Uterus
Endometriosis
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Endometriosis
Epidemiology
Age at diagnosis: 20-40 years (peak
Incidence
age 25 to 29)
Prevalence
: 10-15% of women
Prevalence
in women with
Pelvic Pain
: 82%
Prevalence
in women with
Infertility
: 21%
Eskenazi (1997) Obstet Gynecol Clin North Am 24:235 [PubMed]
Pathophysiology
Ectopic Endometrial Tissue implant Sites
Ovary
(50%)
Uterosacral ligaments
Rectovaginal septum
Sigmoid colon
Serosal surface of
Uterus
or fallopian Tubes
Cervix
, Vagina or vulva
Bladder
Distant intrapelvic or low Abdominal Sites
Appendix or Ileum
Abdominal scars
Umbilicus
Ureter
Distant extrapelvic sites (rare)
Diaphragm, Pleura, or
Lung
s
Spleen
Gallbladder
Kidney
Pathophysiology
Theories of etiology
Implantation during menstruation (Sampson)
Most accepted theory
Endometrial cells spread via tube to peritoneum
Retrograde flow
Retrograde flow likely occurs in most women but at higher volumes in those with Endometriosis
Implantation more likely in the presence of the plasminogen activator inhibitor gene
Vascular and lymphatic spread (Halban)
Associated with abdominal surgery
Would explain distant spread to organs such as lung
Metaplasia (Meyer)
Coelomic epithelium differentiates into endometrium
Decreased Cellular
Immunity
(Dmowski)
Risk Factors
More days of menstrual flow
Early
Menarche
Late
Menopause
Nulliparity
Mullerian abnormalities
Low
Body Mass Index
Mother or sister with Endometriosis (
Odds Ratio
7.2)
Menstrual flow 6 or more days (
Odds Ratio
2.5)
Menstrual Cycle
<28 days (
Odds Ratio
2.1)
References
Mounsey (2006) Am Fam Physician 74:594-602 [PubMed]
Symptoms
Asymptomatic in 25-30% of women with Endometriosis
Chronic Pelvic Pain
(70%,
Odds Ratio
n 5.2)
Dysmenorrhea
(71%,
Odds Ratio
8.1)
Cyclic
Progressively increasing in severity
Affects bilateral lower
Abdomen
Associated with sense of rectal pressure
Refractory to anti-prostaglandins
Dyspareunia
(44%,
Odds Ratio
n 6.8)
Infertility
(15-20%,
Odds Ratio
8.2)
Ovarian Cyst
s (
Odds Ratio
7.3)
Painful
Defecation
(
Dyschezia
)
Premenstrual spotting
Heavy
Menstrual Bleeding
Suprapubic Pain
Dysuria
Hematuria
Constipation
Signs
Pelvic exam
Tender, nodular uterosacral ligaments (pathognomonic for Endometriosis)
Fixed uterine retroversion
Types
Presentations
Endometrial implantation
Ectopic tissue lies superficially on peritoneum
Endometriomas (chocolate cysts)
Edometrial lined
Ovarian Cyst
s
Endometriotic
Nodule
s
Solid, complex mix of endometrium with fibromuscular and fatty tissue
Localized between vagina and
Rectum
Diagnosis
Precaution
Endometriosis is a histologic diagnosis
Presentations are often non-specific and associated with >10 years on average delay in formal diagnosis from symptom onset
Laparoscopy
Red, Brown or blue-black nodular implants
Powder-burn spots
Multiple, tiny, puckered hemorrhagic foci
Ectopic tissue findings predictive factors for Endometriosis
Implants >10 mm wide or >5 mm deep
Implants with mixed coloration
Implants in cul-de-sac, ovarian fossa, or utero-sacral ligaments
References
Stegmann (2008) Fertil Steril 89: 1632 [PubMed]
Histology (confirms visual diagnosis)
Hemosiderin-laden
Macrophage
s
Endometrial tissue (epithelium, glands, stroma) found in ectopic tissue samples
Tests not recommended for diagnosis
CA 125
CA 19-9
MRI
Abdomen
Imaging
Trasvaginal
Ultrasound
Identifies retroperitoneal and uterosacral lesions
Identifies cystic endometriomas (89% sensitivity, 91%
Specificity
)
Misses peritoneal lesions
Differential Diagnosis
See
Dysmenorrhea
See
Dyspareunia
See
Dysuria
See
Infertility
See
Pelvic Pain
See
Chronic Pelvic Pain
Management
First Line
Precautions
First-line management listed below are directed to primary care providers
GnRH are the best studied and most effective agents for Endometriosis
