The diagnosis and management of endometriosis
- Recommendations
1. Diagnosis of endometriosis
1.1 Symptoms:
1.1.1 Clinicians should consider the
diagnosis of endometriosis in women presenting with the following cyclical and
non-cyclical symptoms:
- Dysmenorrhea.
- Deep dyspareunia.
- Dysuria or hematuria.
- Dyschezia or painful rectal bleeding.
- Shoulder tip pain.
- Catamenial pneumothorax.
- Cyclical cough, hemoptysis, chest pain.
- Cyclical scar swelling and pain.
- Fatigue.
- Infertility (GPS).10, 16-19
Justification
Overall, evidence to predict endometriosis based on clinical symptoms alone is weak and incomplete. In women seeking help from general practitioners, the following symptoms were found to be risk factors for endometriosis: abdominopelvic pain, dysmenorrhea, heavy menstrual bleeding, infertility, dyspareunia and/or postcoital bleeding and/or a previous diagnosis of ovarian cyst, irritable bowel syndrome or pelvic inflammatory disease. Reporting multiple symptoms increases the chance of endometriosis. In specialist health care, severe dysmenorrhea was found to be predictive of a diagnosis of endometriosis in infertile women, but this was not found in all studies.
Thus, endometriosis should be considered a possible diagnosis in women presenting with such clinical symptoms as it may result in an earlier diagnosis of endometriosis and in an improved quality of life for the patients.
1.2 Signs:
1.2.1 Perform an abdominal and pelvic
examination to women with suspected endometriosis, to identify abdominal masses
and pelvic signs, such as:
- Reduced organ mobility and enlargement,
- Tender nodularity in the posterior vaginal fornix,
- Visible vaginal endometriotic lesions (GPS).11, 13
1.2.2 If rectal endometriosis is suspected, a rectal examination is indicated to confirm the status of the bowel wall (GPS).9
Justification
During a clinical examination of the pelvis, signs suggestive of endometriosis may be found, including tenderness; tethering of pelvic organs that decrease mobility of the pelvic organs and tissues; palpable plaques, nodules or areas of thickening (commonly in the posterior compartment and along the uterosacral ligaments) that may indicate endometriosis; fixed enlarged or tender ovarian masses; and visible vaginal endometriosis lesions on speculum examination, most commonly in the vaginal fornices (posterior or anterior).
1.3 Diagnostic
Imaging:
1.3.1 In
women with suspected endometriosis, further diagnostic steps, including
imaging, should be considered even if the clinical examination is normal (low
level of evidence, Strong recommendation).10, 20, 21
1.3.2 Clinicians are recommended to use imaging (US or
MRI) in the diagnostic work-up for endometriosis, but they need to be aware
that a negative finding does not exclude endometriosis, particularly
superficial peritoneal disease (low level of evidence, strong recommendation).10, 20, 22-26
1.3.3 Offer a transvaginal ultrasound scan to all women
with suspected endometriosis, even if pelvic or abdominal examination is
normal, to identify ovarian endometriomas and deep endometriosis (very low
level of evidence, conditional recommendation).13
1.3.4 If a transvaginal scan is not appropriate,
consider transabdominal ultrasound scan of the pelvis (GPS).13
1.3.5 Do not use pelvic MRI as the primary
investigation to diagnose endometriosis in people with symptoms or signs
suggestive of endometriosis (very low level of evidence, conditional
recommendation).11
1.3.6 Consider pelvic
MRI to assess the extent of deep endometriosis involving the bowel, bladder or
ureter (very low level of evidence, conditional recommendation).11
Justification
Taking the available data into account, it is likely that particularly dedicated transvaginal ultrasound in experienced hands but also MRI can replace surgery are the gold standard for the diagnosis of ovarian endometriosis cysts and deep endometriosis in the pelvis. However, the non-invasive diagnosis of superficial disease remains a significant challenge and can currently not accurately diagnosed or ruled out by the available imaging modalities. Thus, if symptoms persist, further investigation should be considered. The accuracy of ultrasound for the diagnosis of endometriosis is affected by the techniques used, the thoroughness of the examination and the expertise of the person undertaking the scan.
Although the evidence showed that ultrasound and MRI were reliable tests for identifying site-specific endometriosis in a specialist setting, MRI could not be compared with ultrasound because a person with endometriosis would not initially be sent for an MRI scan. However, if the ultrasound was inconclusive or negative, but deep endometrioses involving the bowel, bladder or ureter was suspected, then the person might be referred for an MRI scan. The recommendations for MRI should not extend to earlier or more superficial disease because the evidence for MRI was limited to the detection of deep infiltrating endometriosis. There are also cost and access implications, because MRI is more expensive than ultrasound and may not be available in all areas.
1.4 Laparoscopy:
surgical diagnosis:
1.4.1 In patients with negative imaging results, or
where empirical treatment (hormonal contraceptives or progestogens) was
unsuccessful, consider offering laparoscopy for the diagnosis and treatment of
suspected endometriosis (GPS).1, 10, 27-30
1.4.2 Laparoscopic identification of endometriotic
lesions should be confirmed by histopathologic examination of the lesions.
However, a negative histology does not entirely rule out the disease (GPS).10, 24
1.4.3 The procedure should be performed by a trained
laparoscopic surgeon, who should perform and document a systematic inspection
of the pelvis and abdomen(GPS).11
Justification
As established above, there exist copious diagnostic challenges for endometriosis in general, in particular for superficial pelvic disease due a variety of factors including the lack of clinically relevant biomarkers, lack of specific symptoms and the inability of current imaging techniques to reliably identify or rule out small lesions. There exists the widespread concept that laparoscopy is the accepted standard to diagnose abdominal endometriosis. However, laparoscopic surgery, albeit its widespread use, is expensive, invasive, and associated with morbidity and mortality. On the other hand, direct, photographic, and histological proof of lesions could potentially be an important psychological factor for women who have been suffering from the symptoms of an otherwise invisible disease creating a platform of acceptance for themselves and their environment. The benefits of laparoscopic surgery need to be weighed up against its risks.
Practically, a two-step approach should be sought which would include a transvaginal (where appropriate) ultrasound followed by empirical treatment (if the patient is not trying to conceive). Particularly in the primary care setting if endometriosis is suspected, imaging results are negative and the affected person is not acutely trying to conceive, symptomatic patients usually are offered hormonal treatment mostly in the form of the oral contraceptive pill or progestogens as a first-line treatment. If symptoms improve, endometriosis is presumed the main underlying condition, although other clinical causes can (co-)exist. This ‘blinded’ approach is widely known as empirical treatment.
Laparoscopies are sometimes performed with inadequate examination of the pelvis, resulting in false negative results. Laparoscopic diagnosis should involve a systematic examination of the pelvis carried out by a gynecologist with training and skills in laparoscopic surgery, because it is possible to miss significant endometriosis. When the findings from a systematic review of the pelvis are negative for endometriosis, or histological samples taken from the pelvis are negative for endometriosis, the person should be reassured that endometriosis is not the cause of their symptoms and should be offered appropriate treatment for persistent symptoms.
