the american college of obstetricians and gynecologists

women ’ s health care physicians

P R AC T I C E
BUL L E T I N
clinical management guidelines for obstetrician – gynecologists

Number 114, July 2010 (Reaffirmed 2016. Replaces Practice Bulletin Number 11, December 1999.)

Management of Endometriosis
Endometriosis represents a significant health problem for women of reproductive age. The etiology, the relationship
between the extent of disease and the degree of symptoms, the effect on fertility, and the most appropriate treatment
of endometriosis remain incomplete. The purpose of this document is to present the evidence, including risks and ben-
efits, for the effectiveness of medical and surgical therapy for adult women who are symptomatic with pelvic pain or
infertility or both. Treatment options for adolescents are discussed in other documents (1).

Background The pathogenesis of endometriosis is complex but is still

thought to be principally associated with attachment and
Incidence implantation of endometrial glands and stroma on the
peritoneum from retrograde menstruation. Other theo-
Endometriosis is a gynecologic condition that occurs
ries such as hematogenous or lymphatic transport, stem
in 6–10% of women of reproductive age (2), with a
cells from bone marrow, and coelomic metaplasia may
prevalence of 38% (range, 20–50%) in infertile women
explain some clinical circumstances (16).
(3–6), and in 71–87% of women with chronic pelvic pain
The complex interaction between aberrant expres-
(7–9). Contrary to much speculation, there are no data to
sion of endometrial genes as well as altered hormonal
support the view that the incidence of endometriosis is
response will predispose patients to the development
increasing (10), although improved recognition of endo-
of endometrial lesions (17–20). Key components in the
metriotic lesions may have led to an increase in the rate development of endometriosis are local overproduction
of detection (11). There also appears to be no particular of prostaglandins by an increase in cyclooxygenase-2
racial predisposition to endometriosis. (COX-2) activity and overproduction of local estrogen
A familial association of endometriosis has been by increased aromatase activity. Progesterone resistance
suggested, and patients with an affected first-degree rela- dampens the antiestrogenic effect of progesterone and
tive have nearly a 7–10-fold increased risk of developing amplifies the local estrogenic effect (19).
endometriosis (12, 13). There is a strong concordance in The resulting endometrial lesions can lead to a
monozygotic twins (14). The proposed inheritance is char- chronic inflammatory disorder with increased numbers
acteristic of a polygenic-multifactorial mechanism. A num- of activated macrophages and proinflammatory cyto-
ber of genetic polymorphisms have been identified (15). kines in the peritoneal fluid that may cause pain and
infertility. The most commonly found inflammatory
Etiology cytokines are tumor necrosis factor alpha and interleu-
Endometriosis is a chronic gynecologic disorder whose kins 1, 6, and 8 (21). These cytokines are associated with
principal manifestations are chronic pain and infertility. pain by several mechanisms, including the induction

Committee on Practice Bulletins—Gynecology. This Practice Bulletin was developed by the Committee on Practice Bulletins—Gynecology with the
assistance of Tommaso Falcone, MD, and John R. Lue, MD. The information is designed to aid practitioners in making decisions about appropriate obstetric
and gynecologic care. These guidelines should not be construed as dictating an exclusive course of treatment or procedure. Variations in practice may be
warranted based on the needs of the individual patient, resources, and limitations unique to the institution or type of practice.
of prostaglandins. Nerve growth factor is also highly and dyschezia in cases of bowel involvement, or dysuria
expressed in endometriotic lesions, especially in recto- and hematuria in cases of bladder involvement (36, 37).
vaginal lesions (22). An increased density of nerve fibers Bladder or bowel symptoms may be present without
in peritoneal endometriosis, especially deep infiltrating lesions directly affecting the organ.
endometriosis, or close proximity of nerves to peritoneal The pain associated with endometriosis may not
lesions also can explain the common manifestation of correlate with the stage of disease but there may be some
pain (23–25). Changes in innervation of the uterus also association with the depth of infiltration of endometrio-
have been reported in patients with endometriosis and tic lesions (38, 39). Painful defecation during menses
may explain the severe dysmenorrhea and the improve- and severe dyspareunia are the most predictable symp-
ment in symptoms from hysterectomy (26, 27). toms of deeply infiltrating endometriosis (40).
Endometriosis is associated with infertility, although
the mechanism by which this occurs with early stage Diagnosis
disease is not clear (28). An abnormal peritoneal environ-
The definitive diagnosis of endometriosis only can
ment characterized by oxidative stress and higher con-
be made by histology of lesions removed at surgery.
centrations of inflammatory cytokines may affect sperm
Neither serum markers nor imaging studies have been
function by a variety of mechanisms, including causing
able to supplant diagnostic laparoscopy for the diagnosis
sperm DNA damage (29, 30). This abnormal peritoneal
of endometriosis. The histologic appearance consists of
environment also can cause abnormalities in oocyte cyto-
endometrial glands and stroma with varying amounts of
skeleton function (30). Antimüllerian hormone, a marker
inflammation and fibrosis. However, the visual appear-
of ovarian reserve, is decreased in early stage endome-
ance of the lesions at laparoscopy is variable. Several
triosis (31). In more advanced endometriosis with ovarian
studies have reported a marked discrepancy between
cysts and adhesions, the anatomic abnormalities can result
the visual appearance and the histology (41–43). False-
in abnormal tubal function.
positive results occur because of the wide variety of
Risk factors for developing endometriosis include
lesions described as classical (black powder-burn lesions)
early menarche (occurring before age 11 years), shorter
or nonclassical (red or white lesions). Lesions may be
cycles less than 27 days), and heavy, prolonged cycles
missed without a careful inspection of the pelvis such as
(32, 33). Higher parity and increased duration of lacta-
under the ovaries (ovarian fossa). Although biopsy is not
tion were associated with a decreased risk of endome-
always required at the time of laparoscopy, it should be
triosis among parous women (33). Regular exercise
performed if there is doubt as to the origin of the lesion.
of more than 4 hours per week was associated with a
Cystoscopy with biopsy is recommended if there is sus-
reduced risk of developing endometriosis (34).
picion of bladder endometriosis.
Imaging studies, such as ultrasonography, magnetic
Clinical Manifestations resonance imaging, and computed tomography appear to
The clinical manifestations of endometriosis are vari- be useful only in the presence of a pelvic or adnexal mass
able and unpredictable in both presentation and course. (44). Ovarian endometriomas visualized with ultrasonog-
Dysmenorrhea, chronic pelvic pain, dyspareunia, utero- raphy typically appear as cysts that contain low-level,
sacral ligament nodularity, and an adnexal mass (either homogeneous internal echoes consistent with old blood.
symptomatic or asymptomatic) are among the well-rec- Imaging studies alone appear to have high predictive
ognized manifestations. A significant number of women accuracy in differentiating an ovarian endometrioma
with endometriosis remain asymptomatic. Endometriosis from other adnexal masses, and transvaginal ultrasonog-
is more likely to be diagnosed in women with classic raphy is the imaging modality of choice when assessing
symptoms, including abdominopelvic pain (odds ratio the presence of endometriosis (45). Transvaginal ultra-
[OR]=5.2), dysmenorrhea (OR=8.1), menorrhagia (OR= sonography is also the imaging technique of choice to
4.0), and dyspareunia (OR=6.0) than in controls (35). detect the presence of deeply infiltrating endometriosis of
Pelvic pain that is typical of endometriosis is the rectum or rectovaginal septum (46–49). Sometimes
characteristically described as secondary dysmenorrhea water contrast in the rectum may aid in the diagnosis
(with pain frequently commencing before the onset of of endometriosis infiltrating the bowel (50). Magnetic
menses), deep dyspareunia (exaggerated during men- resonance imaging should be reserved for equivocal
ses), or sacral backache during menses. Endometriosis ultrasound results in cases of rectovaginal or bladder
that involves specific organs may result in pain or endometriosis (51, 52). The clinical utility of measuring
physiologic dysfunction of those organs, such as peri- CA 125 as a diagnostic marker for endometriosis is lim-
menstrual tenesmus, diarrhea or constipation, cramping ited (53–56).

