Transcript Document

Future Treatment Strategies for
Menopausal Symptom
Management
Richard J. Santen, MD
Professor of Internal Medicine
University of Virginia Health System
Charlottesville, Virginia
Osteoporosis
Hot
Flashes
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
Placebo
Eligible
Patients
Stratify
Randomize
Agent
% Hot Flash Score Reduction (Mean)
Efficacy of Therapies for Hot Flashes
100
Placebo (n = 420)
Soy (n = 78)
Vitamin E (n = 53)
Clonidine (n = 75)
80
60
Venlafaxine (n = 48)
40
Megestrol (n = 74)
20
0
0
1
2
3
Week
Courtesy of C.L. Loprinzi, MD.
4
5
6
Efficacy of Gabapentin for Hot Flashes
Hot Flash Severity
Change from Baseline
in Hot Flash Severity
0
-2
-4
-6
Placebo (n = 113)
Gabapentin 300 mg
(n = 114)
Gabapentin 900 mg
(n = 120)
-8
-10
-12
-14
Baseline
Week 4
Week 8
Reprinted from Guttuso T, et al. Obstet Gynecol. 2003;101:337, with permission from
Lippincott Williams & Wilkins.
Hot Flashes
What Is New?
% Hot Flash Score Reduction (Mean)
Venlafaxine vs MPA for Hot Flashes
100
80
60
Venlafaxine (n = 94)
40
MPA 400 mg (n = 94)
20
MPA 500 mg x 3 (n = 7)a
0
0
aCL
1
2
Loprinzi, Unpublished data.
MPA = depomedroxyprogesterone acetate.
3
4
Week
Adapted from Loprinzi CL, et al. J Clin Oncol. 2006;24:1409, with permission from the
American Society of Clinical Oncology.
5
6
Venlafaxine vs MPA
Symptomatic Differencesa
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
aMean
for treatment week 6 score minus baseline score.
symptoms may be related to positive drug effect; others
likely related to drug toxicity.
MPA = depomedroxyprogesterone acetate.
bSome
Adapted from Loprinzi CL, et al. J Clin Oncol. 2006;24:1409, with permission from the
American Society of Clinical Oncology.
How do these and
other therapies compare?
% Hot Flash Score Reduction (Mean)
Efficacy of Therapies for Hot Flashes
100
Black Cohosh (n = 58)
Placebo (n = 420)
Soy (n = 78)
Vitamin E (n = 53)
Clonidine (n = 75)
80
60
Venlafaxine (vs MPA) (n = 94)
40
Venlafaxine (n = 48)
MPA 400 mg (n = 94)
20
Megestrol (n = 74)
MPA 500 mg x 3 (n = 7)a
0
0
1
2
3
Week
aCL
Loprinzi, Unpublished data.
Courtesy of C.L. Loprinzi, MD.
4
5
6
Desvenlafaxine (DVS)
Approved for Depression; Under Review for Hot Flashes
Reprinted from Speroff L, et al. Obstet Gynecol. 2008;111:77, with permission from
Lippincott Williams & Wilkins.
Osteoporosis
Hot
Flashes
Cardiovascular
Disease
What Does the Future Hold for
Osteoporosis Treatment
and Prevention?
Osteoporosis Prevention
and Treatment
Current Options

Bisphosphonates

Raloxifene

Parathyroid hormone analogs

Calcitonin
Osteoporosis
What 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.
Osteoporosis
Hot
Flashes
Cardiovascular
Disease
Menopausal Hormone Therapy
What Should We Tell Our
Patients After the Recent WHI Updates?
Hormone therapy is safer when
used early after menopause than
many years after menopause
Cardiovascular Disease and Estrogens
Background

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 Age
Estrogen Alone in Women with Hysterectomy
P for interaction = .07
Age(y)
.63
50–59
.94
60–69
1.11
70–79
0.0
aMyocardial
0.5
1.0
Hazard Ratio
infarction or coronary death.
WHI = Women’s Health Initiative
CHD = Coronary heart disease
Hsia J, et al. Arch Intern Med. 2006;166:357.
1.5
WHI—CHD Outcome by Years
Since Menopause
Estrogen + Progestin
Years
P for interaction =.331
P = .036 in reanalysis2
.89
<10
1.22
10–19
1.71
>20
0.0
0.5
1.0
1.5
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.
2.0
2.5
Conclusions

Less concern about coronary artery
disease 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