1.5 Biomarkers:
1.5.1 Do not use serum CA125 to
diagnose endometriosis (moderate level of evidence, Strong recommedation).10, 11,
13
Justification
Numerous biomarkers have been proposed; if these prove to be sufficiently accurate, a blood test could provide a relatively safe and cheap method of diagnosis that is readily available in community settings. Serum CA125 is the most widely studied biomarker in populations with endometriosis, but the quality of evidence is very low and the rate of false negative test results is too high to promote its use in clinical practice at this time. A CA125 test does not add anything to the diagnostic strategy, apart from a possible delay and additional costs for further unnecessary referral and investigation.
2. Treatment of endometriosis
associated pain
2.1 Pain control
in endometriosis
2.1.1 For women with pain associated with endometriosis-, consider a
short trial (for example, 3 months) of a non-steroidal anti-inflammatory drug
(NSAID) alone or in combination with paracetamol, if not contraindicated. If
such a trial does not provide adequate pain relief, consider other forms of
pain management and referral for further assessment (GPS).11
Justification
The
evidence for use of NSAIDs for management of pain symptoms related to
endometriosis is scarce and limited to one small RCT. There is a general
anti-inflammatory effect of some analgesics, they can be used in conjunction
with surgery and/or hormonal treatments and they may possibly prevent of
complications of chronic pain (e.g., peripheral, and central sensitization).
However, analgesics may also have side effects, and NSAIDs specifically may
have some gastrointestinal side effects. There is no evidence that analgesics
have an effect on disease progression. Overall, with limited risks and
considering the wide availability and use of analgesics, the GDG concluded that
NSAIDs or other analgesics may be offered for the treatment of
endometriosis-associated pain.
2.1.2 Advise patients that there is
no evidence for or against the use of anti-neuropathic medications for pain
associated with endometriosis (GPS).11
2.1.3 Women with endometriosis
should be referred to a pain specialist and/or a condition-specific specialist
at any stage if:
• pain is severe and unresponsive to simple analgesics.
• the pain substantially limits daily activities.
• any underlying health condition has deteriorated (GPS).11
2.2
Hormonal
treatment for endometriosis
2.2.1 It is recommended to offer women hormone
treatment (combined hormonal contraceptives, progestogens, GnRH agonists or
GnRH antagonists) as one of the options to reduce endometriosis-associated pain
(moderate level of evidence, strong recommendation).31-35
2.2.2 The GDG recommends that clinicians take a shared
decision-making approach and take individual preferences, side effects,
individual efficacy, costs, and availability into consideration when choosing
hormone treatments for endometriosis-associated pain (GPS). 31-35
Justification
There
is moderate quality evidence of benefit for all listed hormone treatments for
relief of painful symptoms related to endometriosis. As there is no evidence
that hormone treatments have a negative effect on disease progression and they
generally have limited side effects, prescribing hormone treatment is
recommended. Moreover, hormone treatments, such as the contraceptive pill, may
be indicated for contraception anyway. As there is no evidence of superiority
of one hormone treatment compared to others, the GDG recommends a shared
decision-making approach. These overarching recommendations should be read and
applied in consideration of the remainder of this section which provides more
detailed information on the different medical treatments including their
efficacy and side-effect profile.
2.2.3 It is recommended to prescribe women a
levonorgestrel-releasing intrauterine system or an etonogestrel-releasing
subdermal implant to reduce endometriosis-associated pain (moderate level of
evidence, strong recommendation).36-39
Justification
There is
sufficient evidence on the effectiveness of progestogens and anti-progestogens,
including the levonorgestrel-releasing intrauterine system and the
etonogestrel-releasing subdermal implant, to support their use in reducing pain
in women with endometriosis (strong recommendation). The GDG stresses that
clinicians should consider the side-effect profiles to tailor the medical
treatment towards improving symptoms and quality of life. The GDG does not
recommend danazol as a treatment for endometriosis-associated pain and
considered it no longer relevant to include anti-progestogens in the
recommendation.
With
regards to the LNG-IUS, a review of five trials showed that the clinical
efficacy was equivalent to that of GnRH agonist, but also that LNG-IUS may have
some clinical advantages. LNG-IUS and ENG were shown to be equally effective in
one study. A strong recommendation was formulated for both LNG-IUS and ENG as
progestogen-treatment.
2.2.4 Clinicians should consider prescribing combined
hormonal add-back therapy alongside GnRH agonist therapy to prevent bone loss
and hypoestrogenic symptoms (moderate level of evidence, strong
recommendation). 35-37, 40-42
Justification
From the
Cochrane review, it can be concluded that GnRH agonists are effective in the
relief of endometriosis-associated pain (strong recommendation), but evidence
is limited regarding dosage or duration of treatment. Based on the evidence to
date, no specific GnRH agonist can be recommended over another in relieving
endometriosis-associated pain. There is evidence of considerable side effects
with GnRH agonists, which should be discussed with the patient when offering
this treatment. There is moderate quality evidence, summarized in a systematic
review,35 that
addition of add-back therapy when prescribing GnRH agonist treatment prevents
bone loss, while it does not affect the efficacy of the GnRH agonist treatment.
As such, add-back treatment is recommended (strong recommendation). Considering
the possible impact on BMD, The GDG recommends that in young women and
adolescents, GnRH agonist should be used after careful consideration and as
second line of therapy and after discussion with a practitioner in a secondary
or tertiary care setting, considering potential side effects and long-term
health risks (e.g., bone health).
2.2.5 In women with endometriosis-associated pain
refractory to other medical or surgical treatment, it is recommended to
prescribe aromatase inhibitors, as they reduce endometriosis-associated pain.
Aromatase inhibitors may be prescribed in combination with oral contraceptives,
progestogens, GnRH agonists or GnRH antagonist (low level of evidence, strong
recommendation).43, 44
Justification
The
evidence consists of a systematic review from 2011, including mostly
non-randomized controlled studies and case reports in women with rectovaginal
endometriosis or women that are refractory to previous surgical and medical
treatment, and 2 more recent studies. Evidence on the long-term effects of
aromatase inhibitors is lacking. Due to the severe side effects (vaginal
dryness, hot flushes, diminished bone mineral density), aromatase inhibitors
should only be prescribed to women after all other options for medical or
surgical treatment are exhausted. Considering these aspects, aromatase
inhibitors should be preserved for women with endometriosis-associated pain
refractory to other medical or surgical treatment.
2.3
Surgical
treatment for pain in endometriosis
2.3.1 Laparoscopic management should be done by an
expert in laparoscopic surgery (GPS).
2.3.2 When surgery is performed, clinicians may
consider excision instead of ablation of endometriosis to reduce endometriosis-associated
pain (low level of evidence, conditional recommendation).45-48
Justification
The
evidence for ablation versus excision is based on studies that include women
with heterogeneous forms of endometriosis. Some of these studies excluded women
with deep endometriosis, in which ablation is not usually applied anyway. The excisional
approach is likely to be more suitable for deep endometriosis lesions, as it is
impossible to know if the entire lesion is destroyed with ablative techniques.
