Endometriosis Flashcards
Introduction
§ Condition which endometrial tissue grows outside endometrium.
Pelvic endometriosis: fallopian tubes, ovaries, peritoneum
Extra-pelvic endometriosis: GI tract, urinary tract, lungs
* <12%
§ Common condition – exact estimates unknown, 10% of women in
reproductive years
Symptom onset usually adolescence
Pathogenesis
§ Exact cause unknown
§ Genetics:
family history (first degree relative on mothers side) – 7-
10x risk
§ Hormonal factors:
Estrogen – stimulates growth of endometrial lining
In patients with endometriosis there is a reduced response
to progesterone on the endometrium
* lack of progesterone receptors on endometrial
tissue/implants (or lack of sensitivity to receptors)
impaired progesterone activity leads to inability to cause
apoptosis of the endometrial tissue
Pathogenesis: Postulated Origins of
Endometriosis
§ Mechanical factors:
retrograde menstruation:
* Flow of endometrial tissue up
fallopian tubes into
abdominal/peritoneal cavity
* Mechanical factors such as
cervical stenosis increases this
risk
common in women
Pathogenesis: Postulated Origins of
Endometriosis
§ Immunologic disorder:
Altered T and B cell function, altered levels of cytokines and
growth factor in endometrial tissue
Potential theories:
1) immunologic abnormality prevents the clearance of the
endometrial tissue fragments from the peritoneum
2) immune system stimulation caused by the presence of
endometrial tissue in the peritoneum – increase inflammation
other theories (4)
Mullerian embryonic: during embryonic
development remnants in other parts of
body which can form endometrial tissue
Lymphatic & vascular metastases
(extrapelvic) – transport of lesions
through vascular/lymphatic
Coelomic metaplasia (peritoneal):
metaplasia of cells in the mesothelial
lining of the organs (transforms normal
peritoneal cells into endometrium like)
Endometrial stem cell implantation
– originates from stem cells
Endometriosis
Symptoms Based on
Location of Lesion
Symptoms
§ Pain:
Pelvic pain, abdominal area, lower back
* Dysmenorrhea, also with ovulation
§ Dyspareunia (pain with intercourse)
§ Heavy menstrual periods
§ Spotting or bleeding between periods
§ GI symptoms (> if GI tract involved):
Painful bowel movements, diarrhea during menstruation,
abdominal bloating
§ Painful urination or increased urgency (if bladder involved)
one of most common causes of chronic pelvic pain
§ Symptoms do not correlate with severity of endometriosis
(may be linked to location).
§ Some patients are symptom free.
§ Others go on to chronic pelvic pain.
Over 80% of chronic pelvic pain patients are due to
endometriosis.
§ 15 - 20% of women with endometriosis are infertile.
1 of the top 3 causes of infertility
§ Symptoms begin a few years after start of menstruation,
often resolve with menopause.
Diagnosis
§ Signs and symptoms
§ Transvaginal ultrasound (for deep implants or abnormal
sites)
§ Laparoscopy go in to see (+ confirmed with biopsy)
§ CT or MRI
§ Sometimes may do CA-125 however this is not specific for
endometriosis (may be increased if endometriosis on the
ovaries), can see increase in ovarian cancer, if seen with endometriosis it means there is ovarian involvemnet (implants around the ovary)
Revised American Fertility Society (AFS)
Classification
Stage I – minimal disease
§ Stage II – mild disease
§ Stage III – moderate disease
§ Stage IV – severe disease
Note: correlates poorly with symptoms, and not predictive of
infertility
will classify location of implant, how big - NOT with symptoms
Treatment of Endometriosis
tx goals and options
Treatment goals:
§ Relief of pain and symptoms
§ Prevent /delay recurrence
§ Preserve or restore fertility
Treatment options:
§ Pharmacological
§ Surgical
Note: no treatment is curative.
