Bioidentical Hormone Restoration Best Medical Practice

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

2. Topics • Bioidentical Hormones are not Drugs • Hormone Loss with Age • The Problem with Reference Ranges • Cortisol and Thyroid Deficiencies • Testosterone for Men and Women • Estradiol and Progesterone for Menopause • Progesterone prevents Breast Cancer • Pharmaceutical Hormone Substitution • 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! • Male hypogonadism: bioidentical testosterone • 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. Saliva Cortisol Levels with Age 20 30 40 50 60 70 Age (Year) Ahn RS, Yonsei Med J. 2007 Jun 30;48(3):379-88.

15. 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 (!?!)

16. 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! • Aging, and the loss of hormones with age are both natural and bad for you! • Studies of balanced hormone restoration show the expected youthful benefits and improvements in these disorders--and no proof of harm!!

17. 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

18. Reference Range Endocrinology Upper Limit Lower Limit 95% population range Hormone Effect “Everything is Normal” Too much “Disease” Too Little “Disease” But Hormone Effects vary continuously with concentration! Bottom 2.5% Top 2.5% Hormone Level

19. Restorative Endocrinology Tighter range based on young healthy persons and on physiological research Individualized Diagnosis and Treatment Hormone Effect Optimal?? Hormone Level

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 all disease • Essential to our quality of Life!

21. Fatigue, Depression, PainThyroid and Cortisol Deficiencies • Thyroid sets throttle, cortisol delivers the fuel • Our health and quality of life require optimal levels of both hormones! • Women much more affected than men. • Conventional tests and ranges are insensitive. • Irrational fear ofthyroidandcortisol supplementation • Underdiagnosed, undertreated—Docs prescribe pharmaceuticals instead(SSRIs, amphetamines, anti-seizure drugs, anti-psychotics, sedatives, etc.)

22. Cortisol Deficiency Fatigue --“Adrenal Fatigue” Depression Aches & pains Anxiety, irritability Insomnia—frequent awakening Severe PMS Hypoglycemia Allergies Can’t cope with stress, all symptoms worsen Variability: good days, bad days

23. Cortisol Deficiency • Much more common in women than in men • Explains greater incidence of chronic fatigue, pain, depression, and autoimmune diseases in women • 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(near total adrenal gland failure)

24. Cortisol Deficiency ZRT Laboratory www.zrtlab.com

25. 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

26. Restorative Thyroidology • Doctors often order only a TSH test—indirect,fallible test. Detects only one kind of hypothyroidism. • Must measure thyroid hormones: free T4 and free T3 • IF symptoms and suboptimal levels—may benefit from thyroid optimization. • Levothyroxine therapy to “normalize” the TSH can result in lower free T3 levels, persistence of symptoms • Give T4 plus T3 (Armour, levothyroxine+ Cytomel) • Adjust dose according to symptomsand free T4 and free T3 levels, not the TSH test.

27. 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)

28. Male Andropause • Testosterone levels declineslowlyin men—“just getting old.” • Fatigue, reduced mental function • Passivity and moodiness—loss of drive and ambition • Loss of muscle, increased abdominal fat • Increased blood sugar and blood pressure • Loss of libido, spontaneous erections, and eventually erectile function.

29. Testosterone Restoration for Men • Improves mood and sociability • Restores energy and ambition • Improves cognition, probably protects against Alzheimer’s disease • Increases libido and sexual performance • Increases muscle and bone mass • Reduces abdominal fat, improves insulin sensitivity, lowers blood pressure--counteracts metabolic syndrome (Syndrome X) Haider A, Exp ClinEndocrinol Diabetes. 2009

30. Testosterone and the Heart • Lowtestosterone levels correlate with coronary artery disease and stroke Arterioscler Thromb. 1994; 14:701-706 Eur Heart J 2000; 21; 890–4 Int J Cardiol. 1998 Jan 31;63(2):161-4 Arterioscler Thromb Vasc Biol. 1996 Jun;16(6):749-54 • Testosteronedilates coronary arteries—improves angina • T increases heart muscle size, strength • Tdecreases fibrinogen levels—prevents blood clots Endocr Res. 2005;31(4):335-44

