Systematic Reviews

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GYNECOLOGY

Continuous versus cyclic oral contraceptives

after laparoscopic excision of ovarian
endometriomas: a systematic review
and metaanalysis
Ludovico Muzii, MD; Chiara Di Tucci, MD; Chiara Achilli, MD; Violante Di Donato, MD;
Angela Musella, MD; Innocenza Palaia, MD; Pierluigi Benedetti Panici, MD

ndometriosis is dened as the

presence of endometrial-like tissue outside the uterus. Endometriosis
may be present as peritoneal implants,
adhesions, deeply inltrating lesions,
or ovarian endometriomas. Endometriomas are present in 17-44% of the
patients with endometriosis1 and are
usually associated with pelvic pain
and infertility.2,3
Medical therapy may be considered a
cost-effective treatment in case of
endometriosis-associated pain symptoms. Oral contraceptives (OCs) and
progestins are considered the rst-line
option for medical therapy.4,5 Surgical
excision is considered the standard
treatment when an ovarian endometrioma is present because endometriomas do not respond to medical
therapy.1,4,5 Surgery may be needed in
particular when pain persists under
medical treatment or in the case of
enlarging or suspect endometriotic
cysts.
In patients not currently seeking
pregnancy, medical treatment is usually administered after surgical excision
of the endometrioma to reduce postoperative cyst recurrence and pain

From the Department of Obstetrics and

Gynecology, Sapienza University of Rome,
Rome, Italy.
Received Feb. 27, 2015; revised Aug. 6, 2015;
accepted Aug. 31, 2015.
The authors report no conict of interest.
Corresponding author: Ludovico Muzii, MD.
ludovico.muzii@uniroma1.it
0002-9378/$36.00
2016 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.ajog.2015.08.074

In the lack of evidence consistently supporting the use of continuous vs cyclic oral
contraceptives after surgery for endometriosis, we conducted a systematic review and
metaanalysis with the objective of comparing a continuous vs a cyclic oral contraceptive
schedule administered after surgical excision of ovarian endometriomas. A PubMed,
MedLine, and Embase search through December 2014 was conducted, with the use of a
combination of key words and text words related to endometrioma, endometriosis, oral
contraceptives, oral estroprogestins, laparoscopy, and surgery. Studies directly
comparing a continuous vs a cyclic schedule administered after surgical treatment of
endometriomas were included, with pain and endometrioma recurrence rates as the
primary outcomes. Three reviewers independently assessed methodology and extracted
data from selected studies. The primary outcomes were considered pain recurrence
(evaluated separately for dysmenorrhea, noncyclic chronic pelvic pain, and dyspareunia)
and endometrioma recurrence evaluated at ultrasonography. Dichotomous outcomes
from each study were expressed as risk ratio (RR) with a 95% confidence interval (CI).
Three randomized clinical trials and 1 prospective controlled cohort study were included,
for a total of 557 patients with endometriosis, 343 patients of whom had ovarian
endometriomas completing the assigned treatment and follow-up. Lower recurrence
rates for dysmenorrhea were obtained with a continuous schedule (RR, 0.24; 95% CI,
0.06e0.91; P .04). Nonsignificant differences were present for chronic pelvic pain
and dyspareunia. A continuous oral contraceptive schedule was associated with a
nonsignificant reduction of cyst recurrence rates compared with a cyclic schedule (RR,
0.54; 95% CI, 0.28e1.05; P .07). A continuous oral contraceptive regimen, as
opposed to a cyclic regimen, may be suggested after surgery for endometriomas
because of lower dysmenorrhea recurrence rates. Due to the small number and small
sample sizes of the included studies, further randomized clinical trials are needed to
confirm the findings of the present systematic review. Also, outcomes related to patient
satisfaction and quality of life should be addressed.
Key words: endometrioma, endometriosis, laparoscopy, medical treatment, oral
contraceptives

recurrence rates. Several studies have

compared
postoperative
medical
treatment vs placebo or no treatment,
with conicting results.3-6 A Cochrane
metaanalysis on postoperative medical
therapy did not report a signicant
reduction of pain and cyst recurrence
rates.6 However, 3 recent systematic
reviews7-9 have demonstrated that a
postoperative OC is effective in

reducing the recurrence rates, particularly when administered in the long

term.8
OCs may be administered either with
a conventional cyclic schedule or
continuously with no pill-free interval.
International guidelines on the medical
treatment of endometriosis do not suggest either administration schedule as
preferable. Few studies compared a