2 Practice Bulletin No. 114

Classification Clinical Considerations and
Numerous classification schemas have been proposed to
describe endometriosis by anatomic location and sever-
Recommendations
ity of disease. The American Society for Reproductive In women with endometriosis-related
Medicine (ASRM) classification, which is the most infertility, what is the value of surgical
commonly used system, was revised for the third time in therapy for endometriosis?
1996 (see Fig. 1) but still has limitations (57). The sys-
tem is not a good predictor of pregnancy after treatment Medical suppressive therapies such as oral contracep-
despite adjustments to the point scores and cut-points tives (OCs) or gonadotropin-releasing hormone (GnRH)
for disease stage. The ASRM system does not correlate agonists for endometriosis-associated infertility are inef-
well with the symptoms of pain and dyspareunia or fective according to a 2007 Cochrane review (58).
infertility. The value of the ASRM revised system is in Surgical management of endometriosis-related infer-
uniform recording of operative findings and perhaps for tility does improve pregnancy rates, but the magnitude
82
comparing the results ofENDOCRINOLOGY
REPRODUCTIVE various therapies. of improvement is unclear. Two randomized controlled

American Society for Reproductive Medicine

Revised Classification of Endometriosis

Patient’s name Date

Stage I (minimal) — 1–5

Stage II (mild) — 6–15
Stage III (moderate) — 16–40 Laparoscopy Laparotomy Photography
Stage IV (severe) — >40 Recommended treatment

Total Prognosis
Peritoneum

Endometriosis <1 cm 1–3 cm >3 cm

Superficial 1 2 4
Deep 2 4 6
R Superficial 1 2 4
Deep 4 16 20
Ovary

L Superficial 1 2 4
Deep 4 16 20

Posterior Partial Complete

cul-de-sac
obliteration 4 40

Adhesions <1/3 Enclosure 1/3 – 2/3 Enclosure >2/3 Enclosure

R Filmy 1 2 4
Ovary

Dense 4 8 16
L Filmy 1 2 4
Dense 4 8 16
R Filmy 1 2 4
Dense 4* 8* 16
Tube

L Filmy 1 2 4
Dense 4* 8* 16
*If the fimbriated end of the fallopian tube is completely enclosed, change the point assignment to 16.
Denote appearance of superficial implant types as red [(R), red, red-pink, flamelike, vesicular blobs,
clear vesicles], white [(W), opacifications, peritoneal defects, yellow-brown], or black [(B), black,
hemosiderin deposits, blue]. Denote percent of total described as R %, W %, and B %. Total
should equal 100%.

Additional endometriosis: Associated pathology:

Figure 1. Modified from the revised American Fertility Society classification of endometriosis. (Reprinted with permission from the
American Society for Reproductive Medicine. Fertility and Sterility 1996;67(5):819–820.)

To be used with normal To be used with abnormal

tubes and ovaries tubes and/or ovaries
L R L R
Practice Bul­le­tin No. 114 3
trials (RCT) investigated the effect of surgical treatment Dysmenorrhea-associated withdrawal bleeding can
of stage I-II (minimal and mild) disease (59, 60) with be avoided with the use of extended-cycle pills. In a
contradictory results. A pooled analysis of these two tri- 2-year prospective study of women with endometriosis-
als shows an OR of 1.65 (95% confidence interval (CI), associated dysmenorrhea that was not responsive to
1.06–2.58) for postsurgery conception, and a number cyclic combined OCs, continuous combined OC admin-
needed to treat of 12 (61). The number of laparoscopies istration was found to provide significant pain reduction
performed to obtain a pregnancy will depend on the from baseline (P<.001) (72). If the initial therapy fails
prevalence of disease. For example, a prevalence of 25% in patients with suspected endometriosis, a diagnostic
implies that 48 laparoscopies need to be performed to laparoscopy to confirm the presence of endometriosis
obtain an extra pregnancy. may be offered. Alternatively, empiric treatment with
There are no RCTs that have assessed the value another suppressive medication may be offered.
of surgery with advanced disease. Although advanced The need for laparoscopy in the diagnosis or treat-
endometriosis is difficult to manage surgically, with a ment of pelvic pain secondary to suspected endometrio-
resulting low monthly fecundity rate (62, 63), removal sis has been the subject of debate (9). Arguments against
of endometriomas can significantly improve pregnancy the requirement to perform surgery to definitively diag-
rates. Excision of the endometrioma is more effective nose endometriosis include the imprecision of surgical
than simple drainage and ablation of the cyst wall (64, diagnosis as well as the inherent risks of surgery.
65). In a pooled analysis of data from two RCTs, the In a woman with pelvic pain, diagnostic evaluation
pregnancy rate was 60.9 % for excision versus 23.4% should include a thorough history and physical exami-
with the drainage and ablation technique (OR, 5.11; nation to rule out other gynecologic causes of pain.
95% CI, 2.03–12.85) (61). Because most endometrio- Nongynecologic causes of pain, such as irritable bowel
mas can be identified by ultrasonography, the number of syndrome, interstitial cystitis, and urinary tract problems
laparoscopies needed to achieve results is the same. It is may be ruled out by appropriate testing and referrals.
important in all surgery for removal of endometriomas Consideration also should be given to pelvic ultrasonog-
that the patient be informed that the surgery may damage raphy, complete blood count, urinalysis, and endocervi-
the ovary and reduce ovarian reserve (66, 67). cal testing for gonococcal and chlamydial infection if
The value of excision of deeply infiltrating endome- signs and symptoms warrant.
triosis solely to improve pregnancy is unclear and may A randomized controlled, double-blind clinical trial
adversely affect fertility (61). After initial unsuccessful has shown that after an appropriate pretreatment evalu-
surgery for endometriosis-associated infertility, in vitro ation (to exclude other causes of chronic pelvic pain)
fertilization is the best option rather than reoperation and failure of initial treatment with OCs and nonste-
unless pain is still an important issue (68). Repetitive roidal antiinflammatory drugs, empiric therapy with a
ovarian surgery has been shown to have a significant 3-month course of a GnRH agonist is appropriate (9). This
negative impact on in vitro fertilization outcomes (69). approach is associated with clinically and statistically sig-
nificant improvement in dysmenorrhea, pelvic pain, and
In women with suspected endometriosis- pelvic tenderness. It is important to explain to the patient
related pain who desire future fertility, what that response to empiric therapy does not confirm the
is the initial treatment? diagnosis of endometriosis.
Comparing costs of empiric medical management
Evidence suggests that pain associated with endo- versus definitive surgical diagnosis is more difficult to
metriosis can be reduced with the use of a variety of address. Although there is a lack of well-designed studies
medications (progestins, danazol, combined OCs, non- that compare the actual costs between the two approaches,
steroidal antiinflammatory drugs [NSAIDS], and GnRH it has been estimated that the cost of 3 months of empiric
agonists). Although there is no conclusive evidence that therapy is less than a laparoscopic procedure (73).
NSAIDS improve pain associated with endometriosis,
these agents are reasonable options in appropriately In women with pain, a known history of
selected patients (70). endometriosis, and desire for future fertility,
A recent Cochrane review examined the use of what medical options are available?
combined OCs for endometriosis in 57 women allocated
to either a combined OC or a GnRH analogue (71). No In these patients, NSAIDS or combined OCs can be
evidence of a significant difference in dysmenorrhea offered as discussed previously. In patients with known
between the two groups was observed at 6 months after endometriosis and dysmenorrhea, in addition to OCs,
stopping treatment (OR, 0.48; 95% CI, 0.08–2.90). oral or depot medroxyprogesterone acetate (DMPA) are

