Endomateriosis:
It is a medical condition in which tissues similar to normal endometrial tissues in
structure and function found in sites outside the uterine cavity.
Sites :
a-pelvis b-ovary c-pelvic peritoneum d-fallopian tubes
e-broad ligament f-uterosacral ligament g-umbilicus
h-abdominal scars i-nasals passages j-pleural cavity.
Fate:
The ectopic endometrial tissues response to cyclic changes from ovarian hormones so at
each menstrual cycle endometrial deposit proliferate then break down and the bleeding
cause local inflammatory reaction followed over prolonged period of time by fibrosis,
chronic repetition of this process disrupt and distort the affected tissues and typically
dense scar tissues and adhesion may form.
Atiology:
It is still unknown but there are many theories and there is no single theory to explain its
occurrence.
1-menstrual regurgitation and implantation theory:
Sampson's implantation theory postulates retrograde menstrual regurgitation of viable
endometrial glands and tissue within the menstrual fluid and subsequent implantation on
the peritoneal surface.
2-coelomic epithelium transformation theory:
Meyer's coelomic metaplasia theory describes the de-differentiation of peritoneal cells
lining the mullerian duct back to their primitive origin which then transform into
endometrial cells. This transformation into endometrial cells may be due to hormonal
stimuli or inflammatory irritation.
3- genetic and immunological factors:
It has been suggested that genetic and immunological factors may alter the susceptibility
of a women and allow her to develop endometriosis this appears to be an increased
incidence in first degree relatives of patients with this disorders and racial differences,
with increased incidence among oriental women and a low prevalence in women of
Afraco - Caribbean origin.
4-vascular and lymphatic spread theory:
vascular and lymphatic embolization to distant sites has been demonstrated and explains
the rare finding of endometriosis in sites outside the peritoneal cavity.
Pathogenesis:
Endometriomas, known as a" chocolate cyst" it is a retention cysts that develop as a
consequence of ovarian endometriosis. They commonly form when adhesions develop
between endometriotic deposits on the ovary and the pelvic side wall or may result from
inflammatory reaction to superficial ovarian lesion, leading to adhesion developing
around the lesion, producing progressive inversion of the surrounding cortex.
Endometrioma may be multiple and very large and they interfere with fertility by
adhesion and distortion the fallopian tubes.
In some women the endometriotic lesions affecting the utero sacral ligaments, marked
fibrosis and scaring may develop, with infiltration of active endometriotic tissue into the
rectovaginal septum. Dense adhesion involving the rectum may lead to partial or
complete obliteration of the pouch of Douglas. Both processes associated with the
development of tender nodules that easily palpable on vaginal examination and are
associated with bowel symptoms. Deep nodular lesions may also be visible as small
tender bluish cysts in the posterior fornix so called deep infiltrating endometriosis may
present on the uterovesical fold leading to bladder involvement.
Incidence :
It is occur in [1- 2 %] of women of reproductive age
Clinical feature:
It is usually occur in the women throughout their reproductive age, they are nulliparous
and delayed their marriage , the classical feature are severe cyclical non colicky pelvic
pain around the time of menstruation, sometimes associated with heavy menstrual loss.
Symptoms may begin few days before menses starts until the end of menses. It is well
recognized that there is poor correlation between extent of disease and the intensity of
symptoms. Deep pain with intercourse can also indicate the presence of endometriosis in
the pouch of Douglas.
Endometriosis in distant sits can cause local symptoms.
a-genital tract : dysmenorrhea, lower abdominal pain and pelvic pain, rupture / torsion
endometrioma, low back pain, infertility .
b-urinary tract: cyclical haematuria, dysuria.
c-GIT: dyschezia [ pain on defecation ], cyclical rectal bleeding.
d-surgical scar / umbilicus: cyclical pain, bleeding.
e-nose and lung: cyclical epistaxis, cyclical haemoptysis and haemo pneumothorax .
physical signs:
1-hard thick nodules of variable size detected on bimanual examination in the utero
sacral ligament, the pouch of Douglas, recto vaginal wall.
2-the uterus may be fixed in retroversion.
3-enlarge ovaries when endometerioma found.
4-speculum examination reveal bluish thick nodules in the posterior fornix , cervical
excitation positive and there is adnexial tenderness.
