Clinical Application of Bio-Identical Hormone Replacement Therapy

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    Clinical

    Application ofBHRT

    Tracy Marsden BScPharm, DHPh

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    Types of Hormones

    Estrogens

    Progesterone

    Testosterone

    Cortisol & DHEA

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    Pre-Menopause

    OVARY

    Testosterone

    Estradiol

    Estrone

    Estriol

    Progesteronearomatase

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    Estrogens

    3 main types: estradiol, estrone, estriol.

    Estradiol is the main estrogen produced bythe ovaries.

    Estrogen receptors found throughout body:

    brain, blood vessels, bone, etc.

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    Progesterone

    Synthetic progestins like Proveraare not

    the same as progesterone.

    Allwomen need progesterone to balance

    effects of estrogens (even women who have

    had the uterus removed!)

    Progesterone increases the bodys

    sensitivity to the estrogens it has.

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    Androgens

    Testosterone is important to women for:

    Bone

    Sex drive Energy, sense of well being

    DHEA and androstenedione are important

    building block hormones: needed to makeandrogens and estrogens (particularly aftermenopause).

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    Cortisol

    Is the primary stress hormone.

    High cortisol levels can interfere with theactions of all the other hormones.

    Prolonged elevation of cortisol can deplete

    the adrenal glands.

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    Post Menopause

    ADRENAL

    GLAND

    Testosterone

    Estradiol

    Estrone

    Estriol

    CortisolDehydroepiandrosterone

    (DHEA)

    Androstenedione

    aromatase

    aromatase

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    Normal Cycles

    Progesterone is produced in quantity after

    ovulation

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    Relative excess of estrogens

    over progesterone. Cyclesare irregular.

    Progesterone peaks after

    ovulation and balances

    estrogens. Cycles are regular.

    Very little progesterone orestrogens released by

    ovaries. No cycles.

    Menstrual Cycle 6 month view

    Peri-menopause 6 month view

    Post-menopause 6 month view

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    Hormone Balance

    There is an intricate balanceamong all the hormones; toomuch of one can create

    an imbalance.

    Maintaining the right balancecan reduce symptoms

    and help prevent disease.

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    Hormone Therapy Missteps

    Giving unopposed estrogen to all women (noprogesterone given to balance estrogens)without testing or proof of need.

    When we found out estrogen alone increasedendometrial cancer risk, we added a syntheticprogestin instead of natural progesterone.

    When we found out synthetic progestinsincreased heart attack and stroke risk, we justdecreased the dose.

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    A better approach

    THREE SIMPLE STEPS

    Symptom assessment

    Hormone testing

    Restore hormone balance with bio-

    identical hormones

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    Step 1: Symptom Assessment

    ijklHot flashes ijklMemory lapses

    ijklNight sweats ijklFoggy thinkingijklWater retention ijklHeart palpitations

    ijklBreast tenderness ijklIrritability

    ijklDecreased sex drive ijklLoss of muscle bulk

    Symptoms:Please rate your symptoms according to the following scale:

    0 - never or rarely experience this symptom (

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    Hormone Testing Options

    Urine

    Measures what the body throws away

    Blood

    Measures what mighteventually get to

    tissue

    Saliva

    Measures what actually gets to tissue

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    What are bio-identical hormones?

    Bio-identical means that the hormones are

    identical in structure to what is produced

    naturally in the body.

    More accurate to call them Human-Identical

    Hormones, but BHRT is a common term.

    Studies showing harm from hormones used

    synthetic or semi-synthetic hormones (horse

    estrogens, synthetic progestins)

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    Principles of BHRT

    Use the identical hormone to that which the

    body produces on its own

    Give bio-identical hormones in the way that

    is closest to the way hormones are released

    in the body

    Use the minimum dose to relieve

    symptoms.

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    Bio-identical Hormone Replacement

    Bio-identical hormone replacement (BHRT)

    includes:

    Estradiol patches and gels

    oral micronized progesterone

    These bioidentical products are notcontroversial

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    Transdermal Estrogens

    However, BHRT also includes:

    compounded oral or transdermal combination

    estrogens (BiEst, TriEst) compounded progesterone creams

    compounded sustained release oral micronizedprogesterone

    . . . which are more controversial types of bio-identical hormone replacement.

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    BiEst and TriEst

    BiEst and TriEst contain mostly estriol, the

    weakest estrogen.