4 Practice Bulletin No. 114

effective compared with placebo and are equivalent to When relief of pain from treatment with a GnRH agonist
other more costly regimens. A large RCT showed com- supports continued therapy, the addition of add-back
bined OCs to be more effective than placebo (74). If therapy reduces or eliminates GnRH agonist-induced
they fail, there are three other forms of medical therapy bone mineral loss and provides symptomatic relief
that may be appropriate: progestins, GnRH agonists, and without reducing the efficacy of pain relief. Add-back
androgens. Oral norethindrone acetate and subcutaneous regimens (using either sex-steroid hormones or other
DMPA have been approved by the U.S. Food and Drug specific bone-sparing agents) have been advocated for
Administration (FDA) for treatment of endometriosis- use in women undergoing long-term therapy (more than
associated pain. Two RCTs have shown that subcutane- 6 months) (82). Such treatment strategies have included
ous DMPA was equivalent to GnRH agonists in reducing progestins alone, progestins and bisphosphonates, low-
pain with substantially less bone loss (75, 76). The bone dose progestins, and estrogens (58, 83, 86). The FDA
loss that occurred with DMPA returned to pretreatment has approved the daily use of norethindrone, 5 mg, as
levels by 12 months. Patients interested in achieving preg- add-back therapy with a GnRH agonist. In a comparison
nancy in the short term may not be candidates for depot of different add-back regimens, GnRH and norethin-
formulations given the delay in resumption of ovulatory drone, with or without a low-dose estrogen (conjugated
cycles. estrogens 0.625 mg daily), were found to decrease the
Intrauterine progestin use with the levonorgestrel side effect profile and maintain efficacy (87). If women
intrauterine system also has been shown to be effective do not tolerate the high-dose norethindrone, transdermal
in reducing endometriosis-associated pelvic pain. Three- estradiol with medroxyprogesterone acetate can be used
year follow-up data showed a persistent benefit of the (transdermal estradiol, 25 micrograms per day plus
levonorgestrel intrauterine system (77), although approxi- medroxyprogesterone acetate 2.5 mg orally daily) (88).
mately 40% of patients discontinued use because of This regimen may not completely prevent bone loss and
unacceptable irregular bleeding, persistent pain, or weight has not been approved by the FDA. It is recommended
gain. In an RCT comparing a GnRH agonist and the levo- that daily calcium supplements (1,000 mg) be prescribed
norgestrel intrauterine system, there was no significant to patients using GnRH agonists with add-back therapy.
difference between the two groups in control of pain (78). Add-back treatment does not diminish the efficacy
The levonorgestrel intrauterine system is not approved by of pain relief observed during 3 months or 6 months of
the FDA for treatment of endometriosis-associated pain. GnRH agonist therapy (89). Therefore, the add-back
Danazol is an androgenic drug that has been used regimen can be started immediately with the GnRH
for the treatment of endometriosis-associated pain. agonist. There appears to be no disadvantages to the use
Although highly effective, Danazol has a side effect pro- of an add-back regimen in combination with a GnRH
file, which includes acne, hirsutism, and myalgias, that is agonist other than the incremental cost associated with
more severe than other drugs available. the additional medication. However, a Cochrane review
Gonadotropin-releasing hormone agonists are highly found little or no difference between GnRH agonist and
effective in reducing the pain syndromes associated other medical treatments for endometriosis, suggesting
with endometriosis (79). However, they are not superior again that this regimen is not recommended as a primary
to other methods such as combined OCs as first-line treatment approach (90).
therapy (71). Gonadotropin-releasing hormone agonists
may have significant side effects, including hot flushes, In women in whom conventional medical
vaginal dryness, and osteopenia. Osteopenia has been options for pain associated with endome-
shown to be reversible with short-term use, but may not triosis have failed, what other medical
be with long-term use or use of multiple cycles (80). As
options are available?
with other suppressive therapy, recurrence of symptoms
is common after the medication is discontinued. The The FDA has only approved the use of a 12-month
recurrence rate at 5-year follow-up, after discontinuing course of GnRH agonist therapy. In patients who have
GnRH agonist treatment, ranges from 53% to as high as responded well to previous GnRH agonist therapy, long-
73% in women with advanced disease (81). There may term treatment with add-back therapy has been reported
be an option for prolonged use of the GnRH agonist for (91). Patients receiving this treatment should be moni-
up to 1 year if add-back therapy is used. tored appropriately for physical findings, bone density,
and serum lipid parameters.
What are the advantages and disadvantages The use of aromatase inhibitors such as anastrozole
of an “add-back” regimen with the use of a or letrozole have been evaluated in women with chronic
GnRH agonist? pain resistant to other forms of medical management or

Practice Bul­le­tin No. 114 5

surgical management. Typically these drugs are used tive side effects of constipation and urinary dysfunction
with a progestin or combined OC to dampen the follicle- (102).
stimulating hormone release, which may lead to chronic
ovarian stimulation. These drugs have been reported to How should endometriomas be managed in
be efficacious in observational trials only with no con- women who desire future fertility?
trols (92, 93). Although promising, there are insufficient
Endometriomas are thought to be the result of progres-
data to recommend their routine use (94, 95).
sion of endometriotic lesions on the ovary that form
cystic structures. They are invariably firmly attached to
In women with endometriosis-related pain
the ovary and the normal ovarian cortex where oocytes
who desire future fertility, how effective is
are embedded. Therefore, removal of the cyst always
surgical therapy? involves the risk that normal tissue also will be removed.
In the first randomized, double-blind controlled trial of These cysts may cause pain and infertility and they are
laser laparoscopy in the treatment of pelvic pain associ- associated with an increased risk of torsion and rupture.
ated with minimal, mild, and moderate endometriosis, There is a small risk of malignancy associated with an
63 patients were assessed 6 months after surgery, at endometrioma (103, 104). Levels of CA 125 may be
which time the randomization code was broken and they increased in the presence of a benign endometrioma.
were assessed again after another 6 months (96). At 6 Although ultrasonography has a high diagnostic accu-
months, 20 out of 32 patients (62.5%) reported symptom racy for endometriomas, it is recommended that endo-
improvement or relief that was significantly different metriomas be removed in women without a previous
from 7 out of 31 patients (22.6%) in the expectant group. diagnosis of endometriosis in order to obtain histologic
In this study, surgical therapy was least effective for confirmation that the cyst is benign. Some societies rec-
stage 1 (minimal) endometriosis. In a similar double- ommend removal if the cyst is more than 3 cm (105).
blind RCT of patients with endometriosis of all stages, Recurrent endometriomas are common. Further ovarian
80% of patients had symptomatic improvement 6 months surgery needs to be considered on a case-by-case basis
after surgery versus 32% of patients in the expectant because reoperation may result in reduced or total loss of
management group (97). The lower nonresponse rate in function of the ovary.
this study was attributed to the fewer number of patients A prospective RCT has shown that laparoscopic exci-
with stage 1 disease. sion of endometriosis has marked benefits over lapa-
In a follow-up of a large number of patients after rotomy with respect to analgesic requirement and recovery
surgical removal of endometriosis, the chance of requir- (106). Simple drainage of an endometrioma is associated
ing further surgery was 36% (98). In this study patients with a high recurrence rate (61). Excision of the cyst com-
were monitored for an average of 3 years (range 2–5 pared with drainage and coagulation of the cyst wall is
years). At reoperation for recurrent chronic pain many associated with lower recurrence of pain symptoms and
patients had no visible endometriotic lesions. In a recent cyst formation as well as a higher pregnancy rate (107).
study, patients with all stages of endometriosis that had
surgical removal of their lesions had a 21%, 47%, and What is the role of preoperative or postopera-
55% reoperation rate at 2, 5, and 7 years of follow- tive medical suppressive therapy?
up, respectively (99). The only variable that predicted
There are no data that support the use of preoperative
reoperation was the age of the patient at the time of the
medical suppressive therapy (108). However, postopera-
index surgery, with younger patients having a higher
tive medical treatment could be useful when residual dis-
probability of reoperation. There is significant short-
ease is expected, when pain is not relieved, or to extend
term improvement in pain after conservative surgical
the pain-free interval after surgery. Some studies support
treatment; however, as with medical management, there
the use of postoperative GnRH agonists to extend the
is also significant recurrence rate of pain.
period of pain relief (109). In a randomized, controlled
What is the role of neurectomies in the man- trial of an intranasal GnRH agonist, the median time to
requirement of additional therapy after the GnRH agonist
agement of pain associated with endometriosis?
was discontinued was more than 24 months in the treated
Several randomized trials have demonstrated the lack group versus 11.7 months in the nontreated group (110).
of efficacy of uterosacral nerve ablation as an adjunct The disadvantage of GnRH agonist therapy is the tempo-
to surgical management of endometriosis (100, 101). rary nature of its benefit after discontinuation of the drug
Presacral neurectomy has benefit for midline pain only. (111). In a 2004 Cochrane review, the use of periopera-
This procedure is associated with potential postopera- tive medical therapy for women with endometriosis did

