Research www.AJOG .

org

GENERAL GYNECOLOGY
A metaanalysis on alcohol consumption and risk
of endometriosis
Fabio Parazzini, MD; Sonia Cipriani, ScD; Francesca Bravi, PhD; Claudio Pelucchi, ScD; Francesca Chiaffarino, ScD;
Elena Ricci, PhD; Paola Viganò, MD

OBJECTIVE: To offer a general figure of the available data on the relation
between alcohol intake and risk of endometriosis, we conducted a sys-
tematic review and a metaanalysis of studies published up to May 2012.
STUDY DESIGN: We carried out a literature search of all case-control
and cohort studies published as original articles in English up to May
2012. Only those papers that were published as full-length articles were
considered. Pooled estimates of the relative risks (RRs) and the cor-
responding 95% confidence intervals (CIs) were calculated using fixed
or, when significant heterogeneity among estimates emerged, random
effects models. A total of 15 studies were identified for the review.
RESULTS: The summary estimate was 1.24 (95% CI, 1.12e1.36) for
any alcohol intake vs no alcohol intake. Considering the results of the
analyses of infrequent, moderate/regular, and heavy alcohol intake vs
no alcohol intake, the summary RR estimates were, respectively, 1.14
(95% CI, 0.86e1.52), 1.23 (95% CI, 1.08e1.40), and 1.19 (95% CI,
0.99e1.43). Three studies reported separate results for current and
former drinkers, and the summary RR were 1.42 (95% CI, 1.14e1.76)
and 1.09 (95% CI, 0.83e1.43), respectively.
CONCLUSION: The present metaanalysis provides evidence for an
association between alcohol consumption and endometriosis risk.
Further studies are needed to clarify whether alcohol consumption may
exacerbate an existing disease or could be related to the severity of the
disease.
Key words: alcohol, endometriosis, epidemiology, risk factor

Cite this article as: Parazzini F, Cipriani S, Bravi F, et al. A metaanalysis on alcohol consumption and risk of endometriosis. Am J Obstet Gynecol 2013;209:106.e1-10.

E ndometriosis is an estrogen-
dependent, chronic inflammatory
gynecological condition. Despite the
high prevalence that has been estimated
between 6-10% in reproductive-age
women,1 and the recognized economic
From the Department of Obstetrics,
Gynecology, and Neonatology, Istituto di
Ricovero e Cura a Carattere Scientifico
Fondazione Cà Granda, Ospedale Maggiore
Policlinico (Drs Parazzini, Cipriani, Chiaffarino,
and Ricci); Istituto di Ricovero e Cura a Carattere
Scientifico–Istituto di Ricerche Farmacologiche
Mario Negri (Drs Cipriani, Bravi, and Pelucchi);
the Department of Clinical Medicine and
Community Health, University of Milan (Dr Bravi);
and the Obstetrics and Gynecology Unit, San
Raffaele Scientific Institute (Dr Viganò),
Milan, Italy.
Received Jan. 31, 2013; revised April 15, 2013;
accepted May 22, 2013.
The authors report no conflict of interest.
Reprints: Fabio Parazzini, MD, First Obstetric
and Gynecologic Clinic, University of Milan and
IRCCS Fondazione, Policlinico Mangiagalli
Regina Elena, Via Commenda 12, 20122
Milano, Italy. fabio.parazzini@marionegri.it.
0002-9378/$36.00
ª 2013 Mosby, Inc. All rights reserved.
http://dx.doi.org/10.1016/j.ajog.2013.05.039
burden associated with the disease,2
potential modifiable risk factors of
the disease are still to be completely
elucidated.
Alcohol has been consistently found to
increase the risk of developing estrogen-
dependent diseases such as breast can-
cer.3-5 It has been demonstrated that
alcohol intake increases circulating bio-
available estrogen level and this is believed
to be one of the mechanisms underlying
the association between alcohol con-
sumption and estrogen-dependent dis-
eases.6 Alcohol increases aromatase
activity, ie, the conversion of testosterone
to estrogens that results in reduced
testosterone and increased estrogens.7
Alcohol may also interact with luteiniz-
ing hormone production from the pitui-
tary gland, resulting in increased estradiol
release from the ovaries.7
On the other hand, long-term alcohol
intake may also affect immune function
and may regulate production of proin-
flammatory cytokines. A significant as-
sociation between alcohol consumption
and selected chronic inflammatory dis-
eases has been observed.8,9
Along these lines, several studies have
analyzed the association between alcohol
drinking and risk of endometriosis but
conflicting results have been published
regarding the potential effect.10-20 To
offer a general figure of the available data
on the relation between alcohol intake
and risk of endometriosis, we conducted
a systematic review and a metaanalysis of
studies published up to May 2012.
M ATERIALS AND M ETHODS
Identification of studies
We carried out a literature search of all
case-control and cohort studies pub-
lished as original articles in English up to
May 2012. We searched the electronic
databases MEDLINE (1966 through May
31, 2012), EMBASE (1985 through May
31, 2012), and Science Citation Index
Expanded (1945 through May 31, 2012)
using the Medical Subject Heading terms
“diet” or “nutrition” or “alcohol” or
“vitamin” or “fat” or “vegetable,” com-
bined with “endometriosis.” Only those
papers that were published as full-length
articles in English language were con-
sidered. Furthermore, we reviewed ref-
erence lists of retrieved articles to search
for other pertinent studies.
Two authors reviewed the papers
and independently selected the articles

