PB#114: Management Of Endometriosis Flashcards
Percentage of reproductive-age pts w/ endo; percentage of infertile pts w/ endo; percentage of chronic pelvic pain pts w/ endo
6-10%; 38%; 71-87%
Is there a racial predisposition to endo?
No
Familial predisposition to endo
7-10-fold increased risk in pts w/ affected 1st degree relative; strong concordance in monozygotic twins
Proposed inheritance pattern for endo
Polygenic-multifactorial mechanism (numerous genetic polymorphisms identified)
Most plausible theory for formation of endo
Attachment and implantation of endometrial glands and stroma on peritoneum from retrograde menstruation
Alternative theories for endo formation (3)
Hematogenous/Lymphatic transport, stem cells from bone marrow, coelomic metaplasia
Key components in development of endo (2)
Local overproduction of prostaglandins by increase in COX-2 activity, overproduction of local E2 by increased aromatase activity
Theoretical effect of progesterone resistance in development endo
Dampens antiestrogenic effect of progesterone and amplifies local estrogenic effect
Pathophysiologic effect of endometrial lesions
Chronic inflammatory disorder, w/ increased numbers of activated macrophages and proinflammatory cytokines in peritoneal fluid that can cause pain/infertility
Most commonly found inflammatory cytokines; their effects
TNF-α, IL-1, IL-6, IL-8; associated w/ pain via several mechanisms, including induction of prostaglandins
Peptide highly expressed in endo lesions, especially rectovaginal lesions
Nerve growth factor
Neurologic theory behind manifestations of pain associated w/ endo
Increased density of nerve fibers in peritoneal endo (especially DIE), close proximity of nerves to peritoneal lesions
Theory that may explain the severe dysmenorrhea and the improvement in endo sxs s/p hyst
Changes in innervation of uterus
Sequelae of peritoneal environment w/ high levels of oxidative stress and high concentrations of inflammatory cytokines (2)
Sperm dysfunction (including sperm DNA damage), oocyte cytoskeleton function
Infertility lab that is decreased in early stage endo
AMH
Endo-related issues that can cause anatomic abnormalities resulting in abnormal tubal function (2)
Ovarian cysts (endometriomas), adhesions
Risk factors for endo (5)
Early menarche (<11 y/o), shorter cycles (<27 days apart), heavy/prolonged cycles, lower parity, shorter duration of lactation
Lifestyle change associated w/ reduced risk of endo
Regular exercise >4 hours/week
Most well-recognized clinical manifestations of endo (5)
Dysmenorrhea, CPP, dyspareunia, USL nodularity, adnexal mass (symptomatic or asymptomatic)
Classic sxs associated w/ endo dx (4)
Abdominopelvic pain, dysmenorrhea, menorrhagia, dyspareunia
Description of pelvic pain 2/2 endo (3)
Secondary dysmenorrhea (w/ pain frequently commencing before onset of menses), deep dyspareunia (exaggerated during menses), sacral backache during menses
Sxs associated w/ endo w/ bowel involvement (5)
Perimenstrual tenesmus, diarrhea, constipation, cramping, dyschezia
Sxs associated w/ endo w/ bladder involvement (2)
Dysuria, hematuria
Does severity of endo pain correlate w/ stage of disease?
No
Does severity of endo pain correlate w/ depth of infiltration of lesions
Yes
Most predictable sxs of DIE (2)
Dyschezia during menses, severe dyspareunia
How to definitively dx endo
Histology of surgically removed lesions
Histology that supports dx of endo lesions
Endometrial glands and stroma w/ varying amounts of inflammation and fibrosis
What lab markers, imaging studies, and visual findings at time of laparoscopy are diagnostic for endo?
None, none, none (all can be variable and are therefore not diagnostic)
Visual appearance of classical vs nonclassical endo lesions
Black powder-burn lesions vs red/white lesions
Where should one look for endo on laparoscopy?