6 Practice Bulletin No. 114

not demonstrate any long-term benefit (111). Long-term In patients with pain arising from known
use of the agonist may be more beneficial but with asso- endometriosis affecting nonreproductive
ciated long-term side effects and costs. organs, what is the evidence for the efficacy
Combined OCs have been investigated as potential of medical therapy for these symptoms?
postoperative medical suppressive therapy, with the
advantages of low cost, few side effects, and potential Extrapelvic endometriosis has been reported in a variety
long-term use. A systematic review of combined OC of sites, including the upper abdomen, the diaphragm,
use for postoperative prevention of symptom recurrence the abdominal wall (particularly the umbilicus), the
included six prospective studies, four of which were RCTs perineum (episiotomy scar), and the thorax (118, 119).
(112, 113). Results demonstrated the efficacy of long- In addition, endometriosis may invade the full thickness
term (at least 24 months) OC use on reducing endome- of the rectum, large and small bowel, ureters, or bladder.
trioma recurrence as well as a reduction in the frequency The symptoms that are associated with endometriosis at
and severity of dysmenorrhea. The main conclusion is these sites vary depending on location and depth of infil-
that while patients are taking combined OCs, symptoms tration and include women with cyclic episodes of gross
are well controlled. Previous users do not seem to have a hematuria, hematochezia, and hemoptysis. Although a
persistent effect. No difference in efficacy was reported number of therapeutic approaches have been used for
between continuous and cyclic combined OCs. women with presumed extrapelvic endometriosis, the
The levonorgestrel intrauterine system has been used reported efficacy of ovarian suppression with a GnRH
postoperatively for the treatment of endometriosis-associ- agonist appears to support it as the first line of therapy
ated pain. Both a small RCT and a Cochrane review con- (120–122) except in cases of obstruction of the ureter or
cluded that the levonorgestrel intrauterine system reduces bowel, which are best treated surgically. Even in some
dysmenorrhea in women after endometriosis surgery (114, cases of rectovaginal endometriosis, suppressive medical
115). therapy may alleviate pain (61). Experience with man-
aging these cases is limited to case series, often from a
In asymptomatic women in whom endo- single center.
metriosis is discovered incidentally, what is
the probability of regression or progression In women who do not desire future fertility
of disease? and in whom conservative medical and
It is difficult to predict the long-term effect of endome- surgical management have failed, how effica-
triosis on an individual woman. There are no data to cious is definitive therapy for endometriosis?
support use of medical treatment to prevent progression
of the disease. Surgical treatment of incidentally found Hysterectomy, with bilateral salpingo-oophorectomy,
endometriosis at laparoscopy performed for other rea- often is regarded as definitive therapy for the treatment
sons needs to be decided on an individual basis. of endometriosis associated with intractable pelvic
There is little systematic research regarding either pain, adnexal masses, or multiple previous conservative
the progression of the disease or the prediction of surgical procedures. Based on the results of a retrospec-
clinical outcomes. The presence of endometriosis among tive analysis of women monitored for a mean duration
asymptomatic patients being treated for infertility var- of 58 months after hysterectomy, ovarian conserva-
ies between 20% and 50% suggesting that it may not tion was associated with a 62% likelihood of recurrent
always be pathologic (116). In an RCT, a second-look symptoms and a 31% chance of requiring additional
laparoscopy was performed at 1 year after the diagnostic surgical treatment (123). In the same study, women who
laparoscopy in all symptomatic control patients. These underwent bilateral adnexectomy had a 10% chance
patients were those who were randomized to the non- of recurrence of symptoms and only a 4% likelihood
treatment arm at the initial laparoscopy. This second of additional surgery. The authors also demonstrated
laparoscopy revealed 7 patients (29%) showing disease that the relative risk for recurrence of pain after total
progression, 7 patients (29%) showing disease regres- abdominal hysterectomy was 6.1 (95% CI, 2.5–14.6)
sion, and 10 patients (42%) having static disease (96, with ovarian preservation when compared with women
117). In another RCT, a second look at laparoscopy in the who have their ovaries removed. The relative risk of
control untreated group, revealed that 8 out of 18 patients additional surgery was 8.1 (95% CI, 2.1–31.3) with
(45%) showed disease progression, 6 patients (33%) had ovarian conservation. The limitation of this study is that
disease that was unchanged, and 4 patients (22%) had it is unclear if the endometriosis was removed at the
disease that improved from their original surgery (97). time of hysterectomy.

Practice Bul­le­tin No. 114 7

 Similar results were seen in a more recent study of
120 patients who underwent excision of the endome-
Summary of
triosis and hysterectomy with or without oophorectomy Recommendations and
(99). These patients were monitored for a median dura-
tion of 7.6–11 years. Most patients did not require reop-
Conclusions
eration, even with conservation of the ovaries. Therefore, The following recommendations and conclusions
in patients with normal ovaries, a hysterectomy with ovar- are based on good and consistent scientific evi-
ian conservation and removal of the endometriotic lesions dence (Level A):
should be considered.
Transvaginal ultrasonography is the imaging modal-
Can patients have recurrent symptoms after ity of choice when assessing the presence of endo-
hysterectomy and oophorectomy? metriosis.
Medical suppressive therapy improves pain symp-
Symptoms may recur in women even after hysterec-
toms; however, recurrence rates are high after the
tomy and oophorectomy. Endometriosis may recur in
medication is discontinued.
up to 15% of women whether or not the patients are
treated with estrogen therapy after bilateral oopho- There is significant short-term improvement in pain
rectomy (124). Consequently, hormone therapy with after conservative surgical treatment; however, as
estrogen is not contraindicated after definitive surgery with medical management, there is also a significant
for endometriosis. Although the true rate of recurrence rate of pain recurrence.
is unknown, in patients with recurrent symptoms under- Medical suppressive therapies such as OCs or
going a surgical procedure, endometriotic lesions may GnRH agonists for endometriosis-associated infer-
be demonstrated. The most common site of recurrent tility are ineffective.
lesions is the large and small bowel (125). These
Surgical management of endometriosis-related infer-
lesions were likely present at the time of surgery and
tility does improve pregnancy rates, but the magni-
not excised. These lesions can be considered persistent
tude of improvement is unclear.
disease rather than recurrent disease. Persistence of dis-
ease in hypoestrogenic states is most likely due to local Excision of an endometrioma is superior to simple
expression of aromatase activity. Treatment is difficult drainage and ablation of the cyst wall.
and often requires surgery. The use of a GnRH agonist When relief of pain from treatment with a GnRH
in this situation of hypoestrogenemia would not seem to agonist supports continued therapy, the addition
be of benefit. Aromatase inhibitors may be considered of add-back therapy reduces or eliminates GnRH
but are not uniformly effective (126). agonist-induced bone mineral loss and provides
symptomatic relief without reducing the efficacy of
What is the role of hormone therapy after pain relief.
definitive surgery for endometriosis-associated
pain? The following recommendations are based on lim-
Currently, there are limited data on the timing of estro-
ited or inconsistent scientific evidence (Level B):
gen therapy after hysterectomy with bilateral salpingo- After an appropriate pretreatment evaluation (to
oophorectomy for endometriosis. It appears there is no exclude other causes of chronic pelvic pain) and
advantage, in terms of recurrence rate, in delaying estro- failure of initial treatment with OCs and NSAIDS,
gen treatment after surgery (124, 127). There are limited empiric therapy with a 3-month course of a GnRH
data to indicate that hormone therapy may stimulate the agonist is appropriate.
growth of residual ovarian or endometrial tissue after
total hysterectomy and bilateral salpingo-oophorectomy In patients with known endometriosis and dysmen-
if all visible disease was removed (128). There is also a orrhea, OCs and oral norethindrone or DMPA are
concern about the possibility of estrogen-induced malig- effective compared with placebo and are equivalent
nant transformation in residual endometriosis implants to other more costly regimens.
(129). This has led some health care providers to recom- Long-term (at least 24 months) OC use is effective
mend the routine addition of a progestin to the estrogen in reducing endometrioma recurrence as well as a
therapy. However, there is no outcomes-based evidence reduction in the frequency and severity of dysmen-
to support this recommendation. orrhea.

8 Practice Bulletin No. 114

 Hormone therapy with estrogen is not contraindi- 9. Ling FW. Randomized controlled trial of depot leuprolide
cated after hysterectomy and bilateral salpingo- in patients with chronic pelvic pain and clinically sus-
pected endometriosis. Pelvic Pain Study Group. Obstet
oophorectomy for endometriosis. Gynecol 1999;93:51–8. (Level I)
In patients with normal ovaries, a hysterectomy with 10. Leibson CL, Good AE, Hass SL, Ransom J, Yawn BP,
ovarian conservation and removal of the endometri- O’Fallon WM, et al. Incidence and characterization of
diagnosed endometriosis in a geographically defined
otic lesions should be considered. population. Fertil Steril 2004;82:314–21. (Level II-3)
11. Ripps BA, Martin DC. Endometriosis and chronic pelvic
The following recommendations are based primar- pain. Obstet Gynecol Clin North Am 1993;20:709–17.
ily on consensus and expert opinion (Level C): (Level III)
12. Malinak LR, Buttram VC Jr, Elias S, Simpson JL.

When medical management has failed, undergoing Heritage aspects of endometriosis. II. Clinical charac-
definitive surgical management is appropriate in teristics of familial endometriosis. Am J Obstet Gynecol
those who do not desire future fertility. 1980;137:332–7. (Level II-2)
13. Matalliotakis IM, Arici A, Cakmak H, Goumenou AG,
Koumantakis G, Mahutte NG. Familial aggregation of
endometriosis in the Yale Series. Arch Gynecol Obstet
Proposed Performance 2008;278:507–11. (Level II-2)
Measure 14. Hadfield RM, Mardon HJ, Barlow DH, Kennedy SH.

