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Advances in Social Sciences Research Journal – Vol. 10, No. 11
Publication Date: November 25, 2023
DOI:10.14738/assrj.1011.15985.
Andrade, A. P. P., Oliveira, C. V. B. L., Araújo, L. B. F., Donald, M. E. D., Portugal, F. F. D., Costa, M. S., Andrade, C. P., Chianca, B. L.,
& Bacha, E. (2023). Management of Endometriosis: An Integrative Review of National and International Guidelines. Advances in
Social Sciences Research Journal, 10(11). 328-342.
Services for Science and Education – United Kingdom
Management of Endometriosis: An Integrative Review of National
and International Guidelines
Ana Paula Portela Andrade
ORCID: 0009-0000-3194-1557
School of Medicine, University Center, Alagoas, Brazil
Clara Vitória Braz Lima de Oliveira
ORCID: 0009-0000-8280-9839
School of Medicine, University Center, Alagoas, Brazil
Luísa Barros Fragoso de Araújo
ORCID: 0009-0009-3625-4911
School of Medicine, University Center, Alagoas, Brazil
Maria Eduarda Dantas Donald
ORCID: 0009-0000-4047-2940
School of Medicine, University Center, Alagoas, Brazil
Fernanda Freire Dantas Portugal
ORCID: 0000-0002-3953-6158
School of Medicine, University Center, Alagoas, Brazil
Meyrielle Santana Costa
ORCID: 0009-0000-3146-4930
School of Medicine, University Center, Alagoas, Brazil
Carolina Portela de Andrade
ORCID: 0009-0004-1564-3065
School of Medicine, University Center, Alagoas, Brazil
Bruna Lins Chianca
ORCID: 0009-0008-8319-220X
School of Medicine, University Center, Alagoas, Brazil
Elizabeth Bacha
ORCID: 0000-0002-8971-8582
School of Medicine, University Center, Alagoas, Brazil
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Andrade, A. P. P., Oliveira, C. V. B. L., Araújo, L. B. F., Donald, M. E. D., Portugal, F. F. D., Costa, M. S., Andrade, C. P., Chianca, B. L., & Bacha, E.
(2023). Management of Endometriosis: An Integrative Review of National and International Guidelines. Advances in Social Sciences Research
Journal, 10(11). 328-342.
URL: http://dx.doi.org/10.14738/assrj.1011.15985
ABSTRACT
Endometriosis is a disease characterized by the presence of endometrial tissue
outside the uterus, affecting 2 to 22% of women worldwide, resulting in inferior
quality of life as the condition often causes pain (dysmenorrhea, dyspareunia) and
infertility. It is notable that clinical practice has changed in the last decade, with
endometriosis receiving much more media attention and patients taking a more
active role through different disease organizations. Considering these changes and
identifying which practices are justified by medical evidence is essential. Using the
descriptors: "Treatment", "Endometriosis" and "Guidelines" in the PUBMED,
MEDLINE and SciELO databases, a total of 312 articles were found and,
subsequently, eight articles were submitted to the selection criteria. Regarding
pharmacological therapies associated with endometriosis, most of the guidelines
included in this study suggest progestins, either in the form of dienogest or
medroxyprogesterone acetate, and combined oral contraceptives as first-line
therapy with considerable evidence. GNRH agonists and the levonorgestrel system
are used as second-line treatment. Surgery also has a significant role in the
treatment of endometriosis-related pain, with the excision of endometrial implants
or endometriomas. Handling ovarian tissue as thoroughly as possible is
recommended in order to limit the decrease in ovarian reserve. Despite very well- established guidelines, relevant diagnostic tests such as Magnetic Resonance
Imaging (MRI) are inaccessible and expensive for most women, as is laparoscopic
surgery, hindering the diagnosis and treatment of the disease, especially in
underdeveloped countries.
Keywords: endometriosis, guidelines, treatment, diagnosis, management
INTRODUCTION
Endometriosis is a chronic benign gynecological disorder defined by the presence of
endometrial glands and stroma outside the normal site. First identified in the mid-19th century,
it is often found in the pelvic peritoneum, but may also be seen in the ovaries, rectovaginal and
ureter, being difficult to appear in the bladder, pleura and pericardium [1].