106.e1 American Journal of Obstetrics & Gynecology AUGUST 2013

www.AJOG.org
eligible for the systematic review. Studies
were selected for review if they met all of
the following criteria:
- case-control or cohort study report-
ing original data;
- diagnosis of endometriosis was clini-
cally and/or histologically based;
- number or percentage of subjects
with and without endometriosis ac-
cording to alcohol intake were
provided;
- full-length articles, published in
English.
If multiple published reports from
a same study were available, we in-
cluded only the one with the most de-
tailed information, or published more
recently.
One study21 was excluded because
the level of alcohol intake was pro-
vided as Michigan Alcoholism Screening
Test score <5, 5-6, or
7, where a
Michigan Alcoholism Screening Test
score >5 is suggestive of alcoholism.
Thus, for this study the reference
category would not be comparable
with other studies included (ie, we
could not disentangle subjects with
no or low alcohol consumption). The
selection procedure is shown in
Figure 1.
FIGURE 1
Flowchart of publications selection
Parazzini. Alcohol and endometriosis. Am J Obstet Gynecol 2013.
General Gynecology
Data collection for metaanalysis
Data were extracted independently by 2
investigators and discrepancies were
resolved by discussion. For each study,
the following information was collected:
first author’s last name; year of publica-
tion; country of origin; study design;
number of subjects; age, if available;
category amounts of alcohol intake, if
available; site of endometriosis for cases,
if available; relative risks (RRs), hazard
ratios or odds ratios (ORs) of endome-
triosis and corresponding 95% confi-
dence intervals (CIs) for every category
of alcohol intake; and covariates adjusted
in the statistical analysis.
Statistical analysis
We combined the RR estimates from
each study. We computed unadjusted RR
from the exposure distributions of cases
and controls as reported in the publica-
tions. For the study by Heilier et al,17 we
used the method proposed by Hamling
et al,22 which allows combining the es-
timates originally shown in the paper,
changing the reference category and
taking into account the correlation be-
tween categories. For the study by
Signorello et al,12 we summed the data
concerning fertile and infertile controls
AUGUST 2013 American Journal of Obstetrics & Gynecology
Research
(Figures 2-4) other than for the sub-
group analyses (Figure 6). Three sepa-
rate estimates were given in the Figures
2, and 4-6 for the study by Hemmings
et al,15 according to different subgroups
of surgery type (ie, diagnostic laparos-
copy, tubal ligation, or hysterectomy).
The inverse variance method was used
to pool the RR. A fixed effect model was
used as the combination method. To
assess the heterogeneity across studies
we conducted a test based on the c2
distribution. When heterogeneity was
significant (ie, P < .05), the pooled esti-
mate was calculated using random ef-
fects model analysis. The Egger test and
funnel plot23,24 were used to detect
publication bias. In this graph, the effect
measure estimates are plotted against
corresponding sample size and, if there is
no publication bias, it should have the
shape of a funnel with a wide dispersion
of results among small studies and a
narrower range of results for large ones.
Subgroups analyses
We performed the subgroups’ analysis by
type of controls (fertile, infertile, both,
or not specified).
The statistical analyses were per-
formed using software (STATA, version
10.0; StataCorp LP, College Station, TX).
R ESULTS
Figure 1 shows a flowchart for selection
of articles. A total of 15 studies were
identified for the review.
The main methodological character-
istics of identified papers are presented
in Table 1. Most of them were retro-
spective case-control studies. One
cohort study was identified.25 A total of
5 studies were conducted in the United
States,12,19,20,26,27 4 in Europe,16,17,25,28
2 in Canada,13,15 1 in the United
States and Canada,11 1 in Japan,29
1 in Australia,30 and 1 in Taiwan.31
Simple “No” or “Yes” questions were
used in 6 studies to evaluate alcohol
intake.19,20,25,26,28,31
Table 2 reports the cutoffs of alcohol
drinking in different studies according
to the classification levels used in this
metaanalysis. Cutoffs used in differ-
ent studies were fairly homogeneous,
except for a somewhat lower cutoff for
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Research General Gynecology www.AJOG.org

