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Ministry of Public Heals Service of Ukraine
«Ukrainian Medical Stomatological Academy»
«APPROVING»
on the sitting of chair of obstetrics and
gynecology №1 of UMSA
(protocol №1 from 28. 08. 2019)
Acting manager of chair of obstetric
and gynecology №1
professor ____________A.M. Gromova
METHODICAL POINTING
for the teacher of higher medical educational establishment in relation of
educational process
Educational
subject
Obstetric
Modul № 1
Subject of
lesson
Endometriosis
Course IV
faculty medical
Poltava – 2019
Endometriosis
Amount of hours: 4 hours in practical classes
The topic includes etiology and pathogenesis. Classification. Diagnosis.
Symptoms. Modern methods of treatment. Medical rehabilitation of women with
endometriosis.
Gynecological diseases of children and teens. Peculiarities of symptomatic,
diagnostics and treatment of the most widespread types of gynecological pathology of
youg girls and teens. Hyperanteflexion, retrodeviation of the uterus. Treatment,
prophylaxes. Development defects of the reproductive organs. Infantilism, impaired
sexual development, gonadal dysgenesis.
Endometriosis – benign hormone-dependent disease, which is based on
heterotopias of endometrium (glandular and stromal components), the signs of which
are nonspecific inflammation and elevated levels of enzymes on the background of
disturbances of hypothalamic-pituitary-ovarian system, immune balance in the
presence of genetic predispositions. The problem of endometriosis is medical and
social - a common cause of disruptions of working capacity and reproductive function
of women, therapeutic and diagnostic - the complexity of early clinical diagnosis and
conservative treatment in the later stages of the disease, cancer - an increasing
number of observations of malignant diseases at an early stage have been diagnosed
as endometriosis, The occurrence in general population - 5 - 10%, it occupies the
third place in the structure of gynecological diseases after inflammation and uterine
fibroids and affects, according to WHO, 25 - 30% of women of reproductive age.
27% of women who gave birth , 30 - 40% woman with infertility, 10% of girls at the
age of menarcheand approximately 2 - 5% of women in menopause are diagnosed
with endometriosis.
The hypothesis of origin according to P. J. Q. van der Linden, 1997 are: in situ
formation, transplantation, the combination of the formation of transplantation and
implantation of endometrium, embriological hypothesis, hypothesis of metaplasia due
to inflammation or hormonal stimulation, immunological theory. The risk factors
include: history of abnormal births, gynecological operations, abortions, hormonal
disorders, the decline of immunological tolerance, hereditary predisposition, early
menarche, age older than 35-45 years, reducing the length of the menstrual cycle, the
increase of menstrual blood loss, inflammatory diseases of the genitalia, the first labor
families in the older age, waiver of breast feeding, the abuse of alcohol, caffeine,
adiposity. Factors that lower the risk are: use of
hormonal contraceptives, previous use of IUD, smoking, belonging to a
particular race.
Topical classification
І. Genital endometriosis
Internal endometriosis (adenomiosis)
o Endometriosis of corpus uteri
І,ІІ,ІІІ stages depth of invasion into
endometrium : glandular, cystic, fibrous (focal, nodular, diffuse) form
o Endomeetriosis of the cervical canal
o Endometriosis of the isthmic part of the fallopian tubes
External
endometriosis
o Peritoneal
endometriosis
of ovaries (infiltrative and tumor forms)
of fallopian tubes
of pelvic peritoneum (red, black, white form)
o Extraperitoneal endometriosis
vaginal part of cervix
of vagina, vulva
retrocervical
of uterine ligaments
Parametrial, paravezical, paravaginal tissue with or
without invasion into the bladder, rectum
External-internal endometriosis
Combinations of endometriosis (genital or extragenital pathology)
Extragenital endometriosis (gastrointestinal tract, urinary organs,
skin, navel, postoperative wounds, lungs, pleura, etc.
Symptoms include: pain (pelvic pain, algodismenorrhea, dyspareunia),
infertility, hemorrhagic syndrome, long ineffective treatment of chronic genital
inflammation, mental disorders, impaired function of adjacent organs, absence of
symptoms. Typical symptoms include: dysmenorrheal, dyspareunia (sexual
disorders), infertility, pelvic pain. Less typical symptom - dysheziya (disturbance of
bowel movements), dark bloody discharges before and after menses, dysfunctional
uterine bleeding, dysuria. More rare symptoms are frequent urge to urination,
haematuria, bleeding from the rectum. Very rare symptoms are haemoptyzys (bloody
cough), intestinal obstruction, edema of the kidney and ureter, skin nodes.
Chronic pelvic pain. This is the most common symptom of endometriosis. The
intensity depends on localization of ectopy (especially pronounced in endometriosis
of isthmus, sacro-uterine ligaments, nodular form), the extent of the process, duration
of disease, individual characteristics. Menstrual cycle disturbances include
progressive algomenorrhea, menometrorragia, bloody discharges before and after
menstruation, contact bloody discharges, irregular menstruation. The disease for a
long time may be hiding under the mask of various pathological processes.
Special methods of diagnosis include: X-ray examination, ultrasound,
endoscopic methods including hysteroscopy and oth., CT, MRI ( fiber – accuracy
of diagnostics - 98-100%), cytological, histological (diagnostic accuracy 98-
100%), determination of the levels of tumor markers (CA-125, HE - 4) .
Hysterosalpingography The accuracy of diagnosis ranges from 33.2 to 97.4%.
Its not posssible to diagnose a focal or nodal form. The procedure is done 2-3 days
after menstruation or 24 hours after thorough curettage of the uterus, or 6- 8 days
after endometrial curettage because of the best penetration of contrast in endometrioid
moves. During the procedure aqueous solutions are preferred.
