Transcript endometriosis-ed-1

Endometriosis
Jolanta Zegarska
Chair and Clinic of Obstetrics, Gynecological
Diseases and Oncological Gynecology
Collegium Medicum in Bydgoszcz
Nicolaus Copernicus University in Torun
Endometriosis
• Occurrence of the cells of uterine mucosa
(glandular and stromal) outside its natural
localization
• Functionally corresponds to the
endometrium
• Estrogen-dependent
• Occurs in 5–15% total population of
women
– mainly in women of child-bearing potential
Endometriosis—pathogenesis
• First reports date back to 1600 B.C. (Egyptian
reports on papyrus)
• Until 1920's, endometriosis was considered
as a benign hyperplasia appearing under
different names: cystadenoma, cystic
fibrosis, adenomyoma
• Sampson (1927): the term “endometriosis”
and “retrograde menstruation” — ectopic
implantation of live endometrial fragments
Endometriosis—pathogenesis
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Recklinghausen
Cullen
Iwanhofen
Meyer
into
1885
1896
1898
1903
proinflammatory factors,
Pick
1905
Sampson
1922
Halban
1924
Navrital & Kramer1936
Mc Weigh
1955
Weed et al.
1980
Malick
1982
activity
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from the Wolffian ducts,
from the Müllerian ducts,
metaplasia of peritoneal epithelium,
as above, invagination of epithelium
submucosa; inducers:
hormones,
as above, affects germinal epithelium
of the ovary,
“retrograde menstruation”,
hyperplasia of lymphatic ducts ,
vascular hyperplasia ,
from the corona radiata cells
around oocyte,
failure of
immune system
originating from the Müllerian
ducts,
innate or acquired impairment of
peritoneal fibrinolytic
Endometriosis—pathogenesis
• Implantation theory coexists with theories
of metaplasia (1870) and induction (1955)
• Since early 1980s, it is known that
menstrual blood reflux occurs in nearly all
women of child-bearing potential
• Therefore, mechanisms preventing
implantation are sought
• Cellular and humoral immunity are crucial
for the pathogenesis of endometriosis
Endometriosis—pathogenesis
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Genetic predispositions
Immune system dysfunction
Environmental influence
Mental, emotional and personalityrelated factors may be relevant
Endometriosis
Three types of endometriosis have been
characterised
Peritoneal
Ovarian
Deep
infiltrating
Diagnostics
• Anamnesis
• Physical examination
• Diagnostic imaging
Symptoms
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Lower abdominal pain
Painful menstruation
Abundant menstruation
Dysuria
Dyspareunia
Pain in sacrum area
Diarrhoea during menstruation
Constipation, tympanites
Less typical symptoms
• Recurring sciatic-type limb pain
• Recurring rectal bleeding
• Recurring bleeding from urinary tract
Less typical symptoms
• Often diagnosed accidentally
– During surgeries
– Reduced fertility!
Physical examination
• Palpation of adnexal area may reveal
pathological resistance—endometrial
cysts
Physical examination
• Transvaginal and transrectal
examinations help to examine
uterosacral and rectovaginal septum
ligaments, the locations of
endometriotic nodules
• Performed during menstruation
increases the likelihood of finding foci
of deep infiltrating endometriosis
Deep infiltrating endometriosis
(DIE)
• During a speculum examination,
lesions pathognomonic of
endometriosis are first sought
Cyanotic foci located at
1/3 of upper rear vaginal wall
Endometriosis seen in the rear vaginal fornix
Deep infiltrating endometriosis
(DIE)
• Palpation of vaginal walls usually
reveals nodular lesions,
• painful infiltration of
– uterosacral ligaments,
– vesicouterine pouch
– Douglas's sinus
• Finding these lesions is not necessary
for a full diagnosis of DIE
Endometrial cysts
• In adnexal area: tissue resistance and
tenderness
• Normal ovaries are not always palpable
• Endometrial cysts are often
accompanied by tissue adhesions and
thickening in adnexal area
Diagnostic imaging
• Transabdominal and transvaginal
ultrasound examinations are the
primary diagnostic tools for detecting
nodular lesions of the adnexa and for
the evaluation of other pelvis minor
structures
Diagnostic imaging
• Magnetic Resonance Imaging shows
high specificity in diagnosing
endometrial cysts
• Computed Tomography is not a
standard method of the diagnostics of
endometrial cysts
Deep infiltrating endometriosis
(DIE)
• Surgical procedure is of particular
importance
• For the proper and effective procedure,
it is necessary to establish a map of
existing pathological lesions using
various imaging methods
Diagnosis
• Suspected based on clinical signs and history
• Confirmed using US and MRI
Deep infiltrating endometriosis
(DIE)
• MRI
– thorough simultaneous evaluation of front
and rear pelvic areas
– a map of all occurring DIE foci can be
established
• Transrectal Ultrasonography (TRUS)
– accurate evaluation of the depth of
endometriosis infiltration of the colorectal
wall
TRUS—indications
– functional disorders of the intestines