Endometriosis in monozygotic twins. Fertil Steril
Percentage of patients with suspected endometriosis 1997;68:941–2. (Level III)
receiving OC therapy for pain management before more 15. Bedaiwy MA, Falcone T, Mascha EJ, Casper RF. Genetic
advanced therapies polymorphism in the fibrinolytic system and endometrio-
sis. Obstet Gynecol 2006;108:162–8. (Level II-2)
16. Sasson IE, Taylor HS. Stem cells and the pathogenesis
References of endometriosis. Ann N Y Acad Sci 2008;1127:106–15.
(Level III)
1. Endometriosis in adolescents. ACOG Committee Opinion 17. Garrido N, Navarro J, Garcia-Velasco J, Remoh J, Pellice A,
No. 310. American College of Obstetricians and Gynecol- Simon C. The endometrium versus embryonic quality
ogists. Obstet Gynecol 2005;105:921–7. (Level III) in endometriosis-related infertility. Hum Reprod Update
2002;8:95–103. (Level III)
2. Giudice LC, Kao LC. Endometriosis. Lancet 2004;364:
18. Meresman GF, Vighi S, Buquet RA, Contreras-Ortiz O,
1789–99. (Level III)
Tesone M, Rumi LS. Apoptosis and expression of Bcl-2
3. Balasch J, Creus M, Fabregues F, Carmona F, Ordi J, and Bax in eutopic endometrium from women with endo-
Martinez-Roman S, et al. Visible and non-visible endo- metriosis. Fertil Steril 2000;74:760–6. (Level III)
metriosis at laparoscopy in fertile and infertile women and 19. Bulun SE. Endometriosis. N Engl J Med 2009;360:268–
in patients with chronic pelvic pain: a prospective study. 79. (Level III)
Hum Reprod 1996;11:387–91. (Level II-3)
20. Guo SW. Epigenetics of endometriosis. Mol Hum Reprod
4. Rawson JM. Prevalence of endometriosis in asymptom- 2009;15:587–607. (Level III)
atic women. J Reprod Med 1991;36:513–5. (Level III) 21. Bedaiwy MA, Falcone T, Sharma RK, Goldberg JM,

5. Strathy JH, Molgaard CA, Coulam CB, Melton LJ 3rd. Attaran M, Nelson DR, et al. Prediction of endometriosis
Endometriosis and infertility: a laparoscopic study of with serum and peritoneal fluid markers: a prospective con-
endometriosis among fertile and infertile women. Fertil trolled trial. Hum Reprod 2002;17:426 –31. (Level II-2)
Steril 1982;38:667–72. (Level II-2) 22. Anaf V, Simon P, El Nakadi I, Fayt I, Simonart T, Buxant F,
et al. Hyperalgesia, nerve infiltration and nerve growth
6. Verkauf BS. Incidence, symptoms, and signs of endome-
factor expression in deep adenomyotic nodules, perito-
triosis in fertile and infertile women. J Fla Med Assoc
neal and ovarian endometriosis. Hum Reprod 2002;17:
1987;74:671–5. (Level II-2)
1895–900. (Level II-3)
7. Carter JE. Combined hysteroscopic and laparoscopic 23. Tokushige N, Markham R, Russell P, Fraser IS. Nerve
findings in patients with chronic pelvic pain. J Am Assoc fibres in peritoneal endometriosis. Hum Reprod 2006;21:
Gynecol Laparosc 1994;2:43–7. (Level III) 3001–7. (Level III)
8. Koninckx PR, Meuleman C, Demeyere S, Lesaffre E, 24. Mechsner S, Kaiser A, Kopf A, Gericke C, Ebert A,

Cornillie FJ. Suggestive evidence that pelvic endometrio- Bartley J. A pilot study to evaluate the clinical relevance
sis is a progressive disease, whereas deeply infiltrating of endometriosis-associated nerve fibers in peritoneal
endometriosis is associated with pelvic pain. Fertil Steril endometriotic lesions. Fertil Steril 2009;92:1856–61.
1991;55:759–65. (Level III) (Level II-3)

Practice Bul­le­tin No. 114 9

 25. Wang G, Tokushige N, Markham R, Fraser IS. Rich inner- mild endometriosis could be considered a non-disease.
vation of deep infiltrating endometriosis. Hum Reprod Ann N Y Acad Sci 1994;734:333–41. (Level III)
2009;24:827–34. (Level III) 40. Chapron C, Barakat H, Fritel X, Dubuisson JB, Breart G,
26. Tokushige N, Markham R, Russell P, Fraser IS. High Fauconnier A. Presurgical diagnosis of posterior deep
density of small nerve fibres in the functional layer of the infiltrating endometriosis based on a standardized ques-
endometrium in women with endometriosis. Hum Reprod tionnaire. Hum Reprod 2005;20:507–13. (Level II-3)
2006;21:782–7. (Level III)
41. Walter AJ, Hentz JG, Magtibay PM, Cornella JL, Magrina JF.
27. Atwal G, du Plessis D, Armstrong G, Slade R, Quinn M. Endometriosis: correlation between histologic and visual
Uterine innervation after hysterectomy for chronic pel- findings at laparoscopy. Am J Obstet Gynecol 2001;
vic pain with, and without, endometriosis. Am J Obstet 184:1407-11; discussion 1411–3. (Level II-3)
Gynecol 2005;193:1650–5. (Level II-3)
42. Stratton P, Winkel C, Premkumar A, Chow C, Wilson J,
28. Akande VA, Hunt LP, Cahill DJ, Jenkins JM. Differences Hearns-Stokes R, et al. Diagnostic accuracy of laparos-
in time to natural conception between women with unex- copy, magnetic resonance imaging, and histopathologic
plained infertility and infertile women with minor endo- examination for the detection of endometriosis. Fertil
metriosis. Hum Reprod 2004;19:96–103. (Level II-2) Steril 2003;79:1078–85. (Level III)
29. Said TM, Agarwal A, Falcone T, Sharma RK, Bedaiwy MA, 43. Mettler L, Schollmeyer T, Lehmann-Willenbrock E,

Li L. Infliximab may reverse the toxic effects induced by Schuppler U, Schmutzler A, Shukla D, et al. Accuracy
tumor necrosis factor alpha in human spermatozoa: an in of laparoscopic diagnosis of endometriosis. JSLS 2003;
vitro model. Fertil Steril 2005;83:1665–73. (Level III) 7:15–8. (Level III)
30. Mansour G, Aziz N, Sharma R, Falcone T, Goldberg J, 44. Guerriero S, Mais V, Ajossa S, Paoletti AM, Angiolucci M,
Agarwal A. The impact of peritoneal fluid from healthy Melis GB. Transvaginal ultrasonography combined with
women and from women with endometriosis on sperm CA-125 plasma levels in the diagnosis of endometrioma.
DNA and its relationship to the sperm deformity index. Fertil Steril 1996;65:293–8. (Level II-3)
Fertil Steril 2009;92:61–7. (Level III)
45. Moore J, Copley S, Morris J, Lindsell D, Golding S,
31. Lemos NA, Arbo E, Scalco R, Weiler E, Rosa V, Cunha- Kennedy S. A systematic review of the accuracy of ultras-
Filho JS. Decreased anti-Mullerian hormone and altered ound in the diagnosis of endometriosis. Ultrasound Obstet
ovarian follicular cohort in infertile patients with mild/ Gynecol 2002;20:630–4. (Level III)
minimal endometriosis. Fertil Steril 2008;89:1064–8.
(Level II-2) 46. Bazot M, Malzy P, Cortez A, Roseau G, Amouyal P,
Darai E. Accuracy of transvaginal sonography and rec-
32. Cramer DW, Missmer SA. The epidemiology of endome- tal endoscopic sonography in the diagnosis of deep
triosis. Ann N Y Acad Sci 2002;955:11–22; discussion infiltrating endometriosis. Ultrasound Obstet Gynecol
34–6, 396–406. (Level III) 2007;30:994–1001. (Level II-3)
33. Missmer SA, Hankinson SE, Spiegelman D, Barbieri RL, 47. Hudelist G, Oberwinkler KH, Singer CF, Tuttlies F,