Ultrasound is the best and affordable screening method. There may be
difficulties in accurate diagnosis if adhesive processes are present, it is impossible to
identify depth of the lesion of external genital and extragenital endometriosis In some
of the cases the evaluation and visualization is not accurate.
Hysteroscopy. This method if Miniinvasive and highly informative. During the
procedure there is a high incidence of diagnosing submucous nodes, adenomyosis,
chronic endometritis, hyperplasia of endometrium, polyps. The procedure is done not
only for diagnosis but as a surgical method of treatment too. There is a possibility to
do biopsy or curettage, remove tumors or septas, separate adhesions.
Laparoscopy has a high diagnostic accuracy with direct visualization, ability to
biopsy and histological examination. If it is already diagnosed appropriate therapeutic
rather than diagnostic laparoscopy is applied.
Endometriosis of vagina and perineum The symptoms are: pain in the vagina
and in the pelvis from mild to severe, cyclic pain that is related to the MC, the pain
may be accompanied by local itching. The diagnosis criteria are: during menses
painful nodes may be palpated in the vagina, after the menstruation they decrease in
size or disappear leaving scars, hystological investigation may be performed.
Endometriosis of the cervix During the speculum examination cyanotic cysts
may be seen. To confirm the diagnosis colposcopy and biopsy is performed. The
sysmptoms include dark bloody discharges from vagina before and after menses. This
is the only form that the pain symptom is not present.
Endometriosis of the ovaries Emndometrial cysts of the ovaries as the small
heterotopias may be either unilateral or bilateral with different diameters of the cysts
(from 0.5 up to 10.0 cm in diameter). The symptoms include: pain especially before
and during menses, infertility, disuria, dysheziya. In case of rupture of the cysts the
pain is accompanied by vomiting, unconsciousness, elevated body temperature.
Diagnoses. Bimanual examination: One or both sides tumors are palpated in the
pelvis, inactive painful especially during menstruation, with bumpy surface, located at
the sides or behind the uterus, with a dense capsule, limited mobility, often along with
the uterus are palpated as one conglomerate. The other diagnostic measures include
ultrasound, endoscopic methods (laparoscopy)( small size cyanotic nodes or cysts of
various size).
Retrocervical endometriosis occurs relatively frequently. Behind the cervix a
dense bumpy, sharp pain, formation of different size, limited in mobility is palpated.
The symptoms are - severe pain syndrome, difficulties of bowel movement.
Extragenital endometriosis - endometriosis of the naval, endometriosis of the
postoperative scar and others.
Adenomyosis.
Pathological classification V.I.Zheleznov , AN Strizhakova
I degree. – germination of mucosa to a depth of one field of view
at low magnification of the microscope
II degree - Germination mucosa to the middle of the wall thickness
III degree - the entire muscle layer is involved into the
pathological process Symptoms. It is believed that the clinical
manifestations occur in women
with II and III degree and nodular form, whereas I degree is a histological
finding during hysterectomy . The course may be asymptomatic - 19-40%,
algomenorrhea - 76%, hypermenorrhea - 50-66%, "chocolate“ like vaginal discharges
- 56%, increased dysmenorrhea - 30% (at a depth of myometrial lesions by more than
80%) , pelvic pain, metrorrhagia, dyspareunia, infertility.
Diagnoses.. Bimanual examination (a moderate increase in uterine
anteroposterior size, tenderness, when nodular form dense nodes are palpated,
painfulness and the value of which increase during menstruation), Ultrasound
(increased anterio-posterior uterine size (80%), a thickening of one of the walls of
uterus (81.8%), the presence of zone of increased echogenicity, occupying more than
half the thickness of the myometrium (96%), hysteroscopy, hysterosalpingography,
laparoscopy.
Treatment The choice of treatment strategy depends on the age of woman,
localization and extent of the disease, severity of symptoms and duration of illness,
fertility and the need to restore fertility, the effectiveness of previous treatment,
presence of comorbidity, common therapeutic approaches. The methods of treatment
include surgical therapy, hormonal therapy, during menopause if minimal
manifestations of the disease are present expectant management, auxilary (for all
symptoms) therapy, IVF if infertility
Conservative therapy includes hormonal therapy, non-specific anti-
inflammatory therapy, medications that affect the central nervous system,
immunomodulators, antioxidants, vitamin, medications that support the function of
gastrointestinal and hepatobiliary systems, physiotherapy treatment, treatment of
comorbidity.
According to the consensus for the treatment of chronic pelvic pain syndrome
and endometriosis (2002) the first line of treatment include Monophasic COC +
nonsteroidal anti-inflammatory therapy if treatment failure. The second line of
treatment is surgery (laparoscopic or laparotomy) treatment. In our country the
second-line treatment should be considered a destination of agonist of
gonadotropin-releasing hormone after failure are surgical treatment is
performed. If untreated, the disease progresses with the development of common
tumor forms, malignant degeneration.
Indications for surgical treatment of endometriosis are
internal endometriosis combined with hyperplastic
processes of ovaries and / or endometrial precancerous
adenomyosis (diffuse or nodular form) accompanied by
hyperplasia of endometrium
Endometrial ovarian cysts (larger than 5 cm)
No effect of conservative treatment, which was carried out
continuously for 6 months
pathological involvement of other organs and systems with
violation of their functions
purulent lesions of the uterus, affected by endometriosis
endometriosis of navel
adhesions of the fallopian tube in ampullar departments with
infertility
endometriosis of the postoperative scar
presence of somatic pathology, which precludes
long-term hormone therapy
With the ineffectiveness of hormone therapy, infertility, malignant forms of
internal endometriosis, suspected malignancy In reproductive age – organ retaining
surgery by laparotomy or laparoscopy access, conservative treatment, treatment of
infertility, in perimenopause – radical surgery.