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FIGURE 1

Idenficaon

Flow diagram of studies identified in the systematic review

Records idenfied through
database searching
(n = 13 )

Addional records idenfied

through other sources
(n = 0 )

Eligibility

Screening

Records aer duplicates removed

(n = 8 )

Records screened
(n = 8 )

Records excluded
(n = 4 )

Full-text arcles assessed

for eligibility
(n = 4 )

Full-text arcles excluded,

with reasons
(n = 0 )

Included

Studies included in
qualitave synthesis
(n = 4 )

Studies included in
quantave synthesis
(meta-analysis)
(n = 4 )

Muzii. Continuous vs cyclic OC for endometriomas. Am J Obstet Gynecol 2016.

cyclic vs a continuous OC regimen

administered after excisional surgery for
endometriomas.10-13 Results of these
studies are not consistent as to the
efcacy of either regimen on cyst or
pain recurrence. In light of a lack of
consensus on this issue, we performed a
systematic review of the pertinent medical literature.
The objective of the present study was
to conduct a systematic review and
metaanalysis of the available literature
comparing the efcacy of a cyclic vs
continuous OC regimen on pain
and cyst recurrence after surgery for
endometrioma.

Materials and Methods

Eligibility criteria and study selection
The present systematic review involved
all published research articles that
compared the efcacy of a continuous

vs a cyclic OC regimen after surgery

for ovarian endometriomas in the prevention of endometriosis recurrence.
Studies assessing endometrioma recurrence at ultrasonography and/or pain
recurrence at follow-up were included.
Pain symptoms were evaluated separately for dysmenorrhea, noncyclic
chronic pelvic pain, and dyspareunia.
Studies evaluating only a cyclic or a
continuous regimen were excluded.
Studies reporting OC treatment after
surgery for endometrioma recurrence
were excluded.
Information sources and search
strategy
An electronic database search was performed using PubMed, MEDLINE, and
Embase for the identication of articles
published through December 2014, using the combination of the following

204 American Journal of Obstetrics & Gynecology FEBRUARY 2016

search terms: endometrioma, endometriosis, oral contraceptives, oral estroprogestins, laparoscopy, and surgery.
Only articles in English were included.
Only full-length articles from peer review journals were considered. Congress
abstracts were excluded.
Outcome measures
The primary analyses were aimed at
determining the recurrence of endometrioma and the recurrence of pain after
continuous OCs compared with cyclic
OCs.
The recurrence of endometrioma had
to be evaluated at transvaginal ultrasonography. The recurrence of pain, separately for dysmenorrhea, noncyclic
chronic pain, and dyspareunia, had to be
reported either as a dichotomous variable (symptom either present or absent)
or as a continuous variable expressed
with any validated scale (visual analog
scale, for example). The pain outcome
was evaluated separately for dysmenorrhea, noncyclic chronic pelvic pain,
and dyspareunia. In the case of studies
reporting all symptoms together, the
authors were contacted to obtain the
data for each symptom separately.
Secondary outcomes included discontinuation of treatment because of
side effects, reoperation rates, patient
satisfaction, and quality of life expressed
with any validated method.
In the case of studies reporting on OC
treatment after surgery for endometriosis in which the data from the population of patients with endometriomas
were not reported separately from
those of patients with endometriosis
but without an endometrioma, the
authors were contacted to obtain the
missing data for the former population.
In case the missing data could not be
obtained, the studies were considered
at the primary analysis for the evaluation
of pain recurrence and secondary outcomes; a secondary analysis after the
exclusion of these studies was planned
for the evaluation of endometrioma
recurrence.
A sensitivity analysis was planned
after the exclusion of nonrandomized
studies and randomized clinical trials
(RCTs) at high risk of bias.

Gynecology

>6
>6
27.0  2.7 28.0  2.4 30 mg EE 3 mg
drospirenone
21/84 14/54
(25.0%) (25.9%)

Assessment of risk of bias

Risk of bias assessment for the RCTs
included in this review was performed
using the Cochrane risk of bias assessment tool. Six domains were evaluated:
random sequence generation, allocation
concealment, blinding of outcome
assessor, completeness of outcome data
reporting, selective outcome reporting,
and other potential sources of bias. The

4.5  1.4 4.8  1.7

Muzii. Continuous vs cyclic OC for endometriomas. Am J Obstet Gynecol 2016.

