Published via DMIHER School of

Open Access Review Article Epidemiology and Public Health

Endometriosis: A Review of Clinical Diagnosis,

Treatment, and Pathogenesis
Received 08/18/2022
Saurabh Chauhan 1 , Akash More 2 , Vaishnavi Chauhan 1, Aditya Kathane 1
Review began 08/22/2022
Review ended 08/31/2022 1. Clinical Embryology, School of Allied Health Science, Datta Meghe Institute of Medical Sciences (DU), Wardha, IND
Published 09/06/2022
2. Anatomy, Wardha Test Tube Baby Center, Datta Meghe Institute of Medical Sciences (DU), Wardha, IND
© Copyright 2022
Chauhan et al. This is an open access
Corresponding author: Akash More, aakashmore87@[Link]
article distributed under the terms of the
Creative Commons Attribution License CC-
BY 4.0., which permits unrestricted use,
distribution, and reproduction in any
medium, provided the original author and Abstract
source are credited.
Endometriosis is a condition that affects women of reproductive age, and it is distinguished by the
DOI: 10.7759/cureus.28864 development of endometrial-like tissue outside the uterine cavity. It is frequently accompanied by persistent
pelvic discomfort and infertility. This investigation looks into recent findings on clinical manifestation to
help doctors and improve women's health. PubMed and Google Scholar were used to review on clinical
diagnosis of endometriosis. The search strategy contained the terms “endometriosis” and “clinical
diagnosis.” All research articles published between 1960 and 2021 were included in the search. The findings
were then categorized to summarize the evidence. There was a total of 29 instances of endometriosis
discovered. The patients' ages varied from 20 to 45 years old, with a median of 28.8 years and a mean of
29.4±7.7 years. Dysmenorrhea is a common disorder among adolescent girls experiencing various physical
and emotional symptoms which have a detrimental influence on their quality of life. In this study, scar
endometriosis was shown to be the more common variety of endometriosis, with 50% of cases
predominantly developing at the lower segment cesarean section (LSCS) scar site. As a result, women with
endometriosis are more likely to have miscarriages, and the quality of their embryos declines as a result.

Categories: Obstetrics/Gynecology
Keywords: infertility, endometrial, uterus, scar, endometriosis

Introduction And Background

Endometriosis is the most perplexing gynecological condition [1-3]. Endometriosis influences 10%-15% of
all reproductive-age females and 70% of women with persistent pelvic pain [4]. The ovaries and pelvic
peritoneum are the most common sites for developing endometriotic lesions. Endometriotic lesions can also
develop in other places including the fallopian tube, abdominal wall, bowels, cervix, bladder, and
vagina [5,6]. The pathophysiology of endometriosis and pain is poorly known, with most gynecologists
believing that inflammation is a crucial source of irritation in endometriosis [7]. After successful surgery,
some women seem to be “cured” of the disorder, but the majority will have a recurrence of symptoms.
Endometriosis costs roughly 1 to 2 lakhs per woman in India, according to a survey [8]. The uterosacral
ligaments, the upper third part of the posterior vaginal wall, the rectovaginal space, the intestine, and the
urinary system are frequently involved in the latter [9]. Researchers have previously looked at apoptosis, cell
cycle changes, and granulosa cell oxidative stress as indicators of oocyte quality as a source of endometriosis
subfertility [10-12].

Endometriosis is a female reproductive system disorder where the endometrium-like tissue develops outside
of the uterus; it usually affects the ovaries and peritoneum, causing premenstrual discomfort and
dysmenorrhea [13,14]. The most widely recognized explanation of endometriosis is that endometrial tissue
is implanted in the peritoneal cavity by retrograde menstruation. The first theory describing the origin of
endometriosis is the retrograde menstruation theory. According to this idea, endometriosis develops when
sloughed endometrial cells and debris after menstruation travel retrogradely down the fallopian tubes and
enter the pelvic cavity. 76%-90% of women having patent fallopian tubes experience retrograde
menstruation, albeit not all of these women have endometriosis [15]. Endometrial cell resorption into the
abdominal wall during menstrual flow is a common occurrence in 90% of menstrual females with patent
fallopian tubes, even though it is only seen in those with hormonal or immunological issues [16,17]. The
peritoneal fluid of women with endometriosis has higher amounts of macrophages, T-lymphocytes, and B-
lymphocytes, which are more susceptible to apoptosis [18,19].