Endometriosis is a diseases characterized by the presence of a tissue similar to
endometrium in areas other than the lining of the uterus. Unlike endometrium the
endometrioid tissue is less liable to cyclic changes, less reacts to gestagens, does not
undergo secretory transformation.
The disease ranks third in the structure of gynecological disorders and affects
15–50 % of women at the childbearing age; 30–40 % endometriosis patients are
sterile. The importance of timely diagnostics and correct treatment of endometriosis
is explained by a characteristic property of the disease activity – gradual progress of
the severity of the pathological process, which leads to menstrual dysfunction,
bleeding, anemia, and development of persistent pain syndrome.
Etiology and Pathogenesis
Endometriosis is an estrogen-dependent disease. The origin of endometriosis
foci and the reasons for its dissemination have not been completely studied yet. There
are a couple of theories of endometriosis pathogenesis.
І. The transport theory is based on lymphogenous, hematogenous, and
iatrogenic (at surgical interventions, hysteroscopy, hysterosalpingography)
dissemination.
ІІ. The implantation theory is a theory of retrograde menstruation, which
explains the retrograde ingress of endometrium cells into the abdominal cavity. The
reasons for pathological implantation:
- hypoluteinism (progesterone synthesis reduction); normally in the
peritoneal fluid there is a high (higher than in blood) sex steroid concentration, which
inactivates endometrioid cells;
- protracted menstruation, cervical canal constriction, and a wide
uterotubal lumen lead to an increase in the amount of retrograde menstrual blood;
- immune dyscrasia;
- burdened heredity.
ІІІ. The theory of celomic metaplasia (degeneration) of the peritoneal
mesothelium in response to the irritant action of the endometrial tissue.
ІV. The embryonal theory explains the dysembrioplastic genesis of
endometriosis from the remains of the Mullerian ducts and primordial kidney.
Some authors regard endometriosis as an autoimmune disease, in which
immune protection disturbance leads to an increase of macrophage content in the
peritoneal fluid, activation of acid phosphatase and neutral protease. In women with
endometriosis in the peritoneal fluid there is observed disbalance of the cells
providing peritoneum resistance. Thus, there lowers the level of natural killers and
rises the content of IL-1, IL-6, IL-8. The factor, which significantly promotes
endometrium cell retention, is mesothelium integrity damage, since intact peritoneum
is a barrier for invasion.
The hormonal factor, as a reason for sterility in endometriosis, undoubtedly
plays one of the leading roles, however, the literature data on sex hormone secretion
are ambiguous and mainly testify to their increase except for progesterone, whose
content reduces.
It has been found that hormones do not influence the cells of the hormone-
dependent organs directly, but mediately by means of growth factors, gene
expression, specific proteins, and apoptosis. The balance of molecular-genetic indices
of the proliferation and apoptosis processes in the endometriosis foci is disturbed.
The study of apoptosis processes in endometriosis is a new tendency in the treatment
of this pathology.
Classification
1. Internal (70–90 %) – of the uterine body, isthmus, and the interstitial
parts of the uterine tubes. If the uterine walls thicken, internal endometriosis is called
adenomyosis.
2. External (10–30 %):
- peritoneal (of the ovaries, uterine tubes, small pelvis peritoneum);
- extraperitoneal (of the uterine neck, vagina, external genitals, retrocervical).
The most widespread external endometriosis classification was worked out by
А. Асоstа and co-authors (1973). According to this classification, there are
differentiated such stages of external endometriosis.
Minor forms:
- isolated heterotopies on the pelvic peritoneum;
- isolated heterotopies on the ovaries without adhesions and scars.
Moderate endometriosis:
- heterotopies on the surface of one or both ovaries with small cyst
formation;
- latent periovarial or peritubal adhesion abscess;
- heterotopies located on the peritoneum of the extrauterine space with
scarring process and uterus displacement without the large intestine being affected by
the pathological process.
Severe form of external endometriosis:
- endometriosis of one or both ovaries with formation of cysts larger than
2 cm;
- ovary affection with evident periovarial and/or peritubal scarring
process;
- uterine tube affection with deformation, scarring, blockade;
- peritoneum affection with extrauterine space obliteration;
- affection of the sacrouterine ligaments and peritoneum of the
extrauterine space;
- affection of the urinary tracts and/or bowels.
Many countries of the world use the classification of the American Society for
Reproductive Medicine (Table 1); this classification takes into account the extent to
which affection has spread, affection depth, and severity degree at different
endometriosis localization, for this purpose the numerical score of the indicated
parameters is formed. There are singled out four stages of the disease: I – 1–5 points,
II – 6–15 points, III – up to 16–40 points, IV – 40 points and more.
Table 1
Endometriosis Classification
(American Society for Reproductive Medicine)
Endometriosis < 1 > 3
1
cm
–3
cm
cm
Peritoneum superficial 1 2 4
deep 2 4 6
Ovaries ri
ght
superficial 1 2 4
deep 4 1
6
20
le
ft
superficial 1 2 4
deep 4 1
6
20
Extrauterine
space obliteration
p
artial
–40 c
ompl
ete
–
40
Adhesions c
over
< 1/3
c
over
<
1/3–
2/3
cover
> 2/3
Ovaries ri
ght
soft 1 2 4
dense 4 8 16
le
ft
soft 1 2 4
dense 4 8 16
Uterine tubes ri
ght
soft 1 2 4
dense 4 8 16
le
ft
soft 1 2 4
dense 4 8 16
Note: A completely soldered fibrial part of the tube scores 16 points.
According to the pathological process localization there are singled out:
І. Genital endometriosis.
1. Internal endometriosis.
1.1. Endometriosis of the uterine body of the I, II, III
(adenomyosis) stages depending on the depth of myometrium affection:
glandular, cystic, fibrous forms (focal, nodal, and diffuse forms).