According to Ruiz-Velasco2 (2004), endometriosis may be divided into three subtypes
according to its location: deep, peritoneal and ovarian endometriosis. Deep endometriosis is
known as a lesion that penetrates the retroperitoneal space or the wall of the pelvic organs,
with a depth of 5mm or more. Peritoneal endometriosis is described by the presence of a
peritoneal implant. Ovarian endometriosis is characterized by superficial implantation in the
uterus or cysts (endometriomas) [2].
Endometriosis symptoms are numerous and correlate to the degree of the disease and the sites
affected; usually they present as dysmenorrhea, pelvic abdominal pain, as well as difficulty in
sexual intercourse, dyspareunia, hypermenorrhea, non-menstrual pelvic pain, difficulty
urinating, ovulation pain and chronic fatigue [3].
The incidence of endometriosis is a complex matter to be quantified, since the people affected
by the disease are almost always asymptomatic and imaging tests have low sensitivity for
diagnosis. In asymptomatic women, the prevalence of endometriosis varies from 2 to 22%,
depending on the population studied [4].
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Studies suggest that 6% to 10% of women in reproductive age, 50% to 60% of adolescents with
disabling pelvic pain and up to 50% of women with infertility are affected by the disease.
However, in the early stages or in asymptomatic or oligosymptomatic infertile women, the
disease may be underdiagnosed [5].
The approach to patients with endometriosis and infertility should be based on age, clinical
condition, symptoms, and whether there are other factors causing infertility in addition to
endometriosis [5].
The clinical diagnosis of endometriosis is based on pelvic pain, severe dysmenorrhea (pain
intensity score of 8 or more on a scale of 0 to 10 points, pain during defecation and dyspareunia
(especially premenstrual and menstrual [6].
Magnetic Resonance Imaging (MRI) is the non-invasive method of choice proposed by the
European Society of Urogenital Radiology (ESUR) for diagnosing endometriosis. As it is a
difficult test to access, ESUR recommends that transvaginal ultrasound (US) should be the first
choice to investigate endometriosis and that MRI should only be requested when the results
are negative on US (despite the suggestive symptoms), in cases of lesions in the upper abdomen
or in the presence of multiple endometriotic sites, especially during pre-surgery [7].
Nevertheless, the main diagnostic method, according to Kennedy (2005), is laparoscopy, with
or without biopsy for histological diagnosis, and may be difficult to access in less developed
countries.
Lastly, about diagnosis, it should be noted that the average time from the onset of symptoms to
the surgical diagnosis of endometriosis varies from five to ten years. This delay has negative
consequences as it prevents early treatment, which is important to improve pain levels, as well
as physical and psychological well-being [5].
The treatment of endometriosis needs to be individualized, prioritizing the symptoms and the
impact of the disease on the patient. Therefore, drug therapies are used for this disease as it
responds well to hormones [8].
Medroxyprogesterone acetate (MPA) and gestrinone are used to treat endometriosis, and both
are associated with side effects. Regarding MPA, the main side effect is acne and 30% of patients
were unable to benefit from the treatment after 12 months of use. Gestrinone is associated with
side effects such as amenorrhea, spotting, acne, hirsutism and weight gain of up to three kilos,
which prevents some patients from continuing treatment [8].
Combined oral contraceptives (COCs) are the first option for clinical treatment according to
numerous guidelines, as a simple, inexpensive, easy-to-manage treatment with good results
supported by literature. In patients whose main symptom is dysmenorrhea, continuous use of
COCs should be considered [5].
The main drawback of using GnRH is the occurrence of adverse effects secondary to
hypoestrogenism: hot flushes and vaginal dryness (90% of cases), headaches, dizziness,
emotional lability, acne, myalgia, edema, reduced breast volume, weight gain, decreased libido
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Andrade, A. P. P., Oliveira, C. V. B. L., Araújo, L. B. F., Donald, M. E. D., Portugal, F. F. D., Costa, M. S., Andrade, C. P., Chianca, B. L., & Bacha, E.
