ENDOMETRIOSIS
One of the most common gynae conditions
affecting women of reproductive age
DEFINITION
 presence of tissue, histologically similar to
endometrium, at sites outside of uterine cavity
Definite histological dx needs 2 of the 3 following
features:
 endometrial glands
 stroma
 haemosiderin pigment
= endometriosis externa
Endometriosis interna/adenomyosis = presence of
nests of endometrium in myometrium of uterine
wall  should be 2 low-power fields (≥3mm)
below endomyometrial junction
INCIDENCE & PREVALENCE
General population 15-50 yrs: 2.5-33%
Females evaluated for acute/chronic pain: 12.5%
Females w/ localised pain/severe dysmenorrhoea:
32%
Infertile females: 30%
Chapter34 pg 416
AETIOLOGY
Unknown, but many theories postulated
Transplantation of shed endometrium
Retrograde menstruation
Endometrial cells regurgitated through FT at time of menstruation
- Endometriosis common at site of entry into peritoneal cavity i.e. FT ostia & near uterosacral
ligaments at base of broad ligaments
- Transplantation of free-floating endometrial cells appears to be influenced by gravity; found in most
dependant portion of pelvic cavity
- Pelvic peritoneum presents favourable site for implantation
o One cell layer thick w/ highly vascularised underlying stroma
o Ovarian surface covered by same mesothelium which is broken down at time of ovulation,
enhancing likelihood of attachment
o Ovary present as most common site for ectopic endometrium
Lymphatic & haematogenous dissemination
- Microscopic endometrial tissue found in lymphatic channels, lymph nodes & umbilicus
- Multiple reports of endometriosis in well-vascularised organs: lungs, skin, muscles
Iatrogenic dissemination
Accidental transplantation of endometrium in surgical scars after CS/hysterectomy & in lower genital
tract following surgical procedure, delivery/open wound
- Not more frequently observed due to ‘take’ rate of surgically excised endometrium highest in
interval phase of menstrual cycle and lowest during pregnancy
Coelomic metaplasia
Repeated irritation of peritoneal coelomic epithelium, ass w/ variety of factors (hormonal/infectious stimuli) can
induce pluripotential coelomic cells to transform into endometrial tissue
Activation of embryonic cell rests
Areas adjacent to developing Mullerian ducts, cells of Mullerian origin may be present w/ potential to form
functioning endometrium
Familial & genetic factors CLINICAL PRESENTATION
Occurs more frequently in 1st degree than in 2nd degree relatives of affected women – more likely to
have severe Endometriosis most commonly occurs w/in pelvis – on or w/in
Race ovaries, on peritoneum, beneath serosa of pelvic viscera
 incidence in Japanese women Depends on location of disease
Symptoms don’t correlate directly w/ extent of disease
Menstrual factors
Women w/ short cycle length and longer flow had > double risk than women w/ longer cycle Symptoms (from most frequent to least):
lengths and shorter duration of flow  Dysmenorrhoea
- Menorrhagia in hx of 76% of pts  Pelvic pain
- Early menarche & dysmenorrhoea significant  risk  Infertility
- Prostaglandin-induced  in intrauterine pressure, which causes dysmenorrhoea, may raise  Dyspareunia
sufficiently to  volume of retrograde menstrual flow  Menstrual irregularities
 Cyclical dysuria/haematuria
Delayed childbearing  Dyschezia – painful bowel movement (cyclic)
 Rectal bleeding (cyclic)
Outflow obstruction
Women w/ Mullerian duct anomalies ass w/ outflow obstruction (non-communicating Most common clinical manifestations:
rudimentary uterine horns, cervical stenosis, cervical atresia, vaginal agenesis, imperforate
hymen) more likely Dysmenorrhoea
 Initially mild, more intense w/ subsequent cycles
Hormones
 Characteristically begins several days before &
Usually related to reactivation of pre-existing disease by high levels of oestrogen ass w/
continues to onset/throughout menses
obesity or oestrogen replacement therapy
 Dull & aching in lower abdomen, pelvis, back
- No cases before puberty, therefore, responsive to steroid hormones
 Occasional radiation to lower extremities
- Smoking & regular exercise identified as significant protective factors  ass w/
menorrhagia  oestrogen levels
Pelvic pain
 Frequently found w/ endometriosis and vice versa
