# Presentation: 265575

## Effectiveness of E2 and CEE on Postmenopausal Hot FlashesPreliminary Results of Review and Meta-analysis of Randomized Controlled TrialsHeidi D. Nelson MD, MPHOregon Health & Science University

## Background

**   ****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.**

## Objective

**To determine the relative effectiveness of conjugated equine estrogen (CEE) and 17-beta estradiol (E2) in relieving hot flashes in peri and postmenopausal women.**

## Methods

**  ****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**

## Results

**reviewed**

**119 Papers **
**retrieved**

**16 Transdermal **
**E2 vs placebo**

**11 Oral **
**E2 vs placebo**

**6 Oral CEE vs **
**transdermal E2**

**6 oral **
**CEE vs placebo**

**0 Oral **
**CEE vs oral E2**

**Results**

## 6 oral 

**CEE vs placebo**

**Studies not included:**
**    ****No frequency data**
**    ****Data in graph**
**    ****No SD data**

**Met criteria **
**for meta-analysis**

**11 oral **
**E2 vs placebo**

**5**

**6**

**5**

**1**

## Oral E2 and CEE versus Placebo

**Difference in weekly number of hot flashes**

**–****50**

**–****40**

**–****30**

**–****20**

**–****10**

**Viklylaeva, 1997: E2+P**

**Freedman, 2002: E2**

**Derman, 1995: E2+P**

**Conard, 1995: E2+P**

**Baerug, 1998: E2+P**

**Coope, 1975: CEE**

**  ****0  **

**DL pooled weighted mean difference = –16.9  (–22.8 to –11.0)**

**Notes:**
Coope 1975 is the only study of conjugated equine estrogen (CEE). All other studies are of estrodial (E2).

## 10 Studies not included:

**    ****No frequency data**
**    ****Data in graph**
**    ****No SD data**

**6 Met criteria **
**for meta-analysis**

**16 Transdermal **
**E2 vs placebo**

## Transdermal E2 versus Placebo

**Hot flash effect size**

**–****12**

**–****10**

**–****8**

**–****6**

**–****4**

**–****2**

**von Holst, 2002:**
** ****+P**

**von Holst, 2000**

**Speroff, 1996**

**Gordon, 1995**

**de Vrijer, 2000**

**Bacchi–Modena,**
**1997**

**  ****0****  **

**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)**

**Notes:**
Data from these studies were presented as differences between transdermal E2 groups and placebo groups instead of being presented as each treatment arms’ mean weekly number of hot flashes. So the pooled difference is estimated directly instead of as a weighted mean difference.

## 3 Studies not included:

**    ****Duplicate data**
**    ****Data in graph**
**    ****No SD data**

**3 Met criteria **
**for meta-analysis**

**6 Oral CEE vs**
**Transdermal E2**

## Oral CEE versus Transdermal E2

**Difference in weekly number of hot flashes**

**–****10**

**–****5**

**5**

**10**

**15**

**Studd, 1996: +P**

**Studd. 1995: +P**

**Gordon, 1995**

**  ****0  **

**DL pooled weighted mean difference = –0.3  (–3.4 to 2.7)**

**Oral CEE versus Transdermal E2**

**Favors CEE**

**Favors E2**

## Other 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.**

## Conclusions

**   ****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.**