2.3.3 It can be concluded that LUNA is not beneficial
as an additional procedure to conventional laparoscopic surgery for
endometriosis, as it offers no additional benefit over surgery alone. Presacral
Neurectomy (PSN) is beneficial for treatment of endometriosis-associated
midline pain as an adjunct to conventional laparoscopic surgery, but it should
be stressed that PSN requires a high degree of skill and is associated with an
increased risk of adverse effects such as intraoperative bleeding, and
postoperative constipation, urinary urgency and painless first stage of labor (GPS).49-53
2.3.4 When performing surgery in women with ovarian
endometrioma, clinicians should perform cystectomy instead of drainage and
coagulation, as cystectomy reduces recurrence of endometrioma and
endometriosis-associated pain (low level of evidence, strong recommendation).54-60
2.3.5 When performing surgery for ovarian endometrioma,
specific caution should be used to minimize ovarian damage (very ow level of
evidence, strong recommendation). 54-60
Justification
Cystectomy
is probably superior to drainage and coagulation in women with ovarian
endometrioma (≥ 3cm) regarding the recurrence of endometriosis-associated pain
and the recurrence of endometrioma (Hart, et al., 2008), which supports the
formulation of a strong recommendation. Longer follow-up data show similar
recurrence rates for cystectomy and CO2 laser vaporization. Whilst superiority
of excision over drainage and coagulation/ablation can be expected, possible
difficulties in removal of very small endometriomas should be kept in mind due
to lack of a clear surgical plane. With regards to ovarian reserve, data show
that ovarian surgery may have an impact on ovarian reserve, but the data
comparing the impact of different techniques should be interpreted with
caution. When contemplating surgery for endometriomas, particularly for
recurrent endometriomas, ovarian reserve and ovarian damage should be carefully
considered. For the comparison of cystectomy and CO2 laser vaporization, one
RCT and one retrospective study were available 56, 61, both
concluding that there are similar recurrence rates beyond the first year for
the treatment of endometriomas both techniques, Carmona et al. also reported
that the recurrence rates may be lower after cystectomy in the first year. In
the included studies, patients were included with endometriomas and
endometriosis-associated symptoms (pain and/or infertility). The guideline
group would like to clarify that in women with a diagnosed endometrioma and
pain symptoms, other forms of endometriosis including deep endometriosis is
commonly detected during surgery. Although not discussed, nor considered in
most of the studies, this needs to be considered in clinical practice.
2.3.6 Clinicians can consider performing surgical
removal of deep endometriosis, as it may reduce endometriosis-associated pain
and improves quality of life (low level of evidence, conditional
recommendation).62-65
2.3.7 The GDG recommends that patients undergoing
surgery particularly for deep endometriosis are informed on potential risks,
benefits, and long-term effect on quality of life (GPS). 62-65
2.3.8 Due to the heterogeneity of patient population,
presentation, surgical approaches and techniques, it is difficult to make
definitive recommendations on the specific techniques to be applied for the
treatment of pain associated with deep endometriosis (GPS) 62-65
Justification
Overall,
data show that surgery improves pain and quality of life in women with deep
endometriosis. Still, the literature regarding treatment and outcome of deep
endometriosis surgery should be interpreted with caution. It is of paramount
importance that type of study, surgical approach, surgical technique, and the way
outcome is measured is taken into account. There is a lack of consistency in
the way the studies reported outcome, and the systematic review on this topic
was based on small studies and case reports. These limitations are reflected in
the evidence level. As surgery in women with deep endometriosis is possibly
associated with significant intraoperative and postoperative complication
rates, the recommendation was formulated as a conditional recommendation and
complemented with a GPS suggestion that such surgery is ideally performed in a
center of expertise, and only after the patient is informed on potential risks,
benefits, and long-term effects.
2.3.9 In case of bowel endometriosis, a conservative approach
should be chosen whenever possible It is concluded that a conservative approach
should be chosen whenever possible. Radical resection of all endometriosis
nodules does not mean that a conservative attitude towards surgical
technique/options could not be maintained. A least traumatic, but radical
resection with a more tailored/patient-centered approach with perioperative
decision-making is preferred (GPS).63, 66
2.3.10 Clinicians can consider hysterectomy (with or
without removal of the ovaries) with removal of all visible endometriosis
lesions, in those women who no longer wish to conceive and failed to respond to
more conservative treatments. This may be a particularly good option in women
with significant concomitant adenomyosis. Women should be informed that
hysterectomy will not necessarily cure the symptoms or the disease (low
level of evidence, Conditional recommendation).67, 68
2.3.11 When a decision is made whether to remove the
ovaries, the long-term consequences of early menopause and possible need for
hormone replacement therapy should be considered (GPS). 67, 68
2.3.12 The GDG recommends that when hysterectomy is
performed, a total hysterectomy is preferred. This recommendation is based on possible
risk of persistent endometriosis and adenomyosis within the retained cervix
and/or adjacent to it (GPS). 67, 68
Justification
Hysterectomy
for endometriosis-associated pain seems to be effective for relieving symptoms
and significantly reduces the need for re-operation. This may be a particularly
good option in women with significant concomitant adenomyosis. It should be
considered that hysterectomy, especially when combined with bilateral
salpingo-oophorectomy, is not an option for women still wishing to conceive.
Additionally, hysterectomy with bilateral salpingo-oophorectomy may have a
significant long-term impact and may create a need for hormone replacement
therapy. The GDG stresses that women with endometriosis may still experience
pain symptoms after hysterectomy, due to residual endometriosis or centralization
of pain. The GDG recommends that when hysterectomy is performed, a total hysterectomy
(i.e., removal of uterus and cervix) is preferred. This recommendation is based
on possible risk of persistent endometriosis and adenomyosis within the
retained cervix and/or adjacent to it with subtotal hysterectomy
2.3.13 Studies should evaluate factors that can be
assessed prior to surgery and can predict a clinically meaningful improvement
of pain symptoms. Such prognostic markers can be used to select patients that
may benefit from endometriosis surgery (GPS).66, 69, 70
Justification
The
guideline group confirms the recommendation from the previous ESHRE guideline. Considering
this (strong) recommendation, the GDG acknowledges that in clinical practice,
surgeons prescribe preoperative medical treatment with GnRH agonists as this
can facilitate surgery due to reduced inflammation, vascularization of
endometriosis lesions and adhesions. However, there are no controlled studies
supporting this. From a patient perspective, medical treatment should be
offered before surgery to women with painful symptoms in the waiting period
before the surgery can be performed, with the purpose of reducing pain before,
not after, surgery.
2.3.14 Women may be offered postoperative hormone
treatment to improve the immediate outcome of surgery for pain in women with
endometriosis if not desiring immediate pregnancy (low level of evidence, conditional
recommendation).71-75
Justification
Based on
the current evidence from the Cochrane review by Chen et al., the GDG concluded
that there is only a very moderate benefit of postoperative hormone therapy
(within 6 months after surgery) if this treatment is prescribed with the sole
aim of improving the outcome of surgery. Furthermore, there is inconsistency
between the studies on whether postoperative hormone treatment has a favorable
effect on pain recurrence or disease recurrence after surgery. With no proven
harm, postoperative hormone therapy may be prescribed for other indications,
such as contraception or secondary prevention.