– pain recurring during menstruation
– incidents of lower gastrointestinal
bleeding
– suspected lesions in colorectal wall
– large focal lesion near the rear vaginal
fornix (diameter ≥ 3 cm)
Deep infiltrating endometriosis
(DIE)
• Double-contrast colorectal imaging:
lesions covering the front wall of the
large intestine, impaired spatial
structure of surrounding tissues
• When the lateral areas of pelvis minor
are affected by DIE: urography
• When foci in the urinary bladder are
suspected: cystoscopy
Laparoscopy
• Gold standard in the diagnostics of
endometriosis
– The only exception to this rule is the
presence of endometriotic foci visualized
during speculum examination of the
vagina
• Histopathological examination is
recommended for all collected or
excised tissues for a clear diagnosis
Laparoscopy—indication
• Patients with pelvic pain:
– suffering from
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dyspareunia
painful menstruation
dyschezia
chronic pain
Patients whose quality of life deteriorates
and in whom pharmacological treatment
is ineffective or contraindicated
Laparoscopy—indication
• Patients with a suspected acute
condition, e.g., adnexal torsion or
adnexal cyst rupture
• Patients with suspected endometriotic
infiltration of
– intestines
– urinary bladder
– ureters
– pelvic area nerves
Laparoscopy—indication
• Patients with painful nodules on the
uterosacral ligaments detected during
gynaecological examination
• Patients with diagnosed nodular
lesions of the adnexa
• Patients with infertility and no
pathological lesions detected during
gynaecological examination and
additional imaging examinations
Noninvasive diagnostics
• Concentrations of the glycoproteins Ca125 and
Ca 19-9
• do not provide definitive answers but
help in making decisions and targeting
further procedures, therefore remain a
recommended complementary tool
Conservative treatment
• Reduction or elimination of pain
• Inhibition of further development and
regression of endometrial foci
• Restoration of fertility
Conservative treatment
• Possibility of starting pharmacological
treatment of endometriosis only based
on the clinical image without the need
to confirm the disease in a laparoscopic
examination (empiric therapy)
Conservative treatment
• May be used as preparation for surgery
• Complementary procedure in the
postoperative period
• Best therapeutic effects are achieved
by combining surgical and
pharmacological treatment
Conservative treatment
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Estrogen–progestogen products
oral progestogen products
depot progestogen products
intrauterine device releasing
progestogen
• GnRH agonists
• danazol
Conservative treatment
• The efficacy of these drug groups is
similar
• Differences occur in the severity and
type of adverse effects resulting from
hypooestrogenism
• Emerging GnRh-related adverse effects
limit the therapy to six months
Conservative treatment
• First-line medications:
– Nonsteroidal antiinflammatory drugs
(NSAIDs)
– oestrogen–progestogen products
– progestogen products
Conservative treatment ???
• Nonsteroidal antiinflammatory drugs
– inhibit prostaglandin synthesis
– contribute to the reduction of inflammation
– contribute to the reduction of pain
• Complex oestrogen-progestogen therapy
may be used periodically or continuously
• Progestogens are given orally or as
hormonal intrauterine system
Conservative treatment
• Dienogest is a new drug with
endometriosis as an authorized
indication, administered orally at
2 mg/day
• Exhibits selective activity of
– 19-nortestosterone and progesterone
Conservative treatment
• Danazol, due to its numerous adverse
effects: body weight gain, acne,
seborrhoea, hirsutism, atrophic
vaginitis, hot flushes, lowered libido,
virilism, change in voice pitch, negative
impact on lipid profile,
• is currently used only occasionally
Surgical treatment
• Indications for the surgical treatment
of endometriosis:
– Pain in the pelvis minor area
– Infertility in endometriosis
– Deep infiltrating endometriosis
– Endometrial cysts of the ovaries
Surgical treatment
• Conservative
– In adolescent patients and women of
child-bearing potential planning
pregnancy
• Radical
– In patients not planning pregnancy or
those with persisting pain despite
appropriate pharmacotherapy
– Intended to induce surgical menopause
following bilateral ovariectomy
Surgical/conservative treatment
• Release of adhesions, particularly periovarian
and peritubal
• Resection or ablation of endometriotic foci
• Removal of endometrial cysts
• Resection of endometriotic foci in adjacent
organs
Ablation of endometriotic lesions can be
performed using electrodiathermy or laser
Surgical treatment
• The recommended operating
technique in the treatment of
endometriosis, irrespective of the
degree of the disease, is laparoscopy
Surgical treatment—DIE
• The primary method of DIE treatment
is radical resection of endometriotic
foci.