Immunological factors
 Endometriosis must be considered in adolescent w/
Moderate or severe endometriosis highly significant depression of cytotoxic responses
significant dysmenorrhoea, pelvic pain, irregular
vaginal bleeding or chronic GIT sy, origin of which
remains unclear
  Apart from pelvic and menstrual pain, can present w/
abdominal pain
- Less frequently, manifest as acute abdominal
emergency w/ haemoperitoneum ass w/
spontaneous rupture of ovarian endometriomas
Infertility
 When adhesions are severe enough to produce
anatomic distortion, limitation of fimbrial mobility and
tubal occlusion or tubal destruction – mechanical basis
 Pts remain ovulatory
- Slight  frequency of corpus luteum insufficiency
  incidence of luteinised unruptured follicle (LUF)
syndrome
 Peritoneal macrophages & peritoneal inflammatory
response can be hypothetical mechanism
 No convincing evidence polyclonal autoimmunity plays
role
 Doubtful that abnormal prolactin secretion has
causative role
 No substantial  of spontaneous abortions
Dyspareunia
 w/deep penetration & more intense before
menstruation
 Positional, couple cans alleviate sy by varying coital
positions
Other menstrual dysfunctions
 Menorrhagia & shorter cycle common
 Premenstrual spotting 3-7 days before menses
CHARACTERISITCS OF EXTRAPELVIC ENDOMETRIOSIS
 lesions found in sites other than the uterus, FT, ovaries, surrounding
peritoneum
= cervix, vagina, vulva, intestinal tract, urinary tract, abdominal wall, thoracic
cage, lung, extremities, CNS
Lower incidence than pelvic
Not been classified into stages
Intestinal tract endometriosis
Bowel endometrisis = sigmoid, rectosigmoid, rectal areas
 Ileocaecal area & appendix also frequently involved
Sy: abdominal pain, distention, diarrhoea, vomiting, constipation, rectal
bleeding.
Obstrucitve lesions favour rectosigmoid & ileocaecal area
Urinary tract endometriosis
Surface implants of bladder observed during laparoscopy
 dysuria & frequency
Urethral orifice, bladder wall or ureter
 dysuria, urgency, frequency, haematuria, flank pain, fever, N+V
 characteristically cyclic pattern
 intermittent hydronephrosis & UTIs
Pulmonary & thoracic endometriosis
Rare condition
Presentation: pleuritic pain, pneumothorax, haemothorax, haemoptysis
concurrent w/ menstruation
Endometriosis of other sites
Found anywhere except the spleen – suppresses endometriosis
Sy: Cyclical pattern related to menses, except peripheral nerve involvement
Dx: after biopsy – histological presence of endometriosis
DIAGNOSIS OF PELVIC ENDOMETRIOSIS CLINICAL APPEARANCE
3 forms recognised:
Bimanual exam
1) Peritoneal
May reveal:
2) Ovarian
- Tender uterosacral ligaments
3) Endometriosis of rectovaginal septum
- “cobblestone”/”shotty” feel in POD
- Tender nodules
Peritoneal endometriosis
- Thickened rectovaginal septum
3 types of lesions:
- Retroverted & fixed uterus
1. Red lesions
- Generalised/localised pelvic tenderness
- Red vesicles, polypoid lesions or flame-like
- Enlarged, tender ovaries
- More active forms
All be referred for laparoscopy
- Vascularisation of endometriotic implants one of the most NB factors in growth &
invasion of endometrial glands into other tissue
Laparoscopy
- High stromal vascularisation suggests angiogenesis induced by recent implantation via
Biopsy at time of laparoscopy – golden standard for dx
growth factors or cytokines secreted in stroma
Scanning electron microscopy has revealed 2 characteristics:
2. Black lesions
 Implant can be located intraperitoneally or
- Typical burn-out/powder-blue lesions
subperitoneally
- Result of presence of intraluminal debris in implants
 Size of implant in terms of endometrial tissue cannot be - Scarification process probably responsible for reduction in vascularisation
evaluated by laparoscopy - Some cases, inflammatory process & subsequent fibrosis totally devascularise
endometriotic foci
Ovarian tumour-associated antigen (CA 125) - White plaques of old collagen are all that remain of ectopic implant
Cannot be used to differentiate cancer from endometriosis – 3. White opacification & yellow-brown lesions
overlapping range - Latent stages of endometriosis
Conflicting data when CA125 & stage evaluated - Probably non-active lesions that could be quiescent for long time