FIGURE 2

EE, ethinyl estradiol; NR, not reported; RCT, randomized controlled trial.

138
Vlahos et al, Prospective 293
cohort
201313

Systematic Reviews

Data collection and extraction

Three investigators conducted the search
independently. Following the electronic
search, all articles considered pertinent
on the basis of the title and abstract were
retrieved, and their reference list was
searched for additional potential studies.
Subsequently, the same investigators
independently read the full text to verify
the pertinence of the article to the systematic review on continuous vs cyclic
OCs after surgery of ovarian endometrioma. The data were extracted independently by each investigator and
recorded on apposite forms. In the case
of missing data, or data expressed as diagrams, plots, or rates with no absolute
numbers, the authors were contacted to
obtain the missing or incomplete data.
Disagreements between authors were
resolved by mutual discussion or by
involvement of further investigators.

NR

6-12-18-24
24
20 mg EE 0.075 mg
gestodene
29.6
30.2
NR
NR
NR
NR
187
187
Seracchioli RCT
et al, 201011

148
148
Seracchioli RCT
et al, 201010

NR

6-12-18-24
24
8/75
11/73
(10.7%) (15.1%)
4.9  0.8 5.1  1.1
>4

29.7  2.8 28.6  2.4 20 mg EE 0.075 mg

gestodene

>6
6
30.3  2.9 30.6  3.1 20 mg EE 0.150 mg
desogestrel
NR
NR
5.0  0.9 5.1  1.0
>3
57
57
Muzii et al, RCT
201112

Minimum
Mean diameter SD, Patients with
Patients with cyst
cm
bilateral cysts, n, % Mean age SD, y
Oral contraceptive
Patients, endometrioma, diameter for
Continuous Cyclic Continuous Cyclic
Continuous Estrogen Progestin
inclusion, cm Cyclic
n
n
Authors
and year of Study
publication design

Descriptive data of the studies included in the systematic review

TABLE

Duration of
treatment, Follow-up,
mo
mo

ajog.org

Risk of bias assessment for the

included studies

Muzii. Continuous vs cyclic OC for endometriomas. Am J

Obstet Gynecol 2016.

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FIGURE 3

Forest plot for endometrioma recurrence

CI, confidence interval; M-H, Mantel-Haenszel.

Muzii. Continuous vs cyclic OC for endometriomas. Am J Obstet Gynecol 2016.

possibility of a publication bias was

assessed visually using a funnel plot for
asymmetry for the primary outcomes.
Data synthesis
The data were pooled using RevMan
software (Review Manager version 5.1,
the Cochrane Collaboration, 2011).
Dichotomous outcomes from each study
were express as a risk ratio (RR) with a
95% condence interval (CI). Heterogeneity between studies was based on the
results of the I2 and X2 statistics. A
random-effect model was used at metaanalysis in case of high heterogeneity (I2
> 50% or P <.10), whereas a xed-effect
model was used in case of low heterogeneity between studies. A value of P < .05
was considered statistically signicant.
Trial registration
The systematic review was registered in
the PROSPERO International Prospective

Register of Systematic Reviews with the

registration number of CRD4201
5016616. The Preferred Reporting Item
for Systematic Reviews and Meta-analysis
was followed.

Results
Study selection
The electronic search identied 13
potentially relevant papers. After removal
of duplicates, 8 records were considered.10-17 On the basis of the title and
abstract, 4 articles were included,10-13
whereas 4 were excluded14-17 (Figure 1),
for the following reasons: 2 were review
studies,15,17 and 2 studies did not
compare a cyclic vs a continuous OC
regimen14,16 (Figure 1).
After reading of the full text, 4
studies were included at nal analysis,
for a total of 557 patients evaluated. A
total of 496 patients completed the
assigned treatment and scheduled

FIGURE 4

Forest plot of sensitivity analysis for endometrioma recurrence

CI, confidence interval; M-H, Mantel-Haenszel.

Muzii. Continuous vs cyclic OC for endometriomas. Am J Obstet Gynecol 2016.