moderate/regular alcohol consumption

in the study by Parazzini et al16 and for FIGURE 2
heavy alcohol consumption in the study Any vs no alcohol consumption
by Berubé et al.13

Systematic review
Figure 2 shows the study-specific and
pooled RR for any vs no alcohol intake.
All but 2 of the RR estimates were above
unity ranging from 0.34 to 2.28. The
summary estimate was 1.24 (95% CI,
1.12e1.36). In a sensitivity analysis, we
excluded results from 1 study that pro-
vided prevalence ORs,13 and we found
a summary RR of 1.23 (95% CI,
1.11e1.36).
Figures 3-5 present, respectively, the
results of the analyses of infrequent,
moderate/regular, and heavy alcohol
intake vs no alcohol intake. The sum-
mary RR estimates were, respectively,
1.14 (95% CI, 0.86e1.52), 1.23 (95%
CI, 1.08e1.40), and 1.19 (95% CI,
0.99e1.43). We also performed 2 sensi- Parazzini. Alcohol and endometriosis. Am J Obstet Gynecol 2013.
tivity analyses. One by excluding the
study where heavy drinkers were women
consuming relatively low amounts (ie,

9 drinks/mo) as compared to other and OR, 0.8; 95% CI, 0.3e2.4 [fertile consumption were associated with the
studies13; the estimate for heavy vs and infertile controls, respectively]), and risk of endometriosis.
no alcohol consumption was 1.14 (95% liquor (OR, 0.9; 95% CI, 0.9e2.2; Figure 7 shows the funnel plot for any
CI, 0.93e1.39). Another sensitivity and OR, 1.8; 95% CI, 0.6e5.3 [fertile vs no alcohol consumption. There was
analysis was performed by excluding the and infertile controls, respectively]) no asymmetry in the funnel plot, thus
study where moderate/regular drinkers
were women consuming relatively low
amounts (ie, 0.5-8 drinks/wk) as com-
FIGURE 3
pared to other studies16; the estimate for
Infrequent vs no alcohol consumption
moderate/regular vs no alcohol con-
sumption was 1.29 (95% CI, 1.12e1.49).
When we performed subgroup analysis
by type of controls, the estimates were
1.35 (95% CI, 0.97e1.87) for studies
based on infertile controls, 1.50 (95% CI,
1.15e1.95) for those of fertile controls,
and 1.19 (95% CI, 1.06e1.33) for those
of both fertile and infertile or unspecified
controls.
Only 1 study12 analyzed separately
the role of different types of alcoholic
beverages on endometriosis risk. White
wine consumption (OR, 3.5; 95% CI,
1.2e10.4; and OR, 1.5; 95% CI, 0.4e4.9
[fertile and infertile controls, respec-
tively]) but not red wine (OR, 1.3; 95% CI,
0.5e3.7; and OR, 0.8; 95% CI, 0.3e2.5
[fertile and infertile controls, respec- Parazzini. Alcohol and endometriosis. Am J Obstet Gynecol 2013.
tively]), beer (OR, 1.0; 95% CI, 0.4e2.5;