1.2. Endometriosis of the cervical canal.
1.3. Endometriosis of the intramural part of the uterine tubes.
2. External endometriosis.
2.1. Peritoneal endometriosis:
- endometriosis of the ovaries (infiltrative and tumor forms);
- endometriosis of the uterine tubes;
- endometriosis of the pelvic peritoneum (red, black, and
white forms).
2.2. Extraperitoneal endometriosis:
- endometriosis of the vaginal part of the uterine neck;
- endometriosis of the vagina, vulva;
- retrocervical endometriosis;
- endometriosis of the uterine ligaments;
- endometriosis of the parametral, paravesical, and
paracolpal fat with and without invasion to the urinary bladder,
rectum.
3. Externointernal endometriosis.
4. Combined forms of genital endometriosis (genital endometriosis in
combination with some other genital or extragenital pathology).
II. Extragenital endometriosis (endometriosis of the gastrointestinal tract,
urinary organs, skin, navel, postoperative wounds, lungs, pleura, etc.).
Clinical Presentation
Genital endometriosis (GE) is characterized by a diversity of the clinical
course: from asymptomatic to the presentation of acute abdomen. The most
frequently observed clinical sign of endometriosis is pain syndrome connected with
menstrual cycle – it appears before and increases during menstruation.
Symptom polymorphism is conditioned by different localization of GE foci,
the extent to which they have spread, genital organ dysfunction, and concomitant
pathologies.
Pains are usually considerable in GE, their intensity increases as the disease is
progressing. The patients note weakness, rapid fatigability, significant loss of
exercise performance, which leads to feeling anxiety and fear.
In endometriosis pains are bilateral, their intensity does not correspond to the
process severity. Even a large endometrioid ovarian cyst may produce no pain
symptomatology, and sometimes it causes pains, especially on the eve of and during
menstruation, which may be accompanied by nausea, vomiting, loss of
consciousness. At microperforation of endometrioid cysts there not infrequently arise
peritonitis phenomena. Most uterine GE patients have profuse protracted
menstruations, metrorrhagia, sensation of heaviness, spreading in the lower abdomen.
The character of menstrual dysfunction depends largely on the localization of
endometriosis foci, the degree of affection of the genitals and pelvic organs.
Concerning some endometriosis varieties, which are characterized by serious
derangements of anatomical organizations in the region of uterine appendages, it has
been proved that fertility becomes a direct consequence of such injuries as salpingian
occlusion, adhesion deformation of the fimbriae, total isolation of the ovaries with
periovarial adhesions, direct injury of the ovarian tissue with endometrioid cysts, etc.
However, in many cases endometriosis and sterility may develop parallel for
one or a couple of common reasons. Concomitant diseases are of big importance in
this case. Different factors of sterility in endometriosis may be divided into a couple
of groups: 1) mechanical; 2) peritoneal; 3) immunological; 4) endocrine disorders.
Disorders of the general condition of the organism lead to a considerable
decrease of women’s exercise performance. In order to improve the quality of the
diagnostics of such disorders and rational choice of the treatment method there was
offered a method of assessing the degree of severity of disorders of the general
condition of the organism and exercise performance of the woman (numerical
system) in endometriosis (Table 2).
Table 2
Pain Intensity Assessment
(according to C.M. Mac Laverty, R.W. Shaw, 1995)
Pain Cause Intensity Score, points
Pain in the pelvic
region not connected with
coitus or menstruation
No.
Weak, sometimes
sensation of discomfort or
pain before menstruation.
Moderate, evident
discomfort during the most
part of the cycle.
Severe during the
whole menstrual cycle, the
patients must take
analgesics.
0
1
2
3
Dysmenorrhea No.
Weak, with some
disorders of working
capacity.
Moderate, makes the
patients stay in bed for a
couple of hours a day,
sometimes – loss of
working capacity.
Severe, makes the
patients stay in bed during
the whole day or a couple
0
1
2
3
of days.
Dyspareunia No.
Weak, tolerable.
Moderate, so
intensive that makes the
patients interrupt coitus.
So severe that makes
the patients avoid coitus.
0
1
2
3
Diagnostics
Despite the fact that modern highly informative diagnostic methods of are
being introduced, GE verification still presents difficulties.
The most typical signs and manifestations of GE are:
- syndrome of pelvic pains, which worsen during menstruations;
- sterility;
- dysfunction of the genital organs (hemorrhagic syndrome, premenstrual
spotting, hyperpolymenorrhea, metrorrhagia);
- continuous ineffective treatment of chronic inflammatory processes of the
genitals;
- psychoneurological disorders;
- dysfunction of the adjacent organs (dysuria, dyschezia).
Only complex examination of the patient in consideration of anamnesis data,
clinical manifestations, and standard methods (objective examination and results of
special methods of investigation) enable the doctor to establish the localization form
and the degree of endometriosis prevalence, and correspondingly, to administer and
successfully provide pathogenetically conditioned treatment.
Of big importance is the general examination of the genitals and examination
by means of specula, which allow finding endometrioid heterotopies. Bimanual,
vaginal-abdominal, and rectovaginal types of examination are auxiliary diagnostic
methods. Palpation of the uterus shows its form, dimensions, mobility, and
painfulness. One should pay attention to the condition of the uterine isthmus
(induration, dilation, painfulness) and posterior fornix of the vagina (infiltration, scar
changes). Examination of the uterine appendages detects their size, mobility,
painfulness, and consistency. One assesses the state of the sacrouterine ligaments
(thickening, tension, painfulness).
