Bioidentical Hormone Restoration

Best Medical Practice

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Hormones

Neuro-endocrine-immune system

Travel via blood to tissues

Control cells’ metabolism, functions

The most powerful molecules in biology

Optimal levels Essential for Health

Bioidentical: Same molecular structure as our natural hormones

Cortisol, DHEA,Aldosterone, Pregnenolone

Estradiol, ProgesteroneTestosterone

Testosterone

InsulinAdrenalin

T4, T3

GH, FSH, LH,TSH, and ACTH

control other glands

CRH, TRH, etc. control pituitary

Bioidentical Hormones are NOT DrugsNo side effects, interactions, or reactionsNon-toxic, inherently safe Proper fit in receptors, easily eliminatedBlood levels can be monitored Restore health vs. modify diseaseThe only potential problems:

Excessive doseLack of balance with other hormonesUnphysiological delivery: route, timing, etc.

Hormone Ignorance:The Tyranny of the Lab Report

Reference Range=95% of the populationNeither a normal nor an optimal range!Disease/No Disease instead of ContinuumMale free testosterone: 35-155 5x!Female testosterone: 2-45 22x!

Free T4: 0.6-1.8 3x!AM serum cortisol: 5-25 5x!Within RR: No diagnosis; pharmaceuticalsBelow RR (<97.5%): replace to within-RR

Hypometabolism—Thyroid and Cortisol InsufficienciesThyroid sets throttle (metabolic rate)Cortisol delivers the fuel (glucose)Optimal levels of both are required for healthEven mild deficienciesreduced cellular metabolismfatigue, brain dysfunction, depression, pain, and diseaseUsual lab tests and ranges (TSH, AM cortisol) are insensitiveUnderdiagnosis, Undertreatment

Mild-to-Moderate Cortisol Insufficiency

Partial Secondary Insufficiency: brain (H-P) fails to maintain levels

Fatigue, depression, pain, allergies, inflammation, hypoglycemia, low blood pressure, nausea, insomnia

Clue: Prednisone improves mood, energy

Diagnosis: saliva testing reveals free cortisol levels 4 times during the day

Normal Saliva Cortisol Profile

Common Dysfunctional Pattern

Cortisol Insufficiency

Addison’s Disease

Cortisol Restoration

Mild insufficiency—improves with stress, rest, and nutrients

Moderate-to-severe insufficiency—requires cortisol restorationLow physiological doses are safe40 years’ experience: see Dr. Jeffries’ Safe Uses of Cortisol

Thyroid InsufficiencyMental fogginessFatigue, depression, anxietyCold extremities, low body temperatureAches and painsThinning hair, dry skin Weight gainConstipationPuffy ankles and faceElevated cholesterol

Continuum: Higher Thyroid Hormone Levels within the RRs:

Reduced risk of severe atherosclerosis by 50% Clin Cardiol. 2003

Dec;26(12):569-73

Lower cardiac risk factors: cholesterol, triglycerides, C-reactive protein, homocysteine and lipoprotein(a)Lower blood pressure, dilates arteriesReduced tendency to form blood clotsRelieve depressionReduced weight, increased weight loss

The Increase in Fatigue, Fibromyalgia, and Depression

Pre-1970s: Dessicated thyroid extract: T2, T3 and T4 dosed to eliminate symptoms

Post-1970s: T4-only to “normalize” TSH TSH: Patient’s doses lowered by 30-50%

TSH “normalizing” T4 doselow free T3, persistence of symptoms, weight gain Symptomatic persons with within-RR labs often improve with T3/T4 optimization

Cortisol and Thyroid Optimization

Any Questions?

The Big Controversy

What do we do about hormones lost to normal

aging?

