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Endometrial Hyperplasia Endometrial Hyperplasia and Estrogen Therapy and Estrogen Therapy Fred Ueland, MD Fred Ueland, MD Division of Gynecologic Oncology Division of Gynecologic Oncology University of Kentucky University of Kentucky

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Page 1: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky

Endometrial Hyperplasia

Endometrial Hyperplasia

and Estrogen Therapy

and Estrogen Therapy

Fred Ueland, MD

Fred Ueland, MD

Division of Gynecologic Oncology

Division of Gynecologic Oncology

University of Kentucky

University of Kentucky

Page 2: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky

Are You Reading?

Are You Reading?

“It is astonishing with

“It is astonishing with

how little reading a

how little reading a

doctor can practice

doctor can practice

medicine, but it is not

medicine, but it is not

astonishing how badly

astonishing how badly

he may do it”

he may do it”

W. Osler

W. Osler

Page 3: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky

Mt Sopris

Carbondale, CO

Page 4: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky

Endometrial Hyperplasia

Endometrial Hyperplasia

Synonyms

Synonyms

Simple hyperplasia

Simple hyperplasia

Glandular hyperplasia

Glandular hyperplasia

Cystic glandular hyperplasia

Cystic glandular hyperplasia

Endometrial hyperplasia

Endometrial hyperplasia

Page 5: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky

Endometrial Hyperplasia

Endometrial Hyperplasia

Hyperplasia, simple or complex

Hyperplasia, simple or complex

Glandular architecture

Glandular architecture

Glandular crowding at expense of stroma

Glandular crowding at expense of stroma

“Back to back” crowding

“Back to back” crowding

Cytological atypia, absent or present

Cytological atypia, absent or present

Nuclear enlargement

Nuclear enlargement

Hyperchromasia

Hyperchromasia

Irregularity in shape

Irregularity in shape

Page 6: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky

Hyperplasia Risk Factors

Hyperplasia Risk Factors

Anovulation-PCO

Exogenous estrogen

Endogenous estrogen

Family history

Nulliparity

Age

Infertility

Tamoxifen

Early menarche

Late menopause

Diabetes

Hypertension

Granulosa cell tumors

History of breast of

colon cancer

Menstrual irregularities

Page 7: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky

Endometrial Hyperplasia

Endometrial Hyperplasia

Page 8: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky

Simple Hyperplasia

Simple Hyperplasia

Page 9: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky

Simple Hyperplasia

Simple Hyperplasia

Page 10: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky

Simple Hyperplasia

Simple Hyperplasia

Page 11: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky

Complex Hyperplasia

Complex Hyperplasia

Page 12: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky

Complex Hyperplasia

Complex Hyperplasia

Page 13: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky

Hyperplasia with Atypia

Hyperplasia with Atypia

Page 14: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky

Atypical Endometrial Cells

Atypical Endometrial Cells

Page 15: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky

Atypical Glandular Cells

Atypical Glandular Cells

Cystic Hyperplasia

Cystic Hyperplasia

Page 16: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky

Diagnosis of Hyperplasia

Diagnosis of Hyperplasia

Page 17: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky

Evaluation of the Endometrium

Evaluation of the Endometrium

48

48

-

-

80

80

80

80

-

-

90

90

PPV=9%

PPV=9%

Cheap, easy,

Cheap, easy,

NPV=99%

NPV=99%

TVS

TVS

NA

NA

94

94

Anesth

Anesth

,

,

perforation

perforation

Reusable,

Reusable,

hysteroscopy

hysteroscopy

Curette

Curette

NA

NA

83

83

$, equip,

$, equip,

perforation

perforation

Pain

Pain

Vabra

Vabra

99

99

45

45

-

-

100

100

Disposable

Disposable

Cheap,

Cheap,

office

office

Pipelle

Pipelle

% Spec

% Spec

% Sens

% Sens

Cons

Cons

Pros

Pros

Options

Options

Page 18: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky

Endometrial Biopsy

Endometrial Biopsy

Page 19: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky

Management of Hyperplasia

Management of Hyperplasia

Page 20: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky
Page 21: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky

Endometrial

Endometrial

Hyperplasia

Hyperplasia

Page 22: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky

Estrogen Therapy

Estrogen Therapy

Page 23: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky

Steroid Pathway

Steroid Pathway

Page 24: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky

Menstrual Cycle

Menstrual Cycle

Page 25: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky
Page 26: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky
Page 27: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky
Page 28: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky
Page 29: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky

Endometrial Stimulation

Endometrial Stimulation

Estrogen

Estrogen

Cancer Initiated Cells

Cancer Initiated Cells

Non

Non

-

-

initiated Cells

initiated Cells

Neoplasia

Hyperplasia

Hyperplasia

Page 30: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky
Page 31: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky
Page 32: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky
Page 33: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky
Page 34: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky

The Women’s Health Initiative

The Women’s Health Initiative

Randomized Trial

Randomized Trial

This multi

This multi

-

-

million dollar, 15

million dollar, 15

-

-

year project,

year project,

sponsored by the National Institutes of

sponsored by the National Institutes of

Health (NIH), National Heart, Lung, and

Health (NIH), National Heart, Lung, and

Blood Institute (NHLBI), involves 161,808

Blood Institute (NHLBI), involves 161,808

women aged 50

women aged 50

-

-

79, and is one of the most

79, and is one of the most

definitive, far

definitive, far

-

-

reaching clinical trials of

reaching clinical trials of

post

post

-

-

menopausal women's health ever

menopausal women's health ever

undertaken in the U.S.

undertaken in the U.S.

Page 35: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky

The Women’s Health Initiative

The Women’s Health Initiative

Randomized Trial

Randomized Trial

The WHI has two major parts: a randomized Clinical

The WHI has two major parts: a randomized Clinical

Trial and an Observational Study. The randomized

Trial and an Observational Study. The randomized

controlled Clinical Trial (CT) enrolled 68,132

controlled Clinical Trial (CT) enrolled 68,132

postmenopausal women between the ages of 50

postmenopausal women between the ages of 50

-

-

79

79

into trials testing three prevention strategies. If

into trials testing three prevention strategies. If

eligible, women could choose to enroll in one,

eligible, women could choose to enroll in one,

two, or all three of the trial components. The

two, or all three of the trial components. The

components are:

components are:

Hormone Therapy Trials (HT)

Hormone Therapy Trials (HT)

Dietary Modification Trial (DM)

Dietary Modification Trial (DM)

Calcium/Vitamin D Trial (

Calcium/Vitamin D Trial (

CaD

CaD

)

)

Page 36: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky

Effects of Conjugated Equine Estrogen on

Effects of Conjugated Equine Estrogen on

Stroke in the Women’s Health Initiative

Stroke in the Women’s Health Initiative

Circulation.

Circulation.

2006;113:2425

2006;113:2425

-

-

2434

2434

Conclusions:

Conclusions:

CEE increases the risk of

CEE increases the risk of

ischemic stroke in generally healthy

ischemic stroke in generally healthy

postmenopausal women. The excess risk

postmenopausal women. The excess risk

appeared to be present in all subgroups of

appeared to be present in all subgroups of

women examined, including younger and

women examined, including younger and

more recently menopausal women. There

more recently menopausal women. There

was no convincing evidence to suggest that

was no convincing evidence to suggest that

CEE had an effect on the risk of

CEE had an effect on the risk of

hemorrhagic stroke.

hemorrhagic stroke.

Page 37: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky

Venous Thrombosis and Conjugated Equine

Venous Thrombosis and Conjugated Equine

Estrogen in Women Without a Uterus

Estrogen in Women Without a Uterus

Arch Intern Med.

Arch Intern Med.

2006;166:772

2006;166:772

-

-

780.

780.

Conclusion

Conclusion

: An early increased VT risk is

: An early increased VT risk is

associated with use of estrogen, especially

associated with use of estrogen, especially

within the first 2 years, but this risk increase

within the first 2 years, but this risk increase

is less than that for estrogen plus progestin.

is less than that for estrogen plus progestin.

Page 38: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky

Conjugated Equine Estrogens and Coronary

Conjugated Equine Estrogens and Coronary

Heart Disease

Heart Disease

Arch

Arch

InternMed

InternMed

.

.

2006;166:357

2006;166:357

-

-

365

365

Conclusions:

Conclusions:

Conjugated equine estrogens

Conjugated equine estrogens

provided no overall protection against

provided no overall protection against

myocardial infarction or coronary death in

myocardial infarction or coronary death in

generally healthy postmenopausal women

generally healthy postmenopausal women

during a 7

during a 7

-

-

year period of use. There was a

year period of use. There was a

suggestion of lower coronary heart disease

suggestion of lower coronary heart disease

risk with CEE among women 50 to 59 years

risk with CEE among women 50 to 59 years

of age at baseline.

of age at baseline.

Page 39: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky

Effects of Conjugated Equine Estrogens on

Effects of Conjugated Equine Estrogens on

Breast Cancer and Mammography Screening in

Breast Cancer and Mammography Screening in

Postmenopausal Women With Hysterectomy

Postmenopausal Women With Hysterectomy

JAMA.