    Theoretically, estriol raises estrogens levels

    when they are low, and competes with

    stronger estrogens for receptor sites when

    estrogen levels are high.

    Some research suggests that estriol may be

    protective against breast cancer.

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    Bi-Est

    BiEst (bi-estrogen) is a combination of estriol

    and estradiol in oral or transdermal form

    Various combinations available: 80:20, 70:30,

    50:50

    First number refers to the estriol component

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    Tri-Est

    Tri-Est not used often as most women do

    not require estrone.

    TriEst (tri-estrogen) is a combination of

    estriol, estrone, and estradiol

    Various combinations available: 80:10:10,

    90:5:5, 60:20:20

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    Estriol (E3)

    Effective for hot flashes, insomnia, poormemory. Head K. Alt Med Review 1998;Vol. 3(2)

    Intravaginal use may be effective for vaginaldryness, infections, recurrent UTIs anddyspareunia.Head K. Alt Med Review 1998;Vol. 3(2)

    Estriol has been safely used in Europe fordecades, although is not approved for use inNorth America.

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    TriEst and BiEst

    Unconventional compounded estrogens do

    not appear to be worth the extra cost and

    effort they exact, but they do represent anaddition therapeutic option for women who

    cannot tolerate conventional prescription

    estrogens.

    Taylor M, Clin Obstet Gynecol; 2001 Dec;44(4):864-79

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    Bio-identical Progesterone

    Progesterone (bio-identical hormone)

    compared to Provera (medroxyprogesterone

    acetate)

    Progesterone cream versus oral micronized

    progesterone

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    Acts with estrogen to relax

    blood vessels

    Does not increase risk ofbreast cancer

    Does not increase

    inflammatory markers in

    blood

    Protects against natural brain

    cell death.

    Inhibits relaxation of blood

    vessels by estrogens

    Increases risk of breast cancer

    Increases inflammation

    causing C-Reactive Protein

    (CRP)

    Does not protect against

    natural brain cell death.

    Progesterone MPA

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    Bio-identical progesterone

    Oral micronized progesterone (Prometrium) isbio-identical

    Effectively protects the endometrium (lining ofthe uterus)

    Giving progesterone orally creates metabolitesthat have an anti-anxiety and sedative effect.

    Pregnanolone

    Allopregnanolone

    Hydroxypregnanone

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    Progesterone Cream

    Progesterone cream is also effective, andmay be less sedating than the oral form.

    Progesterone is better absorbed throughskin than either testosterone or estradiol

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    Progesterone Cream

    Efficacy:

    Some evidence that progesterone cream can

    protect the endometrium

    No bone building effects

    May help reduce hot flashes

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    Compounded Progesterone Cream

    Quality depends on

    how finely ground the progesterone

    powder is

    the type of base used

    the compounding skills of the pharmacist.

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    BHRT Study

    189 women between the ages of 45 and 60

    prescribed BHRT: all received progesterone

    and BiEst topically. Some also receivedtestosterone, DHEA.

    70% complained of brain fog

    55% complained of weight gain.

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    Study Results

    90% completely or partially improved on

    symptoms of brain fog.

    60% of women who gained weight, lost weight.

    Average weight loss was 14.8 pounds.

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    Cortisol Effects

    High levels of cortisol can compete with

    the other hormones, creating a functional

    deficiency of hormones. Progesterone or testosterone in normal range,

    but the bodyfunctionsas if there is not enough

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    Cortisol and DHEAS

    Cortisol is catabolic, meaning it breaks down

    muscle and bone

    DHEA is anabolic, meaning it builds up

    muscle and bone

    Balance becomes more catabolic with age as

    DHEA levels decline and cortisol levels

    increase

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    Adrenal Fatigue

    High cortisol levels over time cause damage,

    and the body slows cortisol release to

    prevent further damage.

    Decreased cortisol release leads to adrenal

    fatigue and inability to regulate other

    hormones.

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    Thyroid

    Thyroid issues more common as

    perimenopause is reached: higher overall

    estradiol levels in perimenopause reducedamount of free thyroid hormone.

    Too low or too high cortisol can also affect

    thyroid.

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    BHRT Summary

    Bio-identical hormone replacement (BHRT) is an

    accepted standard of hormone replacement,

    although there is controversy around custom

    compounded forms of BHRT

    Oral progesterone is accepted, and progesterone

    cream is gaining acceptance.

    BiEst and TriEst are still unproven therapies, but

    preferred by many women.