US Ovarian endometriosis
Not recommended as sole method of dx – no echo pattern Result of metaplasia of coelomic epithelium invaginated into ovarian cortex
specific for endometriosis 2 types:
May give additional & confirmatory info & serve as ancillary 1. Superficial implants
technique - Peritoneal implants that resulted from implantation of endometrial cells from
May be of great assistance in confirming presence & measure retrograde menstruation
size of ovarian endometrioma 2. Intraovarian endometriosis
- Consequence of metaplasia of invaginated mesothelial inclusions
MRI - Epithelium & stroma of cyst wall are able to invaginate secondarily, creating extracystic
No adequate to evaluate superficial lesions endometriotic lesions
Can’t supplant info obtained by laparoscopy & histological study
Endometriosis of rectovaginal septum (adenomyotic
nodules)
- AKA rectovaginal nodular endometriosis/
adenomyosis
- Large and deep nodule (>2cm in size), largest
area of which is under peritoneal surface
- Originates form rectovaginal septum
- Consists of smooth muscle hyperplasia w/
active glandular epithelium & scanty stroma
- Histologically similar to uterine adenomyosis
 theory that they develop from Mullerian
remnants
- Clinical dx made when smooth muscle
proliferation is sufficiently large to be felt on
vaginal exam
- Endometriotic foci involving smooth muscle
are typically ass w/ striking proliferation of
smooth muscle, creating an
adenomyomatous appearance similar to that
of adenomyosis in myometrium
CLASSIFICATION OF ENDOMETRIOSIS
Scheme designed by ASRM
- Enables uniform & objective description of
Depends on:
various forms of clinical presentation &
degrees of severity
- Based on natural progression of disease,
considerations made for uni-/bilateral
involvement, differentiation between
superficial & invasive lesions of peritoneum
or ovaries or both, stratification for severity
as minimal (Stage I), mild (Stage II), moderate
(Stage III) or severe (Stage IV) &
quantification of tubo-ovarian adhesions
Table pg423
Note:
 Complete pouch of Douglas obliteration =
severe disease
 Tubal endometriosis is documented under
‘additional endometriosis’
 Place for recording less frequently
encountered endometriosis i.e. bowel,
urinary tract, vagina, cervix, skin & other
 Low prevalence of extragenital disease
precludes its direct incorporation into
staging of severity
 Points have been randomly assigned to
different structures & severity of
involvement which is a weakness in this
system
 Purpose of system is to predict fertility
outcome for every category, but poor
comparison
 Gives an idea of severity based on
morphological grounds & makes universal
report & comparison possible
TREATMENT
 Age
 Duration of hx
 Desire for fertility or pain relief
 Degree of symptoms
 Extent of disease, site of lesion(s)
 Prev attempts at therapy &
 Primary or recurrent endometriosis
Indications for rx
 Pain – pelvic, dysmenorrhoea,
dyspareunia
 Abnormal bleeding
 Pelvic pathology – ovarian cyst
 Infertility
 Bowel symptoms
 Urinary tract symptoms, incl. ureter
obstruction
 Prophylactic
Surgical rx
 Laparoscopy
 Laparotomy – conservative, complete
Surgical rx – conservative
Surgery superior to non-surgical approaches in
improving crude pregnancy rates
- Doubt regarding advantage in Stage I&II
- Does seem to improve fertility outcome
compared to pts w/ idiopathic infertility
- Surgery rx of choice in Stage III&IV due to
ass anatomic distortion
- Laparoscopy better outcome than
laparotomy
- Pouch of Douglas & rectovaginal septum
are where deep infiltrating endometriosis
can be found
o Difficult to dissect
