycle Anti-TNF-α drugs increase cortisol and DHEAS levels. Straub RH, Arthritis Rheum. 2008 Apr;58(4):976-84. Arthritis Rheum. 2003 Jun;48(6):1504-12, Ernestam S, J Rheumatol. 2007 Jul;34(7):1451-8.

41. Steroids in Rheumatic Disease Doctors view steroids as drugs, not hormones Long-term , low-dose treatment is actually hormone replacement (prednisone ≤7.5mg, Medrol ≤6mg) Low-dose prednisone (≤7.5mg/d) generally safe Da Silva JA, Ann Rheum Dis. 2006 Mar;65(3):285-93. Short-term, high dose treatment is pharmacological—for disease suppression. Hydrocortisone preferred, but short-acting, long-acting tablets under development Prednisone/prednisolone are closest in structure to cortisol, but have more negative effects.

42. DHEA in Rheumatic Diseases Taking oral steroids drastically reduces DHEA levels DHEA prevents “side effects” of steroids and reduces pain and inflammation All patients on steroids should be given DHEA. Straub RH, Z Rheumatol. 2000;59 Suppl 2:II/108-18. Best taken sublingually 2x/day, 12.5-25mg/day for women, 25 to 50mg/day for men. (Life Extension, dissolve-in-the-mouth 25mg tablets) Women may experience pimples, oily skin initially Start with low dose and work up gradually

43. Vitamin D A powerful hormone with anti-inflammatory effects Vit. D levels low in SLE patients, contributing to inflammation. Supplementation improves immune system abnormalities. Cutolo M, Lupus 2008;17(1):6-10. Kamen D, Aranow C. CurrOpinRheumatol. 2008 Sep;20(5):532-7. Higher Vit. D levels assoc. with lower TNF-α. Peterson CA, J Inflamm (Lond). 2008 Jul 24;5:10. Levels must be >30ng/ml for significant benefit Optimal levels 55-70ng/ml, usually requires 4000IU Vit. D3 daily.

44. Fish Oils—Omega-3 Fatty Acids Decrease the production of inflammatory eicosanoids, cytokines, and reactive oxygen species. Calder PC. Am J ClinNutr. 2006 Jun;83(6 Suppl):1505S-1519S. Reduce TNF- α levels. Fetterman JW Jr, Am J Health Syst Pharm. 2009 Jul 1;66(13):1169-79. Improve SLE disease activity and have cardiovascular benefits. Duffy EM, J Rheumatol. 2004 Aug;31(8):1551-6. Wright SA, Ann Rheum Dis. 2008 Jun;67(6):841-8. Proven to be beneficial in Rheumatoid Arthritis. Proudman SM, Rheum DisClin North Am. 2008 May;34(2):469-79. Dose: 1500 to 3000mg EPA +DHA daily

45. Sex Hormones in Autoimmune Diseases Low testosterone and progesterone levels seen in men and women with RA. Testosterone and progesterone have immunosupressive effects. Wilder RL. J Rheumatol Suppl. 1996 Mar;44:10-2. Schust DJ, Hum Reprod. 1996 May;11(5):980-5. RA and MS improve during pregnancy worsen during breast feeding (low progesterone/estrogen). Higher testosterone levels helpful in autoimmune diseases that affect women>men Estrogen and testosterone beneficial in MS. Gold SM, Prog Brain Res. 2009;175:239-51.

46. 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)

47. 30 Speroff L, Fritz M Clinical Gynecologic Endocrinology and Fertility, 7th Ed.

48. 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.

49. 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. Dincreases bone densitybetter than bisphosphonatesand preserves normal bone remodeling • Women on prednisone 5 to 15mg/day gained bone mass with either estradiol/progesterone or DHEA replacement. Lukert BP, J Bone Miner Res. 1992 Sep;7(9):1063-9. Mease PJ, J Rheumatol. 2005 Apr;32(4):616-21.

50. Estradiol Restoration • Eliminates hot flashes, restores sleep • Restores cognitive function and mood • Maintains thickness, fullness of skin and hair • Maintains genital/pelvic health-helps with vaginal lubrication, incontinence, bladder infections • Protects against colon cancer and macular degeneration • Protects against dementia • Prevents atherosclerosis, hypertension • Improves insulin sensitivity—prevents diabetes • Prevents osteoporosis and osteoarthritis • Must be accompanied by progesterone