206 American Journal of Obstetrics & Gynecology FEBRUARY 2016

follow-up, 343 of which had ovarian

endometriomas.
Study characteristics
The main characteristics of the included studies are detailed in the Table.
In all the included studies, surgical
treatment was performed by laparoscopic excision of the cyst wall. In no
case nonexcisional techniques or oophorectomies were performed. Three
studies were RCTs,10-12 and 1 was a
prospective cohort trial.13 Comparable
patient characteristics and exclusion
rates for the 2 treatment arms are reported in the 4 included studies.
None of the 3 RCTs was at high risk of
bias (Figure 2). Funnel plots for the
primary outcomes did not reveal any
publication bias. Two of the RCTs were
conducted by the same principal investigator10,11: the rst of the 2 studies
evaluated endometrioma recurrence at

Gynecology

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Systematic Reviews

FIGURE 5

Forest plot for dysmenorrhea recurrence

CI, confidence interval; M-H, Mantel-Haenszel.

Muzii. Continuous vs cyclic OC for endometriomas. Am J Obstet Gynecol 2016.

ultrasonography,10 whereas the second

one evaluated the recurrence of pain in
patients with ovarian endometriomas,11
with the latter study including additional patients with smaller endometriomas compared with the former
study. The other 2 studies evaluated both
endometrioma and pain recurrence.12,13
Two studies compared a continuous
vs a cyclic OC regimen,12,13 whereas 2
studies included also a third group of
untreated patients, which was not
included in this metaanalysis.10,11
Three studies evaluated endometrioma
recurrence at ultrasonograpy.10,12,13
Three studies evaluated pelvic pain: 2
studies analyzed dysmenorrhea, chronic
pelvic pain, and dyspareunia separately,11,13 whereas 1 study reported pain
symptoms together.12 In this latter case,
the authors were contacted to obtain data
for each symptom separately: separate
data were provided by the authors for
dysmenorrhea and noncyclic pelvic pain,

whereas dyspareunia was not among the

evaluated outcomes.12 In 2 studies,12,13
pain recurrence was expressed as a
dichotomous variable (ie, presence or
absence of pain), whereas in a third study,
pain was expressed both as a categorical
variable and as a continuous variable
expressed with a visual analog scale
scale.11
A metaanalysis was performed for the
presence or absence of recurrent pain as
a dichotomous variable expressed as RR
with 95% CI, considering separately
dysmenorrhea, chronic pelvic pain, and
dyspareunia. For the study reporting
pain both as a dichotomous and as a
continuous variable,11 only pain expressed as a dichotomous variable was
included in the metaanalysis, for consistency with the other studies.
One study13 reported on patients with
endometriosis, and, among the outcomes considered in the present systematic review, only the outcome of cyst

recurrence was reported separately for

the subgroup of patients with ovarian
endometriomas. Both the rst author
and corresponding author were contacted to have separate data for the
endometrioma patients and also for the
other outcomes considered, but no
response was obtained. Therefore, a
secondary analysis was conducted, with
the exclusion of this study.13 The same
study is also the only nonrandomized
study among the included studies.
Therefore, the same secondary metaanalysis is valid as a sensitivity analysis
performed after exclusion of nonrandomized studies.
The follow-up timing schedule varied
between a minimum of 6 months13 and a
maximum of 24 months after surgery.10,11 In most studies, multiple
follow-up visits were planned, at either 6
or 12 month intervals (Table). For some
outcomes, however, results were reported only at 12 months. For

FIGURE 6

Forest plot of sensitivity analysis for dysmenorrhea recurrence

CI, confidence interval; M-H, Mantel-Haenszel.

Muzii. Continuous vs cyclic OC for endometriomas. Am J Obstet Gynecol 2016.

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FIGURE 7

Forest plot for chronic pelvic pain recurrence

CI, confidence interval; M-H, Mantel-Haenszel.

Muzii. Continuous vs cyclic OC for endometriomas. Am J Obstet Gynecol 2016.

