Bioidentical Hormone Replacement Therapy:

Myth vs FactWhat you really need to

knowMark D Filidei, D.O.

Director of Integrative MedicineAmen Clinics

The two main principles of Bio-identical Hormone Therapy (BHRT):

1) Use of natural (human bio-identical) hormones: exactly like those produced in the body 2) Physiological replacement to levels of a young adult

Many doctors are unaware they are prescribing BHRT!

Vivelle Estrace Estraderm Femring Femtrace Climara Alora Prometrium

BHRT-The main players Thyroid Estrogen Testosterone Progesterone Dhea Growth Hormone

Hypothyroidism is an epidemicThe Colorado thyroid disease prevalence study:25,000+ participantsCONCLUSIONS:“The prevalence of abnormal biochemical thyroid function reported here is substantial and confirms previous reports in smaller populations. Among patients taking thyroid medication, only 60% were within the normal range of TSH. Modest elevations of TSH corresponded to changes in lipid levels that may affect cardiovascular health. Individual symptoms were not very sensitive, but patients who report multiple thyroid symptoms warrant serum thyroid testing. These results confirm that thyroid dysfunction is common, may often go undetected, and may be associated with adverse health outcomes that can be avoided by serum TSH measurement.”

Signs and Symptoms of Low Thyroid

Fatigue Increased sensitivity to cold Constipation Dry skin Unexplained weight gain Puffy face Hoarseness Muscle weakness Elevated blood cholesterol level Muscle aches, tenderness and stiffness Pain, stiffness or swelling in your joints Heavier than normal or irregular menstrual periods Thinning hair Slowed heart rate Depression Impaired memory

Standard ranges for thyroid testing (Labcorp):

Free T4 0.82-1.77Free T3 2.0-4.4 >3.50TSH 0.45-4.50 <1.50

With co-morbidities use:fT3/rT3 >20

D1 (but not D2!) is suppressed and down-regulated by:

Physiologic and emotional stressDepressionDietingWeight gain/Weight LossInsulin resistance and DiabetesObesityInflammationAutoimmune diseaseSystemic illnessChronic fatigue syndromeFibromyalgiaChronic painExposure to toxins, mold, heavy metals, and plastics

Thyroid hormone replacement

T4 only (most common) Synthroid, levothyroxine

Natural thyroid (Armour, Westhroid, NP thyroid) contains natural ratios of T4 and T3

T3 only (Cytomel, compounded T3)

The Three Forms of Estrogen

Estrone: Produced in peripheral tissues; implicated in some cancers (breast, uterine)

Estradiol: Secreted by ovaries; most active form, supports cognitive function and mood, higher levels associated with youthful appearance. Deficiencies associates with osteoporsis, dementia, heart desease

Estriol: safest and weakest form of estrogen; may have anti-cancer effects, useful for vaginal dryness and MS (reverses brain lesions)

Signs of Low Estrogen(From Unleash the Power of the Female Brain)

Weight gain Bladder incontinence and infection Mood changes/depression Insomnia Low libido Heart palpitations Osteoporosis Painful intercourse Foggy headedness Irritability Fatigue Weepiness Hot flashes Pain

Signs of Excess Estrogen (From Unleash the Power of the Female Brain)

Puffiness Heavy bleeding Fibrocystic breasts Low libido Cravings for carbohydrates Weight gain around the hips Vaginal or oral yeast (thrush) Mood swings/easy to tear Tender breasts Headaches or migraines

Benefits of Estrogen replacement

Helps reduce/eliminate menopausal symptoms

Can help maintain bone density Anti-Aging benefits May decrease risk of Alzheimer’s and

and other brain related problems Supports cognitive function and

mood (serotonin function)

Estrogen enhances brain function “Authors suggested this study supports previous results showing

that the effect of estrogen therapy on mood may be independent of antidepressant effects mediated by alleviation of vasomotor symptoms and that estrogen therapy may be of benefit to perimenopausal women experiencing moderately severe depression.”