106.e3 American Journal of Obstetrics & Gynecology AUGUST 2013

www.AJOG.org
FIGURE 4
Moderate/regular vs no alcohol consumption
Parazzini. Alcohol and endometriosis. Am J Obstet Gynecol 2013.
suggesting the absence of publication
bias; the Egger test was not significant
(P ¼ .902).
Table 3 reports the study-specific and
summary risk estimates of endometriosis
for current and former drinkers as
FIGURE 5
Heavy vs no alcohol consumption
Parazzini. Alcohol and endometriosis. Am J Obstet Gynecol 2013.
General Gynecology
compared to never drinkers. Three studies
reported separate results for current and
former drinkers, and the summary RR
were 1.42 (95% CI, 1.1e1.8) and 1.09
(95% CI, 0.83e1.43), respectively. Two
other studies gave results for current and
AUGUST 2013 American Journal of Obstetrics & Gynecology
Research
former drinkers combined, vs never
drinkers, and the summary RR was 1.95
(95% CI, 1.26e3.04).
C OMMENT
A relation between alcohol drinking and
endometriosis risk is biologically plau-
sible since alcohol has been shown to
increase levels of endogenous estrogens.7
Indeed, a potential association between
alcohol intake and risk of endometriosis
has been suggested since the early
1990s.11,21 As a matter of fact, the general
results of this metaanalysis confirm that
any alcohol intake is associated with
an increased risk of endometriosis
compared to no alcohol consumption.
No clear dose-risk relationship emerged.
However, we have to underline the fact
that the definition of irregular, regular/
moderate, and heavy alcohol drinking
included different doses of alcohol intake.
In the interpretation of the association
between alcohol intake and risk of
endometriosis, potential confounding
factors should be considered. Alcohol
consumption has been shown to affect
reproduction in animal and human
research. For example, animal research
indicates that alcohol decreases steroid
hormone levels, reduces ovarian weight,
and causes amenorrhea in rats and
monkeys.5 Alcohol intake has been
shown to increase time to pregnancy,
and the risk of (subclinical) spontaneous
abortions. Further, alcohol consumption
has been also associated with infer-
tility.32,33 Thus, it is possible that the
association between alcohol drinking
and endometriosis risk may be, at least in
part, explained by the role of infertility.
However, the studies that have consid-
ered the potential confounding role of
parity or have analyzed data separately
for women with diagnosis of endome-
triosis due to pelvic pain or ovarian cysts
have generally confirmed the associa-
tion. In the study conducted by Signo-
rello et al,12 the OR estimates were
largely similar for alcohol drinkers in
comparison with teetotalers when in
the analysis fertile or infertile controls
were considered. Further, published
studies differ in the population defini-
tion, depending on the choices to select
both cases and controls from fertile and
106.e4
Research General Gynecology
FIGURE 6
Any vs no alcohol consumption, by type of controls
Parazzini. Alcohol and endometriosis. Am J Obstet Gynecol 2013.
infertile women, and controls from
healthy subjects or patients with condi-
tions other than endometriosis. This
heterogeneity may have an impact on the
results. Among other confounding fac-
tors, we have to consider socioeconomic
status and body mass. High socioeco-
nomic status has been associated with an
increased risk of endometriosis. The
prevalence of alcohol drinking in various
social strata may vary in different coun-
tries, but various studies conducted in
high-income countries reported that
alcohol consumption was more frequent
in women with high education/in-
come.34,35 Likewise, high body mass in-
dex, which is associated with high alcohol
intake, was reported to lower the risk
of diagnosis of endometriosis.16 Only
a few studies included adjustment for
106.e5 American Journal of Obstetrics & Gynecology AUGUST 2013
these covariates, therefore we cannot
totally exclude the possibility that con-
founding plays some role in the associa-
tion we found between alcohol and
endometriosis.
Considering the results of each study