Malspeis S, Willett WC, et al. Reproductive history and Rauter G, Ritter O, et al. Combination of transvaginal
endometriosis among premenopausal women. Obstet
sonography and clinical examination for preoperative
Gynecol 2004;104:965–74. (Level III)
diagnosis of pelvic endometriosis. Hum Reprod 2009;24:
34. Signorello LB, Harlow BL, Cramer DW, Spiegelman D, 1018–24. (Level II-2)
Hill JA. Epidemiologic determinants of endometrio-
48. Hudelist G, Tuttlies F, Rauter G, Pucher S, Keckstein J.
sis: a hospital-based case-control study. Ann Epidemiol
Can transvaginal sonography predict infiltration depth in
1997;7:267–741. (Level II-2)
patients with deep infiltrating endometriosis of the rec-
35. Ballard KD, Seaman HE, de Vries CS, Wright JT. Can tum? Hum Reprod 2009;24:1012–7. (Level II-2)
symptomatology help in the diagnosis of endometriosis?
Findings from a national case-control study––Part 1. 49. Piketty M, Chopin N, Dousset B, Millischer-Bellaische A,
BJOG 2008;115:1382–91. (Level II-2) Roseau G, Leconte M, et al. Preoperative work-up for
patients with deeply infiltrating endometriosis: trans-
36. Seracchioli R, Mabrouk M, Guerrini M, Manuzzi L,
vaginal ultrasonography must definitely be the first-line
Savelli L, Frasca C, et al. Dyschezia and posterior deep imaging examination. Hum Reprod 2009;24:602–7.
infiltrating endometriosis: analysis of 360 cases. J Minim (Level II-2)
Invasive Gynecol 2008;15:695–9. (Level II-3)
50. Valenzano Menada M, Remorgida V, Abbamonte LH,
37. Villa G, Mabrouk M, Guerrini M, Mignemi G, Montanari G, Nicoletti A, Ragni N, Ferrero S. Does transvaginal
Fabbri E, et al. Relationship between site and size of ultrasonography combined with water-contrast in the rec-
bladder endometriotic nodules and severity of dysuria. J tum aid in the diagnosis of rectovaginal endometriosis
Minim Invasive Gynecol 2007;14:628–32. (Level II-3) infiltrating the bowel? Hum Reprod 2008;23:1069–75.
38. Fauconnier A, Chapron C, Dubuisson JB, Vieira M,
(Level II-2)
Dousset B, Breart G. Relation between pain symptoms 51. Bazot M, Bornier C, Dubernard G, Roseau G, Cortez A,
and the anatomic location of deep infiltrating endometrio- Darai E. Accuracy of magnetic resonance imaging
sis. Fertil Steril 2002;78:719–26. (Level II-3) and rectal endoscopic sonography for the prediction of
39. Koninckx PR, Oosterlynck D, D’Hooghe T, Meuleman C. location of deep pelvic endometriosis. Hum Reprod 2007;
Deeply infiltrating endometriosis is a disease whereas 22:1457–63. (Level II-3)

10 Practice Bulletin No. 114

 52. Balleyguier C, Chapron C, Dubuisson JB, Kinkel K, 66. Catenacci M, Sastry S, Falcone T. Laparoscopic surgery
Fauconnier A, Vieira M, et al. Comparison of magnetic for endometriosis. Clin Obstet Gynecol 2009;52:351–61.
resonance imaging and transvaginal ultrasonography in (Level III)
diagnosing bladder endometriosis. J Am Assoc Gynecol 67. Busacca M, Vignali M. Endometrioma excision and ovar-
Laparosc 2002;9:15–23. (Level III) ian reserve: a dangerous relation. J Minim Invasive Gyne-
53. Barbati A, Cosmi EV, Spaziani R, Ventura R, Montanino G. col 2009;16:142–8. (Level III)
Serum and peritoneal fluid CA-125 levels in patients with 68. Pagidas K, Falcone T, Hemmings R, Miron P. Comparison
endometriosis. Fertil Steril 1994;61:438–42. (Level II-2) of reoperation for moderate (stage III) and severe (stage
54. Franchi M, Beretta P, Zanaboni F, Donadello N, Ghezzi F. IV) endometriosis-related infertility with in vitro fertil-
Use of serum CA125 measurement in patients with ization-embryo transfer. Fertil Steril 1996;65:791–5.
endometriosis. Ital J Gynaecol Obstet 1993;5:149–52. (Level III)
(Level II-3) 69. Barnhart K, Dunsmoor-Su R, Coutifaris C. Effect of endo-
55. Moretuzzo RW, DiLauro S, Jenison E, Chen SL, metriosis on in vitro fertilization. Fertil Steril 2002;77:
Reindollar RH, McDonough PG. Serum and peritoneal 1148–55. (Meta-analysis)
lavage fluid CA-125 levels in endometriosis. Fertil Steril 70. Allen C, Hopewell S, Prentice A, Gregory D. Nonsteroidal
1988;50:430–3. (Level II-2) anti-inflammatory drugs for pain in women with endome-
56. Pittaway DE, Fayez JA. The use of CA-125 in the diag- triosis. Cochrane Database of Systematic Reviews 2009,
nosis and management of endometriosis. Fertil Steril Issue 2. Art. No.: CD004753. DOI: 10.1002/14651858.
1986;46:790–5. (Level II-2) CD004753.pub3. (Meta-analysis)
57. Revised American Society for Reproductive Medicine 71. Davis LJ, Kennedy SS, Moore J, Prentice A. Oral contra-
classification of endometriosis: 1996. Fertil Steril 1997; ceptives for pain associated with endometriosis. Cochrane
67:817–21. (Level III) Database of Systematic Reviews 2007, Issue 3. Art. No.:
CD001019. DOI: 10.1002/14651858.CD001019.pub2.
58. Hughes E, Brown J, Collins JJ, Farquhar C, Fedorkow DM, (Meta-analysis)
Vanderkerchove P. Ovulation suppression for endome-
triosis for women with subfertility. Cochrane Database of 72. Vercellini P, Frontino G, De Giorgi O, Pietropaolo G,
Systematic Reviews 2007, Issue 3. Art. No.: CD000155. Pasin R, Crosignani PG. Continuous use of an oral con-
DOI: 10.1002/14651858.CD000155.pub2. (Meta-analysis) traceptive for endometriosis-associated recurrent dys-
menorrhea that does not respond to a cyclic pill regimen.
59. Marcoux S, Maheux R, Berube S. Laparoscopic surgery Fertil Steril 2003;80:560–3. (Level III)
in infertile women with minimal or mild endometriosis.
Canadian Collaborative Group on Endometriosis. N Engl 73. Winkel CA. A cost-effective approach to the man-
J Med 1997;337:217–22. (Level I) agement of endometriosis. Curr Opin Obstet Gynecol
2000;12:317–20. (Level III)
60. Parazzini F. Ablation of lesions or no treatment in mini-
mal-mild endometriosis in infertile women: a randomized 74. Harada T, Momoeda M, Taketani Y, Hoshiai H, Terakawa N.
trial. Gruppo Italiano per lo Studio dell’Endometriosi. Low-dose oral contraceptive pill for dysmenorrhea asso-
Hum Reprod 1999;14:1332–4. (Level I) ciated with endometriosis: a placebo-controlled, double-
blind, randomized trial. Fertil Steril 2008;90:1583–8.
61. Vercellini P, Somigliana E, Vigano P, Abbiati A, Barbara G, (Level I)
Crosignani PG. Surgery for endometriosis-associ-
75. Crosignani PG, Luciano A, Ray A, Bergqvist A. Subcu-
ated infertility: a pragmatic approach. Hum Reprod
taneous depot medroxyprogesterone acetate versus leup-
2009;24:254–69. (Level III)
rolide acetate in the treatment of endometriosis-associated
62. Guzick DS, Silliman NP, Adamson GD, Buttram VC Jr, pain. Hum Reprod 2006;21:248–56. (Level I)
Canis M, Malinak LR, et al. Prediction of pregnancy
76. Schlaff WD, Carson SA, Luciano A, Ross D, Bergqvist A.
in infertile women based on the American Society for
Subcutaneous injection of depot medroxyprogesterone
Reproductive Medicine’s revised classification of endo-
acetate compared with leuprolide acetate in the treat-
metriosis. Fertil Steril 1997;67:822–9. (Level III)
ment of endometriosis-associated pain. Fertil Steril 2006;
63. Osuga Y, Koga K, Tsutsumi O, Yano T, Maruyama M, 85:314–25. (Level I)
Kugu K, et al. Role of laparoscopy in the treatment
77. Lockhat FB, Emembolu JO, Konje JC. The effica-
of endometriosis-associated infertility. Gynecol Obstet
cy, side-effects and continuation rates in women with
Invest 2002;53(suppl 1):33–9. (Level III)
symptomatic endometriosis undergoing treatment with
64. Beretta P, Franchi M, Ghezzi F, Busacca M, Zupi E, Bolis P. an intra-uterine administered progestogen (levonorges
Randomized clinical trial of two laparoscopic treatments trel): a 3 year follow-up. Hum Reprod 2005;20:789–93.
of endometriomas: cystectomy versus drainage and coag- (Level III)
ulation. Fertil Steril 1998;70:1176–80. (Level I) 78. Petta CA, Ferriani RA, Abrao MS, Hassan D, Rosa E
65. Alborzi S, Momtahan M, Parsanezhad ME, Dehbashi S, Silva JC, Podgaec S, et al. Randomized clinical trial of a
Zolghadri J, Alborzi S. A prospective, randomized study levonorgestrel-releasing intrauterine system and a depot
comparing laparoscopic ovarian cystectomy versus fenes- GnRH analogue for the treatment of chronic pelvic pain
tration and coagulation in patients with endometriomas. in women with endometriosis. Hum Reprod 2005;20:
Fertil Steril 2004;82:1633–7. (Level I) 1993–8. (Level I)