2.4
Non-medical
interventions in endometriosis
No
recommendations can be made for any specific non-medical intervention (Chinese
medicine, nutrition, electrotherapy, acupuncture, physiotherapy, exercise, and
psychological interventions) to reduce pain or improve quality of life measures
in women with endometriosis, as the potential benefits and harms are unclear.
Adequately
designed trials are needed to define the potential benefits of non-medical
interventions (nutrition, Chinese medicine, electrotherapy, acupuncture,
physiotherapy, exercise, and psychological interventions) in endometriosis.
Further research into such interventions for women with endometriosis that
employ evidence-based protocols with high intervention integrity is recommended
(GPS).76-80
3. Treatment of endometriosis
associated infertility
3.1
Ovarian suppression
3.1.1 In infertile women with endometriosis, clinicians
should not prescribe ovarian suppression treatment to improve fertility (low level of evidence, strong recommendation).10, 81
3.1.2 Women seeking pregnancy should not be prescribed
postoperative hormone suppression with the sole purpose to enhance future
pregnancy rates (low level of evidence, strong recommendation).
3.1.3 Those women who cannot attempt to or decide not
to conceive immediately after surgery may be offered hormone therapy as it does
not negatively impact their fertility and improves the immediate outcome of
surgery for pain (low level of evidence, conditional recommendation).10, 71, 82
3.1.4 In infertile women with endometriosis, clinicians
should not prescribe pentoxifylline, other anti-inflammatory drugs or letrozole
outside ovulation-induction to improve natural pregnancy rates (very low
level of evidence, strong recommendation).10, 83, 84
Justification
Based
on the results of the Cochrane review, suppression of ovarian function (by
means of danazol, GnRH agonists, progestogens, OCP) to improve fertility in
women with endometriosis is not effective and should not be offered for this
indication alone (strong recommendation).
It should be noted that several patients included in the
Hughes et al. review had undergone surgical treatment before randomization
for ovarian suppression or no treatment. This observation complicates any
recommendations regarding ovarian suppression and post-surgical ovarian
suppression, discussed in the following section.
Studies show no benefit of pentoxifylline, postoperative
aromatase inhibitor (letrozole), or postoperative GnRH agonist (triptorelin) to
improve pregnancy rates in women with endometriosis. Therefore, the
intervention is not recommended (strong recommendation).
The GDG
considered that ovarian suppression after surgical treatment for endometriosis
should not be prescribed to improve pregnancy rates (strong recommendation).
The GDG also considered that ovarian suppression after surgical treatment does
probably not have a negative effect on the chances of pregnancy, and therefore,
it may be prescribed for pain management, or in women that cannot attempt to
conceive immediately after surgery, but not with the sole aim of improving
pregnancy rates (conditional recommendation). This is consistent with the
earlier recommendation “Women may be offered postoperative hormone treatment to
improve the immediate outcome of surgery for pain in women with endometriosis.”
3.2
Surgical
treatment
3.2.1 The GDG
recommends that the decision to perform surgery should be guided by the
presence or absence of pain symptoms, patient age and preferences, history of
previous surgery, presence of other infertility factors, ovarian reserve, and
estimated EFI (GPS).
3.2.2 Regarding peritoneal endometriosis Although
laparoscopic surgery was found to increase (natural) viable intrauterine
pregnancy rates, no data were found on live birth rates. Operative laparoscopy
could be offered as a treatment option for endometriosis associated infertility
in rASRM stage I/II endometriosis as it improves the rate of ongoing pregnancy (low level of evidence, conditional recommendation) 10, 27, 56, 85
3.2.3 Regarding ovarian endometriosis Clinicians may
consider operative laparoscopy for the treatment of endometrioma associated
infertility as it may increase their chance of natural pregnancy, although no
data from comparative studies exist (very low level of evidence, conditional
recommendation).10, 86
3.2.4 Regarding deep endometriosis Although no
compelling evidence exists that operative laparoscopy for DE improves
fertility, operative laparoscopy may represent a treatment option in
symptomatic patients wishing to conceive (very low level of evidence, conditional
recommendation).10, 87
Justification
In
the review of Bafort et al., surgery in women with rASRM stage I/II
endometriosis improved the rate of ongoing pregnancy. The GDG formulated a conditional
recommendation to offer operative laparoscopy. However, the GDG also
acknowledges that data on live birth rates and direct comparison with medically
assisted reproduction are lacking
Similar
considerations were made for endometrioma and deep endometriosis surgery; with
a lack of comparative studies evaluating spontaneous conception after surgery
compared to no surgery, no strong recommendations could be formulated. The GDG
added clarification that the decision to perform surgery should be guided by
other factors.
3.3
Assessing the
need for assisted reproduction after surgery
3.3.1 Women should be counselled of their chances of
becoming pregnant after surgery. To identify patients that may benefit from ART
after surgery, the Endometriosis Fertility Index (EFI) should be used as it is
validated, reproducible and cost-effective. The results of other fertility
investigations such as their partner’s sperm analysis should be taken into
account (GPS) 10, 88
Justification
It is suggested that the EFI is used for better patient
phenotyping in studies on surgical treatment and/or the place of medically
assisted reproduction (MAR) in endometriosis-related infertility. The role of
the EFI as a pre-surgical triage tool should be validated.
3.4
Medically
assisted reproduction
3.4.1 Intrauterine insemination in
women with endometriosis
3.4.1.1 In infertile women with rASRM stage I/II endometriosis,
clinicians may perform intrauterine insemination (IUI) with ovarian
stimulation, instead of expectant management or IUI alone, as it increases
pregnancy rates (very low level of evidence, conditional recommendation). 10, 89-92
3.4.1.2 Although the value of IUI in infertile women with rASRM
stage III/IV endometriosis with tubal patency is uncertain, the use of IUI with
ovarian stimulation could be considered (very low level of evidence, conditional
recommendation).10, 89-92
Justification
In
women with AFS/ASRM stage I/II endometriosis, IUI with ovarian stimulation may
be effective in increasing live birth rate, compared with expectant management
and effective in increasing biochemical pregnancy rate, compared to IUI alone (conditional
recommendation). In these women, clinicians may consider performing
intrauterine insemination with ovarian stimulation within 6 months after
surgical treatment, since pregnancy rates are similar to those achieved in
unexplained infertility.90
3.4.2 Assisted reproductive technology
in women with endometriosis.