JAMA.

2006;295:1647

2006;295:1647

-

-

1657

1657

Conclusions:

Conclusions:

Treatment with CEE alone for

Treatment with CEE alone for

7.1 years does not increase breast cancer

7.1 years does not increase breast cancer

incidence in postmenopausal women with

incidence in postmenopausal women with

prior hysterectomy. However, treatment

prior hysterectomy. However, treatment

with CEE increases the frequency of

with CEE increases the frequency of

mammography screening requiring short

mammography screening requiring short

interval follow

interval follow

-

-

up. Initiation of CEE should

up. Initiation of CEE should

be based on consideration of the individual

be based on consideration of the individual

woman's potential risks and benefits.

woman's potential risks and benefits.

Page 40: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky

Conjugated Equine Estrogens and Global

Conjugated Equine Estrogens and Global

Cognitive Function in Postmenopausal Women

Cognitive Function in Postmenopausal Women

JAMA.

JAMA.

2004;291:2959

2004;291:2959

-

-

2968

2968

Conclusion:

Conclusion:

For women aged 65 years or

For women aged 65 years or

older, hormone therapy had an adverse

older, hormone therapy had an adverse

effect on cognition, which was greater

effect on cognition, which was greater

among women with lower cognitive

among women with lower cognitive

function at initiation of treatment.

function at initiation of treatment.

Page 41: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky
Page 42: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky
Page 43: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky

Effect of Estrogen Plus Progestin on Stroke in

Effect of Estrogen Plus Progestin on Stroke in

Postmenopausal Women

Postmenopausal Women

JAMA.

JAMA.

2003;289:2673

2003;289:2673

-

-

2684

2684

Conclusions:

Conclusions:

Estrogen plus progestin

Estrogen plus progestin

increases the risk of ischemic stroke in

increases the risk of ischemic stroke in

generally healthy postmenopausal women.

generally healthy postmenopausal women.

Excess risk for all strokes attributed to

Excess risk for all strokes attributed to

estrogen plus progestin appeared to be

estrogen plus progestin appeared to be

present in all subgroups of women

present in all subgroups of women

examined.

examined.

Page 44: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky

Estrogen Plus Progestin and Risk of Venous

Estrogen Plus Progestin and Risk of Venous

Thrombosis

Thrombosis

JAMA.

JAMA.

2004;292:1573

2004;292:1573

-

-

1580

1580

Conclusions:

Conclusions:

Estrogen plus progestin was

Estrogen plus progestin was

associated with doubling the risk of venous

associated with doubling the risk of venous

thrombosis. Estrogen plus progestin therapy

thrombosis. Estrogen plus progestin therapy

increased the risks associated with age,

increased the risks associated with age,

overweight or obesity, and factor

overweight or obesity, and factor V Leiden.

Page 45: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky

Estrogen plus Progestin and the Risk of

Estrogen plus Progestin and the Risk of

Coronary Heart Disease

Coronary Heart Disease

NEJM volume 349:523

NEJM volume 349:523

-

-

534, August 2003

534, August 2003

Conclusions:

Conclusions:

Estrogen plus progestin does not

Estrogen plus progestin does not

confer cardiac protection and may increase

confer cardiac protection and may increase

the risk of CHD among generally healthy

the risk of CHD among generally healthy

postmenopausal women, especially during

postmenopausal women, especially during

the first year after the initiation of hormone

the first year after the initiation of hormone

use. This treatment should not be prescribed

use. This treatment should not be prescribed

for the prevention of cardiovascular disease

for the prevention of cardiovascular disease.

Page 46: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky

Effect of Estrogen Plus Progestin on Global

Effect of Estrogen Plus Progestin on Global

Cognitive Function in Postmenopausal Women

Cognitive Function in Postmenopausal Women

JAMA.

JAMA.

2003;289:2663

2003;289:2663

-

-

2672

2672

Conclusions:

Conclusions:

Among postmenopausal women aged

Among postmenopausal women aged

65 years or older, estrogen plus progestin did not

65 years or older, estrogen plus progestin did not

improve cognitive function when compared with

improve cognitive function when compared with

placebo. While most women receiving estrogen

placebo. While most women receiving estrogen

plus progestin did not experience clinically

plus progestin did not experience clinically

relevant adverse effects on cognition compared

relevant adverse effects on cognition compared

with placebo, a small increased risk of clinically

with placebo, a small increased risk of clinically

meaningful cognitive decline occurred in the

meaningful cognitive decline occurred in the

estrogen plus progestin group.

estrogen plus progestin group.

