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Future Treatment Strategies for

Menopausal Symptom

Management

Richard J. Santen, MD Professor of Internal Medicine

University of Virginia Health System

Charlottesville, Virginia



Hot

Flashes

Osteoporosis

Cardiovascular

Disease



Menopausal hormone therapy works well

for hot flashes but in some women,such as women with breast cancer, estrogens

are contra-indicated. What is available to ameliorate

their hot flashes?



Alternatives to

estrogen

What is the evidence of efficacy?



Basic Study Design

Double Blind

Eligible

PatientsStratify Randomize

Placebo

Agent



0

20

40

60

80

100

0 1 2 3 4 5 6

Week

Placebo (n = 420)Soy (n = 78)

Clonidine (n = 75)

Megestrol (n = 74)

Venlafaxine (n = 48)

Vitamin E (n = 53)

Efficacy of Therapies for Hot Flashes

Courtesy of C.L. Loprinzi, MD.



Placebo (n = 113)

Gabapentin 300 mg

(n = 114)

0

-10

-6

Week 4

C h a n g e f r o m

B a s e l i n e

i n H o t F l a s h

S e v e r i t y

Baseline

-8

-4

-2

Week 8

Gabapentin 900 mg

(n = 120)-12

-14

Reprinted from Guttuso T, et al. Obstet Gynecol . 2003;101:337, with permission from

Lippincott Williams & Wilkins.

Efficacy of Gabapentin for Hot FlashesHot Flash Severity



Hot FlashesWhat Is New?



0

20

40

60

80

100

0 1 2 3 4 5 6

Week


MPA 400 mg (n = 94)

MPA 500 mg x 3 (n = 7)a

Adapted from Loprinzi CL, et al. J Clin Oncol . 2006;24:1409, with permission from the American Society of Clinical Oncology.

Venlafaxine vs MPA for Hot Flashes

MPA = depomedroxyprogesterone acetate.

aCL Loprinzi, Unpublished data.



Symptomb MPA

(400 mg)

Venlafaxine P -value

Constipation 6.8 -5.2 <.0001

Hot flash distress 50.2 28.9 <.0001

Abnormal sweating 39.0 20.4 .0002

Hot flash control

satisfaction

59.1 39.6 .0002

Venlafaxine vs MPASymptomatic Differencesa

Adapted from Loprinzi CL, et al. J Clin Oncol . 2006;24:1409, with permission from the

American Society of Clinical Oncology.

aMean for treatment week 6 score minus baseline score.bSome symptoms may be related to positive drug effect; others

likely related to drug toxicity.

MPA = depomedroxyprogesterone acetate.



How do these andother therapies compare?



0

20

40

60

80

100

0 1 2 3 4 5 6

Week

Placebo (n = 420)Soy (n = 78)

Clonidine (n = 75)

Megestrol (n = 74)


Vitamin E (n = 53)

Black Cohosh (n = 58)

Venlafaxine (vs MPA) (n = 94)

MPA 400 mg (n = 94)

MPA 500 mg x 3 (n = 7)a

Efficacy of Therapies for Hot Flashes

Courtesy of C.L. Loprinzi, MD.

aCL Loprinzi, Unpublished data.



Reprinted from Speroff L, et al. Obstet Gynecol . 2008;111:77, with permission from

Lippincott Williams & Wilkins.

Desvenlafaxine (DVS) Approved for Depression; Under Review for Hot Flashes



Hot

Flashes

Osteoporosis

Cardiovascular

Disease



What Does the Future Hold for

Osteoporosis Treatmentand Prevention?



OsteoporosisWhat Is New?



Strontium Ranelate for Preventing and

Treating Postmenopausal Osteoporosis

Efficacy of 2 g/day

Vertebral fractures at 3 years, RR 0.59

(0.46 –0.74)

Nonvertebral fractures at 3 years RR 0.86

(0.75 –0.98)

BMD 3 years, lumbar spine 11% increase

BMD 3 years, total hip 3.6% increase

O’Donnell S, et al. Cochrane Database Syst Rev . 2006;(4):CD005326.



Hot

Flashes

Cardiovascular

Disease

Osteoporosis



Menopausal Hormone Therapy

What Should We Tell Our

Patients After the Recent WHI Updates?

Hormone therapy is safer whenused early after menopause than

many years after menopause



Cardiovascular Disease and EstrogensBackground

What has happened in this field is that

clinicians re-analyzed the same data and

came to different conclusions from them

It all depends on your perspective



WHI—CHD Outcomea by AgeEstrogen Alone in Women with Hysterectomy

Age(y)

50 –59

60 –69

70 –79

0.0 0.5 1.0 1.5

Hazard Ratio

.63

.94

1.11

P for interaction = .07

aMyocardial infarction or coronary death.

WHI = Women’s Health Initiative

CHD = Coronary heart disease

Hsia J, et al. Arch Intern Med. 2006;166:357.



WHI—CHD Outcome by YearsSince Menopause

Estrogen + Progestin

0.0 0.5 1.0 1.5 2.0 2.5

Years

Hazard Ratio1 WHI = Women’s Health Initiative

1. Manson JE, et al. N Engl J Med. 2003;349:523.

2. Grodstein F, et al. J Womens Health (Larchmt). 2006;15:35.

<10

10 –19

>20

.89

1.22

1.71

P for interaction =.331

P = .036 in reanalysis2



Conclusions

Less concern about coronary arterydisease for the first 10 years after

menopause

Risk of stroke still remains

For women with symptoms of menopause,

many more will choose hormone therapy in

the future

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