In order to fiagnose GE one uses the following instrument investigation
methods: 1) roentgenological; 2) urological (cystoscopy, chromocystoscopy,
radionuclide diagnostics); 3) US (transabdominally and transvaginally); 4)
endoscopic (colposcopy, proctosigmoidoscopy, laparoscopy); 5) nuclear magnetic
resonance (NMR) tomography; 6) cytological investigation method; 7) histological
study of the material taken by means of biopsy.
In order to diagnose GE, the degree and character of vascular disorders one
resorts to dopplerometric investigations of blood flow in the arteries of the organs of
the small pelvis. Among roentgenological techniques of GE diagnostic there is used
hysterosalpingography and bicontrast gynecography performedon the 2nd
–3rd
day
after menstruation or after diagnostic curettage. In this case preference is given to the
use of water solutions of radiographic contrast media.
The most typical roentgen sign in internal endometriosis is the presence of
edge shadows of different length. Their form depends on the localization of the
endometrioid foci.
Hysteroscopy shows endometrioid eyes in the form of dark red pin holes
against the background of pink-pale hue of the uterine cavity mucosa; at multiple
localization of endometriosis foci the endoscopic picture reminds the honeycomb
structure. The nodular form of adenomyosis is characterized by enlargement and
deformation of the uterine cavity due to bulging of its affected walls, on which there
are localized pathological formations with a yellow or yellow-pale hue without clear
limits, sometimes with the presence of superficial endometrioid “pupils”
Laparoscopy is the most accurate and basic diagnostic technique under modern
conditions. The diagnosis must be necessarily confirmed histologically after a biopsy
of endometrioid areas taken during laparoscopy. Laparoscopy is a first choice
procedure, because it enables examining the whole abdominal cavity from the pouch
of Douglas to the diaphragm. Endometriosis manifestations may be easily found by
their typical appearance – of the so-called “gunpowder burns”, stellar-scarry injuries
surrounded by red-blue implants on the ovaries and on the peritoneal surface of the
uterus, urinary bladder, or small intestine. The condition is characterized by
“chocolate”, bluish uni- or bilateral cysts of the ovaries, adhesive process in the small
pelvis; adhesions between immobile fixed organs and structures – under ovarian
fusions – between the ovary and the posterior folium of the broad ligament, posterior
wall of the vagina, immobile part of the sigmoid colon. The utypical signs are:
petechial peritoneum, “fiery spots”, hypervascular zones, white non-transparent
plates surrounded by scar tissue, glandular structures on the peritoneum.
The degree of the spread of external genital endometriosis is assessed in points
(see Table 1).
Microscopical endometriosis foci are the foci found by histological study of the
peritoneum, which looks unaltered. Discovery of microscopical endometriosis foci
plays an important role in the understanding of the disease pathogenesis and its
relapses after treatment.
The technique of NMR tomography in Т2-image allows detecting diffuse
formations without clear contours independent of the morphological structure of
endometrioid heterotopies. If the gastrointestinal tract may be involved in the
pathological process, and for the prophylaxis, it is expedient to conduct
fibrogastroscopy, irrigoscopy, and rectoromanoscopy.
The biochemical markers of endometriosis are not known at the moment.
According to statistics, the level of СА-125 – the substance, which is synthesized by
celomic epithelium derivatives and is an ovarian cancer marker – rises in medium-
severe and severe endometriosis and remains normal in minimal and minor process.
If endometriosis is suspected, one is recommended to detect the oncomarker twice:
during menstruation and in the follicular phase of the menstrual cycle. If the ratio of
the indices of СА-125 levels during menstruation to the index during the follicular
phase exceeds 1.5, endometriosis is possible. Reduction of the СА-125 level may
testify to treatment efficiency, and its further lowering – to a relapse.
Treatment
The therapeutic approaches, which are applied today to treat endometriosis,
include: observation, palliative, hormonal, surgical, and combination therapy.
Taking into account that endometriosis is a disease of the whole organism, and
not of a single organ, the therapy must be complex and include:
1) hormonal treatment (Table 4);
2) immunocorrectors;
3) prostaglandin inhibitors;
4) antioxidants (a combination of
vitamins А, Е, С, Р), a complex of vitamins-antioxidants (selmevit,
complevit);
5) physical therapy .
Presently, there is a certain consensus in the treatment of GE in both sterile
patients and women without reproductive intentions.
Consensus statement for the management of chronic pelvic pains and
endometriosis (Gambone J., Mittman B. et al., Fertil. Steril., 2002):
- the first-line treatment: monophase COCs + nonsteroid anti-inflammatory
therapy;
if the treatment is ineffective:
- the second-line treatment: surgical (laparoscopic or laparotomic) treatment.
Extensive clinical material allowed studying the effectiveness of such groups
of preparations as gestagens (gestrinone, norethisterone acetate, provera, linestrenol,
dydrogesterone), antigonadotropins (danazol), gonadotropin-releasing hormone
agonists (decapeptides: tritorelin, goserelin; nonapeptides: buserelin, leuprolein),
whose application ultimately brings to hypoestrogenia and, as a consequence, to the
involution of pathological implants.
