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Hormone Balance & Health

Rebecca L. Glaser M.D., F.A.C.S.

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www.hormonebalance.org

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Conventional Medicine

• The fifth leading cause of death in the United States is prescription medications given in the correct dose

• 2.2 million people per year have an ‘in hospital’ adverse reaction to drugs

• 7.5 million unnecessary medical and surgical procedures are performed per year

• Total number of deaths caused by conventional medicine is 800,000 per year

• Overmedicating seniors– The average senior receives 20 new prescriptions per year– Common side effects include confusion, dizziness, apathy,

problems with balance, memory and sedation

Balance

• Hormones, in balance, are critical to health and disease prevention

• Hormones, in balance, protect against breast cancer

• Hormones out of balance, may contribute to an increased risk of breast cancer

• Synthetic chemical hormones (Prempro, Provera,

Estratest, Methyl testosterone) increase the risk of breast cancer

• Diet and lifestyle are critical to hormone balance and overall health

• Stress affects hormone balance

Conventional HRTWomen's Health Initiative Trial

• Prempro, Premphase, Provera• 41% increase in strokes• 29% increase in heart attacks• 26% increase in breast cancer• Twice the rate of blood clots• Possible contributor to Alzheimer's vs.• Estrogen alone arm (Premarin)

– No increase in breast cancer

Synthetic (Chemical) Progestins

• Increase the risk of breast cancer• Increase the risk of heart disease

– Coronary vasoconstrictor– Negate the beneficial effects of estrogen

• Fluid retention and edema• Increase incidence of blood clots

– Venous thrombosis – Pulmonary embolism– Stroke

• Cause weight gain

Synthetic Progestins (cont.)

• Negative effect on mood, mental status and well being

• Increase the risk of dementia• Headaches• Birth defects• Hair loss • Acne, skin discoloration• Patentable…profitable

Progesterone

• Does not increase the risk of breast cancer• Does not have toxic effects on the vascular

system– Does not negate the beneficial effects of estrogen– Vasodilator

• Does not adversely affect lipids• Neuro-protective• Necessary to maintain pregnancy

Synthetic chemical v.s. hormone

Provera

is not

Progesterone

So, how can they say…

• “But there's no evidence that bioidenticals are any safer and they may even have other risks”

Dr. Robert Vigersky AMA

“…the risks and benefits of all estrogens and all progesterones are equivalent.”

Rossouw 07 WHI branch of the NIH

Million Women Study 1,084,110

• No difference between ‘estrogen formulations’– Topical vs. oral, Estradiol vs. Premarin vs. Ethinyl-estradiol– BUT Vaginal estrogen therapy (estriol) did NOT increase the

risk of breast cancer RR 0.67

• No difference between synthetic chemical ‘progestins’– BUT Progesterone, the hormone, was not used in the study

2003 Lancet

Fournier 07 (BCRT)

• ‘E3N’ French Prospective Cohort Study 1990– 98,995 women 40-65 risk factors for cancer

• Results on >80,000 post menopausal women – Estrogen alone increased the risk of breast cancer– No difference between oral estrogen (RR 1.32)

and percutaneous/TD estrogen (RR 1.28)• Oral 13/3598 Non-oral 56/14,826

– Progesterone (RR 1.0) did not increase the risk of breast cancer vs. synthetic progestins (RR 1.69)

– Oral or vaginal estriol (RR 0.7) or Promestriene did not increase the risk of breast cancer (RR 0.9)

Bioidentical (Human) Hormones

• Are chemically converted from yams or soy and are identical in composition to human hormones

• Are not patentable• Have been used in Europe (and the US) for over 60

years• Have been extensively researched• Estradiol, progesterone, and testosterone are FDA

approved– FDA approval is required for implanted medical devises and

medications which are to be marketed to the public

• In balance, they do NOT have the same risks as CHRT

Patented/Conventional Bio-identical Hormones

• Prometrium• Crinone, Utrogestin• Estrace, Climera• Estraderm, Vivelle• Estrogel, Sandrena• Androgel, Testim• Androderm• ESTring, Menoring,