• This may require the resection of
– uterosacral ligaments
– upper rear vaginal wall
– part of urinary bladder wall
– segment of the intestine
Surgical treatment—DIE
• It is not recommended to resect foci of
DIE detected in diagnostic laparoscopy
• In such cases, it is required to perform full
preoperative diagnostics and obtain the
patient's written consent for the
necessary enhancement of surgical
procedures, e.g., partial resection of
urinary bladder wall or intestine
Surgical treatment—cysts
• Often coexist with advanced
endometriosis.
• When planning treatment, patient's
plans regarding reproduction need to
be considered
• This is related with surgical procedures
maximally sparing the ovary and/or
fallopian tube structure
Surgical treatment—cysts
• Complete resection of endometrial cyst
increases fertility
• Reduces risk of
– recurrence of the disease
– painful menstruation
– dyspareunia
– pain in the pelvis minor area
– reoperation
Surgical treatment—cysts
• Resection of endometrial cyst may also
involve unintentional resection of
normal ovarian structures and thus
reduction of “ovarian reserve”
• It is recommended to resect
endometrial cysts greater than 3 cm in
diameter
Surgical treatment—cysts
• Recurrence of endometrial cysts after
laparoscopic resection reveal in 30%
patients
• Postoperative hormonal suppression
reduces the risk of recurrence and
helps to reduce the severity of
symptoms of endometriosis
Endometriosis—infertility
• Pregnancy rate in healthy couples: 15–
20 %/month
• Pregnancy rate in untreated women
with endometriosis: 2–10%
• There is no clear mechanism explaining
the link between endometriosis and
infertility but several hypotheses and
mechanisms are considered
Endometriosis
Confirmed
fertility
Treatment for
infertility
Incidence of
endometriosis
5–10%
~50%
Pregnancy rate
15–20%
2–10%
Endometriosis
• 25–50% women treated for infertility
have endometriosis
• 30–50% women with endometriosis
have problems with fertility
Endometriosis—infertility
• Adhesions and altered anatomical structure of
pelvis minor
• Disrupted function of the peritoneum
– Increased amount of fluid in the peritoneal
cavity
– Increased concentration of prostaglandins,
proteases, cytokines (IL-1, IL-6, TNF-α),
proangiogenic cytokines (IL-8) and VEGF
• Increased concentration of proinflammatory
cytokines in the blood serum of women with
endometriosis
– Generalized inflammation?
Endometriosis—infertility
• Altered functions of hormones and
mediators
– Levels of IgG and IgA antibodies and
lymphocytes are increased in the
endometrium of women with
endometriosis (alters endometrial
function and impairs implantation)
– Antiendometrial antibodies are produced
Endometriosis—infertility
• Ovulatory and endocrine disorders
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Unruptured Follicle Syndrome
Luteal Phase Defect
Disrupted follicle growth
Premature and multiple LH peaks
Follicular phase may be longer with lower
oestradiol levels in blood serum and lower
LH-dependent progesterone secretion in the
second phase of the cycle
• Incorrect implantation
Endometriosis—infertility
• Follicle disturbances
• Poor quality of oocytes and thus
disturbed embryogenesis
• Impaired endometrial receptivity
• Impaired fallopian transport
Surgical treatment
• Operator experience is important
• Involvement of the ureter
– 5% cases: hydronephrosis
– 18% cases: ureter damage
• Late complications
– Intestine perforation
– Rectovaginal and uretrovaginal fistulae
Infertility
• Impact of deep endometriosis of
infertility has never been proved
• Dubious effect of inflammation in pelvis
minor
• Very often coexists with peritoneal
endometriosis
• Few articles comparing the impact of
potential treatment on improving fertility
are available
Endometriosis—
contraception
• Endometriosis was diagnosed more often
in patients using OC in the past
• When the reason for using contraception
was severe primary dysmenorrhoea, DIE
was diagnosed more frequently
• Using OC in the past due to
dysmenorrhoea may be considered as a
marker of endometriosis, especially DIE
Chapron C. Hum Reprod 2011
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