o If nodules completely removed =
good pregnancy rate
Surgical rx for pelvic pain
Not well studied
- resolution of sy 6months after surgery noted
in 62.5% of treated pts compared to 22.5% in
untreated
- Return of sy expected by at least 10-20% of
pts treated annually for pain
Deep lesions incl. lesions that invade rectovaginal
septum are responsible for severe pain
- Rx: complete excision for these & ovarian
endometriomas
- Cysts: drained & ablated
2 schools of thought supporting either excision or
ablations:
- Depending on size, may be necessary to first
drain cyst, then treat pt w/ GnRH analogues
& then operate after 3 months w/ excision or
ablation
- Excision is ass w/ less recurrence
Pain relief after surgery observed in 61-100% of pts
Surgical rx – extensive
Pain may be reduced in some pts by hysterectomy &
bilateral salpingo-oophorectomy
For pt who have:
 Completed their families
 Sterility is acceptable
 Conservative surgical and/or medical rx has
failed
Bowel & bladder surgeries will reduce pain if lesions
are localised there
NB to seek help from experts
Careful dx prior to operation
Team approach in severe cases nb
- 2 gynaes, colon surgeon +/- urologist
90% of pts will have pain relief w/ correct surgical
approach
Surgical adjunctive procedures
LUNA
- Effective in relief of dysmenorrhoea (70-
90%) & dyspareunia (70-94%)
- Especially when uterosacral ligaments
involved
Presacral neurectomy (PSN)
- Severing sympathetic nerves to uterus at
level of superior hypogastric plexus
- Not advised as routine procedure
Role of new reproductive technologies
Mild endometriosis/microscopic disease
- GIFT procedure accepted tool for rx of
infertility
Moderate to severe involving tubal obstruction
- IVF indicated following failed reconstructive
surgery
Medical rx
NSAIDS
First-line rx
MOA: inhibit biosynthesis of prostaglandins (PGs)
synthesised by ectopic endometrium
Sy due to PGs: pelvic pain & dysmenorrhoea
Oestrogen-progestogen combination
Cyclic/continuous
Continuous use of low-dose oral contraceptives =
anovulation & amenorrhoea (pseudopregnancy) 
progressive decidualisation & ultimate necrobiosis
& resorption of ectopic endometrial tissue
SE: Table pg 426
Progestogens
Produce hypo-oestrogenic acyclic hormonal
environment by suppressing gonadotropin 
amenorrhoea
Effects: acyclicity & decidualisation
Not popular due to break-through bleeding
interest due to low cost & fewer SE than other
drugs
Parenteral
- Medroxyprogesterone acetate (MPA)/
Depo Provera
Oral
- MPA
- Gestrinone
- Dydrogesterone (Duphaston)
MPA
Dose: 150mg IM x 3monthly for 1 year
Drawback: prolonged interval between cessation of
therapy & resumption of ovulation
Administration of 30mg/day arrests progression of
endometriotic implants
SE: intermittent break-through bleeding, nausea, breast
tenderness, fluid retention & depression
Generally well tolerated
Gestrinone
Weak progestin & androgen agonist/antagonist that
forms a relatively unstable interaction w/ progesterone
receptor
MOA: acts on hypothalamic-pituitary system to suppress
midcycle surges of LH & FSH & folliculogenesis,
diminishing oestrogen synthesis
Dose: 2.5mg 2-3x a week for 6months
Amenorrhoea & symptom relief observed in 85-90% of
pts
SE: related to androgenic & anabolic activity
High cost
Dienogest
Progestogen that combines pharmacologic advantages of
19-nortestosterone & progesterone derivatives. Beneficial
oestrogenic activity in CVS, CNS, bone & vagina and
hepatic tolerability
Reduces but not completely suppress endogenous
oestradiol production. Lacks any relevant androgenic,
glucocorticoid or antimineralocorticosteroid receptor