Table 4
Hormonal Treatment of Endometriosis
G
roup of
prepara
-tions
Prim
ary clinical
result
Internat
ional name
Prepa
ration name
Dos
age
schedule
Contrai
ndications
1 2 3 4 5 6
C
ombined
and
estrogen
-
gestagen
preparati
ons
Anov
ulation
Ethinyl
estradiol +
testosterone or
progesterone
derivatives
Moder
n COCs
Cycl
ic schedule
–
according
to the
regimen of
COCs
dosage;
prolonged
schedule;
24+4,
42+7,
126+7
days
Thromb
oembolisms,
ischemic heart
disease;
vascular
encephalopathi
es,
considerable
lipoproteinemi
a, hormone-
dependent
tumors, severe
hepatopathies,
sicklemia
Pr
ogestins
False
pregnancy
Norethist
erone acetate
Norco
lut,
Primolut-
Nor
Fro
m the 5th
day of
menstrual
cycle 5–10
mg twice a
day during
4–6(8)
months
Hepatop
athies,
thrombosis
susceptibility,
genital tumors
Medroxy
progesterone
acetate
Prover
a, depo-
provera
5–
10 mg a
day during
6 months,
100–150
mg i.m.
once in 2
weeks
during 6
months
Tumors
of the genital
organs and
mammary
glands
Dydroge
sterone
Dupha
ston
Fro
m the 5th
day of
menstrual
cycle 5–10
mg a day
during 4–6
months
Hyperse
nsitivity to the
preparation
components
Microniz
ed
progesterone
Utrog
estane
Fro
m the 5th
day of
menstrual
cycle 5–10
mg a day
during 4–6
months
Severe
hepatopathies,
hypersensitivit
y to the
preparation
G
onado-
tropin-
releasing
hormone
Medi
camental
castration
Triptorel
in
Diphe
reline
Fro
m the 3rd
day of
menstrual
cycle 3.75
Hyperse
nsitivity to the
preparation
components
agonists mg i.m.
every 28
days;
11.25 mg
once in 3
months up
to 6
months
Gosereli
n
Zolad
ex
3.6
mg under
the skin of
the
anterior
abdominal
wall every
28 days
during 6
months
Hyperse
nsitivity to the
preparation
components
Nafareli
ne acetate,
buserelin
Nonap
eptides
200
mcg
intranasall
y in the
morning
and in the
evening up
to 6
months
Hormon
e-dependent
tumors
G
onadotro
pin
antagoni
Pseu
domenopau
se
Danazol Danov
al, danol,
danogen
400
–800
mg/day
during 6
Porphyri
a
sts months
Gestrino
ne
Neme
stran
2.5
mg twice a
week
during 6
months
Cardiac
insufficiency,
severe hepatic
and renal
diseases,
vascular
diaseases,
dysbolism
Notes: 1) 24+4 (24-day intake, 4-day interval);
2) 42+7 ( 42-day intake, 7-day interval);
3) 126+7 (126-day intake, 7-day interval);
4) all the preparations are contraindicated in pregnancy and lactation.
Medical indications to the application of COCs (M. Silltm et al., 2001) on
prolonged schedule are endometriosis, premenstrual syndrome, dysfunctional uterine
bleedings, anemia, polycystic ovary syndrome, hemophilia, “menstrual” migraine.
Antigonadotropins cause artificial pseudomenopause. Their action consists in
blocking the release of FSH and LH, their basal secretion level being preserved.
Gonadoliberin agonists. In the last decade, there have been successfully used
such decapeptides: diphereline, decapeptyl, zoladex, and nonapeptides: buserelin,
leuprolein. These preparations have a strong antigonadotropic action and bring on
“medicamental castration”. Their application requires additional correction of
menopausal vegetovascular and metabolic disorders. The maximal term of
uninterrupted intake of the preparations makes 6 months.
Antiestrogens. Tamoxifen, toremifene (fareston) are administered only in case
of high or moderate hyperestrogenism. The dose makes 10 mg twice a day during 6
months. In hypoestrogenism tamoxifen stimulates estrogen synthesis.
Prostaglandin inhibitors. Since endometrioid foci have few estrogen- and
progesterone-binding receptors, the hormonal treatment may be ineffective.
Inactivation of these receptors is connected with a high concentration of
prostaglandins F2a in pathological implants. Therefore administration of nonsteroid
anti-inflammatory preparations, which block cyclooxygenase synthesis and increase
the sensitivity of endometriosis foci to the action of gestagens, is pathogenetically
expedient.
Enzymotherapy. There are provided independent enzymotherapy courses in
the intervals between other medicamental treatment techniques or in combination
with gestagens, and also in the rehabilitation of postoperative patients. Enzyme
preparations provide both immunomodulatory and local effects (microcirculation
improvement, edema elimination, hematoma and adhesion resorption).
Immunotherapy – systemic application of immunomodulators, which promote
endogenous production of IL-12 and gamma-interferon.
It is expedient to resort to acupuncture and hardware-controlled
physiotherapy. Physiotherapeutic procedures aim at the activation of metabolic
processes, reduction of inflammatory phenomena, prevention of hereditary process
development, restoration of regulating bonds between the control centers and target
organs of the reproductive system (laser therapy, pulse sequence ultrosund, constant
and alternating magnetic fields, iodine and zinc electrophoresis, radon baths in
hyperestrogenism, microclyster and vaginal irrigations).
In sterile women after hormonal treatment of endometriosis there is applied the
therapy aimed at hormonal disbalance correction and ovulation stimulation.
If the conservative treatment of endometriosis is ineffective, surgical
treatment is administered (laparoscopy or laparotomy).
The surgical treatment of GE has always been and remains the only technique,
which allows removing the morphological substrate of endometriosis mechanically or
eliminating it by means of laser, electrical, or thermal influence. Medicamental
therapy in the pre- and postoperative period makes it possible to optimize the results
of surgical treatment.
As for the choice of intervention volume, it is believed in recent years that even
at extensive endometriosis in women concerned with reproductive function
restoration one should follow the principles of reconstructive conservative surgery
and resort to radical operations only in the cases, when all other possibilities of both
surgical and medicamental treatment have been exhausted.
The technique and volume of surgical intervention are chosen individually.
The purpose of laparoscopic treatment is the removal of all visible foci and
restoration of normal anatomical correlations in the pelvic cavity.
The treatment of generalized and combined forms of endometriosis with
dysfunction or endometriosis affection of the adjacent organs (ureters, bowels,
urinary bladder). If endometrioid cysts are large, endometriosis is combined with
other gynecological disorders, their adequate treatment requires the application of
surgical methods, and at the same time there are no conditions to perform the
operation in full volume laparoscopically – the method of choice is laparotomy.