separately we observed that in most
studies, women with endometriosis re-
ported a higher intake of alcohol
drinking than those without the con-
dition.11-13,19,20,30 However this associ-
ation was not confirmed in other
studies.15,16
A main methodological problem in
the epidemiology of endometriosis is the
choice of controls.36 In this review, a
direct association between alcohol intake
and risk of endometriosis was observed
both in studies that have included con-
trols recruited in hospital for different
www.AJOG.org
acute conditions16 or women without
endometriosis confirmed by surgery or
ultrasounds.25
Endometriosis is a chronic, long-
lasting condition. It has been suggested
that women with pelvic painerelated
endometriosis may drink alcohol to alle-
viate pain.11 Some studies have analyzed
separately the role of alcohol drinking
among women with or without pain,11 or
considered only women without severe
pain13: in these studies the association
between alcohol and endometriosis was
consistent with the general findings of this
metaanalysis. Otherwise it has been sug-
gested that women with endometriosis
are more frequently depressed than the
general population37 and women with
depression problems are more common
to drink more alcohol.38 Thus it is highly
plausible that patients with endometriosis
suffer from their condition physically and
emotionally and may resort to drinking as
a coping mechanism. In the analysis, we
are not able to take into account the po-
tential confounding role of depressed
mood.
In general, a limitation of this analysis
is the fact that we are not able, from the
published studies, to evaluate if alcohol
exposure preceded the development of
endometriosis. In the 3 studies that have
considered separately former and cur-
rent alcohol drinkers, an association
emerged with current, but not former
use. Thus, we cannot exclude that the
observed association is explained, at least
in part, by reverse causation. However,
some studies analyzed separately the role
of alcohol drinking among women with
or without pain,11 or considered only
women without severe pain,13 reporting
consistent findings.
It has been suggested that the risk
factors (as well as the pathogenesis) of
pelvic and deep endometriosis may
differ.13,39 We cannot analyze separately
the effect of alcohol on the risk of
endometriosis in different sites, given
the small number of studies reporting
this information. In the study by Heilier
et al,17 alcohol drinking increased the
risk of endometriosis among cases with
deep, but not pelvic, endometriosis.
However, most studies showing an as-
sociation between alcohol drinking and
 www.AJOG.org
TABLE 1
Main characteristics of considered studies
Sample size Alcohol consumption
cases/ Confounding factors assessment as
Study Country Study design Cases Controls controls Age, y considered in analysis reported by authors
Berubé Canada Case-control on Infertile women for Women with 329/262 20-39 0, 1-2, 3-8,
et al,13 1998 baseline data collected minimal or mild unexplained infertility
9 drinks/mo
in a prospective study endometriosis
(laparoscopically
diagnosed)
Buck Louis United Hospital-based Women with Women without 32/52 18-40 In utero exposure, None, 1-4,
et al,27 2007 States case-control in endometriosis in endometriosis from age, parity, smoking
5 drinks/mo
cohort of women cohort undergoing same cohort of cases habit, caffeine intake
undergoing laparoscopy for any
laparoscopy gynecologic indication
including sterilization
Eskenazi Italy Cohort study Women with Women without 19/277 30 in 1976 Yes for polytomous Never, former, current
et al,25 2002 endometriosis endometriosis confirmed analysis
confirmed by surgery by surgery or negative
or ultrasound ultrasound examination
examination
Grodstein United Hospital-based Women with primary Fertile women 180/3833 Age, center, smoking No consumption,
et al,11 1994 States, case-control infertility due to habits, lifetime no. of moderate (100 g/wk),
Canada endometriosis sexual partners, heavier (>100 g/wk)
contraception, BMI,
AUGUST 2013 American Journal of Obstetrics & Gynecology