activity
MOA: inhibits proliferation of human endometrial
epithelial cells & the growth of human endometrial
stromal cells
Also anti-inflammatory effect
Dose: 2mg/day minimal effective dose
Effects: amenorrhoea,  LAP, pain during
menstruation, dyspareunia, defecation pain and pain
on examination
Less effect on BMD than GnRHa
SE: irregular bleeding, headache, weight gain,
depression, decreased libido, acne, alopecia,
migraine, sleep disorder, vaginal dryness
Cyproterone acetate
17-hydroxyprogesterone derivative w/ anti-
androgenic, antigonadotropic & progestational
effects
Combo of cyproterone acetate & ethinyl oestradiol
may be as effective as danazol in alleviating painful
sy
Lack androgenic SE of danazol, but may cause
fatigue, loss of libido, depression & weight gain
Antiprogestins
Mifepristone – antiprogestin that’s mostly used for
early preg termination
MOA: inhibit ovulation & disrupt endometrial
integrity, causing ovarian acyclicity
Dose: 100mg/day for 3 months
Found to induce amenorrhoea & to  pelvic pain
SE: atypical flushes, anorexia, fatigue
Danazol
Synthetic derivative of 17-ethinyl-testosterone that
partially supresses gonadotropin levels, ablating
mid-cycle LH surge but preserving basal secretion
MOA
 Direct effect on endometrial androgen &
progesterone receptors
 Displacement of androgens from sex
hormone-binding globulins, augmenting
androgen effect on receptors of
endometrial implants
 Inhibition of ovarian and adrenal
steroidogenesis by suppression of multiple
enzymes
 Probable immunosuppressive properties
Long-term use complications: troublesome
androgenic SE including adverse serum lipoprotein
changes. Hirsutism & deepening of voice may be
irreversible. Therefore less frequently used
Dose: 200-800mg/day
High cost
Gonadotropin-releasing hormone agonist (GnHRa)
Produces an initial stimulation of pituitary
gonadotropes that results in secretion of FSH & LH
Continuous administration of high doses leads to
inhibition of ovarian pituitary axis  pituitary GnRh
receptor down-regulation, gonadal gonadotropin
down-regulation,  gonadotropin secretion & 
ovarian hormone secretion
Pelvic pain almost completely relieved after 2
months of rx
Produces continued relief after 3-6months of rx
GnRHa as effective as danazol in:
  growth of endometriotic implants
 Relieving symptoms during rx phase
 Preventing recurrence of sy
These agents do not eradicate endometriotic
lesions
Recurrence of sy will occur in most pts within 5
years of cessation of therapy
High cost precludes the use of the drug in many pts
MALIGNANT TRANSFORMATION IN
ENDOMETRIOSIS
Malignant degeneration may occur, but rare
Can occur in areas of endometriosis & nr of
histological tumour types have been described 
adenoacanthoma most usual
Although endometriosis can give rise to malignant
tumours, it should be noted that ‘endometrioid
tumours’ of ovary do not arise from endometriosis

GnRHa w/ steroid add-back

Observance of bone loss during GnRHa rx led to
studies evaluating various hormone add-back
regimens

Combo of GnRHa w/ oral conjugated oestrogen

0.625mg dly & MPA 5mg dly led to marked
reduction in bone loss.
Fewer occurrences of menopausal sy, but no
interference w/ efficacy of rx

Non-steroidal etidronate (bisphosphonate) appears

to prevent bone demineralisation during at least
6mnths of GnRHa rx

Combined medical & surgical rx

Surgical rx is cytoreductive
Impossible to resect all endometriotic lesions, and
recurrence of sy & disease is more likely in higher
staging, therefore reasonable that surgery can be
used to reduce endometriotic tissue
Medical rx can then be initiated for 3 months