There are differentiated absolute and relative indications to the surgical
treatment of patients with internal endometriosis. Absolute indications include
combination of GE with diseases of the internals, which require surgical intervention
(hyperplastic processes of the ovaries and/or endometrial precancer, uterine
leiomioma, with rapid growth; severe dysplasia of the uterine neck, atypical
endometrial hyperplasia, endometrioid ovarian cysts larger than 5 cm, the ovaries
function invariably, pathological involvement of other organs and systems with their
dysfunction, suppurative involvement of the uterine appendages affected by
endometriosis, adhesive process with involvement of the ampullar parts of the uterine
tubes, which accompanies endometriosis that is the main reason for sterility;
endometriosis of the navel, endometriosis of the postoperative scar, combination of
endometriosis with some anomalies of the genital organs, a somatic pathology
excluding the possibility of continuous hormonal therapy). Among relative
indications there are differentiated the presence of asymptomatic uterine leiomyoma
in combination with atypical endometrial hyperplasia at the age younger than 40, the
3rd
degree of GE spread, ineffective medicamental treatment, which has been
uninterruptedly conducted during 6 months.
In internal 3rd
degree endometriosis (adenomyosis), when the endometrioid
tissue extends through the full thickness of the myometrium to the serosa, hormonal
treatment is ineffectual, therefore in such cases surgical treatment is indicated –
partial hysterectomy, and in endometriosis of the isthmical-cervical part – complete
hysterectomy.
At endometriosis of the uterine neck in patients of the childbearing age, if there
are solitary superficial foci, it is expedient to remove them by means of cryo- or laser
destruction followed by colposcopic monitoring and hormonal treatment.
The method of choice in the treatment of sterility must be endoscopic
interference. The advantages of this method are being minimally traumatic and with
the least blood loss, safety if one follows the rules of surgical technique and the
surgeon has sufficient experience, and also shortening of the postoperative period.
The most important advantage of this method is the visual control, which allows
complete elimination of endometriosis foci.
Electrocoagulation of solitary endometriosis foci is carried out with the use of
mono- and bipolar electrodes. Small (up to 2 cm) endometryomas are to be incised,
the doctor evacuates the contents, thoroughly enucleates the membrane of the tumor-
like formation and coagulates its bed. Sometimes in order to remove endometryoma
one resects the ovary. Endometrioid implants are often located close to the vital
organs, which creates certain difficulties for the coagulation of such implants because
of the hazard of affecting adjacent organs and anatomical structures. By indications
laparoscopic coagulation is possible and, in some cases, transaction of the
sacrouterine ligaments, which allows decreasing pain syndrome.
Treatment efficiency criteria: no relapses of the disease, reproductive
function recovery, positive dynamics of life quality.
TESTS
1.Lately menstruations at patient gained character hyperpolimenorrhea. She
complains on brown excretions and a few days after, menstruations are painful. In
history – 3 artificial abortions. Bimanual examination: the uterus is insignificaly
enlarged. A hysterosalpingography – infiltration of contrast inside the uterine wall.
Previous diagnosis?
A. endometriosis of uterus body
B. cancer of uterus body
C. myoma
D. endometriosis of uterus cervix
E. horiocarcinima
2.A patient was admitted to the hospital with complaints of periodical pain in
the lower part of abdomen that gets worse during menses, weakness, malaise,
nervousness, dark bloody smears from vagina directly before and after menses.
Bimanual examination revealed that uterus body is enlarged, appendages cannot be
palpated, posterior fornix has tuberous surface. Laparoscopy revealed: ovaries,
peritoneum of rectouterine pouch and pararectal fat have "cyanotic eyes". What is the
most probable diagnosis?
A. disseminated form of endometriosis
B. polycystic ovaries
C. chronic salpingitis
D. tuberculosis of genital organs
E. ovarian cystoma
3.A 28 year old woman has bursting pain in the lower abdomen during
menstruation; chocolate-like discharges from vagina. It is known from the anamnesis
that the patient suffers from chronic adnexitis. Bimanual examination revealed a
tumour-like formation of heterogenous consistency 7х7 cm large to the left from the
uterus. The formation I restrictedly movable, painful when moved. What is the most
probable diagnosis?
A. endometrioid cyst of the left ovary
B. follicular cyst of the left ovary
C. fibromatous node
D. exacerbation of chronic adnexitis
E. tumour of sigmoid colon
4.A 42-year-old woman has had hyperpolymenorrhea and progressing
algodismenorrhea for the last 10 years. Gynaecological examination revealed no
changes of uterine cervix; discharges are moderate, of chocolate colour, uterus is
slightly enlarged and painful, appendages are not palpable, the fornices are deep and
painless. What is the most likely diagnosis?
A. uterine endometriosis B. uterine carcinoma
C. subserous uterine fibromyoma
D. endomyometritis
E. adnexal endmetriosis
5.A 32-year-old patient consulted a doctor about being inable to get pregnant
for 5-6 years. 5 ago the primipregnancy ended in artificial abortion. After the vaginal
examination and USI the patient was diagnosed with endometrioid cyst of the right
ovary. What is the optimal treatment method?
A. surgical laparoscopy
B. anti-inflammatory therapy
C. conservative therapy with estrogen-gestagenic drugs
D. hormonal therapy with androgenic hormones
E. sanatorium-and-spa treatment
6.A 20-year-old female with Mьllerian agenesis is undergoing laparoscopic
appendectomy by a general surgeon. You are consulted intraoperatively because the
surgeon sees several lesions in the pelvis suspicious for endometriosis. You should
tell the surgeon which of the following?
