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

3
Week

Courtesy of C.L. Loprinzi, MD.

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

Loprinzi, Unpublished data.

MPA = depomedroxyprogesterone acetate.

Week

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

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

3
Week

aCL

Loprinzi, Unpublished data.

Courtesy of C.L. Loprinzi, MD.

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

(0.460.74)

Nonvertebral fractures at 3 years RR 0.86

(0.750.98)

BMD 3 years, lumbar spine 11% increase

BMD 3 years, total hip 3.6% increase

ODonnell 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

WHICHD Outcomea by Age

Estrogen Alone in Women with Hysterectomy
P for interaction = .07

Age(y)
.63

5059
.94

6069
1.11

7079
0.0
aMyocardial

0.5

1.0

Hazard Ratio

infarction or coronary death.

WHI = Womens Health Initiative
CHD = Coronary heart disease
Hsia J, et al. Arch Intern Med. 2006;166:357.

1.5

WHICHD Outcome by Years

Since Menopause
Estrogen + Progestin
Years

P for interaction =.331

P = .036 in reanalysis2

.89
<10
1.22

1019

1.71

>20

0.0

0.5

1.0

1.5

Hazard Ratio1

WHI = Womens 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