Title: Effectiveness of E2 and CEE on Postmenopausal Hot Flashes Preliminary Results of Review and Metaanal
1Effectiveness of E2 and CEE on Postmenopausal Hot
FlashesPreliminary Results of Review and
Meta-analysis of Randomized Controlled
TrialsHeidi D. Nelson MD, MPHOregon Health
Science University
2Background
- Most initiators of postmenopausal estrogen
seek relief of menopausal symptoms. - Vasomotor symptoms, such as hot
flashes/flushes, are common, uncomfortable, and
interfere with function and sleep. - Estrogen therapy can diminish symptoms,
although it is not known if different forms of
estrogen have different effects.
3Objective
To determine the relative effectiveness of
conjugated equine estrogen (CEE) and 17-beta
estradiol (E2) in relieving hot flashes in peri
and postmenopausal women.
4Methods
- Systematic review of published literature
- - MEDLINE search (1966-present).
- - Abstract review RCTs of CEE and E2 in
symptomatic peri and postmenopausal women with
hot flash/flush outcomes. - - Study review double-blind RCTs of 12 weeks or
more outcomes measured and reported in
standardized ways. - - Evaluation of study quality using predefined
criteria. - Meta-analysis of eligible studies
5Results
778 Abstracts reviewed
119 Papers retrieved
11 Oral E2 vs placebo
6 oral CEE vs placebo
0 Oral CEE vs oral E2
16 Transdermal E2 vs placebo
6 Oral CEE vs transdermal E2
66 oral CEE vs placebo
11 oral E2 vs placebo
Met criteria for meta-analysis
5
1
Studies not included No frequency data
Data in graph No SD data
5
6
7Oral E2 and CEE versus Placebo
Difference in weekly number of hot flashes
Coope, 1975 CEE
Baerug, 1998 E2P
Conard, 1995 E2P
Derman, 1995 E2P
Freedman, 2002 E2
Viklylaeva, 1997 E2P
50
40
30
20
10
0
DL pooled weighted mean difference 16.9
(22.8 to 11.0)
816 Transdermal E2 vs placebo
6 Met criteria for meta-analysis
10 Studies not included No frequency data
Data in graph No SD data
9Transdermal E2 versus Placebo
Hot flash effect size
BacchiModena, 1997
de Vrijer, 2000
Gordon, 1995
Speroff, 1996
von Holst, 2000
von Holst, 2002 P
0
12
10
8
6
4
2
DL pooled effect size 5.3 (6.9 to
3.7) Difference in weekly number of hot flashes
22.4 (35.9 to 10.4)
106 Oral CEE vs Transdermal E2
3 Met criteria for meta-analysis
3 Studies not included Duplicate data
Data in graph No SD data
11Oral CEE versus Transdermal E2
Difference in weekly number of hot flashes
Gordon, 1995
Studd. 1995 P
Studd, 1996 P
Favors CEE
Favors E2
10
5
5
10
15
0
DL pooled weighted mean difference 0.3 (3.4
to 2.7)
12Other Factors
- Progestins Do not influence effect.
- Dose Higher doses have increased effect, but
may have more adverse effects. - Delivery system Both oral and transdermal E2
have similar effects, not compared head-to-head. - Patient characteristics Women with most
symptoms have most relief.
13Conclusions
- Oral CEE and E2 and transdermal E2 are
effective in reducing hot flashes in symptomatic
peri and postmenopausal women compared to
placebo. - Head-to-head comparisons indicate that
effectiveness is comparable between agents,
although there are only a few small studies
available. - Addition of progestin does not influence
effectiveness.