(2023). Management of Endometriosis: An Integrative Review of National and International Guidelines. Advances in Social Sciences Research
Journal, 10(11). 328-342.
URL: http://dx.doi.org/10.14738/assrj.1011.15985
and insomnia and loss of bone mass (3% to 6%). For this reason, careful considerations should
be made when prescribing GnRH agonists to young women, before the acquisition of peak bone
mass [5].
In short, in the presence of symptoms suggestive of endometriosis and with a normal physical
examination and imaging test (ultrasound), an MRI scan is performed, and the type of treatment
is assessed. If the examination reveals an ovarian endometrioma > 6cm, a lesion in the ureter
(rectum, appendix, rectosigmoid with signs of sub-occlusion) or deep endometriosis, surgical
treatment is performed. (Figure 1) [5].
Figure 1: Endometriosis Management Algorithm
Source: Authors (2023)
This disease has been observed as a public health challenge given its major impact on women's
psychological and physical health, as well as the socioeconomic impact caused in terms of the
costs involved with diagnosis, monitoring and treatment [7].
METHODS
The current study is an integrative review, conducted between March and October 2023, with
the aim of comparing the guidelines established for the management of endometriosis, both
nationally and internationally. Using the PUBMED, MEDLINE and SciELO databases,
"Endometriosis", "Guidelines", "Treatment" and the Boolean operator "AND" between the three
descriptors. From this search, 312 articles were found and then submitted to the selection
criteria.
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The inclusion criteria were: between 2018 and 2023, 88 articles in Portuguese and English
published in the last 5 years were found; 32 articles that addressed the proposed themes for
this research by reading the abstract. Complete and free publications were found in 19 articles,
publications produced by the human species Homo Sapiens were found in 15 articles, adequate
publications after reading titles and abstracts were found in 13 articles and after careful
filtering 8 articles remained. After the articles had been selected, the titles and abstracts were
read, of which only 25 were suitable for the purpose of this study, and 4 were excluded for not
containing the full text. Finally, after reading all the articles and analyzing the methodology, 8
publications were found to fit the objective of the current systematic review (Figure 2).
Figure 2: Flowchart representing the methodology used for the study
Source: Authors (2023)
RESULTS
Results were sorted by the countries that published the guidelines, quoting the organization(s)
or society(ies) referenced in the respective articles.
Japan
• Reproductive Endocrinology Committee, The Japan Society of Obstetrics and Gynecology
• General Rules for the Endometriosis Clinical Management Subcommittee
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Andrade, A. P. P., Oliveira, C. V. B. L., Araújo, L. B. F., Donald, M. E. D., Portugal, F. F. D., Costa, M. S., Andrade, C. P., Chianca, B. L., & Bacha, E.
(2023). Management of Endometriosis: An Integrative Review of National and International Guidelines. Advances in Social Sciences Research
Journal, 10(11). 328-342.
URL: http://dx.doi.org/10.14738/assrj.1011.15985
• The Clinical Practice Guidelines for Endometriosis in Japan (3rd edition) mention that
the use of low-dose estrogen-progestin (LEP) and the progestogen dienogest became
widespread after both were shown to be effective and safe for long-term medical
therapy. Regarding deep endometriosis or endometriosis in less common and rare
locations, laparoscopic surgery is advisable. However, for endometriotic ovarian cysts,
the eggs and normal ovarian tissue must be resected along with the endometrial tissue,
thus decreasing the ovarian reserve; therefore, surgery should be performed with
caution for young women and women who wish to have children in the future [10].
Peru
• The Peruvian Institute of Health Technology Assessment and Research
• Clinical Practice Guideline for Diagnosis and Treatment of Symptomatic Endometriosis
in Women of Reproductive Age, 2022
• The Peruvian guidelines initially indicate hormonal treatment for symptomatic patients,
with preference given to combined oral contraceptives, which have progesterone and
fewer adverse effects. Indications for surgical treatment are: rupture of the
endometrioma, ovarian torsion, refusal to take medication, or refractory treatment [11].