3.4.2.1 ART can be performed for infertility associated with
endometriosis, especially if tubal function is compromised, if there is male
factor infertility, in case of low EFI and/or if other treatments have failed (low
level of evidence, Conditional recommendation).10, 93-97
3.4.2.2 A specific protocol for ART in women with endometriosis
cannot be recommended. Both GnRH antagonist and agonist protocols can be offered
based on patients’ and physicians’ preferences as no difference in pregnancy or
live birth rate has been demonstrated (very low level of evidence,
conditional recommendation).10, 98-101
3.4.2.3 Women with endometriosis can be reassured regarding the
safety of ART since the recurrence rates are not increased compared to those
women not undergoing ART (moderate level of evidence, conditional
recommendation).10, 102
3.4.2.4 In women with endometrioma, clinicians may use antibiotic
prophylaxis at the time of oocyte retrieval, although the risk of ovarian
abscess formation following follicle aspiration is low (GPS).10, 103
Justification
Overall, in infertile women, most of the evidence does not demonstrate a
negative impact of endometriosis (compared to non-endometriosis patients) on
live birth rate after ART, even if the ovarian response and clinical pregnancy
rates are lower. Therefore, ART may be effective for endometriosis-associated
endometriosis, and is recommended (conditional recommendation) in women with
other infertility factors. The severity of the disease might play a role with
stage III-IV endometriosis potentially decreasing the live birth rate. The
available evidence failed to demonstrate that a specific ART protocol should be
favored in patients with endometriosis.
From a systematic
review including moderate quality evidence, ART was not associated with
increased endometriosis recurrence rate. A conditional recommendation was
formulated to inform and/or reassure patients. The use of antibiotic
prophylaxis at the time of oocyte retrieval in women with endometriomas seems
reasonable and is recommended as a good practice point. There is no evidence on
whether IUI or ART is superior in women with endometriosis.
3.4.3 Medical therapies as an adjunct
to MAR
3.4.3.1 The extended administration of GnRH agonist prior to ART
treatment to improve live birth rate in infertile women with endometriosis is
not recommended, as the benefit is uncertain (very low level of evidence,
strong recommendation).10, 104-106
3.4.3.2
There
is insufficient evidence to recommend prolonged administration of the
COC/progestogens as a pre-treatment to ART to increase live birth rates (very
low level of evidence, conditional recommendation).10, 104-106
Justification
Based on the Cochrane review 104, with the limitations as mentioned above,
the merit of 3–6 months GnRH agonist administration to women with endometriosis
prior to ART compared to no pre-treatment is uncertain and requires further
high-quality trials to determine its impact With uncertain benefit, the administration
of GnRH agonist prior to ART treatment cannot be recommended.
The data concerning the use of OCP or progestogens as a
pre-treatment before ART for improving ART outcomes are very limited and do not
allow to draw any conclusion. This does not preclude use of OCP for planning
purposes.
3.4.4 Surgical therapies as an adjunct
to MAR
3.4.4.1
Clinicians
are not recommended to routinely perform surgery prior to ART to improve live
birth rates in women with rASRM stage I/II endometriosis, as the potential benefits
are unclear (low level of evidence, strong recommendation).10, 93, 107, 108
3.4.4.2
Clinicians
are not recommended to routinely perform surgery for ovarian endometrioma prior
to ART to improve live birth rates, as the current evidence shows no benefit
and surgery is likely to have a negative impact on ovarian reserve (low
level of evidence, strong recommendation).10, 93, 107, 108
3.4.4.3
Surgery
for endometrioma prior to ART can be considered to improve endometriosis
associated pain or accessibility of follicles (GPS).10, 93, 107, 108
3.4.4.4
The
decision to offer surgical excision of deep endometriosis lesions prior to ART
should be guided mainly by pain symptoms and patient preference as its
effectiveness on reproductive outcome is uncertain due to lack of randomised
studies (very low level of evidence, strong recommendation).10, 93, 109
Justification
The evidence regarding surgery prior to treatment with
ART in women with stage I/II endometriosis is of low quality and based on a
single retrospective study. Although this study suggests that surgery may have
a beneficial effect on ART outcomes, the GDG considered more data are needed to
confirm the benefit of surgery for peritoneal disease for improving ART outcomes,
and to be able to recommended it in routine practice. A strong recommendation
stating that laparoscopy should not be routinely performed prior to ART with
the aim of improving ART outcomes was formulated.
Based on two systematic reviews and meta-analyses,
surgical removal of endometrioma before ART does not appear to improve the live
birth rate while it is likely reducing ovarian reserve. As such, a strong
recommendation was formulated against surgery with the sole aim to improve ART
outcomes. Additionally, a good practice point was formulated stating that
surgery can be performed for other indications.
When surgical resection of endometrioma prior to ART is
necessary, no specific techniques can be recommended. Ovarian cystectomy has
the potential of reducing the risk of recurrence.
From the
literature, there is no evidence from randomized controlled trials to recommend
performing surgical excision of deep nodular endometriotic lesions prior to ART
to improve reproductive outcomes. However, these women often suffer from pain,
requiring surgical treatment. The GDG strongly recommends basing a decision to
perform surgery on pain symptoms and patient preferences. In symptomatic
infertile women with previous failed ART and deep endometriosis, surgical removal
of the lesions may be (re)considered.
3.4.5 Non-medical treatment strategies
3.4.5.1
No
recommendation can be made to support any non-medical interventions (nutrition,
Chinese medicine, electrotherapy, acupuncture, physiotherapy, exercise, and
psychological interventions) to increase fertility in women with endometriosis.
The potential benefits and harms are unclear (GPS).10, 110, 111
Justification
Only small studies of low quality could be identified investigating
surgery and medication and/or CM to improve subfertility. Though there is a
lack of research specifically addressing the impact of non-medical strategies
in the treatment of endometriosis-related symptoms, more studies are emerging.
It seems evident that patients are searching for alternative ways of managing
and coping without or alongside surgical and pharmacological interventions.
3.4.6 Fertility preservation
3.4.6.1 In case of extensive ovarian endometriosis, clinicians
should discuss the pros and cons of fertility preservation with women with
endometriosis. The true benefit of fertility preservation in women with
endometriosis remains unknown (very low level of evidence, strong
recommendation). 10, 112-116
Justification
Oocyte cryopreservation is expensive and exposes
women to some clinical risks. Although the study of Cobo et al. shows
the feasibility of fertility preservation (oocyte freezing) in women with
ovarian endometriosis, still many questions (e.g. (cost) effectiveness) remain
unanswered, and there is currently insufficient data to support fertility
preservation for all women with endometriosis. It is acknowledged that for some
women with endometriosis, fertility preservation may increase their future
chances of pregnancy, but there is no evidence on criteria to select those
women. Based on these considerations, the GDG formulated a strong
recommendation for counselling and information provision.
3.4.7 Impact of endometriosis on
pregnancy and pregnancy outcome
3.4.7.1
Effect of pregnancy on endometriotic lesions
· Patients should not be advised to become pregnant
with the sole purpose of treating endometriosis, as pregnancy does not always
lead to improvement of symptoms or reduction of disease progression (very
low level of evidence, strong recommendation).10, 117, 118
·
Endometriomas
may change in appearance during pregnancy. In case of finding an atypical
endometrioma during ultrasound in pregnancy, it is recommended to refer the
patient to a center with appropriate expertise (very low level of evidence,
strong recommendation).10, 117, 118
Justification
Although this is considered as a narrative question, recommendations were
formulated on safety aspects. The first strong recommendation is based on the
evidence summarized in high quality systematic reviews, showing a variable
impact of pregnancy on endometriotic lesions. Patients are being advised to
become pregnant to cure their endometriosis, and the data clearly indicate that
this advice is incorrect. The GDG therefore considered it relevant and
important to recommend that women with endometriosis should not be advised to
become pregnant with the sole purpose of treating endometriosis.