Page 47: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky

Symptom Experience After Discontinuing Use

Symptom Experience After Discontinuing Use

of Estrogen Plus Progestin

of Estrogen Plus Progestin

JAMA.

JAMA.

2005;294:183

2005;294:183

-

-

193

193

Conclusions:

Conclusions:

More than half of the women with

More than half of the women with

vasomotor symptoms at randomization to active

vasomotor symptoms at randomization to active

CEE + MPA also reported these symptoms after

CEE + MPA also reported these symptoms after

discontinuing use of the study pills. However,

discontinuing use of the study pills. However,

these participants did not include women who

these participants did not include women who

were unwilling to be randomized or who had

were unwilling to be randomized or who had

stopped taking the study pills earlier. These

stopped taking the study pills earlier. These

findings should be considered when advising

findings should be considered when advising

women to treat menopausal symptoms with

women to treat menopausal symptoms with

hormone therapy for as short duration as possible.

hormone therapy for as short duration as possible.

Investigation of alternative strategies to manage

Investigation of alternative strategies to manage

menopausal symptoms is warranted.

menopausal symptoms is warranted.

Page 48: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky

Estrogen plus Progestin and Colorectal Cancer

Estrogen plus Progestin and Colorectal Cancer

in Postmenopausal Women

in Postmenopausal Women

NEJM, Volume 350:991

NEJM, Volume 350:991

-

-

1004 March 2004

1004 March 2004

Conclusions:

Conclusions:

Relatively short

Relatively short

-

-

term use of

term use of

estrogen plus progestin was associated with

estrogen plus progestin was associated with

a decreased risk of colorectal cancer.

a decreased risk of colorectal cancer.

However, colorectal cancers in women who

However, colorectal cancers in women who

took estrogen plus progestin were diagnosed

took estrogen plus progestin were diagnosed

at a more advanced stage than those in

at a more advanced stage than those in

women who took placebo.

women who took placebo.

Page 49: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky

Effects of Estrogen Plus Progestin on Risk of

Effects of Estrogen Plus Progestin on Risk of

Fracture and Bone Mineral Density

Fracture and Bone Mineral Density

JAMA.

JAMA.

2003;290:1729

2003;290:1729

-

-

1738.

1738.

Conclusions:

Conclusions:

This study demonstrates that estrogen

This study demonstrates that estrogen

plus progestin increases BMD and reduces the risk

plus progestin increases BMD and reduces the risk

of fracture in healthy postmenopausal women. The

of fracture in healthy postmenopausal women. The

decreased risk of fracture attributed to estrogen

decreased risk of fracture attributed to estrogen

plus progestin appeared to be present in all

plus progestin appeared to be present in all

subgroups of women examined. When considering

subgroups of women examined. When considering

the effects of hormone therapy on other important

the effects of hormone therapy on other important

disease outcomes in a global model, there was no

disease outcomes in a global model, there was no

net benefit, even in women considered to be at

net benefit, even in women considered to be at

high risk of fracture.

high risk of fracture.

Page 50: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky

Estrogen Plus Progestin and the Risk of

Estrogen Plus Progestin and the Risk of

Peripheral Arterial Disease

Peripheral Arterial Disease

Circulation.

Circulation.

2004;109:620

2004;109:620

-

-

626

626

Conclusions:

Conclusions:

Among generally healthy

Among generally healthy

postmenopausal women, conjugated

postmenopausal women, conjugated

estrogens with progestin did not confer

estrogens with progestin did not confer

protection against peripheral arterial

protection against peripheral arterial

disease.

disease.

Page 51: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky

Effects of Estrogen plus Progestin on Health

Effects of Estrogen plus Progestin on Health

-

-

Related Quality of Life

Related Quality of Life

NEJM, March 17, 2003

NEJM, March 17, 2003

Conclusions:

Conclusions:

In this trial in postmenopausal

In this trial in postmenopausal

women, estrogen plus progestin did not

women, estrogen plus progestin did not

have a clinically meaningful effect on

have a clinically meaningful effect on

health

health

-

-

related quality of life.

related quality of life.