Short-term use of estradiol for depression in perimenopausal and postmenopausal women: a preliminary report. Am J Psychiatry. 2003 Aug;160(8):1519-22.

“Estrogen in a therapeutic dosage alters brain activation patterns in postmenopausal women in specific brain regions during the performance of the sorts of memory function that are called upon frequently during any given day. These results suggest that estrogen affects brain organization for memory in postmenopausal women.”

Effect of estrogen on brain activation patterns in postmenopausal women during working memory tasks. JAMA. 1999 Apr 7;281(13):1197-202

Premarin Pregnant Mare Urine

Conjugated estrogens, from the urine of pregnant mares (50% equine hormones, not found in humans)

Predominantly E1 (estrone)

Natural Estrogen Replacement Bi-Est: 80% estriol, 20% estradiol

in oral or transdermal form Estradiol only Transdermal is recommended to

avoid “first pass effect” and coagulation issues of oral use

Should always be balanced with natural progesterone in women with an intact uterus

Estrogen MetabolismEstrogens convert into several metabolites. Estrone, for example, may convert into three different forms:

• 2-hydroxyestrone, protective against cancer • 4-hydroxyestrone, promotes cancer • 16-alpha-hydroxyestrone, promotes cancer In women on HRT, the 2/16 ratio should be >2. Lower ratios are associated with breast and ovarian cancer.

March 30, 2013, 9:54 p.m“Study upholds breast cancer mortality for hormone replacement” Though it was generally agreed that woman who took the two hormones to curb their hot flashes and night sweats upped their chances of developing the disease, many studies suggested that the cancers the women developed were less likely to be deadly.

A new analysis of data from the Women's Health Initiative now casts doubt on those findings. The study, published Friday by the Journal of the National Cancer Institute, concludes that the prognosis for cancers related to hormone replacement therapy is just as dire as for other breast cancers. As a result, women who turn to the treatment are more likely to die of breast cancer than their peers who don't take hormones.

“The new findings apply only to women who take estrogen and progestin, a synthesized form of the natural hormone progesterone. Women who have had hysterectomies can take estrogen alone, a regimen that doesn't seem to increase breast cancer risk. But those who still have a uterus must take both estrogen and progestin to avoid developing endometrial cancer.

And hidden much further down in the article we find this:

Hormone therapy for Breast Cancer Survivors?

“We observed lower risks of recurrence and mortality in women who used HRT after breast cancer diagnosis than women who did not” …the results suggest that HRT after breast cancer has no adverse impact on recurrence and mortality”J Natl Cnacer Inst 2001 May

“Continuous combined HRT was associated with reduced risk of death from primary tumour and all cause mortality.”Med H Aus 2002 Oct

“Over a mean follow up of 30 months 17 of 214 users experienced recurrence (4.2% per year), compared with 66 of 623 controls (5.4% per year). HRT did not seem to affect breast cancer recurrence risk”J Clin Oncology 2001 April

“Estrogen replacement therapy apparently does not increase either recurrences or mortality rates. Adding progesterone may even decrease recurrences. Women with early breast cancer should be offered hormone replacement therapy…Am J Obstet Gynecol. 1999

Hormone replacement therapy after breast cancer: 10 year follow up of the Stockholm randomised trial.

“The number of new events did not differ significantly between groups, in contrast to previous reports. The increased recurrence in HABITS has been attributed to higher progestogen exposure. As both trials were prematurely closed, data do not allow firm conclusions. Both studies found no increased mortality from breast cancer or other causes from HRT. Current guidelines typically consider HRT contraindicated in breast cancer survivors. Findings suggest that, in some women symptom relief may outweigh the potential risks of HRT.” Eur J Cancer 2013 Jan

Synthetic Progestins Provera (medroxyprogesterone

acetate) most popular “progesterone” drug

Dozens of adverse effects: decreases blood flow to heart, lowers HDL, and causes edema, weight gain, insulin resistance, insomnia, and, if taken in early pregnancy, birth defects

