Download - BHT-HRT WomenSense Talk
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MENOPAUSAL HORMONE
THERAPY: Putting Talk Shows into
Perspective
Janice Werbinski, MD, Medical Director
Borgess Womens HealthWomenSense Lecture Series
June 2009
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A $SIGN OF THE TIMES
WhoAREthese people??
Christiane Northrup
Lauren Hutton
Sally Field
Patty LaBelle
Oprah Winfrey
Robin McGraw
Suzanne Sommers
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MENOPAUSE AND WOMENS
HEALTH PROVIDERS
Wulf Utian, MD
Holly Thacker, MD
Elizabeth Lee Vliet, MD
Wendy Klein, MD
Nancy Teaff, MD
Jan Werbinski, MD
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REPUTABLE RESOURCES(See Bibliography)
National Womens Health Network
Cleveland ClinicHolly Thacker
Susan Love North American Menopause Society
Harvard Womens Health Watch
DHHS (4Woman.gov) Our Bodies Ourselves
WebMD.com
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MENOPAUSE DEFINITION
Cessation of Menses for 12 months or more
Laboratory Values - Serum (or Saliva?)
FSH > 40 Units
Estradiol < 25 Picograms/Deciliter
Progesterone drops earlier
Invalid if Taking any hormones at all If NON-Menopausal, hormone levels vary
hour-to-hour, depends on day of the cycle.
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ESTROGEN RECEPTORS
Brain Mood
Memory
Hot Flashes*
Breast
Fibrocystic Density
Uterus
Hyperplasia/Carcinoma
Vessels
Hot Flashes*
Hemorrhagic Stroke
Ischemic Stroke
Deep Vein Thrombosis
Bladder Frequency
Urge Incontinence
Bone
Density/Fracture risk
Colon Carcinoma
Liver
Coagulation Factors
Lipids
Heart Palpitations
Atherosclerosis
Ischemic MI
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HT Through the Ages
Nazi Germany
Feminine Forever 1950
Endometrial Ca (1971)
MPA (1980)
Designer Estrogens
Micronization (Prog)
NHS, WHI and HERS
Natural Hormones
Back to Basics
New NAMS Statement
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MENOPAUSAL THERAPIES
Pharmaceutical Hormones FDA Approved after intense study on large numbers
Prospective, Double Blind, Crossover, Placebo
Interesting History
Bioidentical Hormones Identical to the ovarian hormones produced during
reproductive years Some are FDA Approved
Some are Compounded by Pharmacists
Some are sold on the Internet without a prescription
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MENOPAUSAL THERAPIES
Herbals Eastern Medicine, Alchemy, Witchcraft
Can be helpful and safe
Not many studied extensively
Alternative Modalities
Massage, Acupuncture, Relaxation exercises,Chiropractic, Nutritional Medicine, Stellate
Ganglion Injection
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HT TERMINOLOGY
ET
Estrogen Therapy
EPTCombined Estrogen-Progestogen Therapy
HTHormone Therapy (Encompassing both ET andEPT
Progestogen
Encompassing both progesterone andprogestin
Systemic TherapyHT administration that results inabsorption in the blood high enough to provide
clinically significant effects Local TherapyVaginal ET that does not result in
systemic absorption
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WHAT ABOUT FDA
APPROVAL?
What does it take to get approval?
How does a Patent influenceapproval?
What does it mean to use a drug
Off Label?What is informed consent?
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ADDITIONAL TERMINOLOGY
Spontaneous/Natural Menopause Induced Menopause-surgical/chemorx
Perimenopause (8 years around LMP)
Premature Menopause (
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ESTROGENS
Bioidentical Term:
17Beta Estradiol
EstroneEstriol
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ESTROGEN THERAPY OPTIONS
ORAL PATCH TDERMAL VAGINAL
Cenestin Alora Divigel Estrace
Enjuvia Climara Elestrin Estring
Estrace Esclim EstroGel Femring
Estratab Estraderm Estrasorb Premarin
Femtrace Menostar Vagifem
Ortho-Est Vivelle
Menest Vivelle-Dot
Premarin
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Risk of VTE (blood clot) by Route
and Type of Hormone
Cases
(259n)
Controls
(603n)
RR
Nonuse 146 384 1
PO Estrogen 45 39 4.2
TD Estrogen 67 180 0.9
No Prog 14 40 --
Micronized 19 63 0.7
Pregnanes 39 79 0.9
Norpregnan 40 37 3.9
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PROGESTERONE
PROGESTINMicronized Progesterone: BHT
PregnaneNorPregnane
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PROGESTERONE
PROGESTINThe Natural Product
Corpus Luteum
USP Progesterone
Prometrium
MedroxyProgesterone Acetate-Provera
Progestins Norethindrone Acetate (NETA)
Norgestimate Desogestrel
Levonorgestrel
Norethindrone
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Breast Cancer Risk Varies by
Type of Progestin
Progestin Route # RR
Progesterone Transdermal 35,513 1.08
MPA (Provera) Oral 7,035 1.48
Norethindrone
AcetateOral 7,401 2.11
Dydrogesteron Transdermal 25,405 1.18
NomegestrolAcetate
Transdermal 18,826 1.6
Promegestone Transdermal 14,910 1.52
Fournier,A et.al Breast Cancer Res Treatment. 2008; 107:103-111.