consistency, the 12 month visit data were

therefore considered for all outcomes.
As concerns the primary outcomes,
recurrence of endometrioma was not
signicantly different after a continuous
vs a cyclic OC schedule (RR, 0.54; 95%
CI, 0.28e1.05; P .07) (Figure 3).
Heterogeneity for this comparison was
low (I2 0%). At the sensitivity analysis,
after exclusion of the nonrandomized
study,13 the endometrioma recurrence
rates were still not signicantly different
between the 2 schedules (RR, 0.53; 95%
CI, 0.22e1.31, P .17) (Figure 4).
Heterogeneity for this comparison was
low (I2 0%).
For the pain recurrence rates, a
continuous OC regimen was associated
with a signicantly lower RR for dysmenorrhea recurrence (RR, 0.24; 95% CI,
0.06e0.91; P .04) (Figure 5). Heterogeneity for this comparison was high
(I2 67%). After the exclusion of the
nonrandomized study,13 a statistically

signicant difference was not reached for

a lower RR risk after a continuous OC
schedule (RR, 0.10; 95% CI, 0.00e2.70;
P .17) (Figure 6). Heterogeneity for this
comparison was high (I2 80%).
Nonsignicant differences were present for chronic pelvic pain (RR, 0.61;
95% CI, 0.36e1.03; P .06) (Figure 7)
and dyspareunia (RR, 0.77; 95% CI,
0.52e1.12; P .17) (Figure 8). Heterogeneity was high for the former metaanalysis (I2 51%) and low for the latter
(I2 0%). A sensitivity analysis with the
exclusion of the only non-RCT did not
change signicantly the results for
chronic pelvic pain (RR, 0.78, with 95%
CI, 0.56e1.07; P .13, I2 0%)
(Figure 9) and for dyspareunia (RR, 0.87,
with 95% CI, 0.56e1.35, P .53). In this
latter analysis, only 1 study could be
included.11
As to the secondary outcomes,
discontinuation of contraception therapy was not signicantly different for a

FIGURE 8

Forest plot for dyspareunia recurrence

CI, confidence interval; M-H, Mantel-Haenszel.

Muzii. Continuous vs cyclic OC for endometriomas. Am J Obstet Gynecol 2016.

208 American Journal of Obstetrics & Gynecology FEBRUARY 2016

continuous vs a cyclic treatment (RR,

1.74; 95% CI, 0.83e3.64; P .14)
(Figure 10). Heterogeneity for this
comparison was high (I2 51%). A
sensitivity analysis did not signicantly
change the results (RR, 1.47; 95% CI,
0.39e5.59, P .57) (Figure 11). Heterogeneity for this comparison was high
(I2 71%).
Reoperation rates also were not
signicantly different between the 2
schedules (RR, 0.53; 95% CI, 0.16e1.74,
P .30) (Figure 12), with low heterogeneity (I2 0%). Patient satisfaction
rates were reported in only 1 study,12
with nonsignicant differences between
the 2 schedules. No study reported on
quality of life.

Comment
Main ndings
In the present systematic review and
metaanalysis, a continuous regimen of
OCs appears more efcacious than a

Gynecology

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Systematic Reviews

FIGURE 9

Forest plot of sensitivity analysis for chronic pelvic pain recurrence

CI, confidence interval; M-H, Mantel-Haenszel.

Muzii. Continuous vs cyclic OC for endometriomas. Am J Obstet Gynecol 2016.

cyclic regimen as to dysmenorrhea

recurrence rates. The RR for dysmenorrhea recurrence after a continuous OC
regimen is 0.24 (95% CI, 0.06e0.91;
P .04). Nonsignicant differences between the 2 schedules are present for
chronic pelvic pain and dyspareunia.
There is a trend toward lower cyst
recurrence rates for a continuous vs a
cyclic OC regimen, with an RR of 0.54
(95% CI, 0.28e1.05), but statistical signicance was not reached (P .07).
Strengths and limitations
The present study represents the rst
metaanalysis on the comparison of a
conventional OC cyclic schedule vs a
continuous schedule administered after
surgery for endometrioma excision.
Because no recommendation for either
schedule is consistently reported in
evidence-based guidelines,3-5,18,19 a systematic review and metaanalysis on this

topic may bring important information

to the clinician dealing with patients
with endometriosis.
The present metaanalysis has, however, several limitations. First of all, only
4 studies evaluated a continuous vs a
cyclic OC regimen after surgical excision
of the endometrioma,10-13 with inconsistent results. Sample sizes are small for
most of the studies, and the largest study
is not a RCT,13 thus possibly introducing
potential biases. Two studies included
largely overlapping populations,10,11
with 1 study evaluating only pain as the
primary outcome11 and the other evaluating only endometrioma recurrence.10
Therefore, for most comparisons in the
present metaanalysis, only 2 or 3 studies
could be included. At the sensitivity
analysis, only 2 or, for some outcomes,
only 1 study could be included. In most
comparisons with low heterogeneity,
only 2 studies were included, and the low