DHEA—The Most Abundant Steroid Hormone In our BodiesPrecursor of testosterone and estradiolLower levels assoc. with risk of death, diseaseAnabolic—builds tissues, improves immunityReduces pain by increasing endorphinsAnti-inflammatory—approved for SLEImproves immune system functionAnti-atherosclerotic—may prevent heart disease Reduces platelet aggregation Ann N Y Acad Sci. 1995 Dec 29;774:281-90

Anti-cancer effects in animal studies

DHEA-S Levels with AgeAdrenopause

Growth Hormone (GH) Somatopause

Clinical Chemistry 48, No. 12, 2002

Free T3

Endocr Rev. 1995 Dec;16(6):686-715

Thyropause

Male Andropause—Testosterone

Baltimore Longitudinal Study of Aging (BLSA). Harman et al., 2001

Andropause vs. Menopause

pg/ml

DHEA-S 5,000,000pg/ml Cortisol 100,000 pg/ml!

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1 0 0 0

2 0 0 0

3 0 0 0

4 0 0 0

5 0 0 0

6 0 0 0

7 0 0 0

8 0 0 0

Y o u n g O l d Y o u n g O l d

T

P

E

♀ ♀♂ ♂

Men WomenProgesterone

averageTestosterone

Estradiol

Conventional View of Aging

The loss of hormones is adaptive

Higher levels cause heart attacks, cancers of the breast and prostate

Fits Pharmaceutical Agenda: Don’t restore hormone levels: Take drugs for all problems caused by loss of hormones.

Gonadal Steroids:Not Just “Sex Hormones”

Estradiol, Progesterone, TestosteroneEssential to all tissues in both sexes! Brain—Improve function, protect against Alzheimer’s Dz.Immune System Heart and blood vessel healthBlood lipids, clotting Connective tissues—skin, muscle, bone

Menopause: Estradiol DeficiencyHot flashesFatigue, aches and painsDry eyes and vagina, genital atrophyLoss of libido BP, LDL cholesterol, heart diseaseAtrophy of skin and bone (osteoporosis)Poor memory, depression, insomnia’d risk of Alzheimer’s Disease

Estrogen Replacement Prevents Alzheimer’s Disease

Zandi PP, et al., Cache County Study. JAMA. 2002 Nov 6;288(17):2123-9.

Women Killers

Cardiovascular disease (CVD), breast cancer and osteoporosis are rare in premenopausal women They begin in perimenopause when progesterone and testosterone levels are lower.After menopause (loss of estradiol) osteoporosis accelerates and CVD rises faster than in menHigher risk of CVD than men after 65Higher mortality after 70Surgical menopause 2-7x risk of heart attacks

Engl J Med 1987 Apr 30;316(18):1105-10 Am J Obstet Gynecol. 1981 Jan;139(1):47-51.

Menopause and Cardiovascular Disease

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

Osteoporosis

In menopause 5% of bone mass is lost each year for first 5 years=25%50% of women >65 yrs. old have spinal compression fractures14% lifetime risk of hip fracture for 50 yr.old woman, 30% for 80 yr. old.

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

Male Andropause:“Just Gettin’ Old”

Testosterone levels decline slowly Fatigue, passivity and moodinessReduced mental functionLoss of muscle and bone mass; fatLoss of libido and spontaneous morning erectionsBP, blood sugar, heart disease, Alzheimer’s Disease, autoimmune dz.

Hormone Loss with Aging is BAD for UsAging is an auto-destruct program.Starts around age 25! Glands and control systems deteriorate weight, BP, diabetes, heart attacks, autoimmune diseases, osteoporosis, etc.

Occur years after hormone losses begin Occur more often in those with lower levels

Hormone restoration helps prevent these diseases, and does not cause disease.

Hormones and Aging

Any Questions?