Management Approach: Pharmacologic
Anti-inflammatory (ie
NSAID’s)
Can use as needed
depending on degree of
pain
Combined hormonal
contraceptives (CHC):
– Continuous regimen
– MOA: $ endometrial
implants
reduce the lining
§ Progestins: - tend to use higher dose
Medroxyprogesterone (MPA) 20 – 30 mg daily PO
Or norethindrone acetate 5 – 15 mg daily
Or depot medroxyprogesterone, DMPA injectable q3 months
§ LNG-IUS
MOA for progestins: atrophy of endometrial tissue
Progestins
Dienogest (Visane®)
Also a progestin
Indication: Management of pelvic pain from
endometriosis
2 mg oral daily
Same side effects/contraindications as progestins
Shown to be as effective as leuprolide1
almost like a 4th gen progestin but not like drosperinone, indication for endometriosis
targets endometrial implants specifically and thinning the endometiral tissue
Gonadotrophin-Releasing Hormone
(GnRH) agonists
continuous GNH release
gonadotrope desensitization
(note: down-regulation of
receptors)
$ FSH & LH,
$ estrogen levels
§ Response: 85 – 100% of patients
§ Response in 4 – 8 weeks
§ Recommended use x 6 months due to effects on BMD – however,
patients may be on longer
GnRH is released in pulses, when agonist causes continous release, there is downregulation of receptors, you don’t have FSH or LH release as a result and no estrogen
stops ovulatio, like menopause
takes some time for down reg of receptors to happen
tell pt there could be symptoms worsening for a bit before better
GnRH agonists
buserelin acetate
(Suprefact™)
nasal spray
subcutaneous
200 µg (2 sprays) each nostril tid
200 µg subcutaneous daily
goserelin acetate
(Zoladex™)
depot subcutaneous 3.6 mg sq qmonth
leuprolide acetate (most common)
(Lupron Depot™)
depot intramuscular 3.75 mg IM qmonthly
nafarelin acetate
(Synarel™)
nasal spray 200 ug (1 spray) into 1 nostril am
and the other nostril pm
shorter acting
triptorelin pamoate
(TrelstarTM)
depot intramuscular 3.75 mg IM qmonthly
GnRH agonists
§ Adverse effects
menopausal symptoms (medical oopherectomy) –
vasomotor symptoms (hot flashes, night sweats), vaginal
dryness, headache, decreased libido, insomnia, etc
decrease in BMD – 1% per month of use
depot greater menopausal symptoms and bone loss as
compared to short acting
depot has greater fx on meopause symptoms since it has been around longer in body
add back tx
Can add back therapy:
add hormone therapy (estrogen + progesterone), continuous
regimens
same dose as used in postmenopausal women
in much lower doses that body produces, does not affect endometrial implants
GnRH Antagonist
elagolix (Orilissa®)
§ Direct antagonist of GnRH receptors results in ↓ FSH/LH,
↓ estrogen
Reduces endometriosis pain
§ Dose 150 mg daily to 200 mg BID x 3 – 6 months
works right away, no flare effect
Dont know dose
Low dose may have less effect on bone density
§ Adverse effects: vasomotor symptoms (hot flashes, night sweats),
vaginal dryness, headache, decreased libido, insomnia
Reduced BMD (reversible with discontinuation), increased lipids
§ Add back therapy required for high doses of 200 mg bid (lower
doses of 150 mg daily – add back not required)
Danazol (Cyclomen™)
MOA
§ Androgen derived from 17-a ethinyl testosterone – androgenic
effects
§ Suppression of the pituitary-ovarian axis
Decreases LH and FSH release
Directly inhibits ovarian steroidogenesis – decrease in estrogen
levels
§ Induces atrophy of endometrial implants
§ Response: 55 – 90% in 6 months
danazol
AE
Adverse effects: androgenic effects:
* acne, weight gain, fluid retention, hirsutism, deepening of
voice, #LFT, lipids - $ HDL, # LDL
* menopausal symptoms (hot flushes, vaginal dryness)
Most adverse effects reversible, except for deepening of the voice
§ Delays conception (delay is about 6months or more)
§ Dose: 200 – 400 mg bid x 3 – 6 months
§ Contraindications: severe liver disease, hyperlipidemia
§ Monitor LFT if continue >6 months
§ Teratogenic, during this time lower chance of pregnanc with menopause but need to make sure using contraceptives
Note: danazol use is declining
Aromatase Inhibitors
Note studies with aromatase inhibitors (anastrozole, letrozole) but
still investigational. May see use by specialists in women who do
not respond to other therapies.
Surgical Treatment
Conservative surgery:
Laparoscope
Lesions can be ablated or excised
May be warranted in those women wanting to
become pregnant (none of the medical therapies for
endometriosis improve fertility)
Recurrence rates: 20 – 40% in 1 year
help with preganncy
Surgical Treatment
For chronic pelvic pain:
§ LUNA:
Laparoscopic Uterine Nerve Ablation
§ Presacral neurectomy – in conjunction with
conservative surgery
Surgical Treatment
§ Radical surgery:
Hysterectomy +/- removal of both ovaries (bilateral oophorectomy
(BO)
Recurrence in 3 – 5 % of patients with hysterectomy+BO
Can use HT in younger patients or if symptomatic in total
hysterectomy:
* Estrogen +/- progestogen (if unable to resect all endometrial
implants)
Symptom Management: Summary
CHC +/- NSAID or progestin
LNG-IUS or GnRH agonist + add back or GnRH antagonist
laparoscopy
surgical tx
Other Options for Chronic Symptoms
Neuromodulators for chronic pain:
TCA’s, SNRI’s
Gabapentinoids – gabapentin,
pregabalin
§ Muscle relaxants
§ Complementary therapies:
lifestyle: exercise/diet/sleep
mindfulness/CBT
pelvic floor physiotherapy