D- DX:
1-adenomyosis 2-PID 3-carcinoma of ovary
4- carcinoma of rectum and colon. 5-pelvic congestion syndrome.
Investigation:
a-U/S: detect endometrioma or chocolate cyst, in smaller lesion U/S is of limited value
but the use of it is reassurance by excluding other gross diseases.
b-MRI: can detect lesions [>5mm] in size specially in deep tissues, for example
rectovaginal septum.
c-laparoscopy: the most valuable tools for both diagnosis and treatment and can allow
biopsy taken.
d-CA-125: no evidence that this test is useful as screening test but levels is likely to be
raise in severe disease.
Treatment:
The aim of treatment is to relieve pain, control abnormal bleeding and promote
pregnancy.
Prophylaxis:
In patient with family history of disease who seek advise we giving COCPs to prevent
progression of mild disease to severe one that cause infertility and advise for early
pregnancy rather late one in view of family risk for progression of disease.
Medical management of pelvic pain associated with endometriosis:
a-NSAID: this offer a non hormonal approach and it useful in women want to conceive
and are helpful in reducing the severity of dysmenorrhea and pelvic pain.
b-COCPs: it is can be used for both diagnostic and therapeutic purposes COCPs should
be taken continuously for initial [6 months ] to create a pseudo pregnancy and render the
patient amenorrhoeic , if symptoms of cyclical pelvic pain disappear [ in the absence of
any gross lesion on U/S e.g endometrioma ] the diagnosis is one of the minimal / mild
endometriosis. If the symptoms persist then there is likely to be coexisting irritable bowel
disease/ constipation which require its own treatment, if there is symptomatic relief with
the continuous use of COCPs, then this therapy should be continued for several years or
even longer until pregnancy is intended.
c-progestogen: they are given continuously and at high dosage inhibit ovulation and
affect endometriotic implants causing decidualizationand atrophy.
both oral medroxyprogesterone acetate[100 mg daily] and depot MPA [ depo provera
150 mg 3-monthly] were affective in relieving pain symptoms, the most commonly
reported side affect is breakthrough bleeding others include weight gain, breast
tenderness, bloating, headache and nausea. The use of levonorgestrel intrauterine
system [LNG-IUS] has been affective in achieving long term therapy affect.
d-gestrinone: it is [19- nor testosterone] derivative that has progestgenic and
antiprogestgenic action, at dose of [2.5mg] twice weekly for 6 months] but androgenic
and hypo oestrogenic side effect are less frequent, however, there is lack of information
relating to its safety for long term use.
e-danazol: it is [17-ethinyl testosterone] it is act both centrally and locally to suppress
steroid genesis and induce endometrial atrophy. The dose is [400-600 mg ] daily, the side
affect is weight gain, limb tingling, acne, greasy skin, hirsutism, deepening of the voice
and atherogenic effects on lipid profile but danazol is not suitable forlong term use.
f-GnRH analogues: are derived from native hypothalamic GnRH by peptide substitutions
that increase their potency and duration of action. Both agonist analogues and antagonist
have been developed, of which agonist was in established clinical practice for much
longer. The antagonists act by competitive inhibition of pituitary GnRH receptors, with a
rapid onset of action, where as the agonists cause initial stimulation of gonadotrophin
production followed by prolonged down regulation. The antagonists have clear
advantage over the agonists for short term pituitary suppression e.g during super
ovulation prior to IVF but are unlikely to take over from agonists for longer term
indications such as the management of endometriosis.Down regulation of pituitary GnRH
receptors by GnRH agonists leads to inhibition of FSH and LH production and gonadal
suppression.
The administration of GnRH agonists is either by
a-intranasal spray: Nafarelin [200mcg]bd , Buserelin [200mcg]tid .
b-depot injection: Goserelin [3.6mg s.c], Leuprorelin[3.75mg i.m ors.c]
the side effects includes:
a-hot flash b-insomnia c-vaginal dryness
d-reduce of libido e-headaches
longer term use of GnRH agonists cause loss of bone mineral density and it is of major
concern for this reason these should not used as single agents for longer than 6 months.
In women needing longer term treatment, hormonal add back therapy can be used to
reduce the bone loss and prevent unwanted side effects. Examples of add back therapy
a-transdermal oestradiol [2.5mcg twice weekly] +oral MPA [5mg]daily.
b-oral oestradiol [2mg]daily +norethisterone [5mg]daily .
c-conjugated equine oestrogen [0.625mg] daily+ norethisterone [5mg].