Practice Bul­le­tin No. 114 11

 79. Dlugi AM, Miller JD, Knittle J. Lupron depot (leuprolide IV endometriosis patients with chronic pelvic pain. Fertil
acetate for depot suspension) in the treatment of endo- Steril 2006;86:220–2. (Level II-2)
metriosis: a randomized, placebo-controlled, double- 92. Ailawadi RK, Jobanputra S, Kataria M, Gurates B, Bulun SE.
blind study. Lupron Study Group. Fertil Steril 1990;54: Treatment of endometriosis and chronic pelvic pain with
419 –27. (Level I) letrozole and norethindrone acetate: a pilot study. Fertil
80. Pierce SJ, Gazvani MR, Farquharson RG. Long-term Steril 2004;81:290–6. (Level III)
use of gonadotropin-releasing hormone analogs and hor- 93. Amsterdam LL, Gentry W, Jobanputra S, Wolf M,
mone replacement therapy in the management of endo- Rubin SD, Bulun SE. Anastrazole and oral contracep-
metriosis: a randomized trial with a 6-year follow-up. tives: a novel treatment for endometriosis. Fertil Steril
Fertil Steril 2000;74:964–8. (Level I) 2005;84:300–4. (Level III)
81. Waller KG, Shaw RW. Gonadotropin-releasing hormone 94. Patwardhan S, Nawathe A, Yates D, Harrison GR,
analogues for the treatment of endometriosis: long-term Khan KS. Systematic review of the effects of aromatase
follow-up. Fertil Steril 1993;59:511–5. (Level III) inhibitors on pain associated with endometriosis [pub-
82. Surrey ES, Judd HL. Reduction of vasomotor symp- lished erratum appears in BJOG 2008;115:1069]. BJOG
toms and bone mineral density loss with combined 2008;115:818–22. (Level III)
norethindrone and long-acting gonadotropin-releasing 95. Ferrero S, Camerini G, Seracchioli R, Ragni N, Venturini
hormone agonist therapy of symptomatic endometriosis: PL, Remorgida V. Letrozole combined with norethister-
a prospective randomized trial. J Clin Endocrinol Metab one acetate compared with norethisterone acetate alone
1992;75:558–63. (Level I) in the treatment of pain symptoms caused by endome-
83. Rock JA, Truglia JA, Caplan RJ. Zoladex (goserelin triosis. Hum Reprod 2009;24:3033–41. (Level II-2)
acetate implant) in the treatment of endometriosis: a 96. Sutton CJ, Ewen SP, Whitelaw N, Haines P. Prospective,
randomized comparison with danazol. The Zoladex randomized, double-blind, controlled trial of laser lapa-
Endometriosis Study Group. Obstet Gynecol 1993;82: roscopy in the treatment of pelvic pain associated with
198–205. (Level I) minimal, mild, and moderate endometriosis. Fertil Steril
84. Surrey ES, Fournet N, Voigt B, Judd HL. Effects 1994;62:696–700. (Level I)
of sodium etidronate in combination with low-dose 97. Abbott J, Hawe J, Hunter D, Holmes M, Finn P, Garry R.
norethindrone in patients administered a long-acting Laparoscopic excision of endometriosis: a randomized,
GnRH agonist: a preliminary report. Obstet Gynecol placebo-controlled trial. Fertil Steril 2004;82:878–84.
1993;81:581–6. (Level I) (Level I)
85. Vercellini P, Cortesi I, Crosignani PG. Progestins for 98. Abbott JA, Hawe J, Clayton RD, Garry R. The effects
symptomatic endometriosis: a critical analysis of the and effectiveness of laparoscopic excision of endome-
evidence. Fertil Steril 1997;68:393–401. (Level III) triosis: a prospective study with 2–5 year follow-up.
86. Wardle PG, Hull MG. Is endometriosis a disease? Hum Reprod 2003;18:1922–7. (Level II-2)
Baillieres Clin Obstet Gynaecol 1993;7:673–85. (Level 99. Shakiba K, Bena JF, McGill KM, Minger J, Falcone T.
III) Surgical treatment of endometriosis: a 7-year follow-up
87. Hornstein MD, Surrey ES, Weisberg GW, Casino LA. on the requirement for further surgery [published erra-
Leuprolide acetate depot and hormonal add-back in tum appears in Obstet Gynecol 2008;112:710]. Obstet
endometriosis: a 12-month study. Lupron Add-Back Gynecol 2008;111:1285–92. (Level II-3)
Study Group. Obstet Gynecol 1998;91:16–24. (Level I) 100. Daniels J, Gray R, Hills RK, Latthe P, Buckley L, Gupta J,
88. Howell R, Edmonds DK, Dowsett M, Crook D, Lees B, et al. Laparoscopic uterosacral nerve ablation for allevi-
Stevenson JC. Gonadotropin-releasing hormone ana- ating chronic pelvic pain: a randomized controlled trial.
logue (goserelin) plus hormone replacement therapy for LUNA Trial Collaboration. JAMA 2009;302:955–61.
the treatment of endometriosis: a randomized controlled (Level I)
trial. Fertil Steril 1995;64:474–81. (Level I) 101. Proctor M, Latthe P, Farquhar CM, Khan KS, Johnson N.
89. Kiilholma P, Tuimala R, Kivinen S, Korhonen M, Surgical interruption of pelvic nerve pathways for prima-
Hagman E. Comparison of the gonadotropin-releasing ry and secondary dysmenorrhoea. Cochrane Database of
hormone agonist goserelin acetate alone versus gos- Systematic Reviews 2005, Issue 4. Art. No.: CD001896.
erelin combined with estrogen-progestogen add-back DOI: 10.1002/14651858.CD001896.pub2. (Meta-analysis)
therapy in the treatment of endometriosis. Fertil Steril 102. Zullo F, Palomba S, Zupi E, Russo T, Morelli M,

1995;64:903–8. (Level I) Cappiello F, et al. Effectiveness of presacral neurectomy
90. Prentice A, Deary A, Goldbeck-Wood S, Farquhar CM, in women with severe dysmenorrhea caused by endome-
Smith S. Gonadotrophin-releasing hormone analogues triosis who were treated with laparoscopic conservative
for pain associated with endometriosis. Cochrane Data- surgery: a 1-year prospective randomized double-blind
base of Systematic Reviews 1999, Issue 2. Art. No.: controlled trial. Am J Obstet Gynecol 2003;189:5–10.
CD000346. DOI: 10.1002/14651858.CD000346.pub2. (Level I)
(Meta-analysis) 103. Nishida M, Watanabe K, Sato N, Ichikawa Y. Malignant
91. Bedaiwy MA, Casper RF. Treatment with leuprolide transformation of ovarian endometriosis. Gynecol Obstet
acetate and hormonal add-back for up to 10 years in stage Invest 2000;50 Suppl 1:18–25. (Level III)

12 Practice Bulletin No. 114

104. Bedaiwy MA, Hussein MR, Biscotti C, Falcone T.
No.: CD005072. DOI: 10.1002/14651858.CD005072.pub2.
Pelvic endometriosis is rarely associated with ovarian (Meta-analysis)
borderline tumours, cytologic and architectural atypia: a 116. Ozkan S, Murk W, Arici A. Endometriosis and infertility:
clinicopathologic study. Pathol Oncol Res 2009;15:81–8. epidemiology and evidence-based treatments. Ann N Y
(Level III) Acad Sci 2008;1127:92–100. (Level III)
105. Kennedy S, Bergqvist A, Chapron C, D’Hooghe T,
117. Sutton CJ, Pooley AS, Ewen SP, Haines P. Follow-