Page 52: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky
Page 53: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky

WHI Summary

WHI Summary

0.79

0.79

NS

NS

DM

DM

0.89

0.89

(0.63

(0.63

-

-

1.25)

1.25)

NA

NA

PVD

PVD

0.76

0.76

(0.69

(0.69

-

-

0.83)

0.83)

NA

NA

BMD

BMD

0.56

0.56

(0.38

(0.38

-

-

0.81)

0.81)

NA

NA

CRC

CRC

50% at DC

50% at DC

NA

NA

Vasomotor

Vasomotor

(p=0.008)

(p=0.008)

1.47

1.47

(1.04

(1.04

-

-

2.07)

2.07)

Cognition

Cognition

1.24

1.24

(1.0

(1.0

-

-

1.54)

1.54)

0.95

0.95

(0.79

(0.79

-

-

1.16)

1.16)

CAD

CAD

2.06

2.06

(1.57

(1.57

-

-

2.70)

2.70)

1.47

1.47

(1.06

(1.06

-

-

2.06)

2.06)

DVT

DVT

1.31

1.31

(1.02

(1.02

-

-

1.68)

1.68)

1.37

1.37

(1.09

(1.09

-

-

1.73)

1.73)

Stroke

Stroke

E

E

2

2

and MPA

and MPA

Estrogen

Estrogen

Page 54: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky

WHI Summary

WHI Summary

Gynecological Issues

Gynecological Issues

1.87

1.87

(1.61

(1.61

-

-

2.18)

2.18)

2.15

2.15

(1.77

(1.77

-

-

2.62)

2.62)

SUI

SUI

1.58

1.58

(0.77

(0.77

-

-

3.24)

3.24)

NA

NA

Ovarian Ca

Ovarian Ca

0.81

0.81

(0.48

(0.48

-

-

1.36)

1.36)

NA

NA

Endometrial Ca

Endometrial Ca

1.24

1.24

(p<0.001)

(p<0.001)

0.80

0.80

(0.62

(0.62

-

-

1.04)

1.04)

Breast Ca

Breast Ca

E

E

2

2

and MPA

and MPA

Estrogen

Estrogen

Page 55: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky

Influence of Estrogen Plus Progestin on Breast

Influence of Estrogen Plus Progestin on Breast

Cancer and Mammography in Healthy

Cancer and Mammography in Healthy

Postmenopausal Women

Postmenopausal Women

JAMA.

JAMA.

2003;289:3243

2003;289:3243

-

-

3253

3253

Conclusions:

Conclusions:

Relatively short

Relatively short

-

-

term combined

term combined

estrogen plus progestin use increases incident

estrogen plus progestin use increases incident

breast cancers, which are diagnosed at a more

breast cancers, which are diagnosed at a more

advanced stage compared with placebo use, and

advanced stage compared with placebo use, and

also substantially increases the percentage of

also substantially increases the percentage of

women with abnormal mammograms. These

women with abnormal mammograms. These

results suggest estrogen plus progestin may

results suggest estrogen plus progestin may

stimulate breast cancer growth and hinder breast

stimulate breast cancer growth and hinder breast

cancer diagnosis.

cancer diagnosis.

Page 56: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky

Effects of Estrogen Plus Progestin on

Effects of Estrogen Plus Progestin on

Gynecologic Cancers and Associated

Gynecologic Cancers and Associated

Diagnostic Procedures

Diagnostic Procedures

JAMA.

JAMA.

2003;290:1739

2003;290:1739

-

-

1748

1748

Conclusions:

Conclusions:

This randomized trial suggests that

This randomized trial suggests that

continuous combined estrogen plus progestin

continuous combined estrogen plus progestin

therapy may increase the risk of ovarian cancer

therapy may increase the risk of ovarian cancer

while producing endometrial cancer rates similar

while producing endometrial cancer rates similar

to placebo. The increased burden of endometrial

to placebo. The increased burden of endometrial

biopsies required to assess vaginal bleeding

biopsies required to assess vaginal bleeding

further limits the acceptability of this regimen.

further limits the acceptability of this regimen.

These data provide additional support for caution

These data provide additional support for caution

in the use of continuous combined hormones.

in the use of continuous combined hormones.

Page 57: Endometrial Hyperplasia and Estrogen Therapy · Endometrial Hyperplasia and Estrogen Therapy Fred Ueland, MD Division of Gynecologic Oncology University of Kentucky

Effects of Estrogen With and Without Progestin

Effects of Estrogen With and Without Progestin

on Urinary Incontinence

on Urinary Incontinence

JAMA.

JAMA.

2005;293:935

2005;293:935

-

-

948.

948.

Conclusions:

Conclusions:

Conjugated equine estrogen

Conjugated equine estrogen

alone and CEE + MPA increased the risk of

alone and CEE + MPA increased the risk of

UI among continent women and worsened

UI among continent women and worsened

the characteristics of UI among

the characteristics of UI among

symptomatic women after 1 year.

symptomatic women after 1 year.

Conjugated equine estrogen with or without

Conjugated equine estrogen with or without

progestin should not be prescribed for the

progestin should not be prescribed for the

prevention or relief of UI.

prevention or relief of UI.