Review
Clinical diagnosis of endometriosis
Endometriosis lesions are most frequently encountered in the following regions like fallopian tubes, uterus
outer surface, ovaries, and the ligaments which surround the uterus. Lesions from endometriosis can range
in size and frequently take the form of nodules or cysts. The majority of them are blue, black, and brown in
color. They can, however, sometimes occasionally be white, red, or transparent [20,21]. Infertile women with
minor or mild endometriosis have had the condition detected more frequently during in vitro fertilization

How to cite this article

Chauhan S, More A, Chauhan V, et al. (September 06, 2022) Endometriosis: A Review of Clinical Diagnosis, Treatment, and Pathogenesis. Cureus
14(9): e28864. DOI 10.7759/cureus.28864
 Published via DMIHER School of
Epidemiology and Public Health

(IVF) and embryo transfer (ET) cycles than those with moderate or severe endometriosis [1,22-24]. With a
diagnostic age of 28 years, endometriosis predominantly affects women who are of reproductive age, which
may be understood by the estrogenic milieu, which is strongly implicated in its genesis [25]. Extrauterine
endometrial cells on laparoscopy are generally enough for histologic confirmation [26]. Cystic
endometriomas might be reliably recognized utilizing transvaginal ultrasonography, while more modest
endometrial implants are not detected [27,28].

Infertility and severe pelvic discomfort are the two major clinical risk factors for endometriosis [29-32]. The
etiology of infertility in women with minor or mild endometriosis is less understood. However, it might be
linked to a greater prevalence of malformed oocytes, faulty embryos, or unsuccessful implantation [33].
According to several studies, tall women with low Body Mass Index (BMI) appear at a greater risk of
developing endometriosis because they have short menstrual cycles, are more likely to have cervical
canalization problems, and decreased germ cell endowment [34]. Endometriosis has also been found to be
less common among women who have been pregnant [29]. This might be owing to pregnancy's protective
impact, or it could be due to endometriosis patients' lower fertility, as endometriosis risk is inversely
associated with the number of term pregnancies [29,35,36].

Endometriosis was found in 19% of women with persistent pelvic discomfort at the point of surgery [37,38].
Dysmenorrhea, intermenstrual discomfort, and dyspareunia are common symptoms of pelvic pain. The most
prevalent symptom is dysmenorrhea, which, while not predictive, is highly indicative of endometriosis in its
severe form [39]. Dysmenorrhea is frequently progressive, with discomfort beginning before menstrual flow
and lasting for the whole of the menstrual cycle and possibly for many days after that [40,41]. Endometriosis
of the rectovaginal septum and cul-de-sac are common causes of dyspareunia [42]. Dysmenorrhea and
dyspareunia are more likely to be caused by endometriosis if they appear after years of pain-free menses and
coitus [43,44]. The overproduction of uterine prostaglandins aids pathogenesis. Urinary tract endometriosis
can induce hematuria, urgency, dysuria, and frequency [45,46].

Dysmenorrhea

During menstruation, dysmenorrhea is a medical disorder characterized by discomfort around the pubic
bone and lower abdomen [47,48]. Dysmenorrhea is related to a limitation of activity and leaves from school
or work, precisely when it is severe [49]. Mental preparedness and suitable lifestyle changes, such as frequent
physical activity, can help control dysmenorrhea [50]. Dysmenorrhea can be primary or secondary. Primary
dysmenorrhea is a kind of dysmenorrhea that occurs in teenagers shortly after menarche and is caused by a
lack of underlying macroscopic pelvic disease [51]. Early menarche, lengthier menstrual cycles, high
menstrual flow, and a family history of dysmenorrhea are all risk factors [52,53].