exercise, coffee
Heilier Belgium Matched Women with PE Women with no clinical 88 (PE), None Never, <1 time/wk,
et al,17 2007 case-control or DEN suspicion of PE or DEN; 88 (DEN)/88 several times/wk,
without infertility, pelvic every day

General Gynecology
pain, dysmenorrhea;
with normal pelvic
examination and vaginal
echography; with serum
CA-125 <35 U/mL
Hemmings Canada Hospital-based Women with Women with no evidence 896/1881 Premenopausal None, <7,
et al,15 2004 case-control endometriotic lesions at of endometriotic lesion age
7 drinks/wk
time of surgery (surgery at surgery (surgery for
for diagnosis, diagnosis,
fertility-regulating fertility-regulating

Research
surgery, hysterectomy) surgery, hysterectomy)
Huang Taiwan Case-control Women with Women without 28/29 Mean: Backward selection No, yes
et al,31 2010 endometriosis endometriosis cases ¼ 34.3, of confounders
controls ¼ 36.2
106.e6

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106.e7 American Journal of Obstetrics & Gynecology AUGUST 2013

TABLE 1
Main characteristics of considered studies (continued)
Sample size Alcohol consumption
cases/ Confounding factors assessment as
Study Country Study design Cases Controls controls Age, y considered in analysis reported by authors
Marino United Case-control Women with surgically Women without 341/742 18-49 None Never, former, current
et al,20 2009 States confirmed endometriosis endometriosis randomly

General Gynecology
from GH cooperative selected from list of GH
during same period
Matalliotakis United Case-control in Women with pelvic Infertile women (tubal or 535/200 15-56 None No/yes
et al,19 2008 States retrospective endometriosis who had male factor infertility)
review undergone laparoscopy
or laparotomy for pelvic
pain or infertility
within 6 y
Nagle Australia Case-control Women with surgically Women without 268/244 18-55 None Never/occasional,
et al,30 2009 confirmed endometriosis infrequent, regular
endometriosis (defined by author and
not otherwise specified)
Parazzini Italy Hospital-based Women with Women admitted for 504/504 20-65 Age, calendar year, <0.5, 0.5-8,
et al,16 2004 case-control laparoscopically acute nongynecological, education, parity,
8 drinks/wk
(from confirmed nonhormonal, nonneoplastic BMI, study (thresholds based on
2 studies) endometriosis conditions tertiles of control group)
Pauwels Belgium, The Case-control Infertile endometriosis Mechanical infertile 42/27 24-42 Age, BMI, ovulatory <6,
6 drinks/wk
et al,28 2001 Netherlands women women disfunction, smoking
pattern, caffeine
consumption
Signorello United Hospital-based Women with 89 fertile women and 50/(89 23-44 Age, education, height, None, any, <once/wk,
et al,12 1997 States case-control infertility-associated 47 infertile women and 47) weight, regularity of
once/wk; alcohol
endometriosis both without menstrual cycle, consumption was
endometriosis exercise smoking assessed for overall
consumption and for
each type of drink:
beer, liquor, red wine,
white wine
Trabert United Population-based Women with endometriosis Women without 284/660 18-49 None Never, present, former
et al,26 2011 States case-control (ICD-9 ¼ 617.0, .5, .8, .9) endometriosis from
from GH cooperative GH during same period

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Tsukino Japan Case-control Women with stage II-IV Women without 58/81 20-45 Menstrual regularity, None/occasionally,
et al,29 2005 endometriosis endometriosis or stage average cycle (d) weekly, daily
I endometriosis
BMI, body mass index; CA, cancer antigen; DEN, deep endometriotic nodules; GH, group health; ICD-9, International Classification of Diseases, Ninth Revision; PE, peritoneal endometriosis.
Parazzini. Alcohol and endometriosis. Am J Obstet Gynecol 2013.
www.AJOG.org
TABLE 2
Classification of dose of alcohol drinking in different studies
Study
Berubé et al, 199813
Buck Louis et al, 2007 27
Grodstein et al, 1994 11
Heilier et al,17 2007
Hemmings et al, 2004 15
Nagle et al,30 2009
Parazzini et al,16 2004
Pauwels et al,28 2001
Signorello et al, 1997 12
29
Tsukino et al, 2005
a
Categories defined “infrequent” and “regular” by authors; b Tertile of intake, reference category: <0.5 drinks/wk, pure alcohol content was assumed in each type of drink (125 mL wine ¼ 333 mL
beer ¼ 30 mL spirits).
Parazzini. Alcohol and endometriosis. Am J Obstet Gynecol 2013.
endometriosis risk included cases with
pelvic endometriosis.
Some researchers have suggested
that drinks containing higher alcohol
concentrations, ie, liquors and spirits,
could be more deleterious for alcohol-
FIGURE 7
Funnel plot of any vs no alcohol consumption
Parazzini. Alcohol and endometriosis. Am J Obstet Gynecol 2013.
General Gynecology Research
Infrequent Moderate/regular Heavy
1-2 drinks/mo 3-8 drinks/mo
9 drinks/mo
1-4 drinks/mo
5 drinks/mo
100 g/wk ¼ <1 drink/ >100 g/wk ¼
1 drink/d ¼
30 drinks/mo
d ¼ <30 drinks/mo
<Once/wk ¼ <4 drinks/mo Several times/wk ¼ 4-29 drinks/mo Every day ¼
30 drinks/mo
<7 drinks/wk ¼ <30 drinks/mo
7 drinks/wk ¼
30 drinks/mo
a a
0.5-8 drinks/wkb
8 drinks/wkb

