BHT-HRT WomenSense Talk

7/31/2019 BHT-HRT WomenSense Talk

1/43

MENOPAUSAL HORMONE

THERAPY: Putting Talk Shows into

Perspective

Janice Werbinski, MD, Medical Director

Borgess Womens HealthWomenSense Lecture Series

June 2009


2/43

A $SIGN OF THE TIMES

WhoAREthese people??

Christiane Northrup

Lauren Hutton

Sally Field

Patty LaBelle

Oprah Winfrey

Robin McGraw

Suzanne Sommers


3/43

MENOPAUSE AND WOMENS

HEALTH PROVIDERS

Wulf Utian, MD

Holly Thacker, MD

Elizabeth Lee Vliet, MD

Wendy Klein, MD

Nancy Teaff, MD

Jan Werbinski, MD


4/43

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


5/43

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.


6/43

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


7/43

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


8/43

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


9/43

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


10/43

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


11/43

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?


12/43

ADDITIONAL TERMINOLOGY

Spontaneous/Natural Menopause Induced Menopause-surgical/chemorx

Perimenopause (8 years around LMP)

Premature Menopause (


13/43

ESTROGENS

Bioidentical Term:

17Beta Estradiol

EstroneEstriol


14/43


15/43

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


16/43

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


17/43

PROGESTERONE

PROGESTINMicronized Progesterone: BHT

PregnaneNorPregnane


18/43

PROGESTERONE

PROGESTINThe Natural Product

Corpus Luteum

USP Progesterone

Prometrium

MedroxyProgesterone Acetate-Provera

Progestins Norethindrone Acetate (NETA)

Norgestimate Desogestrel

Levonorgestrel

Norethindrone


19/43

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.


20/43

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


21/43

DHEA

DataInteresting

Possibility of Several Uses

No FDA Approval Health food stores

Compounding Pharmacies

Sports Ban

Congressional Bill Pending


22/43

OTHER HORMONES

Serotonin

NorEpinephrine

Dopamine

Melatonin

Pituitary

Growth

Thyroid

Cortisol/Adrenalin

Insulin


23/43

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%


24/43

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


25/43

Where Does The

WHI Leave Us Now?

0

0.5

1

1.5

2

2.5

MI CVA DVT FX Colon Breast

RR


26/43

What Else Can We Use?

Hot Flashes

Bone Density

Cardiovascular Disease

Colon Cancer Incontinence

Breast Cancer

Libido

Mood Changes

Memory Deficits


27/43

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


28/43

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


29/43

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)


30/43

Consensus 2008

ERT or HRT for severe climacteric symptoms(


31/43

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.


32/43

Timing of HT and CVD

Women


33/43

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


34/43

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


35/43

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


36/43

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


37/43

Bottom Line

Provider and Patient must Decide together

on Best Course of Action, Considering:

Risks

Benefits

Desires

History (Family and Personal)

Continuing Research


38/43

Protective Levels

Depending on what one wants to protect:

Heart? Flushes

Vulvovagina

Uterus Bone

Breast

Colon


39/43

Duration of Treatment

SHORT TERM PROTECTION

To manage immediate flushes, palpitations,

sleep disorders, usually


40/43

Goal

Choices which

will allow us to

live the longesttime without

disability or loss

of function


41/43

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.


42/43

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


43/43

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

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