Natural Progesterone Protects against estrogen’s

proliferative effects on endometrium

Helps alleviate PMS symptoms Reduces fibrocystic breast

disease May elevate libido and mood May promote bone formation

Natural progesterone Supports GABA - a major calming

neurotransmitter “natures Valium” Levels drop with low thyroid, chronic

stress, vitamin deficiencies and refined sugar

Symptoms of low progesterone Anxiety/depression Poor sleep Fibrocystic breasts PMS Premenstrual headaches Postpartum depression

Progesterone Replacement

Oral micronized progesterone, 100-300 mg at bedtime

Transdermal natural progesterone creams, 1/4-1/2 teaspoon daily

Available both OTC and prescription

Testosterone for Women (?) Yes! Declines with age, just like in men Increases libido, elevates mood and

energy level Improves ratio of fat to muscle Replacement: Natural testosterone

in transdermal cream or gel. Implanted pellets.

Testosterone for Men Levels fall gradually with age; ”Low T”

syndrome Low levels herald andropause Symptoms include loss of libido, fatigue,

depression, loss of muscle mass, osteoporosis, anhedonia,

“I lost my mojo” Testosterone replacement can be used

for men with history of prostate cancer if they are disease free.

Testosterone Replacement

Injections: 200mg wk, 100mg 2x/wk SQ or IM

Topical in gel or cream: 50-100mg/day

Troche Implanted pellets Avoid oral testosterone HCG injections

DHEA –adrenal hormonePrecursor hormone Low levels associated with

depression, weight gain, heart disease, diabetes, autoimmune disorders, immune dysfunction, obesity, cancer, osteoporosis, memory loss

Replacement improves sense of well-being, mood, memory, immune function, and in women libido

DHEA “DHEA was associated with a

remarkable increase in perceived physical and psychological well-being for both men (67%) and women (84%)...› Morales, AJ et al. Effects of replacement dose

of dehydroepiandrosterone in men and women of advancing age. J. Clin. Endocrinology and Metabolism, 1994; 78(6):1360-1367.

DHEA "... an increase in DHEA-S of

100 mg/dl was associated with a 36% reduction in mortality from any cause and a 48% reduction in mortality from cardiovascular disease."› Barrett-Connor, et al. A perspective

study of dehydroepiandrosterone sulfate, mortality and cardiovascular disease. NEJM, Dec. 11, 1986; 315(24):1519-1524.

DHEA Average doses:

› 5-25 mg women › 25-50 mg men

Check blood levels of DHEA-S to determine optimal dose

Use with caution in patients with hormone-sensitive cancers, such as breast or prostate cancer*

DHEA may protect against breast cancer

Dehydroepiandrosterone (DHEA) has a protective role against cancer…These results suggest that the mechanism of DHEA actions against breast cancer involves the inhibition of cell proliferation and the suppression of migration, indicating that DHEA could be useful in the treatment of breast cancer.

Eur J Pharmacol. 2011 Jun 25

The DHEA metabolite 7β-hydroxy-epiandrosterone exerts anti-estrogenic effects on breast cancer cell lines

Steroids. 2012 Apr;77(5

Human Growth HormoneAfter 6 months of treatment: Increase in muscle mass (8.1%) Reduction of body fat (14.4%) Increase in bone density (1.6%) Rejuvenation of skin (7.1%)

› Rudman, D et al. Effects of human growth hormone in men over 60 years old. New Engl J Med, July 5, 1990; 323(1): 1-6.

Human Growth Hormone “The effects of 6 months of

hGH on lean body mass and adipose-tissue mass were equivalent to the changes incurred during 10 to 20 years of aging.”› Rudman, D et al. Effects of human

growth hormone in men over 60 years old. New Engl J Med, July 5, 1990; 323(1).

Human Growth Hormone Speeds healing after surgery and

recovery from severe illness Excellent therapy for heart

failure: increases cardiac output and exercise capacity

Given by SQ injection Oral “Secretagogues”do not

reliably increase IGF-1