Canada
• Society of Obstetricians and Gynecologists of Canada / La Société des obstétriciens et
gynécologues du Canada.
• Canada prioritizes informing patients about the severity and type of endometriosis
patients have, correlating this with the types of symptoms they may experience, such as
infertility and pain (which is sometimes incapacitating), providing accessible and easy
to understand information about the disease and its prognosis [12].
• In the aforementioned article, Kirubarajan et al. evaluated the conduct of Canadian
doctors with regard to the guidelines and found that 61% of doctors used ACOs and
progestogens as their first line of treatment, while 32% used continuous ACOs and 43%
resorted to second-line drugs: GnRH and SIU-LNG. Meanwhile, 53% had not tried
second-line medical therapy before and 20% had incomplete surgery during the most
recent excision/resection procedure [12].
Organizations or Societies:
• German Guideline (S2k),Society of Obstetricians and Gynecologists of Canada, American
College of Obstetricians (ACOG) and Gynecologists, American Society for Reproductive
Medicine (ASRM) and National Institute for Health and Care (NICE) and two
internationals: World Endometriosis Society and European Society of Human
Reproduction and Embryology (ESHRE). National Guidelines (College National des
Gynecologues et Obstetriciens Francais, National)
• This is a comparative review of the eight most widely accepted guidelines in the world
on the management of endometriosis, conducted by Kalaitzopoulos et al. [13]. Regarding
pharmacological therapies for pain associated with endometriosis, most of the
guidelines included suggest progestins, either in the form of dienogest or
medroxyprogesterone acetate, and combined oral contraceptives as first-line therapy
with a great amount of evidence. GNRH agonists and the levonorgestrel intrauterine
system may be considered as second-line treatment. Regarding the remaining medical
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options, such as danazol, gestrinone, aromatase inhibitors, SERMs and SPRMs due to
limited evidence, there are discrepancies between the guidelines [13].
• Kalaitzopoulos et al draw attention to the role of surgery in treating endometriosis- related pain, where the standard of practice is excision of endometrial implants, as well
as excision of endometriomas. In general, the recommendation is to handle ovarian
tissue as carefully as possible, avoiding a decrease in ovarian reserve. Lastly, the author
mentions that complementary options such as dietary products, acupuncture and
electrotherapy have not yet been studied enough to better understand their potential
role [13].
• Regarding infertility, the therapeutic options available and the therapeutic strategies
differ in comparison to the pain associated with endometriosis. Surgical procedures
such as excision of endometriomas and excision of endometriosis have gained the
highest degree of evidence and consist of the standard approach. Ablation of ovarian
endometriosis is a second-line therapy, while pharmacological therapies are not
recommended in principle, except for GNRH agonists which may be used as negative
regulation therapy before in vitro fertilization or surgery. As with pain, complementary
therapies are not yet considered as a therapeutic option due to the lack of evidence [13].
France
Two articles were selected using the French guidelines:
• French National Health Authority (HAS) and the French College of Gynecologists and
Obstetricians (GENGOV).
• The guideline was developed by a working group brought together by the GENGOV and
the HAS. Numerous experts developed evidence reported by the working group to
establish recommendations, which were given to external reviewers according to the
methodology developed by HAS. Hormone therapy is not recommended for women with
asymptomatic endometriosis, unless contraception is requested. The possibility of
hormonal treatments before surgery for endometriosis exists cyclic CHCs have been
analyzed for endometriomas and minimize the volume of the endometrioma by around
50% over 6 months. For endometriotic disease of the rectovaginal septum,
norethisterone acetate, cyclic oral CHCs, desogestrel contraception, a CHC vaginal ring
and GnRHas are used to reduce the volume of the lesion by 17-21% at 12 months [14].
• Scientific evidence is not yet available to indicate the best systematic preoperative
hormone therapy, which is exclusive to hormone treatments after surgery for
endometriosis. There are couples who do not wish to become pregnant, so post- operative hormone therapy is recommended to reduce the risk of endometriosis-related
pain and also improve the quality of life of patients [14].