Femring• Vagifem • Ovestin (OTC, Europe)• Ovesterin (not Synapause)

• Cortef• Saizon, Genotropin• Cytomel (T3)• Synthroid (T4)• Pellets (Australia, South

Africa, UK and US)

– Fused testosterone – Riselle (E2 25 mg, Organon)

– Testopel

Bio-identical Hormones

• Compounded– Estrone– Estradiol– Estriol– Progesterone– Testosterone– DHEA– Cortisol– HGH (reconstituted)

– T3– T4

• Methods of delivery– Oral– Topical

• Creams

• Gels

– Sublingual drops, troches– Vaginal/mucous

membrane• Cream

• Suppository

– Pellets– SQ injection

Estrogens

• Estrone (E1)……SHBG metabolites• Estradiol (E2)…..SHBG metabolites• Estriol (E3)

– Bi-Estrogen – Used in Europe both orally and vaginally (OTC)

• Data on vaginal and oral use – Absorption, efficacy, side effects

• Vaginal estriol does not stimulate the uterine lining or breast tissue

• Vaginal estriol does NOT increase the risk of breast cancer

• Does not cause weight gain or fluid retention

• Vaginal estriol increases bone density

• Lack of data on topical use (skin)

Balance

Balance vs. Estrogen Dominance

• Estrogen dominance is a condition in which there is too much estrogen, especially the stronger estrogens, insulin and chemical estrogens in proportion to the balancing phyto-nutrients, progesterone and testosterone.

Estrogen

• Estrogen dominance (diet & lifestyle)– Weight gain, fluid retention– Anxiety, irritability, depression, fatigue– Insulin resistance– Breast pain, FCD, endometriosis, fibroids– Increased risk of breast and uterine cancer

• Estrogen deficiency– Breast loose fullness– Low body fat, cannot maintain weight– (Hot flashes, insomnia, bone loss, depression etc.

see testosterone deficiency)

Prevention of Estrogen Dominance

• Balanced hormone therapy– Testosterone– Progesterone (NOT progestins)

• Stress Reduction• Get rid of chemicals, pesticides etc.• Improved diet, reduce carbohydrates, whole

foods– Lower insulin levels

• Exercise• Fiber / supplements / flaxseed

Hormone Deficiency

• Hot flashes, night sweats• Vaginal dryness, urgency, incontinence• Breast loose fullness (estrogen)

• Insomnia• Heart palpitations• Bone loss, aches, pains• Thinning skin, hair loss• Heart disease• Brain deterioration, memory loss

Progesterone Excess

• Sleepiness– Metabolites from oral progesterone– Hepatic overload

• Breast tenderness• Mild depression• Bloating• Water retention

Testosterone Deficiency

• Levels decline with age in both men and women– A 40 yo woman has half the testosterone as a 20 yo

• Decreased libido, erectile dysfunction• Decreased energy, fatigue, lack of endurance• Depression• Lack of motivation, self confidence, insecure• Anxiety, emotional lability, overwhelmed • Sleep disturbances, insomnia, sleep apnea• Decreased concentration, memory loss

Testosterone deficiency

• Bone loss, muscle mass loss • Increased fat • Aches, pains, decreased coordination• Hot flashes, vaginal dryness, incontinence • Dry, thinning skin, wrinkles, hair loss• Alzeheimer’s and Parkinson’s• Increased heart disease • Diabetes, metabolic syndrome• Anemia, poor immune function

Methyl-testosterone

is not

Testosterone

Archives of Internal Medicine

• Oral, synthetic, chemical methyl testosterone increased the risk of breast cancer– Estratest

• Non-oral, testosterone (hormone) prevents the stimulation of breast tissue and lowers the risk of breast cancer