Dyspareunia

Dyspareunia, or pain during penetration, occurs during sexual activity. Deep and superficial dyspareunia are
the two most common kinds of dyspareunia [54]. Deep dyspareunia refers to the expansion of discomfort
into the deeper regions of the vagina or lower pelvis, whereas superficial dyspareunia is restricted to the
vulva or vaginal entrance. Profound penetration is typically correlated with deep dyspareunia [55]. Deep
dyspareunia in endometriosis has a complicated etiology that might involve direct endometriotic lesions,
concomitant diagnosis, and other factors [56]. Deep dyspareunia affects 50% of all female patients, a
disorder that affects 10% of reproductive-age females and is linked to the poor sexual quality of life. Other
forms of pelvic pain, psychiatric comorbidities, and concomitant pain diagnoses can occur in women with
endometriosis [55,57].

Pathogenesis of endometriosis
Endometriosis pathogenesis suggests that the disease's etiology is complicated and multifaceted, involving
genetic, hormonal, immunological, and environmental factors [58]. The pathogenesis of superficial
endometriosis and the genetic factors that prevent ectopic lesions from being removed and allow for
peritoneal remodeling may both be triggered by retrograde menstruation. These are critical for
endometriosis lesion growth [59]. Endometriosis is spread by a change in the peritoneal fluid composition
due to biological, hormone, and environmental factors [60,61]. Deep nodule tumors that are not generally
eliminated during menstruation, might be quickly produced in a baboon model by transplanting basal
endometrial tissue [62,63]. Endometriosis progresses due to genetic changes that damage the cell, since
females with endometriosis have an abnormal endometrial cellular response, favoring extrauterine adhesion
and proliferation [64]. Endometriosis has a genetic inheritance pattern that is believed to include numerous
loci, as well as some chromosomal areas that have been linked to the endometriosis phenotype [65]. Genetic
factors, both inherited and acquired, might predispose females to the adherence of abnormal endometrial
tissues to the peritoneal epithelium as well as the resistance of immune clearing of these lesions [66].
Endometrial fragments that are still viable are pushed into the fallopian tubes by a pressure gradient caused
by dyssynergic uterine contractions [67,68]. They can implant, develop, and infiltrate pelvic bones when they
enter the peritoneal cavity [69,70]. Hyperalgesia is a symptom of nerve pain, which is generally caused by
nerve damage or inflammatory stimulation. Endometriotic stroma cells typically invade sensory nerve
fibers in deep endometriosis [71,72].

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Stage Description

I Isolated implants characterize this minimal disease. There is no adhesions present.

II The peritoneum and ovaries are covered in superficial implants, which are a mild form of the disease. There were no significant adhesions seen.

III Multiple implants, both superficial and highly intrusive, make up the modern disease. Adhesions on the ovaries and fallopian tubes are possible.

IV Severe sickness is defined by several deep and superficial implants, massive ovarian endometriomas, and other symptoms. Typically, dense adhesions are present.

TABLE 1: Stages of endometriosis

Methods
We focused on pelvic endometriosis in this study since it is the most prevalent kind of endometriosis, and it
usually affects women throughout their reproductive years. PubMed and Google Scholar were used to
conduct a review of the clinical diagnosis of endometriosis. In the titles or abstracts of papers, the search
strategy contained the terms “endometriosis” and “clinical diagnosis.” The data from each clinical diagnosis
document were extracted and categorized.

Result
In this study, there were 29 cases of endometriosis in total. The age range of the patients was 20 to 45 years,
with a mean age of 29.4±7.7 and a median age of 28.8 years. The scar endometriosis (16 cases) involving the
anterior abdominal wall at the lower segment cesarean section (LSCS) scar site, ovarian endometriosis (10
cases), urinary bladder endometriosis (two cases), and bowel endometriosis (one case) involving the sigmoid
colon. According to the data, ovarian endometriosis and scar endometriosis are the two types
of endometriosis that are most common in women aged 20 to 35. Scar endometriosis has been the most
frequent kind of endometriosis in this research, accounting for 50% of all cases. In 14 of the 16 patients,
there was a mass in the LSCS scar, which was identified by preoperative Fine Needle Aspiration Cytology
(FNAC) in nine instances (56.25%) and histological analysis of excised tissues in seven cases (43.75%). The
second most prevalent condition was ovarian endometriosis, which accounted for 37.5% of cases, with one
instance being bilateral and another showing torsion. Bowel endometriosis with only one case involving the
sigmoid colon accounted for 4.3% of cases, whereas two cases with urinary bladder endometriosis accounted
for 8.3%.