For the
second (strong) recommendation, there are data showing that endometrioma may
change appearance during pregnancy, but that this is often unknown and not
recognized. As this may lead to surgical intervention and termination of
pregnancy, the GDG formulated a recommendation for referral to a center with
expertise
3.4.7.2
Possible complications during pregnancy from a pre-existing
endometriosis lesion
· Complications related directly to pre-existing
endometriosis lesions are rare, but probably under reported. Such complications
may be related to their decidualization, adhesion formation/stretching and
endometriosis-related chronic inflammation (endometrioma rupture or infection,
gastrointestinal manifestation even bowel spontaneous perforation, urinary
manifestations and even case recorded uterine rupture). Although rare, they may
represent life-threatening situations that may require surgical management (GPS).10, 117, 118
3.4.7.3
Impact of endometriosis on early pregnancy (1st trimester)
·
Clinicians
should be aware that there may be an increased risk of first trimester
miscarriage and ectopic pregnancy in women with endometriosis (low level of
evidence, strong recommendation).10, 117, 118
Justification
Both miscarriage rate and ectopic pregnancy rate are
increased in women with endometriosis versus controls, although this is based
on low/moderate quality data. Therefore, higher vigilance is required in case
of symptoms suggestive of miscarriage or ectopic pregnancy, such as vaginal
bleeding and abdominal pain in the first trimester of pregnancy.
3.4.7.4
Impact of endometriosis on 2nd and 3rd trimester pregnancy
and neonatal outcome
· Clinicians should be aware of endometriosis-associated
complications in pregnancy, although these are rare. As these findings are
based on low/moderate quality studies, these results should be interpreted with
caution and currently do not warrant increased antenatal monitoring or dissuade
women from becoming pregnant (Gestational diabetes (GDM)- Preterm birth /
premature rupture of membranes-Placenta praevia-Hypertensive disorders and
pre-eclampsia-Stillbirth-Caesarean section-Obstetric hemorrhages (placental
abruption, ante- and post-partum bleeding) and small for gestational age,
admission to NICU, neonatal death) (low level of evidence, strong recommendation).10, 119
Justification
While several studies have reported a higher morbidity in 2nd/3rd trimester of pregnancy and delivery to be associated
with endometriosis, these findings are based on low/moderate quality studies.
The discrepancies between the meta-analyses, which are largely based on similar
studies but use different inclusion criteria and divergent sub-analysis, limits
the implications for clinical practice. Although clinicians should be aware of
these potential risks, these findings do currently not warrant increased
antenatal monitoring in individuals with endometriosis, as studies on
appropriate interventions for risk reduction are lacking.
4.
Endometriosis recurrence
4.1
Prevention of
endometriosis recurrence:
4.1.1 When surgery is indicated in women with an
endometrioma, clinicians should perform ovarian cystectomy, instead of drainage
and electrocoagulation, for the secondary prevention of
endometriosis-associated dysmenorrhea, dyspareunia, and non-menstrual pelvic
pain. However, the risk of reduced ovarian reserve should be taken into account
(low level of evidence, strong recommendation).10, 57, 120, 121
4.1.2 Clinicians should consider prescribing the
postoperative use of a levonorgestrel-releasing intrauterine system (52 mg
LNG-IUS) or a combined hormonal contraceptive for at least 18–24 months for the
secondary prevention of endometriosis-associated dysmenorrhea (low level of
evidence, strong recommendation).10, 120, 122-125
4.1.3 After surgical management of ovarian endometrioma
in women not immediately seeking conception, clinicians are recommended to
offer long-term hormone treatment (e.g. combined hormonal contraceptives) for
the secondary prevention of endometrioma and endometriosis-associated related
symptom recurrence (very low level of evidence, strong recommendation).10, 126, 127
4.1.4 For the prevention of recurrence of deep
endometriosis and associated symptoms, long-term administration of
postoperative hormone treatment can be considered (very low level of
evidence, conditional recommendation).10, 128, 129
4.1.5 Long-term administration of progestogen may
reduce the recurrence of ovarian endometriotic cysts (low level of evidence,
conditional recommendation).9, 130
Justification
Cystectomy
is probably superior to drainage and coagulation in women with ovarian
endometrioma (≥3 cm) with regard to the recurrence of endometriosis-associated
pain and the recurrence of endometrioma. A strong recommendation was formulated
in favor of cystectomy. Whenever ovarian surgery is performed, the impact on
ovarian reserve (i.e., the risk) should be carefully considered against the
benefit. Even if efficacy of OCP is documented for dysmenorrhea, it is not
confirmed for non-menstrual pelvic pain or dyspareunia. Still, if they do not
wish to conceive, women can use regular oral contraceptives for prevention of
endometriosis recurrence. For LNG-IUS, evidence shows a positive effect on
postoperative pain, disease recurrence, and patients’ satisfaction after
surgery for endometriosis-associated pain.
Still,
there is no overwhelming evidence to support particular treatments over others
with the aim of secondary
prevention of the disease and of symptoms recurrence (in particular
dysmenorrhea). Combined oral contraceptives, preferably in a continuous
regimen, and progestins can be considered feasible options as first-line
treatments. For both OCP and LNG-IUS, strong recommendations in favor of
postoperative therapy were formulated. Still, the choice of intervention should
be discussed and decided taking into account patient preferences, costs,
availability, risks and side effects. When prescribing such treatment, their
contraceptive properties should be considered and weighed against the wishes of
the women to become pregnant.
4.2
Treatment of
endometriosis recurrence:
4.2.1 Any hormone treatment or surgery can be offered to treat recurring pain
symptoms in women with endometriosis (very low level of evidence, conditional
recommendation).10, 120, 124, 130-133
Justification
Although reviews and studies show a benefit of
postoperative medical therapy for women with endometriosis, data specified per
subtype are scarce. For ovarian endometrioma, a strong recommendation in favor
was considered justified, while for deep endometriosis, only a conditional
recommendation could be formulated.
5.
Adolescent Endometriosis
5.1
Clinical
symptoms
5.1.1 In adolescents, clinicians should
take a careful history and consider the following symptoms as suggestive of the
presence of endometriosis:
§ chronic or a-cyclical pelvic pain,
particularly combined with nausea, dysmenorrhea, dyschezia, dysuria, dyspareunia
§ cyclical pelvic pain (very low level of evidence,
strong recommendation). 10, 134-137
Justification
From the
collected data, it can be concluded that a more varied pain pattern is seen in
adolescents with endometriosis as compared to adults. Careful history taking
and consideration of the differences between adult and adolescent presentation
of endometriosis is strongly recommended.
5.2
Clinical
examination
5.2.1 In case of virgin written
informed consent from the patient and her parents before rectal examination (GPS).
10, 138
5.2.2 The recommendations for clinical examination
in adults can be applied (GPS). 10, 138
Justification
No evidence
was found with regard to clinical examination in adolescents. Whether vaginal
examination and/or rectal examination are acceptable in adolescents should be
discussed with the adolescent and her caregiver and may be depending on age and
cultural background.