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TESTOSTERONE
Available ProductsHistorically for Men (Orchiectomy, Male
Menopause)
Potential for Women (Libido, Energy,Potentiation of Estrogen Therapy)
BioIdenticals and TransdermalsPatch
coming Safety and Effectiveness Research
Black Box Warning
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DHEA
DataInteresting
Possibility of Several Uses
No FDA Approval Health food stores
Compounding Pharmacies
Sports Ban
Congressional Bill Pending
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OTHER HORMONES
Serotonin
NorEpinephrine
Dopamine
Melatonin
Pituitary
Growth
Thyroid
Cortisol/Adrenalin
Insulin
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Use of Nonhormonal Therapies
for Vasomotor Symptoms
AGENT DAILY
DOSE
%
REDUCED
PLACEBO
% REDUC
Paroxetine 25 mg 50% 27%
Venlaxafine 75 mg 51% 15%
Gabapentin 900 mg 45% 29%
Clonidine 0.1 mg 38% 20%
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Benefit:Risk Ratio ofPremPro
(Womens Health Initiative)
Condition Change in Risk Cases per Year
Invasive Breast Ca 26% increase 8 more
Stroke 41% increase 8 more
Clots in veins 107% increase 10 more
Clots in lungs 113% increase 8 more
Heart attacks 29% increase 7 more
Hip fractures 34% less 5 less
Colorectal Cancer 37% less 6 less
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Where Does The
WHI Leave Us Now?
0
0.5
1
1.5
2
2.5
MI CVA DVT FX Colon Breast
RR
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What Else Can We Use?
Hot Flashes
Bone Density
Cardiovascular Disease
Colon Cancer Incontinence
Breast Cancer
Libido
Mood Changes
Memory Deficits
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Individualize, New Drugs
SSRIs, Catapres, Bellergal -FLASHES
Fosamax, Actonel, Boniva, Forteo-BONE
Detrol, Ditropan, Hyoscyamine-INCONT.Topical Estrogen-BLADDER,VAGINA
Testosterone, DHEA -LIBIDO
Progesterone-MOOD, BLEEDING,SLEEPTamoxifen, Evista-BREAST DISEASE
Injections of Neck Nerves-FLASHES
Lifestyle Influences
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Lifestyle Influences
(Diet, Exercise, Nutriceuticals
Meditation, Stress Management) Soy, Black Cohosh-FLASHES
Cruciferous (Indole-3-Carbinol)-BREAST Calcium/Vitamin D-BONE
Folic Acid-MEMORY
B Vitamins-MOODAntioxidants-CANCER
Soluble Fiber-COLON
Melatonin-SLEEP
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What Do the Experts Now Say?
NAMS (North American Menopause Society)
ACOG (American College of Ob/Gyn)
NIH (National Institutes of Health)
AHA (American Heart Association
USPTF (US Preventive Task Force)
NCI (National Cancer Institute)
NWHN (National Womens Health Network)
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Consensus 2008
ERT or HRT for severe climacteric symptoms(
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Menopause Vol.15;4:2008, p.584-602
2008 NAMS Position Statement
Recent data support the initiation of HT
around the time of menopauseto treat
menopause-related symptoms; to treat or
reduce the risk of certain disorders, such asosteoporosis, diabetes, colon cancer or
fractures in select postmenopausal women;
or both. Benefit-risk ratio is favorable closeto menopause, but decreases with aging and
with time since menopause.
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Timing of HT and CVD
Women
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NAMS 2008 Recommendations
(CardioVascular)
HT is not recommended as a sole or primary
indication for coronary protection @ any age
Initiation @ age 50-59 or within 10 yr. of
LMP does not seem to increase CHD risk
Initiation in early postmenopause may
actually reduceCHD risk
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NAMS 2008 Recommendations
(Diabetes)
Large RCTs suggest that HT use
reduces the new onset of type 2 DM
21% reduction in the WHI ET arm ofstudy
20% reduction in the HERS trial
Meta analyses data suggest HT isassociated with improvement in
insulin resistance
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NAMS 2008
(Invasive Breast Cancer Risk)
WHI-EPT use> 5 years: 4-6/10,000 woman-years
Significantly related to EPT useprior to
studyWHI-ET use
Noincreased risk after 7.1 years of use
6 fewercases per 10,000 woman years
This observed in all 3 age groups
(50-59; 60-69; 70-79)
Both may increase pain and density and
impede interpretation of mammograms
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UPCOMING STUDIES
ELITE STUDY (National Institute onAging) 2004-2009
Early vs Late Intervention Trial with Estrogen Measuring Carotid Artery Thickness with Estradiol
504n, 10 yrs. menopausal
KEEPS STUDY Kronos Early Estrogen Prevention Stugy 720n, age 42-58
Oral Premarin, TD Climara, Progesterone
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Bottom Line
Provider and Patient must Decide together
on Best Course of Action, Considering:
Risks
Benefits
Desires
History (Family and Personal)
Continuing Research
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Protective Levels
Depending on what one wants to protect:
Heart? Flushes
Vulvovagina
Uterus Bone
Breast
Colon
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Duration of Treatment
SHORT TERM PROTECTION
To manage immediate flushes, palpitations,
sleep disorders, usually
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Goal
Choices which
will allow us to
live the longesttime without
disability or loss
of function
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Case Presentation
48 y.o. MWF. LMP 18 months ago.
30 Flushes daily. Sweats and Insomnia atNight. Cries easily and has labile moods.
Great Aunt with history of Breast Cancer.Grandmother had a Hip Fracture. Father
had CABG at age 49 for CHD.
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Oral vs Transdermal Estrogen
(pg/ml)
020
40
60
80
100
120
140
160
180
Day
11
Day
11.5
Day
12
Day
12.5
Day
13
Day
13.5
Day
14
Day
14.5
PO EstradiolTD Gel
TD Patch
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PHARMACEUTICAL
INFLUENCE
Number one in sales in US, 2000 (Premarin)
Based on Observational Studies
HERS Study
Healy, NIH, WHI
Only NIH Prospective HRT Study Early Release of Results and Discontinuation