Coming up: Male and Female Hormone Replacement

Testosterone is Man’s Best FriendImproves mood and sociability

Improves energy Improves cognition, protects against Alzheimer’s disease Neurology. 2004 Jan 27;62(2):188-93

Improves libido and erectile function

Increases muscle and bone mass

Reduces abdominal fat, improves insulin sensitivity, lowers blood pressure--counteracts metabolic syndrome X

Testosterone is Good for your HeartLow testosterone levels associated 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

T dilates coronary arteriesT improves endothelial functionT increases heart muscle size, strengthT decreases fibrinogen levels—prevents blood clots Endocr Res. 2005;31(4):335-44

Testosterone Does Not Cause Prostate CancerTestosterone promotes prostate growth to a point. Castration slows prostate cancer growth temporarily.Higher T levels don’t increase risk of prostate cancer.Testosterone restoration does not increase the risk of prostate cancer.Low T levels associated with more aggressive prostate cancers.

Where’s the Beef?

“These results argue against an increased risk of prostate cancer with testosterone replacement therapy.”

Testosterone replacement therapy and prostate risks: where's the beef? Morgentaler A. Can J Urol. 2006 Feb;13 Suppl 1:40-3

Testosterone For Men

Any Questions?

Coming up: Estradiol, Progesterone, and Testosterone for Women

Female Endocrinology:Balance in a Complex System

Reproduction makes special demands on the female body

Breasts, uterus and ovaries undergo a monthly cycle of proliferation and breakdown

No similar process in males

Defects in this cycle can lead to cancers and other medical disorders.

Estrogen—Progesterone Complementarity in Women

Estrogen promotes tissue proliferation and growth which can lead to cancerProgesterone inactivates estrogen, stops proliferation and promotes differentiationDifferentiated cells can’t become cancersHigh average progesterone/estrogen ratio prevents breast, uterine cancers

Normal Cycle and Balance

Menstrual Cycle

Ovulation

Perimenopause Luteal Insufficiency=Estrogen Dominance

Menstrual Cycle

Inadequate Luteal Phaseshorter periods, early spotting

Ovulation

PerimenopauseAnovulation with Estrogen Dominance

Menstrual Cycle

High estrogen, low progesterone

’d risk of cancer

Menopause

Estrogen and Progesterone Deficiency

Estrogen Dominance: Progesterone DeficiencyAllergies

Autoimmune disease

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/painful menses

Migraines

Seizures

Endometriosis

Estradiol for Menopause

Eliminates hot flashes

Eliminates dryness of eyes and vagina

Improves memory and mental function

Maintains skin, bones

Reduces risk of heart disease

Reduces risk of Alzheimer’s disease

Reduces blood sugar, blood pressure

Improves energy, reduces aches

Testosterone for Women

Female testosterone levels decline 50% between age 20 and 45. Menopause. 2003 Sep-Oct;10(5):390-8

Improves energy, moodImproves libido, sexual sensationIncreases muscle strength, stamina Increases bone density J Reprod Med. 1999 Dec;44(12):1012-20

Probably decreases risk of heart attack Womens Health. 1998 Sep;7(7):825-9

Osteoporosis

A hormone deficiency disease (including Vit.D)Estradiol reduces resorption of old boneTestosterone, progesterone, DHEA, and GH build new bone J Clin Endo Metab. 1996; 81:37-43 J Reprod Med. 1999 Dec;44(12):1012-20

Combined hormone restoration increases bone density much better than Fosamax and preserves normal bone remodeling

Perimenopause and Menopause and Their

Disorders

Any Questions?

Coming:The Problems with “HRT”:

Breast Cancer, Strokes, and Heart Attacks

So Why is Everyone Saying that Hormone Replacement

is Dangerous?

Q: What “hormones”? Given how?

Bioidentical Human Steroid Hormones

Testosterone Estradiol

Progesterone Cortisol

DHEA

Do Not Substitute

ComplexInteractive

System

“HRT” has Always been Hormone Substitution!

Pregnant mare’s urine: Premarin in 1942

Progesterone synthesized in 1942, altered to

make patentable “progestins”

“HRT” = pills containing alien molecules

Drug Co.s pushed doctors to use hormone

substitutes and ignore bioidenticals!

Premarin: Close, but Not Human

Estradiol-17β Dihydroequilin-17β

CEE contains at least 10 estrogens, only 3 are found in humans. CEE is similar to human estrogens and has similar long-term benefits.