Cortisol

• Produced in the adrenal gland from progesterone and androstenedione

• It is the body’s major defense against stress, including infections & injuries

• Natural anti-inflammatory hormone• Critical for function of the

immune system• Involved in blood sugar

regulation

Cortisol Deficiency

• Fatigue, immune dysfunction– Infections, pneumonia

• Sugar cravings, salt cravings• Low blood pressure, weak rapid heartbeat• Allergies, asthma, hives, itching, eczema• Sinusitis, chemical sensitivities, dermatitis• Aches, pains, muscle stiffness• Arthritis• Saliva testing to diagnose

Cortisol Excess High potency steroids, chronic

stress

• Fatigue• Sleep disturbances• Bone loss• Weight gain waist• Loss of muscle mass, thinning skin• Memory lapse, anxiety

Cortisol (5 mg three times daily or 10 mg twice daily)

• A physiologic dose (up to 20-30 mg per day) of cortisol does NOT cause:

– Bone loss – Weight gain– Elevated glucose, sugar cravings (a normal level of cortisol

regulates blood sugar)– Anxiety, sleep disturbances– Thinning skin, easy bruising– Suppression of the immune system– Suppression of endogenous adrenal production (it takes 40

mg of cortef for at least 3 months to suppress your natural cortisol production)

Wichers 99, Jodar 03, McConnell 02, McK.Jefferies 96

Side effects

• Vioxx: CVA, CHF, DVT, MI, PE, HTN crisis, acute renal failure, GI bleed, liver failure, death

• Mobic: face edema, anaphylactic rxn, CHF, HTN, MI, dyspnea, liver failure, ulcers, death

• Celebrex: Heart failure, kidney failure, fainting, HTN, ringing in ears, deafness, ulcers, bleeding, blurred vision, death

Thyroid Deficiency

• Basal Body T < 97• TSH > 3.0, low T4 or T3• Decreased metabolism• Weight gain• Fatigue, lack of endurance• Muscle weakness, joint stiffness, aches• Headaches, decreased concentration, brain fog,

memory problems• Dry skin, dry brittle hair, hair loss (balding all over)• Loss of lateral 1/3 of eyebrow, diminished reflexes• Elevated cholesterol, increased ASHD

Wren 1971

• 347 patients, ages 43-86, high risk/sx. Heart dz.• 9% low thyroid by testing • Treated all patients with Thyroid hormone

– Mortality decreased by 50%– 70% reduction in episodes of chest pain– 50% reduction in heart attacks– 22% reduction in cholesterol– 80% of patients felt better, more alert & motivated

Thyroid Excess

• Weight loss/gain• Fatigue, weakness, decreased muscle mass• Shakiness, restlessness, rapid heartbeat• Shortness of breath • Heat intolerance, increased thirst, sweating• Anxiety, panic attacks• Hair loss, brittle nails

Elevated Insulin = weight gain

• Increases inflammation: increases the risk of heart disease, arthritis, and cancer

• Increases hunger and obesity• Increases LDL & Triglycerides/decreases

HDL• Decreases lifespan

Hormone Imbalance

• Symptoms overlap• Men and women at any age• GET TESTED • Low normal may not be optimal for health• Many labs do not have ‘age specific ranges’• Guideline and ranges change

– New ranges for TSH (thyroid)

Testing

• Blood: Estradiol, FSH, Testosterone (total and free), (Estriol and Progesterone ng/ml, not tested)

Thyroid Panel (free T4, TSH, free T3, TPO) Men also need a PSA, Hb & Hct, Hepatic panel

• Saliva: Profile I (estradiol (E2), progesterone, testosterone, DHEAS, and cortisol)

Profile II (as above, am and pm cortisol)

• 24 hour Urine

Bioidentical Hormone ReplacementRx. or compounded

• Capsules (oral)• Creams/gels (skin) • Vaginal Suppositories and Creams• Sublingual lozenges/drops• Patches

• Pellets (testosterone, estradiol)