GnRH (with add-back therapy) should be considered first-line therapy for specialist initiation
Laparoscopy recommended initially
Confirmation of diagnosis
Especially if fertility desired
Analgesic
s
NSAID
s
Oral Contraceptive
s
Use for at least 3-4 months
Norethindrone Acetate
containing OCP may be preferred for
Osteoporosis Management
Desogestrel
OCPs (moderate
Progestin
, low
Estrogen
)
Desogen
(monophasic, 30 mcg
Ethinyl Estradiol
)
Ortho-Cept
(monophasic, 30 mcg
Ethinyl Estradiol
)
Mircette
(monophasic with 20 mcg
Ethinyl Estradiol
)
Cyclessa
(triphasic with 25 mcg
Ethinyl Estradiol
)
Progesterone
Provera
20-30 mg daily for 2 months
Depo Provera
every 3 months
Higher
Incidence
of adverse effects including
Osteoporosis
and weight gain risk
Levonorgestrel
IUD (
Mirena
IUD)
High Dose
Progesterone
(not recommended)
Unclear efficacy and safety
Recent study suggests no benefit over standard dose
Protocol
Start:
Depo Provera
150 mg IM q2 weeks for 4 doses
Next:
Depo Provera
150 mg IM monthly for 4 months
Last
Provera
30-50 mg for 4-6 months
Management
Second Line
Gonadotropin-releasing Hormone Agonist
(
GnRH agonist
)
Efficacy
GnRH are the best studied and most effective agents for Endometriosis
Up to 100% improvement for 6-12 months post-therapy
Mechanism
Initially stimulates LH and FSH release
After 7 days, LH and FSH are depleted
Ultimately results in pituitary GnRH receptor down-regulation
Agents: Used for 6 months as initial course
Leuprolide (Lupron)
Dose: 3.75 mg injected every 4 weeks
Goserelin (Zoladex)
Implanted 3.6 mg SubQ for 6 months or
Nafarelin (
Synarel
)
Dose: 200 mcg intranasal twice daily for 6 month
Buserelin
Decapeptyl
Adverse effects (most women are Hypoestrogenic at 8 weeks)
Risk of
Osteoporosis
Initial Endometriosis symptom flare
Use add-back therapy for most patients
Maintains BMD and decreases hot flash symptoms
Norethindrone Acetate
(Aygestin) 5 mg orally daily
Gonadotropin-Releasing hormone antagonist (GnRH antagonist)
Elagolix (Orilissa)
Oral tablet taken 150 mg once daily, or if
Dyspareunia
, 200 mg twice daily ($870/month in 2019)
Adverse effects include
Menopause
effects (
Osteoporosis
,
Hot Flashes
),
Headache
s,
Insomnia
Not associated with Endometriosis symptom flare (unlike
GnRH agonist
s)
Decreases efficacy of hormonal contraceptives (non-
Hormonal Contraception
is recommended)
(2018) Presc Lett 25(10): 58 [PubMed]
Ford (2019) Am Fam Physician 100(8): 503-4 [PubMed]
Other hormonal agents
Danazol
(androgenic agent)
Dose: 200-800 mg PO qd for 6 months
Efficacy: Improvement in 55-93% of patients
Adverse effects in up to 85% of patients
Older, but effective agent
Gestrinone (anti-
Progestin
agent)
Dose: 2.5 mg PO bid for 6 months
Norethindrone
2.5 mg PO and Premarin 0.625 mg PO qd
Management
Surgical
Laparoscopy for diagnosis and treatment
Laser or electrocautery of implanted endometrium
Ablate as much extopic endometrial tissue as possible for maximal pain relief
Pain Management (unclear efficacy)
Presacral neurectomy (midline pain)
Laparoscopic uterosacral nerve ablation (LUNA)
Refractory cases
Hysterectomy
with oophorectomy and lesion ablation
Endometriosis may still recur in up to 10% of cases
Complications
Infertility
(50-60%)
Catamenial
Pneumothorax
Minimal to no risk of malignancy
However has been associated with clear cell and endometrioid
Ovarian Cancer
Resources
Endometriosis Association
http://www.endometriosisassn.org
References
Jensen (2012) Mayo POIM Conferences, Rochester
Bulun (2009) N Engl J Med 360(3): 268-79 [PubMed]
Mounsey (2006) Am Fam Physician 74:594-601 [PubMed]
Schrager (2012) Am Fam Physician 87(2): 107-13 [PubMed]
Vercellini (2003) Fertil Steril 80:560-3 [PubMed]
Winkel (2003) Obstet Gynecol 102:397-408 [PubMed]
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