Human Horse

Estradiol Ethinyl Estradiol

EE cannot be inactivated by normal oxidation!EE does not interact with estrogen receptor !

Oral EE is more thrombogenic than Premarin or estradiol

Birth Control Pills: Unnatural

Acetylene

The Problems with Oral Estrogens

First-pass effect on the liverIGF-1 (growth hormone), SHBG, CRPclotting factorsblood clots and strokes Transdermal estradiol has none of these effects and does not cause blood clots! Circulation. 2007 Feb 20;115(7):840-5

The BIG Problem with HRT: Progestins

Progesterone MPA (Provera) Megestrol

Many Doctors Do not Know the Difference!

Progesterone Provera

• Maintains pregnancy Causes birth defects• Improves mood Can cause depression• Improves sleep Insomnia, irritability• Diuretic Fluid retention• Lowers blood sugar Raises blood sugar• Maintains estradiol-induced Reduces estradiol-induced arterial

dilation arterial dilation• Improves lipid profile Worsens lipid profile• Prevents heart attacks Causes heart attacks• Reduces estrogenic breast Increases estrogenic breast

stimulation stimulation• Decreases risk of breast cancer Increases risk of breast cancer

Scientific studies show that:

Progestin Zoo

Kuhl, Climacteric 2005;8(Suppl 1)

Progesterone

Provera

2002 WHI Study: “HRT” is Dangerous!>30 studies showed long term protection against heart disease with Premarin WHI: 60-70 y.o.’s started on “HRT” Premarin caused adverse effects in the first year (blood clots and strokes). Adding Provera (Prempro) caused many more adverse effects (breast cancers and heart attacks). Large increase in dementia—probably vascular in origin

Progestins cause Atherosclerosis and Clotting“In both peripheral and cerebral vasculature (of live animals), synthetic progestins caused endothelial disruption, accumulation of monocytes in the vessel wall, platelet activation and clot formation, which are early events in atherosclerosis, inflammation and thrombosis. Natural progesterone or estrogens did not show such toxicity.” Thomas T, Rhodin J, Clark L, Garces A. Progestins initiate adverse events of menopausal estrogen therapy. Climacteric. 2003 Dec;6(4):293-301

Cardiovascular DiseaseMy Conclusions:

Youthful levels of steroid hormones protective.

Estradiol and progesterone are more protective than male testosterone

Oral, not transdermal, estradiol increases the risk of thrombi and strokes

Some progestins cause endothelial inflammation, atherosclerosis, and clotting.

Best Preventative Strategy—maintain youthful levels of natural sex-steroid hormones!

But won’t that increase the risk of breast cancer?

Breast Cancer: Verdict: Progesterone is Innocent

“The balance of the in vivo evidence is that progesterone does not have a cancer-promoting effect on breast tissue.”Progestins and progesterone in hormone replacement therapy and the risk of breast cancer. J Steroid Biochem Mol Biol. 2005 Jul;96(2):95-108.

That’s the conservative interpretation of the evidence!

In Fact: Progesterone Prevents Breast Cancer

E3N-EPIC Cohort study Int J Cancer. 2005 Apr 10;114(3):448-54

55,000 women8 years f/uc/w WHI--16,000, 6 yr. f/u

TD-E2=Transdermal Estradiol

No Hormones

More Progesterone=Less Breast Cancer

ORDET Study: Int. J. Cancer 112 (2004) (2), pp. 312–318. See also Cancer Causes Control. 2004 Feb;15(1):45-53.

6,000 women5 yr. F/U

More Progesterone

Less Breast Cancer

More Evidence

Estradiol cream applied to the breast induces proliferation, adding progesterone reduces proliferation to baseline Fertil Steril 1995; 63:785-91

Premenopausal women with low P levels had 5.4 times greater risk of early breast cancer

Am J Epidem 1981; 114:209-17

Breast cancer victims have signs of progesterone resistance Br J Obstet Gynaecol. 1998 Mar;105(3):345-51

Testosterone Prevents Breast Cancer in Estradiol-Replete Women

Testosterone opposes estradiol-induced breast stimulation. Menopause. 2003 Jul-Aug;10(4):292-8

Endocr Rev. 2004 Jun;25(3):374-88 FASEB J. 2000 Sep;14(12):1725-30

Addition of testosterone to estrogen/progestin reduces breast cancer incidence to baseline.