5.3
Imaging
5.3.1 In case of virgin written
informed consent from the patient and her parents before rectal u/s (GPS).
5.3.2 Pelvic imaging with
ultrasonography, regardless of findings on pelvic examination, also should be
considered during evaluation for secondary dysmenorrhea (GPS).
5.3.3 Transvaginal ultrasound is
recommended to be used in adolescents in whom it is appropriate, as it is
effective in diagnosing ovarian endometriosis (low level of evidence, strong recommendation). 10, 136, 138
5.3.4 If a transvaginal scan is not
appropriate, MRI, trans abdominal, transperineal, or trans rectal scan may be considered
(low level of evidence, conditional recommendation).10
Justification
There is no direct evidence for the
role of ultrasound in adolescents. In adults, transvaginal ultrasound showed
good mean specificity and sensitivity for detection of ovarian cysts with
reasonable confidence intervals and heterogeneity (strong recommendation in
favor). In young women, especially those with an intact hymen, a careful
approach is recommended, Transvaginal US may still be an option, but patients
should be informed on what to expect, and which other options are available to
them.
5.4
Laboratory
parameters
5.4.1 Serum biomarkers (e.g., CA-125)
are not recommended for diagnosing or ruling out endometriosis in adolescents (moderate
level of evidence, strong recommendation). 10, 139, 140
Justification
In adults, clinicians are
recommended not to use biomarkers in endometrial tissue, blood, menstrual or
uterine fluids to diagnose endometriosis. In adolescents, data support the same
conclusion for serum biomarkers, and hence assessment of serum biomarkers is
not recommended (strong recommendation).
5.5
Diagnostic
laparoscopy
5.5.1 In adolescents with suspected
endometriosis where imaging is negative and medical treatments (with NSAIDs
and/or hormonal contraceptives) have not been successful, diagnostic
laparoscopy may be considered (low level of
evidence, conditional recommendation).10, 136, 141
5.5.2 The appearance of endometriosis
may be different in an adolescent than in an adult woman. In adolescents,
endometriotic lesions are typically clear or red and can be difficult to
identify for gynecologists unfamiliar with endometriosis in adolescents (GPS).10, 142
5.5.3 If a laparoscopy is performed,
clinicians should consider taking biopsies to confirm the diagnosis
histologically, although negative histology does not entirely rule out the
disease (low level of evidence, strong recommendation).10, 143
Justification
Data in adolescents show that nearly
two-thirds of adolescents with CPP or dysmenorrhea have laparoscopic evidence
of endometriosis. Laparoscopy to confirm a diagnosis of endometriosis can be
considered but should be weighed against the risks of surgery and postoperative
complications and can be considered if other diagnostic options cannot be used
or have failed, or if medical treatments have not been successful (conditional recommendation).
Diagnosis can also be confirmed through history and ultrasound, and treatment
should not be withheld for adolescents in which laparoscopic diagnosis was not
(yet) performed. Clinicians should be aware that all forms of endometriosis
have been found in adolescents, although some reports suggests that peritoneal
endometriosis in adolescents may have atypical appearance.
Evidence shows that histological
confirmation rate of suspected endometriosis at laparoscopy is high (93%).
Also, varying patterns of adolescent endometriosis have been observed.
Therefore, if diagnostic laparoscopy is performed, clinicians should consider
to taking biopsies to histologically confirm the diagnosis (strong
recommendation). Diagnostic laparoscopy with histology is expensive, but
accessible and feasible. In performing histological assessment, it should be
considered, as in adults, that negative histology does not entirely rule out
the disease. This is covered in a good practice point.
5.6
Medical
treatment
5.6.1 Nonsteroidal anti-inflammatory
drugs should be the mainstay of pain relief for adolescents with endometriosis (GPS). 10
5.6.2 In adolescents with severe
dysmenorrhea and/or endometriosis-associated pain, Clinicians should prescribe
hormonal contraceptives or progestogens (very low level of evidence, strong
recommendation).10, 144, 145
5.6.3 In adolescents with
laparoscopically confirmed endometriosis and associated pain in whom hormonal
contraceptives or progestogen therapy failed, clinicians may consider
prescribing GnRH agonists for up to 1 year, as they are effective and safe when
combined with add-back therapy (very low level of evidence, conditional
recommendation).10, 146
5.6.4 If GnRH agonist treatment is
considered, it should be used only after careful consideration and discussion
of potential side effects and potential long-term health risks with a
practitioner in a secondary or tertiary care setting (GPS).10, 146, 147
Justification
Studies on
the medical treatment of endometriosis-associated pain are mostly performed in
adults. In adolescents, we summarized studies evaluating the use of oral
contraceptives, progestogens, and GnRH agonists, from which it can be
concluded, also considering indirect data from adults, that these treatments
are effective and safe. Considering the possible side effects with regards to
BMD and other long term health risks, the GDG recommends prescribing oral
contraceptives or progestogens as first line (strong recommendation), and GnRH
agonist as second line treatment (conditional recommendation). Although there
are no studies evaluating NSAIDs in adolescents with endometriosis-associated
pain, data from adults and clinical expertise support a good practice point to
consider recommending NSAIDs as an additional treatment option.
5.7
Combined
medical and surgical treatment
5.7.1 In adolescents with
endometriosis, clinicians should consider postoperative hormone therapy, as
this may suppress recurrence of symptoms (very low level of evidence, strong
recommendation).10, 148, 149
Justification
The recommendation
to consider postoperative hormone therapy is based on two retrospective studies
showing benefit in adolescents on recurrence and disease progression (Doyle,
et al., 2009, Seo, et al., 2017). The combination of surgical and
medical treatment is expensive, but it is highly accepted by patients and
doctors, and in line with management in adults. A strong recommendation in
favor of postoperative hormone therapy was formulated.
6. Endometriosis and menopause
6.1
Treatment of
endometriosis in postmenopausal women
6.1.1 Clinicians may consider surgical
treatment for postmenopausal women presenting with signs of endometriosis
and/or pain to enable histological confirmation of the diagnosis of
endometriosis (very low level of evidence, conditional recommendation).10, 150-152
6.1.2 Clinicians should acknowledge the
uncertainty towards the risk of malignancy in postmenopausal women. If a pelvic
mass is detected, the work-up and treatment should be performed according to
national oncology guidelines (GPS).10, 153, 154
6.1.3 For postmenopausal women with
endometriosis-associated pain, clinicians may consider aromatase inhibitors as
a treatment option especially if surgery is not feasible (very low level of
evidence, conditional recommendation).10, 151, 152
Justification
The
available, poor-quality evidence from cohort studies show that surgical
treatment can improve pain in postmenopausal women with endometriosis. In
postmenopausal women with endometriosis, and specifically endometrioma, there
seems to be a significant proportion with concordant malignancy. The GDG
suggests (conditional recommendation) to consider laparoscopy to treat pain and
enable confirmation of the diagnosis of endometriosis.