31. Testosterone and the Prostate • Lowertestosterone levels increase the risk of prostate cancer. Endogenous sex hormones and prostate cancer: a collaborative analysis of 18 prospective studies. J Natl Cancer Inst. 2008 Feb 6;100(3):170-83, also Morgenthaler A, Urology 2006;68:1263-7 • Testosterone supplementation does not increase the risk of prostate cancer. Morgentaler A, Testosterone replacement therapy and prostate risks: where's the beef? Can J Urol. 2006 Feb;13 Suppl 1:40-3 • Lowtestosterone associated with more aggressiveprostate cancers Slater S, Drugs Aging 2000 Dec;17(6):431-9 • Testosterone is a prostate growth factor, but does not promote prostate cancer. • Prostate cancer growth can be temporarily slowed only by eliminating testosterone from the body. Read Testosterone for Life, Dr. Abraham Morgentaler

32. Female Andropause • Young woman’s free testosterone level is 2x her free estradiol • DHEASdeclines with age—main source of androgen effect in women • Female testosterone levels decline 50% between age 20 and 45. • Oral estrogensand birth control pillsreduce free testosterone and DHEAS levels

33. Testosterone for Women • Improves energy and mood • Improves sexual desire and sensation • Increases muscle and tissue strength • With estradiol, increases bone density J Reprod Med. 1999 Dec;44(12):1012-20 • Probably decreases risk of heart attack J Womens Health. 1998 Sep;7(7):825-9 • Opposes estradiol-induced breast stimulation and reduces risk of breast cancer Menopause. 2003 Jul-Aug;10(4):292-8, Endocr Rev. 2004 Jun;25(3):374-88 Menopause. 2004 Sep-Oct;11(5):531-5, FASEB J. 2000 Sep;14(12):1725-30

34. DHEA • Most abundant steroid hormone; yet ignored • Cells make testosteroneand estradiol from it • Levels decline with age, stress and disease • Lower levels assoc. with disease, mortality • Anabolic—builds tissues, improves immunity • Improves sexual function • Anti-cortisol effect, reduces abdominal fat • Reduces pain—restores natural endorphins • Reduces inflammation (IL-6, TNF-, IL-2) • Anti-atherosclerotic, prevents oxidation of LDL • Improvesfertility in older women-egg# and quality Barad D, Brill H, Gleicher N. Update on the use of dehydroepiandrosterone supplementation among women with diminished ovarian function. J Assist Reprod Genet. 2007 Dec;24(12):629-34.

35. Female Endocrinology • Nature makes special demands on the female body for reproduction. • 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. Estradiol • Angel of Life—stimulates growth of female organs necessary for reproduction; maintains female health and quality of life • Angel of Death—promotes cancer and other medical disorders– if notbalancedwith progesterone andandrogens

37. Allergies Autoimmune diseases Anxiety, moodiness Insomnia PMS Depression Bloating, fluid retention Fibrocystic breasts Uterine fibroids Heavy periods Endometriosis Breast cancer Ovarian cancer Uterine cancer Thyroid dysfunction Gallbladder disease Migraines Seizures Estrogen Dominance Progesteronerestoration is the only effective treatment for estrogen dominance

38. Historical Perspective • Throughout human history, women were usually pregnant or breast feeding • Pregnancy=high progesterone • Breastfeeding=low estrogen • Both states are protectiveagainst breast cancer. • Historically— 4 years of cycling on average; Now — 35 years of cycling • Cycling Much greater risk of estrogen dominance (progesterone deficiency)

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

40. Normal Progesterone Dominance Ovulation Ovulation Menstrual Cycle

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

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

43. Menopause Estradiol and Progesterone Deficiency

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

45. 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.

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

47. Estradiol vs. Cardiovascular Disease • Prevents the oxidation of LDL • Improves lipid profile • Reduces lipoprotein (a) • Reduces blood pressure • Improves endothelial function • Reduces plaque formation • Improves insulin sensitivity

48. 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…

49. 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.

50. 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.