Oral Capsules

• Most convenient• Absorb best with a fatty meal• First pass through the liver (metabolites)• Testosterone converts to estradiol and is rapidly

degraded• Conventional (oral) HRT has been shown to cause

liver damage and increase the risk of thrombosis (blood clots)

• Variability in absorption• FDA approved estradiol and progesterone

Creams & Gels

• Variability in absorption: individual, site, surface area, thickness of skin and base

• Depot effect (especially progesterone)• Maintains a consistent level of hormones in the

bloodstream avoiding the peaks and valleys• Avoids first pass through the liver • Does not increase the risk of blood clots• Can transfer hormones through skin contact• Lack of data on Bi-est • FDA approved

– Estradiol for women– Testosterone for men

Mucous Membrane/ Vaginal Application

• Consistent absorption– Relieves menopausal symptoms

• Relieves vaginal dryness, urinary urgency, frequency, incontinence and repeated UTI’s

• Safe– Vaginal estrogens (estriol) do not increase the risk

of breast cancer– No increase in blood clots or metabolites

• Do not develop tolerance• No accumulation of hormones or metabolites

Vaginal application of hormones cont.

• Deliver multiple hormone in a single cream – Convenient– Cost effective

• Small volume of cream• Applied 3 to 6 times

weekly• Can transfer to spouse

Sublingual Drops & Troches

• Avoids first pass through the liver• Rapid onset of action • Careful not to swallow saliva• Multiple doses to maintain blood levels• Drops make it easy to increase or decrease

dosage which is useful in perimenopause• Variability of absorption

Patches

• Patented products (delivery system)• Estradiol: Estraderm, Estradot, Vivelle Dot, Climara

• Testosterone: Androderm (males $$$$)• Consistent delivery over time (…not)• Estrogen applied once or twice weekly• Testosterone applied daily• Only delivers estradiol (women)

– Strong estrogen

• Problems with adhesive, uncomfortable

Hormone Implants: Pellets

• Pellets made up of either testosterone or estradiol compressed into very small, solid cylinders

• There is an ‘FDA approved’ 75 mg testosterone pellet

• In the U.S. other formulations and dosages need to be ‘compounded’ by trained pharmacists

Pellets/Implants

• Used in the United States since 1940• Tremendous amount of data supporting use

– England, Australia and the US• Only licensed form of testosterone for women in England

• Testosterone for men and women• Rarely use an estradiol pellet in women

– Young women with a surgical hysterectomy– Need to gain weight– Problems with bleeding

Hormone Implants cont.

• More effective than oral or topical hormones for relief of menopausal symptoms

• Most effective form of testosterone replacement in men & women

• Not only maintains bone density but increases bone density.

• Most consistent and convenient method of hrt• Safe form of HRT

– Does not increase the risk of blood clots or strokes– Does not effect the liver– Testosterone implants are breast protective

Testosterone pellet implants

• Increases bone density and muscle mass• Decreases fatty tissue• Relieves depression, improves anxiety• Improves memory and concentration• Relieves joint and muscle pain • Improves sleep• Relieves hot flashes and

night sweats• Improves sex drive and libido

Simple procedure

• The insertion of pellets is a simple, 5 minute office procedure done under local anesthesia

• They are placed in the fatty tissue just under the skin of the hip or lower abdomen

• They completely dissolve over time– 3-5 months in women

– 4-6 months in men

Most successful HRT (supported by data)

• Testosterone pellet implant: Men and Women– Vaginal cream (2-6 days per week) may be added

in women• Estriol

– Relieves vaginal and urinary symptoms– Does NOT stimulate breast tissue– Does NOT cause weight gain or fluid retention

• Estradiol (may leave out)• Progesterone

– Does not accumulate, no metabolites, high dose to uterine lining,

• (Testosterone if NOT used as a pellet implant)– Not as effective as pellet implant (bone density,

depression, anxiety, aches, pains, libido, energy etc.)