• Clinical practice guidelines from the French College of Gynecologists and Obstetricians
(CNGOF).
• According to Quazana et al., surgical treatment of asymptomatic superficial peritoneal
endometriosis is not recommended in women of childbearing age to resolve pelvic pain,
especially in the case of proximity to noble organs (ureters, rectum and sigmoid), as
there is no evidence that the disease evolves to become symptomatic (low level of
evidence). In the event ofthe accidental discovery of superficial endometriosis in women
of childbearing age, removal of the lesions is recommended, if surgically accessible, to
improve the quality of life of the patient [15].
• In cases of infertility, it is recommended that excision of superficial endometriosis
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Andrade, A. P. P., Oliveira, C. V. B. L., Araújo, L. B. F., Donald, M. E. D., Portugal, F. F. D., Costa, M. S., Andrade, C. P., Chianca, B. L., & Bacha, E.
(2023). Management of Endometriosis: An Integrative Review of National and International Guidelines. Advances in Social Sciences Research
Journal, 10(11). 328-342.
URL: http://dx.doi.org/10.14738/assrj.1011.15985
lesions be performed instead of monopolar coagulation, as this results in a higher rate
of spontaneous pregnancy, which has been proven with a low level of evidence.
• Furthermore, for patients with pelvic pain, it is suggested that laparoscopy should be
avoided, although this can be decided on a case-by-case basis. Furthermore, depending
on the extent of the adhesions, the topography and the type of surgery considered (low
level of evidence). For asymptomatic patients, it is recommended not to perform
laparotomy due to the lack of clear efficacy in the short or long term and due to the
increased risk of surgical injury [15].
• With regards to adhesions, Quazana et al recommend that women without known
infertility problems do not undergo laparoscopy in order to improve their chances of
pregnancy. For these women, should adhesions be fortuitously discovered during
laparoscopy, it is probably best not to resolve complex adhesions, but only tubo-ovarian
adhesions that are minimal or mild, as this may improve the chances of a spontaneous
pregnancy. However, it is important to stress that everything must be decided on a case- by-case basis, depending on other unknown potential causes and the risks of
complications inherent in the surgery [15].
Argentina
• Argentina Federation of Obstetrics and Gynecology Societies (FASGO)
• In 2019, FASGO published a practical guide to the diagnosis and treatment of
endometriosis, with the aim of making it easier for gynecologists to diagnose their
patients and offer them therapeutic alternatives [16].
• For pain management in patients with chronic pelvic pain of unknown cause, after
excluding specific or oncological causes, non-hormonal anti-inflammatory drugs should
be used. Therefore, Paracetamol should be combined with NSAIDs, due to its central
action which will cooperate with the local action of NSAIDs. If there is no improvement
in cyclical pain, hormonal treatment should be started, with progestogens,
contraceptives, IUDs with Levonorgestrel or GNRH agonists [16].
Brazil
• Brazilian Federation of Gynecology and Obstetrics (FEBRASGO)
• Imaging tests such as pelvic and transvaginal ultrasound and/or magnetic resonance
imaging are essential for therapeutic decisions. Clinical hormonal treatment is effective
in controlling pelvic pain and should be chosen if there is no indication for surgery. The
first-choice medications are combined oral contraceptives and progestogens; however,
they are contraindicated in women with a reproductive desire [5].
• Surgical treatment needs to be offered to patients when clinical treatment is impotent
or if there are bulky ovarian endometriomas, ureter lesions causing hydronephrosis, sub
occlusive lesions, intestinal obstructions, appendix lesions. There is a strong association
between endometriosis and infertility, which is why both surgery and assisted
reproduction techniques can be offered to treat couples [7].
• Prevalence of endometriosis is high, especially in patients who complain of infertility
and chronic pelvic pain, so treatment must always be individualized, considering the
effectiveness of the various therapies, not forgetting the promotion of improved quality
of life [5].