PB#114: Management Of Endometriosis Flashcards by Gordon Skeoch

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%

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Is there a racial predisposition to endo?

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Familial predisposition to endo

7-10-fold increased risk in pts w/ affected 1st degree relative; strong concordance in monozygotic twins

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Proposed inheritance pattern for endo

Polygenic-multifactorial mechanism (numerous genetic polymorphisms identified)

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Most plausible theory for formation of endo

Attachment and implantation of endometrial glands and stroma on peritoneum from retrograde menstruation

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Alternative theories for endo formation (3)

Hematogenous/Lymphatic transport, stem cells from bone marrow, coelomic metaplasia

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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

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Theoretical effect of progesterone resistance in development endo

Dampens antiestrogenic effect of progesterone and amplifies local estrogenic effect

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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

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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

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Peptide highly expressed in endo lesions, especially rectovaginal lesions

Nerve growth factor

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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

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Theory that may explain the severe dysmenorrhea and the improvement in endo sxs s/p hyst

Changes in innervation of uterus

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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

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Infertility lab that is decreased in early stage endo

AMH

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Endo-related issues that can cause anatomic abnormalities resulting in abnormal tubal function (2)

Ovarian cysts (endometriomas), adhesions

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Risk factors for endo (5)

Early menarche (<11 y/o), shorter cycles (<27 days apart), heavy/prolonged cycles, lower parity, shorter duration of lactation

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Lifestyle change associated w/ reduced risk of endo

Regular exercise >4 hours/week

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Most well-recognized clinical manifestations of endo (5)

Dysmenorrhea, CPP, dyspareunia, USL nodularity, adnexal mass (symptomatic or asymptomatic)

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Classic sxs associated w/ endo dx (4)

Abdominopelvic pain, dysmenorrhea, menorrhagia, dyspareunia

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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

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Sxs associated w/ endo w/ bowel involvement (5)

Perimenstrual tenesmus, diarrhea, constipation, cramping, dyschezia

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Sxs associated w/ endo w/ bladder involvement (2)

Dysuria, hematuria

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Does severity of endo pain correlate w/ stage of disease?

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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?

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?

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?

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?

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?