Dunselman G, Greb R, et al. ESHRE guideline for the up report on a randomized controlled trial of laser
diagnosis and treatment of endometriosis. ESHRE Special laparoscopy in the treatment of pelvic pain associated
Interest Group for Endometriosis and Endometrium Guide- with minimal to moderate endometriosis. Fertil Steril
line Development Group. Hum Reprod 2005;20: 2698–704.
1997;68:1070–4. (Level I)
(Level III)
118. Hughes ML, Bartholomew D, Paluzzi M. Abdominal
106. Mais V, Ajossa S, Guerriero S, Piras B, Floris M,

wall endometriosis after amniocentesis. A case report. J
Palomba M, et al. Laparoscopic management of endome-
Reprod Med 1997;42:597–9. (Level III)
triomas: a randomized trial versus laparotomy. J Gynecol
Surg 1996;12:41–6. (Level I) 119. Shimizu I, Nakanishi R, Yoshino I, Yasumoto K. An
107. Hart R, Hickey M, Maouris P, Buckett W, Garry R. endometrial nodule in the lung without pelvic endome-
Excisional surgery versus ablative surgery for ovar- triosis. J Cardiovasc Surg 1998;39:867–8. (Level II)
ian endometriomata: a Cochrane Review. Hum Reprod 120. Espaulella J, Armengol J, Bella F, Lain JM, Calaf J.
2005;20:3000–7. (Meta-analysis) Pulmonary endometriosis: conservative treatment with
108. Muzii L, Marana R, Caruana P, Mancuso S. The impact GnRH agonists. Obstet Gynecol 1991;78:535–7. (Level
of preoperative gonadotropin-releasing hormone agonist III)
treatment on laparoscopic excision of ovarian endometri- 121. Johnson WM 3rd, Tyndal CM. Pulmonary endometriosis:
otic cysts. Fertil Steril 1996;65:1235–7. (Level II-1) treatment with danazol. Obstet Gynecol 1987;69:506–7.
109. Yeung PP Jr, Shwayder J, Pasic RP. Laparoscopic man- (Level III)
agement of endometriosis: comprehensive review of best 122. Shek Y, De Lia JE, Pattillo RA. Endometriosis with
evidence. J Minim Invasive Gynecol 2009;16:269–81. a pleural effusion and ascites. Report of a case treated
(Level III) with nafarelin acetate. J Reprod Med 1995;40:540 –2.
110. Hornstein MD, Hemmings R, Yuzpe AA, Heinrichs WL. (Level III)
Use of nafarelin versus placebo after reductive laparo- 123. Namnoum AB, Hickman TN, Goodman SB, Gehlbach
scopic surgery for endometriosis. Fertil Steril 1997; DL, Rock JA. Incidence of symptom recurrence after
68:860–4. (Level I) hysterectomy for endometriosis. Fertil Steril 1995;64:
111. Yap C, Furness S, Farquhar C, Rawal N. Pre and
898–902. (Level III)
post operative medical therapy for endometriosis sur- 124. Redwine DB. Endometriosis persisting after castration:
gery. Cochrane Database of Systematic Reviews 2004, clinical characteristics and results of surgical manage-
Issue 3. Art. No.: CD003678. DOI: 10.1002/14651858. ment. Obstet Gynecol 1994;83:405–13. (Level III)
CD003678.pub2. (Meta-analysis)
125. Kinkel K, Chapron C, Balleyguier C, Fritel X, Dubuisson
112. Seracchioli R, Mabrouk M, Manuzzi L, Vicenzi C,
JB, Moreau JF. Magnetic resonance imaging charac-
Frasca C, Elmakky A, et al. Post-operative use of oral teristics of deep endometriosis. Hum Reprod 1999;14:
contraceptive pills for prevention of anatomical relapse 1080–6. (Level III)
or symptom-recurrence after conservative surgery
for endometriosis. Hum Reprod 2009;24:2729–35. 126. Bohrer J, Chen CC, Falcone T. Persistent bilateral

(Level III) ureteral obstruction secondary to endometriosis despite
treatment with an aromatase inhibitor. Fertil Steril
113. Seracchioli R, Mabrouk M, Frasca C, Manuzzi L,
2008;90:2004.e7,2004.e9. (Level III)
Montanari G, Keramyda A, et al. Long-term cyclic and
continuous oral contraceptive therapy and endometrioma 127. Hickman TN, Namnoum AB, Hinton EL, Zacur HA,
recurrence: a randomized controlled trial. Fertil Steril Rock JA. Timing of estrogen replacement therapy fol-
2010;93:52–6. (Level I) lowing hysterectomy with oophorectomy for endome-
triosis. Obstet Gynecol 1998;91:673–7. (Level II-3)
114. Vercellini P, Frontino G, De Giorgi O, Aimi G, Zaina B,
Crosignani PG. Comparison of a levonorgestrel-releas- 128. Matorras R, Elorriaga MA, Pijoan JI, Ramon O,

ing intrauterine device versus expectant management Rodriguez-Escudero FJ. Recurrence of endometriosis
after conservative surgery for symptomatic endometrio- in women with bilateral adnexectomy (with or without
sis: a pilot study. Fertil Steril 2003;80:305–9. (Level I) total hysterectomy) who received hormone replacement
therapy. Fertil Steril 2002;77:303–8. (Level I)
115. Abou-Setta AM, Al-Inany HG, Farquhar C. Levonor-
gestrel-releasing intrauterine device (LNG-IUD) for 129. Gucer F, Pieber D, Arikan MG. Malignancy arising in
symptomatic endometriosis following surgery. Cochrane extraovarian endometriosis during estrogen stimulation.
Database of Systematic Reviews 2006, Issue 4. Art. Eur J Gynaecol Oncol 1998;19:39–41. (Level III)

Practice Bul­le­tin No. 114 13

 Copyright July 2010 by the American College of Ob­ ste­
t-
The MEDLINE database, the Cochrane Library, and the ri­cians and Gynecologists. All rights reserved. No part of this
American College of Obstetricians and Gynecologists’ publication may be reproduced, stored in a re­triev­al sys­tem,
own internal resources and documents were used to con­ posted on the Internet, or transmitted, in any form or by any
duct a lit­er­a­ture search to lo­cate rel­e­vant ar­ti­cles pub­lished means, elec­tron­ic, me­chan­i­cal, photocopying, recording, or
be­tween January 1985 –January 2010. The search was oth­er­wise, without prior written permission from the publisher.
re­strict­ed to ar­ ti­
cles pub­ lished in the English lan­ guage.
Pri­or­i­ty was given to articles re­port­ing results of orig­i­nal Requests for authorization to make photocopies should be
re­search, although re­view ar­ti­cles and com­men­tar­ies also directed to Copyright Clearance Center, 222 Rosewood Drive,
were consulted. Ab­stracts of re­search pre­sent­ed at sym­po­ Danvers, MA 01923, (978) 750-8400.
sia and sci­en­tif­ic con­fer­enc­es were not con­sid­ered adequate ISSN 1099-3630
for in­clu­sion in this doc­u­ment. Guide­lines pub­lished by The American College of Obstetricians and Gynecologists
or­ga­ni­za­tions or in­sti­tu­tions such as the Na­tion­al In­sti­tutes
409 12th Street, SW, PO Box 96920, Washington, DC 20090-6920
of Health and the Amer­i­can Col­lege of Ob­ste­tri­cians and
Gy­ne­col­o­gists were re­viewed, and ad­di­tion­al studies were Management of endometriosis. Practice Bulletin No. 114. American
located by re­view­ing bib­liographies of identified articles. College of Obstetricians and Gynecologists. Obstet Gynecol 2010;
When re­li­able research was not available, expert opinions 116:223–36.
from ob­ste­tri­cian–gynecologists were used.
Studies were reviewed and evaluated for qual­i­ty ac­cord­ing
to the method outlined by the U.S. Pre­ven­tive Services
Task Force:
I Evidence obtained from at least one prop­ er­
ly
de­signed randomized controlled trial.
II-1 Evidence obtained from well-designed con­ trolled
tri­als without randomization.
II-2 Evidence obtained from well-designed co­ hort or
case–control analytic studies, pref­er­a­bly from more
than one center or research group.
II-3 Evidence obtained from multiple time series with or
with­out the intervention. Dra­mat­ic re­sults in un­con­
trolled ex­per­i­ments also could be regarded as this
type of ev­i­dence.
III Opinions of respected authorities, based on clin­i­cal
ex­pe­ri­ence, descriptive stud­ies, or re­ports of ex­pert
committees.
Based on the highest level of evidence found in the data,
recommendations are provided and grad­ed ac­cord­ing to the
following categories:
Level A—Recommendations are based on good and con­
sis­tent sci­en­tif­ic evidence.
Level B—Recommendations are based on limited or in­con­
sis­tent scientific evidence.
Level C—Recommendations are based primarily on con­
sen­sus and expert opinion.

14 Practice Bulletin No. 114