6 drinks/wk ¼
24 drinks/mo
<Once/wk ¼ <4 drinks/mo
Once/wk ¼
4 drinks/mo
Weekly Daily
related diseases than drinks with lower The only study that presented separately
alcohol concentrations, although the the effect of different alcoholic bever-
issue is still under discussion.40 Again, ages showed a (positive) association only
available data do not allow us to address with wine drinking, in particular white
the role of different types of alcoholic wine.12 Further studies examining this
beverages on the risk of endometriosis. topic are thus needed.
Compared with metaanalysis of ran-
domized clinical trials, those including
observational studies are potentially
more subject to bias and other sources
of heterogeneity.41 In all the studies in-
formation regarding alcohol use was
self-reported, thus some misclassifica-
tion may have occurred. More in general
alcohol drinking, and in particular heavy
drinking, may be misreported in obser-
vational studies.42,43 However, studies
investigating reproducibility and validity
of self-reported alcohol drinking in
various populations found satisfactory
correlation coefficients (between 0.61-
0.99).44-49 In general, however, any
misclassification should tend to reduce
the OR estimates. With reference to
other sources of bias, the contour-
enhanced funnel plot and the Egger
test for funnel plot asymmetry did not
show any evidence of publication bias,
providing further indication of the
robustness of our results. Moreover,
only one of the included studies inves-
tigated as main endpoint the association
between alcohol drinking and endo-
metriosis risk: thus it is unlikely that
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Research General Gynecology
TABLE 3
Alcohol drinking and risk of endometriosis according to time of intake
Nevera
Author Case/control
Eskenazi et al, 2002 25
14/171
Marino et al,20 2009 92/258
26
Trabert et al, 2011 78/228
Pooled OR
Huang et al, 201031
25/26
Matalliotakis et al, 2008 19
193/83
Pooled OR
CI, confidence interval; OR, odds ratio.
a
Reference category.
Parazzini. Alcohol and endometriosis. Am J Obstet Gynecol 2013.
positive or negative results regarding
the association between alcohol drink-
ing and endometriosis risk were de-
terminants of publication. Among other
strengths of our analysis is the relatively
large number of studies and total sub-
jects considered, which provided ade-
quate statistical power to detect also
limited summary risk estimates.
Although alcohol consumption may
adversely affect endometriosis probably
through an endocrine-mediated effect, it
cannot be excluded that multiple mech-
anisms could be involved. Alcohol intake
may influence the immune response in
various ways, affecting functions and
mechanisms of both innate and acquired
immunity.9 Alcohol is generally be-
lieved to suppress the immune response.
However, recent data suggest that acute
alcohol intake decreases inflammation
and immunity whereas chronic expo-
sure leads to opposite effects, inducing
proinflammatory cytokine production in
various cell types as well as increasing
lymphocyte proliferation and activa-
tion.9 Therefore, since endometriosis is
characterized by a chronic inflammatory
reaction, alcohol-mediated effect may
interfere with this phenomenon.
In conclusion, the present meta-
analysis provides evidence for a signifi-
cant positive association between alcohol
consumption and endometriosis risk,
although the issue of causality remains
open to discussion. Further studies are
106.e9 American Journal of Obstetrics & Gynecology AUGUST 2013
Current Former
Case/control OR (95% CI) Case/control OR (95% CI)
3/950.39 (0.11e1.38) 2/112.22 (0.45e11.02)
159/3071.45 (1.07e1.97) 62/1621.07 (0.74e1.57)
154/2921.54 (1.12e2.13) 51/1401.06 (0.71e1.61)
1.42 (1.1e1.8) 1.09 (0.83e1.43)
e e
e e
needed to clarify whether alcohol con-
sumption may exacerbate an existing
disease or could be related to the severity
of the disease. - 10. Grodstein F, Goldman MB, Ryan L,
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