Entire pelvis (including under ovaries); include cysto if suspicion for bladder endo
US appearance of endometrioma
Ovarian cyst w/ low-level, homogenous internal echoes c/w old blood
Is US generally accurate in differentiating endometriomas from other adnexal masses?
Yes, high accuracy
Modality of choice if using imaging to assess for endo/DIE
TVUS
Second-line imaging for endo, and when to utilize
MRI, reserved for equivocal US results in cases of rectovaginal or bladder endo
How well does ASRM endo classification correlate w/ pain sxs, dyspareunia sxs, infertility?
Not well, not well, not well
Value of ASRM endo classification
Uniformity of reporting op findings
Are medical suppressive therapies effective for endo-associated infertility?
No
Is surgical management effective for endo-associated infertility?
Yes (improves pregnancy rates, though magnitude is unclear)
OR, NNT for post-surgery conception in pts w/ endo-associated infertility
OR=1.65, NNT=12
Potential surgery that does significantly improve fertility in endo-associated infertility pts
Excision of endometrioma
Recommended surgical management of endometrioma
Excision (more effective than simple drainage and ablation of cyst wall)
Risks associated w/ endometrioma (2)
Ovarian damage, reduced ovarian reserve
After initial unsuccessful surgery for endo-associated infertility, is IVF or reoperation superior re fertility?
IVF (unless pain is still a significant issue), as repetitive ovarian surgery has been shown to have a significant negative impact on IVF outcomes
Medical management options for endo-associated pain (5)
Progestins, danazol, COCs, NSAIDs, GnRH analogs
Superior option 6 months s/p tx when comparing COCs to GnRH analogs
No significant pain differences
Prescribing rec for pts w/ endo-associated pain on COCs
Continuous COCs
Next step if initial tx fails in pts w/ suspected endo (2 options)
Diagnostic lap, empiric tx w/ another med
Common non-gyn causes of pelvic pain to r/o (3)
IBS, PBS, urinary tract problems
Testing to consider to r/o alternative etiologies to endo (4)
Pelvic US, CBC, UA, GC/CT
First-line tx options for suspected endo-associated pain (2)
COCs, NSAIDs
Next option if failure to control endo-associated pain w/ first-line therapies
3 months course of empiric GnRH analog
Sxs that improve w/ empiric GnRH analog therapy (3)
Dysmenorrhea, pelvic pain, pelvic tenderness
Does response to empiric GnRH analog tx confirm dx of endo?
No
Progestin-only options for pts w/ endo-associated pain and dysmenorrhea (3)
PO progesterone, Depo, LNG-IUD
Is bone loss that occurs w/ Depo reversible?
Yes, return to pre-tx levels by 12 months
Endo pts who should avoid Depo tx
Pts interested in timely pregnancy (2/2 delay in resumption of ovulatory cycles)
Med category of danazol
Androgenic
Potential side effects of danazol (3)
Acne, hirsutism, myalgias (more severe than other available meds)
How long can GnRH agonists be used w/ add-back therapy?
1 year
Potential side effects of GnRH agonists (3)
Hot flushes, vaginal dryness, osteopenia (which may or may not be reversible w/ prolonged use or repeated cycles)
Endo sx recurrence rate at 5 years s/p discontinuation in pts w/ advanced disease
53-73%
Point of using add-back therapy w/ GnRH analog
Reduce/eliminate BMD loss
First-line add-back regimen
PO norethindrone 5mg daily +/- PO conjugated estrogen 0.625mg daily
Second-line add-back regimen (for pts who cannot tolerate high-dose progestin)
PO Provera 2.5mg daily + transdermal estradiol 25mcg daily
Other medication to provide along w/ add-back tx (and dose)
Calcium supp (1000mg PO daily)
Disadvantages to adding add-back therapy to GnRH analog
None (besides cost of additional rx)
Additional med to consider for pts who have failed conventional med tx, and why
Aromatase inhibitor (ie anastrozole, letrozole), typically prescribed w/ progestin or COC to dampen FSH release and prevent chronic ovarian stim
Reoperation rate for endo pts at 2 years postop, 5 years postop, and 7 years postop
21%, 47%, 55%
One variable that predicts reoperation for endo
Younger age at time of index surgery
Does uterosacral nerve ablation have demonstrated efficacy for tx of endo-associated pain?