Hormones in balance do not cause breast cancer

• Hormones are critical for health

• High levels of unopposed strong estrogens increase the risk of breast cancer– Bio-identical estradiol and Premarin

– Vaginal estriol relieves menopausal symptoms and does not increase the risk of breast cancer

• Synthetic chemical progestins (Provera) and synthetic chemical testosterone (Methyl-test, Estratest) increase the risk of breast cancer

• Progesterone, the hormone, does not increase the risk of breast cancer

Hormones in balance do not cause breast cancer

• Testosterone is breast protective– Balances estrogen– Prevents the proliferation of breast tissue by estrogen with

progestins– Prevents the growth of breast cancer cells– Lowers the risk of breast cancer – Has been used to treat breast cancer

• Stress creates hormone imbalance and increases the risk of breast cancer– DHEA and cortisol are critical for immune function

• Cancer cells over-express insulin receptors and feed on glucose

TI BCa P 0108Testosterone Implant Breast Cancer Prevention Trial 0108

• Dimitrakakis, Glaser, Khera• IRB approved 10 year, prospective trial

looking at the incidence of breast cancer in women treated with testosterone implants– A study from Australia found that women who

received testosterone pellet implants in addition to estrogen/progestin therapy had a lowered risk of breast cancer

Bio-identical hormone balance

• Hormones in balance maintain health and PREVENT disease

• Hormones, in balance, do NOT increase the risk of breast cancer

• Bio-identical hormones (not given orally) do not increase the risk of blood clots

• Hormone replacement therapy should be individualized

• Sensationalism sells news• Pharmaceutical companies are powerful forces in

medicine, politics and the economy (in the US)• Doctors often adamantly state what they ‘think’…

without research or knowledge

Conclusion

• BALANCE• Individual• Baseline Levels• Bioidentical Hormones• Diet and Lifestyle • Exercise• Disease Prevention• Active Participant

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Commentary

Evista Barrett-Connor 06 NEJM

• Effects of Raloxifene on CV Events and Breast Cancer in Postmenopausal Women

• Raloxifene (Evista) SERM prevents bone loss without stimulating breast or uterus

• 10,101 patients placebo or Raloxifene 5.6 yrs

Evista

• No effect on coronary events• Raloxifene reduced the risk of invasive (ER pos)

breast cancer – 40 vs. 70, 30 cases over 5 years in 5000 females, 1.2 breast

cancers per 1000 women per year – No difference in death rate

• Raloxifene increased risk of:– fatal strokes (59 vs. 39, .7 per 1000 women per year)

– venous thromboembolism (103 vs. 71, 1.2 per 1000 women years)

• Reduced the risk of clinical vertebral fx. (64 vs. 97)

Raloxifene (Evista)

• Prevented less than 1 (0.6) breast cancers per 100 patient treated for 5 years (.65 vert fx)

• Cost 100 x 365 x 5 x $2 $365,000 – over $600,000 to prevent one breast cancer

• Side effects besides DVT, PE, Stroke– More common

• Bloody or cloudy urine;  chest pain;  difficult, burning, or painful urination;  fever;  frequent urge to urinate;  infection, including body aches or pain, congestion in throat, cough, dryness or soreness of throat, and loss of voice;  runny nose ;  leg cramping;  skin rash ;  swelling of hands, ankles, or feet;  vaginal itching 

– Less common • Abdominal pain (severe);  aching body pains;  congestion in lungs; 

decreased vision or other changes in vision;  diarrhea ;  difficulty in breathing;  hoarseness;  loss of appetite;  nausea;  trouble in swallowing;  weakness 

– More common • Hot flashes, including sudden sweating and feelings of warmth (especially

common during the first 6 months of treatment);  increased white vaginal discharge;  joint or muscle pain;  mental depression;  problems of stomach or intestines, including passing of gas, upset stomach, or vomiting;  swollen joints;  trouble in sleeping;  weight gain (unexplained) 

Rebecca L. Glaser M.D., FACS

Millennium Wellness CenterFor Men & Women

937.436.9821

*****www.hormonebalance.org