Menopause. 2004 Sep-Oct;11(5):531-5

In vitro: Testosterone and DHT inhibit growth of breast cancer cell lines. Gynecol Endocrinol 2002; 16: 113-120

Testosterone is an effective treatment for breast cancer. Cancer Detect Prev. 1992;16(1):31-8(review)

Breast CancerMy Conclusions:

Unopposed estradiol promotes breast cancer.

Some progestins promote breast cancer.

Progesterone and testosterone help prevent breast cancer.

Estradiol restoration is safe if accompanied by sufficient progesterone and testosterone to restore youthful balance.

Hormone Restoration for WomenKeeping a woman premenopausal by restoring natural hormones in the most physiological way and in natural balance should be considered beneficial until proven otherwise.

Since perimenopausal and menopausal hormone deficiencies are known to be harmful and to diminish quality of life, those who would deny women the restoration of their hormones have the burden of proof that there is harm that outweighs the benefits.

What Your OB/GYN is ToldACOG NEWS RELEASE October 31, 2005

The American College of Obstetricians and GynecologistsA private organization funded by drug companies

Washington, DC -- There is no scientific evidence to support claims of increased efficacy or safety for individualized estrogen or progesterone regimens prepared by compounding pharmacies,…all of them should be considered to have the same safety issues as those hormone products that are approved by the FDA (including Premarin, Provera, BCPs)and may also have additional risks unique to the compounding process… Furthermore, hormone therapy does not belong to a class of drugs with an indication for individualized dosing…

“HRT”, Breast Cancer, Strokes, and Heart Attacks

Any Questions?

What Else Can Hormone Restoration Help?Infertility, PMS, heavy bleeding

Headaches and insomnia—almost always

Heart failure, angina

Mental disorders

Autoimmune diseases (SLE, rheumatoid arthritis, ulcerative colitis, Crohn’s, etc.)

Intra-abdominal fat (pot belly)

Allergies, skin diseases

Every disease and disorder!

Why Use Compounded Hormones?FAR less expensive than FDA-approved bioidentical products ($10-30 vs. $200/mo.)

More convenient

Individualized

Physiological delivery—progesterone

Reliable: Compounding pharmacies are PCCA members: standardized materials and procedures (http://www.pccarx.com)

Where Do They Come From?Chemically synthesized from diosgenin (wild Mexican yams and soy)

Compounding pharmacists prepare creams, tablets, etc. using USP-certified bulk hormones

Doing HRPhysician fee—according to time

Forms available online

Initial visit: order blood tests, saliva cortisol

F/U visits: Review results—prescribe—retest

F/U testing: blood, not saliva

Office visit every 6 months, test only as needed.

Telephone Consults—same hourly rate

E-mail—No charge for brief responses

CostsPhysician time only as required--first year ~$200-$500; then <$200/yr. No Medicare or insurance billing; may submit claim for recognized diagnosis Hormones—$10 for 1 hormone, to $80/month for all, ±covered by insuranceDiurnal salivary cortisol test—$120Blood tests—insurance pays, lab kits $170-$220, Saliva/blood kit—$299 Out-of-pocket expenses tax-deductible

For More Information

The Miracle of Natural Hormones David Brownstein, MD How to Achieve Healthy Aging—Look, Live, and Feel Fantastic After 40 Neal Rouzier, MDThe Hormone Solution—Stay Younger Longer Thierry Hertoghe, MD Life Extension Foundation: www.lef.orgHormonerestoration.com (articles, abstracts)Henry@hormonerestoration.comOffice: 570-836-0359