No
Specific pts who may benefit from presacral neurectomy
Pts w/ midline pelvic pain
Potential postop side effects of presacral neurectomy (2)
Constipation, urinary dysfunction
Suspected pathophysiology of endometriomas
Progression of endometriosis lesions on ovary that form cystic structures (they are firmly attached to ovary and normal ovarian cortex where oocytes are embedded)
Risks associated w/ endometriomas (2 chronic; 2 acute)
Pain, infertility; torsion, rupture
Is there a risk of malignancy associated w/ endometrioma?
Yes, though small
Role of CA-125 in evaluating endometrioma
May be increased in presence of benign endometrioma, so not useful
When should endometriomas be removed surgically?
If >3cm (to confirm that cyst is benign), or if symptomatic
When should reoperation be considered for pts w/ recurrent endometriomas?
On case-by-case basis, 2/2 risk of repeated damage to ovary
Preferred approach for endometrioma removal
Laparosopic
Is preop medical suppressive tx recommended prior to surgery for endo?
No
Conditions in which postop medical tx may be indicated after surgery for endo (3)
Residual disease expected, pain not relieved, in order to extend pain-free interval after surgery
Should incidentally identified endo at laparoscopy done for other indications be treated surgically?
Individualized basis
Percentage of asymptomatic pts being treated for infertility w/ incidentally identified endo
20-50%
At time of second-look lap for endo in asymptomatic pts, percentage of pts w/ progression, percentage of pts w/ unchanged disease, percentage of pts w/ disease improvement
45%, 33%, 22%
Possible locations of extrapelvic endo (5)
Upper abdomen, diaphragm, abdominal wall (ie umbilicus), perineum (ie episiotomy scar), thorax
Non-gyn organs that may exhibit full-thickness endo invasion (4)
Rectum, large/small bowel, ureters, bladder
Possible sxs of nonreproductive endo (3)
Cyclic hematuria, cyclic hematochezia, cyclic hemoptysis
First-line med tx for extrapelvic endo
GnRH analogs
Situation in which surgery is recommended in cases of extrapelvic endo
Ureter/bowel obstruction
Definitive therapy for tx of endo associated w/ intractable pelvic pain, adnexal masses, and/or multiple previous conservative surgical procedures
Hyst + BSO
Likelihood of sx recurrence w/ ovarian conservation, likelihood of additional surgical tx w/ ovarian conservation; likelihood of sx recurrence s/p BSO, likelihood of additional surgical tx s/p BSO
62%, 31%; 10%, 4%
RR for pain recurrence s/p TAH alone compared to TAH/BSO, RR for need for additional surgery s/p TAH alone compared to TAH/BSO
RR=6.1, RR=8.1
When should ovarian conservation be considered, and what is alternative surgery in such cases?
In younger pts w/ normal ovaries, hyst + removal of endo lesions
Risk of endo recurrence s/p BSO
15%
Is endo recurrence s/p BSO affected by use of postop hormone therapy?
No, theoretical concerns about hormone therapy stimulating growth of residual ovarian/endometrial tissue and/or estrogen-induced malignant transformation of residual endo implants are not proven
Most common site of endo lesion recurrence/persistence s/p hyst + BSO
Large/small bowel
Pathophysiologic theory for persistence of disease in hypoestrogenic state s/p BSO
Local expression of aromatase activity
Tx for endo recurrence s/p hyst/BSO
Surgery (GnRH analogs in hypoestrogenic state would not be beneficial)
Is there an advantage to delaying estrogen tx s/p surgery?
No
