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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
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Hot
Flashes
Osteoporosis
Cardiovascular
Disease
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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?
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Alternatives to
estrogen
What is the evidence of efficacy?
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Basic Study Design
Double Blind
Eligible
PatientsStratify Randomize
Placebo
Agent
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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.
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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
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Hot FlashesWhat Is New?
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0
20
40
60
80
100
0 1 2 3 4 5 6
Week
Venlafaxine (n = 94)
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aCL Loprinzi, Unpublished data.
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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.
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How do these andother therapies compare?
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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)
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.
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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
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Hot
Flashes
Osteoporosis
Cardiovascular
Disease
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What Does the Future Hold for
Osteoporosis Treatmentand Prevention?
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OsteoporosisWhat Is New?
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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.
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Hot
Flashes
Cardiovascular
Disease
Osteoporosis
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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
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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
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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.
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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
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