Treatment of endometriosis
The goal of medical therapy for endometriosis has been to change the menstrual period hormonally to
induce a pseudopregnancy, pseudo-menopause, or persistent anovulatory state [73]. The recommended daily
dose of danazol for the treatment of endometriosis is 600-800 mg; even so, the dose has significant steroid
side effects, including increased hair growth, changes in mood, an irreversible deepening of the voice, bad
impacts on serum lipids, and, in rare cases, irreversible and life-threatening liver injury [74]. Endometriosis
is typically treated with progesterone-based medications. They induce endometrial cells to decidualize,
resulting in atrophy. Abnormal uterine bleeding, vomiting, breast discomfort, and depression are all
possible side effects [75,76]. Hypoestrogenism's adverse effects include vaginal heavy bleeding, vaginal
dryness, reduced libido, breast discomfort, sleeplessness, and depression [77]. Endometriosis has been
treated with a variety of hormones and medicines. Hormone therapy often prevents ovulation by preventing
the ovaries from releasing hormones, including estrogen. This could aid in reducing the rate of local
development and activity of the endometrium and endometrial lesions. Because of their negative side
effects, several hormones, such as methyltestosterone and estrogen, have been phased out. Other
medications have been inadequately investigated, including clomiphene, tamoxifen, and the anti-
progestational drug mifepristone [78]. Laparoscopic surgery is used to surgically diagnose endometriosis. A
laparoscope, a narrow viewing tube, is inserted into the belly through a tiny incision during laparoscopy. For
a second entrance for the surgical tools, a second incision may be created in the lower abdomen. Your doctor
can view the outside of the ovaries, uterus, fallopian tubes, and other organs up close using a laparoscope.
Surgical tools for removing scar tissue or obtaining tissue samples can also be attached to the laparoscope
[79]. For ovarian cysts greater than 4 to 5 cm in diameter, laparoscopic endometrioma removal is
suggested [80]. Endometriosis has been treated with a range of devices, from monopolar cautery and scissors
to a wide variety of lasers and ultrasonic scalpels [81]. Endometriosis pain is treated surgically by
interrupting the brain circuits that carry pain signals [82]. Various considerations should be taken, including
the best method of gaining access to the pelvis and abdomen, which can be accomplished by laparoscopy or
laparotomy. Laparoscopy is less expensive and takes less time to recuperate. Magnetic resonance imaging
(MRI) scan not only shows morphologic defects in the bladder but can also identify other common areas,
such as the uterosacral joints, where ultrasonography is less accurate [83].

Discussion

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Endometriosis affects people and cultures all over the world; however, there are significant delays in
diagnosis. More illness awareness in inpatient healthcare should result in earlier diagnosis, less suffering,
and increased productivity [84,85]. Gravidity, endometriosis in the family, dyspareunia, tiredness,
dysmenorrhea, pelvic surgery, diarrhea, pelvic discomfort, and premenstrual spotting are all risk factors for
endometriosis [86]. Several explanations for the connection between endometriosis and infertility have been
claimed, but despite substantial investigation, no conclusion has been achieved. These mechanisms include
distorted pelvic anatomy, altered peritoneal function, endocrine, and ovulatory abnormalities, and altered
hormonal and cell-mediated functions in the endometrium [87,88]. Increased obstetric surgery results in the
direct mechanical implantation of endometrial cells, which is one of the major risk factors for scar
endometriosis [89].