A. endometriosis may arise in patients with Mllerian agenesis as a
result of coelomic metaplasia
B. endometriosis cannot occur in patients with Mьllerian agenesis since
they do not have a uterus
C. endometriosis is common in women with Mьllerian agenesis since they
have menstrual outflow obstruction
D. endometriosis probably occurs in patients with Mьllerian agenesis as a
result of retrograde menstruation
E. endometriosis cannot occur in patients with Mьllerian agenesis because
they have a 46,XY karyotype
7.A patient presents to you for evaluation of infertility. She is 26 years old and
has never been pregnant. She and her husband have been trying to get pregnant for 2
years. Her husband had a semen analysis and was told that everything was normal.
The patient has a history of endometriosis diagnosed by laparoscopy at age 17. At the
time she was having severe pelvic pain and dysmenorrhea. After the surgery, the
patient was told she had a few small implants of endometriosis on her ovaries and
fallopian tubes and several others in the posterior cul-de-sac. She also had a left
ovarian cyst, filmy adnexal adhesions, and several subcentimeter serosal fibroids.
You have recommended that she have a hysterosalpingogram as part of her
evaluation for infertility. Which of the patient’s following conditions can be
diagnosed with a hysterosalpingogram?
A. hydrosalpinx
B. endometriosis
C. subserous fibroids
D. minimal pelvic adhesions
E. ovarian cyst
8.You have just performed diagnostic laparoscopy on a patient with chronic
pelvic pain and dyspareunia. The patient had multiple implants of endometriosis on
the uterosacral ligaments and ovaries and several on the rectosigmoid colon. At the
time of the procedure, you ablated all of the visible lesions on the peritoneal surfaces
with the CO2 laser. But because of the extent of the patient’s disease, you
recommend postoperative medical treatment. Which of the following medications is
the best option for the treatment of this patient’s endometriosis?
A. danazol
B. continuous unopposed oral estrogen
C. dexamethasone
D. gonadotropins
E. parlodel
9.A 28-year-old nulligravid patient complains of bleeding between her periods
and increasingly heavy menses. Over the past 9 months, she has had two dilation and
curettages (D&Cs), which have failed to resolve her symptoms, and oral
contraceptives and antiprostaglandins have not decreased the abnormal bleeding.
Which of the following options is most appropriate at this time?
A. perform hysteroscopy
B. perform a hysterectomy
C. perform endometrial ablation
D. treat with a GnRH agonist
E. start the patient on a high-dose progestational agent
10.You are treating a 31-year-old woman with danazol for endometriosis.You
should warn the patient of potential side effects of prolonged treatment with the
medication. When used in the treatment of endometriosis, which of the following
changes should the patient expect?
A. lighter or absent menstruation, since danazol causes endometrial
atrophy
B. occasional pelvic pain, since danazol commonly causes ovarian
enlargement
C. heavier or prolonged periods, since danazol causes endometrial
hyperplasia
D. more frequent Pap smear screening, since danazol exposure is a risk
factor for cervical dysplasia
E. postcoital bleeding caused by the inflammatory effect of danazol on the
endocervical and endometrial glands
SITUATIONAL TASKS
1.A 39-year-old G3P3 complains of severe, progressive secondary
dysmenorrhea and menorrhagia. Pelvic examination demonstrates a tender, diffusely
enlarged uterus with no adnexal tenderness. Results of endometrial biopsy are
normal. Which of the following is the most likely diagnosis?
2.A 28-year-old woman, gravida 0, presents for evaluation of worsening
chronic pelvic pain. She had been diagnosis with endometriosis by diagnostic
laparoscopy 6 years prior but had been lost to care since that time. She reports cyclic,
left-sided pelvic pain that is no longer controlled with NSAIDs. On physical
examination, she is noted to have thickening and nodularity of her left uterosacral
ligament and her cervix is deviated to the right. She has no uterine, cervical, or right
adenexal tenderness. She is noted to have 5 cm left adenexal mass, which is tender to
palpation and fi xed to the pelvic sidewall. Transvaginal ultrasound demonstrates a
4.5-cm complex left ovarian cyst consistent with an endometrioma. The next best
step in management of this patient is:
3.A 36-year-old woman, gravida 0, with a history of endometriosis noted at a
laparoscopy performed for pelvic pain 5 years ago presents for a second opinion for
evaluation of worsening pelvic pain. Her endometriosis has been poorly controlled
with combined oral contraceptives. Over the past 8 months she has noted worsening
dysmenorrhea, dyspareunia with deep penetration, and increased constipation. She
also states that her endometriosis is making her urinate two to three times a night. She
has been taking NSAIDs maximum dose daily with little relief. She has taken GnRH
agonists in the past year for treatment for endometriosis without relief of her
symptoms. Your next step would be:
4.A 40-year-old woman, gravida 3, para 3, presents for severe central
dysmenorrhea, 8/10 in severity associated with menorrhagia. Her pain is
nonradiating, she has no exacerbating or mitigating factors. She fi nds little relief
with NSAIDs. Her pain has been getting progressively worse since the cesarean
delivery of her last child, 2 years prior. That delivery was complicated by
chorioamionitis, endometritis, and subsequent wound infection. Transvaginal
ultrasound demonstrated an 11-cm enlarged uterus without obvious pathologic fi
ndings. MRI of the pelvis is signifi cant for adenomyosis. The patient reports that she
has completed her childbearing. All of the following her appropriate plans of care
except:
5.A 32 y.o. woman consulted a gynecologist about having abundant long
menses within 3 months. Bimanual investigation: the body of the uterus is enlarged
according to about 12 weeks of pregnancy, distorted, tuberous, of dense consistence.
Appendages are not palpated. Histological test of the uterus body mucosa:
adenocystous hyperplasia of endometrium. Optimal medical tactics:
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