Surgical management of pelvic pain associated with endometriosis
1-laproscopic local ablation by diathermy, laser vaporization or excision and adhesiolysis
2-laproscopic uterosacral nerve ablation.
3-ovarain endometrioma excision, if large and severe unilateral oopherectomy, in severe
bilateral disease bilateral oopherectomy with preservation of the uterus for donor
oocytes if want pregnancy.
4-TAH+BSO if patient complete her family .
Endometriosis and infertility :
It is estimated that between [30 -40%] of patients with Endometriosis have difficulty in
conceiving , in many patients there is a multifactorial pathogenesis to this sub fertility. It
has yet to be shown how the presence of a few small endometriotic deposits might
render a patient subfertile. In the more severe stages of Endometriosis, there is
anatomical distortion with peri adnexal adhesions and destruction of ovarian tissue when
endometrioma develop. Medical treatment of Endometriosis does not improve fertility
and should not be given to patients wishing to conceive.
However, surgical ablation/excision of minimal and mild Endometriosis improve fertility
chances. Surgical treatment of endometriomas increases spontaneous pregnancy rates,
including IVF success rates. The possible mechanisms are:
a-ovarian function: luteolysis caused by PGF2, Oocyte maturation defects,
endocrinopathies,Luteinized unrupture follicle syndrome, altered prolactin release and
anovulation.
b-tubal function: impaired fimbxszrial oocyte pick up, altered tubal mobility.
c-coital function: deep dyspareunia-reduce coital frequency.
d-sperm function: antibodies causing inactivation, macrophages phagocytosis of
spermatozoa.
e-early pregnancy failure: PG induced, immune reaction, luteal phase deficiency.
Adenomyosis :
Definition : it is characterized by the presence of endometrial glands & stroma in the
myometrium with adjacent smooth muscle hyperplasia.
Incidence : The incidence of Adenomyosis is unknown, it is present in (15-30%) of
hysterectomy specimens. It is common in multiparous middle aged women.
Etiology:
The cause remains speculative, but the adenomyotic tissues is presumed to be derived
from the endometrium. It may be triggered by a weakness in the smooth muscle of
myometrium, by increased intrauterine pressure or by surgical trauma. The incidence is
increased with increasing parity, a history of miscarriage, induced abortion & C/S. it is
decreased in smokers compared with non-smokers. The relationship between the
presence of adenomyosis & both endometrial hyperplasia & uterine fibroids has been
reported, but this may be related to the age & symptomatology of the women Clinical
feature :The women usually present with menorrhagia & dysmenorrheoa, clinically the
uterus may be bulky & tender but both history & examination are very nonspecific.
Investigation :
1-TVS : it is used as primary screening modality for the diagnosis & the sonographic
feature includes : diffuse echogenicity, myometrial cysts, sub endometrial nodules, sub
endometrial linear striations, poor definition of endometrial / myometrial border &
asymmetric myometrial thickening.
2-MRI : because TVS lack specificity, especially in distinguishing adenomyosis from
fibroids so MRI should be used, but both techniques even when used in combination, may
lack accuracy for evaluation of very large uteri with a volume gjreater than (400 ml).
3-hystroscopic & laparoscopic myometrial biopsy have been described but have limitation
when compared to non-invasive methods.
Treatment :
1-medical treatment: the current medical treatment of menstrual disorders includes
NSAIDs, COCP, high dose progestogens & LNG-IUS. As most of these therapies are
affective in the management of menorrhagia, dysmenorrhea & endometriosis they
should theoretically be beneficial for adenomyosis, but only LNG-IUS is found to be
affective & should be used as first line management
2-surgical treatment: there is some evidence that the presence of deep lesions of
adenomyosis is associated with failure of endometrial ablation resulting in both
regeneration of the endometrium & glandular activity within the myometrium. However
at this stage it may not be possible to distinguish between preexisting & iatrogenic
lesions. On the current evidence the use of LNG-IUS may preferred to endometrial
ablation but the definitive treatment to adenomyosis is hysterectomy & need not be
accompanied by oophorectomy unless there is a specific indication for it.
This lecture by Dr-Nadia AL-Assady
CABOG & FIBOG