When a patient experiences dysmenorrhea after experiencing pain-free menstrual cycles for years,
endometriosis should be suspected [90]. Endometriomas having a maximal diameter of 3-4 cm are best
treated through transvaginal cystectomy. Less than 1% of women develop ovarian endometriosis
malignancy, which most frequently manifests as endometrioid/clear cell carcinoma [91]. Between 1% and 5%
of women with endometriosis have urinary tract involvement, with the urinary bladder being the most
commonly affected, followed by the ureter, urethra, and kidney [92,93]. In 3%-37% of instances,
endometriosis was known to have an impact on the digestive system, with the recto-sigmoid colon as the
most often affected area [94]. Although comparable findings have been documented in cancer patients, the
link between diagnostic delay and health care funding for endometriosis is unique [95-97]. The majority of
endometriosis patients have normal pelvic findings; hence a laparoscopy is required to make a conclusive
diagnosis. It is likely that ultimately a combination of biochemical indicators and clinical evaluation will
lessen the requirement for surgical confirmation, even if no single laboratory test has demonstrated proven
clinical usefulness [98,99]. Endometriosis is more frequent among Caucasian, middle-aged, upper-class
women who are ambitious. This could happen because these women have more access to medical treatment
and diagnostic procedures like laparoscopy [100]. This might be because these women have easier access to
medical treatment and diagnostic testing like laparoscopy [101,102]. As endometriosis frequently exhibits
symptoms that resemble those of other disorders and cause a diagnostic delay, early suspicion of the
condition is crucial for prompt diagnosis. In addition to a patient's medical history, secondary centers with
access to further investigations may need to be referred from the main health care level [103,104].

Ovarian Endometriosis

Ovarian endometriomas account for 35% of all benign ovarian cysts and are seen in 17%-44% of female
patients [105]. Endometrial cell growth may be induced by ovarian follicular fluid [106]. Left ovary
endometriomas are more prevalent than right ovary endometriomas [107]. The amount of normal ovarian in
the swollen ovarian cortex was decreased in endometrioma patients' ovarian cortical tissue, a result not seen
in other benign cysts to a similar extent [108]. The ovary with endometrial cysts exhibits lower reactivity to
exogenous gonadotropin activation, with more follicular atresia, and a higher rate of follicular atrophy [109].
The most prevalent histologic forms of ovarian cancer resulting from ovarian endometriosis
are endometrioid adenocarcinoma and clear cell carcinoma [110,111].

Scar Endometriosis

Scar endometriosis occurs when endometrial tissue is implanted directly in scars during surgery [112]. Other
surgical disorders such as hematoma, hernia, scar tissue, neuroma, abscess, granuloma, or even metastatic
cancer can easily be coupled with scar endometriosis [113,114]. The presence of morphological and
physiological stroma and endometrial gland beyond the uterine cavity is a persistent gynecologic
condition [115]. The kidneys, pleura, bladder, lungs, colon, lymph nodes, omentum, and abdominal wall are
all common locations for extra pelvic endometriosis [116].

Urinary Bladder Endometriosis

Extragenital endometriosis most commonly affects the gut and urinary system [117]. The urinary bladder is a
rare location of endometrial localization, with just around 1% of people that are suffering from the illness
having lesions affecting the urine system [118]. To avoid kidney function loss, urinary tract endometriosis
must be diagnosed and treated early. For women who complain of bladder pain but have a negative
urine test, the doctor may not examine if the discomfort is cyclic or whether bladder endometriosis is a
possibility. Endometriosis in the urinary system is uncommon, occurring in about 1%-6% of females with
initially diagnosed endometriosis [119].

Conclusions
Long-term conditions like endometriosis with symptoms like dyspareunia, dysmenorrhea, dysuria,
dyschezia, and chronic pelvic pain (CPP) vary based on the organ affected, but not the illness itself. For early
identification and management of bladder, ovarian, and intestine endometriosis, a higher index of concern
is essential to improve the quality of life and decrease infertility. Dysmenorrhea is a fairly prevalent
condition in adolescent girls, as they suffer from a variety of mental and physical symptoms that negatively

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impact their quality of life. Scar endometriosis has been the most common site of endometriosis in this
research, with 50% of cases developing solely at the LSCS scar site. Minimal peritoneal endometriosis and
also the most severe phases of the disease can be treated with laparoscopic surgery. Therefore, women with
endometriosis are at a higher risk of miscarriage, and their embryo quality suffers.

Additional Information
Disclosures
Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the
following: Payment/services info: All authors have declared that no financial support was received from
any organization for the submitted work. Financial relationships: All authors have declared that they have
no financial relationships at present or within the previous three years with any organizations that might
have an interest in the submitted work. Other relationships: All authors have declared that there are no
other relationships or activities that could appear to have influenced the submitted work.

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