There are
no data on complications of surgery in postmenopausal women, but surgery for
endometriosis is considered a relatively safe procedure (see section II.3.a).
The benefits of surgical treatment with regards to pain symptoms and to reduce
the risk of future malignancy, seem to outweigh the possible complications of
surgery.
Although
evidence is limited to case reports in postmenopausal women, the efficacy of
AIs can be deduced from studies in premenopausal women. Based on the biological
aspects, AIs are probably the most appropriate medical treatment for
endometriosis-related pain symptoms in postmenopausal women and could be
considered a treatment option, for instance when surgery is not feasible,
contra-indicated, or when surgery was insufficient to resolve symptoms (conditional
recommendation).
6.2 Menopausal
symptoms in women with a history of endometriosis
6.2.1 Clinicians may consider combined
menopausal hormone therapy (MHT) for the treatment of postmenopausal symptoms
in women (both after natural and surgical menopause) with a history of
endometriosis (low level of evidence, conditional recommendation).10, 155, 156
6.2.2 Clinicians should avoid
prescribing estrogen-only regimens for the treatment of vasomotor symptoms in
postmenopausal women with a history of endometriosis, as these regimens may be
associated with a higher risk of malignant transformation (low level of
evidence, strong recommendation).5, 10
6.2.3 Clinicians should continue to
treat women with a history of endometriosis after surgical menopause with
combined estrogen-progestogen at least up to the age of natural menopause (GPS).5, 10, 157
Justification
Efficacy
of MHT for the relief of menopausal symptoms in women with endometriosis has
not been studied but can be deduced from studies in the general population
concluding that MHT is the effective treatment for relieving vasomotor symptoms
and urogenital atrophy, with possible beneficial effects on other
menopause-related complaints and quality of life. The impact of MHT on
recurrence of endometriosis (2 small RCTs, 4 observational studies and 33 case
reports) was recently summarized in a systematic review, showing a possibly
increased risk. For malignancy, very few cases have been reported for combined
MHT or tibolone. Considering the benefits and risks, combined MHT can be
considered for the treatment of postmenopausal symptoms in women with a history
of endometriosis (conditional recommendation).
As the
reported cases of malignancy could mainly be linked to unopposed estrogens, the
risks for estrogen-only regimens seem to outweigh the benefits, and their use
should be avoided (strong recommendation).
6.3 Menopause-related
major health concerns in women with endometriosis
6.3.1 Clinicians should be aware that
women with endometriosis who have undergone an early bilateral
salpingo-oophorectomy as part of their treatment have an increased risk of
diminished bone density, dementia, and cardiovascular disease. It is also
important to note that women with endometriosis have an increased risk of
cardiovascular disease, irrespective of whether they have had an early surgical
menopause (GPS).
Justification
Clinicians
should be aware that women with endometriosis who have undergone an early
bilateral salpingo-oophorectomy as part of their treatment have an increased
risk of diminished bone density, dementia, and cardiovascular disease. It is
also important to note that women with endometriosis have an increased risk of
cardiovascular disease, irrespective of whether they have had an early surgical
menopause.
7. Extra pelvic endometriosis
7.1 Clinicians should be aware of symptoms of extra-pelvic
thoracic endometriosis, such as cyclical shoulder pain, cyclical spontaneous
pneumothorax, cyclical cough, or nodules which enlarge during menses. (GPS).158-167
7.2 For abdominal extrapelvic endometriosis, surgical removal
is the preferred treatment, when possible, to relieve symptoms. Hormone
treatment may also be an option when surgery is not possible or acceptable (conditional).158-167
7.3 It is advisable to discuss diagnosis and management of
extra-pelvic & thoracic endometriosis in a multidisciplinary team in a center
with sufficient expertise (GPS).158-167
Justification
There is
limited evidence on extrapelvic endometriosis. Cyclic pain is the most common
presenting symptom, and the diagnosis is usually made by histological
confirmation. Additional imaging and endoscopic investigations specific to the
location may also be used. MRI provides better contrast resolution than CT and
TAS and is superior to CT for depicting the delineation between muscles and
abdominal subcutaneous tissues and infiltration of abdominal wall structures. Diagnosis
of thoracic endometriosis syndrome is challenging, as these women’s symptoms may
not immediately be attributed to endometriosis, MRI technique provides a good
diagnostic accuracy. As there were no comparative studies identified that
compared different imaging modalities, we are unable to determine which imaging
tool is optimal for abdominal or thoracic disease
8. Asymptomatic endometriosis
8.1 Clinicians should inform and counsel women about any
incidental finding of endometriosis (GPS).10
8.2
Clinicians should not routinely perform surgical
excision/ablation for an incidental finding of asymptomatic endometriosis at
the time of surgery (very low level of evidence, strong recommendation).10
8.3 Clinicians should not prescribe medical treatment in
women with incidental finding of endometriosis (very low level of evidence,
strong recommendation) 10
Justification
Based on the lack of evidence and despite the small risk that asymptomatic minimal disease will become symptomatic or progress, the conclusion from the GDG is that medical or surgical treatment of incidental finding of asymptomatic endometriotic lesions is not routinely recommended (strong recommendation). The GDG recommends that clinicians follow national guidelines for the management of ovarian cysts detected incidentally on ultrasound scan.
It is considered good practice to inform and counsel patients about any incidental finding of endometriosis.
8.4 Routine ultrasound monitoring of asymptomatic endometriosis can be considered (very low level of evidence, conditional recommendation). 168
Justification
Even in the absence of solid data on the benefit of monitoring of asymptomatic endometriosis, the GDG suggests considering US monitoring as it is cost effective and safe (conditional recommendation). There is no information as to how often and how long the monitoring should continue. Alternatively, women with asymptomatic endometriosis can be advised to seek medical help in case of occurrence of any endometriosis-related symptoms.
9. Primary prevention of endometriosis
9.1 Although there is no direct evidence of benefit in
preventing endometriosis in the future, women can be advised of aiming for a
healthy lifestyle and diet, with reduced alcohol intake and regular physical activity
(low level of evidence, conditional recommendation). 10, 169-172
9.2 The usefulness of hormonal contraceptives for the primary
prevention of endometriosis is uncertain (low level of evidence, conditional
recommendation).10, 173
Justification
The evidence on a healthy lifestyle and diet, with reduced alcohol intake and regular physical activity for the prevention of endometriosis is summarized in systematic reviews and meta-analyses of epidemiological/observational studies. The benefits of a healthy lifestyle are well known, regardless of endometriosis. To the best of our knowledge, the proposal of healthy lifestyle/diet could be considered a feasible and acceptable option to improve general health, and it may also be beneficial towards the risk of endometriosis. However, the underlying cause of endometriosis remains unknown, thus, due to a lack of scientific data it remains unclear whether preventative measures exist and, if so, how effective they may be.
The evidence on a reduced risk of endometriosis during oral contraceptive use is controversial, as summarized in systematic reviews and meta-analyses of epidemiological/observational studies. To date, it is not possible to exclude the possibility that the apparent protective effect of oral contraceptive against endometriosis is the result of postponement of surgical evaluation due to temporary suppression of pain symptoms.