I2 might be expected because of the low

number of included studies.
Comparison with existing literature
Two recent systematic reviews on postoperative OC suggested that continuous
and cyclic schedules may have comparable efcacy7,8 and that the choice of
regimen should be modulated on patient
preference.7 In both systematic reviews,
however, a direct comparison of a
continuous vs a cyclic schedule was not
among the outcomes evaluated. In fact,
both reviews were aimed only at evaluating the effect of any postoperative OC
vs no treatment.
A systematic review comparing the
use of a continuous vs a cyclic OC after
surgery was recently published by Zorbas et al.20 The authors of the systematic
review concluded that the use of a
continuous OC schedule may be more
benecial than a cyclic schedule. In the

FIGURE 10

Forest plot for discontinuation of treatment

CI, confidence interval; M-H, Mantel-Haenszel.

Muzii. Continuous vs cyclic OC for endometriomas. Am J Obstet Gynecol 2016.

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FIGURE 11

Forest plot of sensitivity analysis for discontinuation of treatment

CI, confidence interval; M-H, Mantel-Haenszel.

Muzii. Continuous vs cyclic OC for endometriomas. Am J Obstet Gynecol 2016.

study by Zorbas et al, however, a metaanalysis was not performed, and only a
descriptive analysis of the literature
was provided, with inconsistent results
among the selected studies. Also, 1 of
the 3 available RCTs10-12 was missed by
the search performed, therefore limiting
the validity of the systematic review.
As to the studies included in the
present systematic review, 3 RCTs and
1 prospective cohort trial could be
identied. Seracchioli et al investigated
the efcacy of a continuous vs a cyclic
24 month OC schedule after surgical
excision of endometriomas in 2 RCTs,
one evaluating cyst recurrence10 and a
second one evaluating pain recurrence.11 The authors demonstrated a
crude endometrioma recurrence rate
of 14.7% after a cyclic schedule vs
8.2% after a continuous schedule, a
difference that was not statistically
signicant.10 As to associated pain,
dysmenorrhea recurrence rates were

signicantly lower for the continuous

vs the cyclic schedule, whereas no difference was found for chronic pelvic
pain and dyspareunia.11
Muzii et al,12 evaluating a continuous
vs a cyclic postoperative 6 month OC
course in an RCT on 57 patients, reported no signicant difference in cyst
recurrence rates (respectively, 0% and
4% for a continuous vs a cyclic regimen)
and in pain recurrence rates (respectively, 17% and 32%). Discontinuation
rates were signicantly higher for the
continuous schedule (41% vs 14%).
In a prospective cohort study on 356
patients, Vlahos et al13 reported better
results for endometrioma recurrence,
dysmenorrhea, and noncyclic pelvic
pain recurrence after a continuous vs a
cyclic postoperative schedule, whereas
no difference was found for dyspareunia.
As detailed above, the currently available literature reports inconsistencies
as to the preferable OC schedule to

FIGURE 12

Forest plot for reoperation

CI, confidence interval; M-H, Mantel-Haenszel.

Muzii. Continuous vs cyclic OC for endometriomas. Am J Obstet Gynecol 2016.

210 American Journal of Obstetrics & Gynecology FEBRUARY 2016

be administered after endometrioma

surgery.
Conclusions and implications
In conclusion, a continuous OC regimen
may be suggested after surgery for endometriomas, particularly in patients in
whom dysmenorrhea is the main associated symptom. A continuous OC
schedule is in fact associated with lower
dysmenorrhea recurrence rates compared
with a cyclic schedule. However, the evidence from the present systematic review
is not conclusive because of the small
number of included studies. Moreover,
for other important clinical outcomes,
such as endometrioma recurrence, noncyclic pain, and dyspareunia, statistical
signicance is not reached.
Further RCTs are therefore needed to
conrm the ndings of the present study
because of the small number and small
sample sizes of the included studies,
which constitute a major limitation of the

ajog.org
present systematic review. Also, important outcomes not addressed in the
included studies, such as patient satisfaction and quality of life, should be
evaluated in further studies. When treatment is administered in the long term, as
is the case for postoperative OCs, patient
compliance to therapy is very important.
In this context, studies comparing different molecules, dosages, and routes of
administration, or extended-cycle schedules, should be conducted.
-

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