Endometriosis
Cheryl A. Glass and Rhonda Arthur
Definition
A.Endometriosis is ectopic endometrial tissue that exhibits hormonal responsiveness but is located outside the uterine cavity. Bleeding from this ectopic endometrial tissue causes pelvic inflammation and scarring, resulting in chronic pelvic pain and infertility. Endometrial lesions have been found in the vagina, gastrointestinal (GI) tract (especially the sigmoid colon), thoracic cavity, limbs, and gallbladder.
Incidence
A.The true incidence of endometriosis is unknown, with ranges of 5% to 10%. Positive family history (mother or sister) increases the risk tenfold. Endometriosis does not have a higher incidence for any particular race or socioeconomic group.
Pathogenesis
A.Retrograde menstruation is the most popular theory for the etiology of endometriosis. Menses are suspected of flowing backward
through the fallopian tubes, resulting in the seeding
of endometrial tissue outside the uterus.
Predisposing Factors
A.Positive family history, mother and/or sister.
B.History of progressive dysmenorrhea.
C.History of prolonged uninterrupted menstrual cycles; first pregnancy at a late age; nulliparity.
D.Limited or no prior use of hormonal contraceptives.
E.Uterine abnormalities.
Common Complaints
A.Pain prior to period, pain with menstrual periods that increases over time (dysmenorrheal).
B.Pain with intercourse (dyspareunia).
C.Pain with bowel movements, may include constipation from the fear or pain of having a bowel movement (dyschezia).
D.Spotting and bleeding.
Other Signs and Symptoms
A.Dyspareunia and/or pain that radiates to the thigh and back.
B.Chronic, noncyclic pelvic pain.
C.Abnormal vaginal bleeding: Premenstrual spotting and dysfunctional uterine bleeding (DUB).
D.Other bowel symptoms: Diarrhea and rectal bleeding.
E.Urinary symptoms: Dysuria, urgency, and hematuria.
Subjective Data
A.Review the onset, duration, and course of complaints.
B.Obtain a menstrual history: Interval and duration of menstrual cycles and history of dysmenorrhea.
C.Review for a history of nonmenstrual pelvic pain/cramping.
D.Obtain a contraceptive history.
E.Question the patient regarding change in bowel patterns or habits or pain with defecation.
F.Obtain a sexual history, including incidence of dyspareunia.
G.Note patient parity and/or history of infertility.
H.Obtain a family history, asking about similar complaints in female relatives
Physical Examination
A.Temperature (if indicated), pulse, respirations, blood pressure (BP), height, and weight to calculate body mass index (BMI).
B.Inspect:
1.Note general appearance for discomfort before, during, and after examination.
2.Perform detailed external genitalia exam.
C.Auscultate abdomen for bowel sounds in all quadrants. Auscultation of the abdomen should precede any palpation or percussion due to the changes in intensity and frequency of sounds after manipulation.
D.Palpate:
1.Palpate abdomen for masses.
2.Check for suprapubic tenderness.
3.Back: Check for costovertebral angle (CVA) tenderness.
E.Pelvic examination:
1.Speculum examination: Inspect the cervix for cervicitis; friability; and discharge color, odor, and amount. Note any cutaneous lesions of the vagina, or cervix that resemble powder burn or chocolate spots.
2.Bimanual examination: Check for cervical motion tenderness (CMT), adnexal masses; check uterine size, consistency, position, and mobility.
3.Rectovaginal examination: Palpate uterosacral ligaments for pain and nodularity. Evaluate for masses and polyps of rectum.
The most common indicator for endometriosis is a fixed retroverted uterus with nodularity. Palpation of endometrial implants may result in exquisite pain for the patient.
Diagnostic Tests
There are no specific diagnostic tests for endometriosis. Definitive diagnosis may be done by laparoscopy with tissue biopsy. Presumptive diagnosis is based on clinical signs and symptoms with imaging; this approach is usually appropriate as a conservative first step. If the patient is unresponsive to treatment or if higher-risk therapies (e.g., donazol) are being considered, laparoscopy should be performed first to confirm diagnosis.
A.Serum beta human chorionic gonadotropin (HCG), to rule out ectopic pregnancy.
B.Complete blood count (CBC) to rule out infection.
C.Cervical culture for Chlamydia trachomatis (CT) and gonorrhea (GC) to rule out sexually transmitted infections (STIs) and pelvic inflammatory disease (PID).
D.Urine culture, if indicated.
E.Transvaginal ultrasonography, to rule out cysts and masses.
F.GI series or barium enema, if indicated.
Differential Diagnoses
A.Endometriosis.
B.Dysmenorrhea.
C.Ovarian cysts.
D.PID.
E.Premenstrual syndrome (PMS).
F.Mittelschmerz.
G.Trauma.
H.Appendicitis.
I.Pregnancy: Normal, missed abortion, or ectopic.
J.GI: Diverticular disease, inflammatory bowel disease (Crohn’s disease [CD] or irritable bowel syndrome [IBS]).)
K.Genitourinary: Interstitial cystitis (IC) or urinary tract infection (UTI).
Plan
A.General interventions:
1.The patient may be managed empirically if she is suspected of having endometriosis with
pharmacologic and nonpharmacologic therapies.
2.The American Society of Reproductive Medicine Practice Committee states that endometriosis should be viewed as a chronic disease that requires a lifelong management plan with the goal of maximizing medical treatment and avoiding repeated surgical procedures.
B.Patient teaching:
1.Treatment goals include prevention of disease progression, alleviation of pain, and preservation of fertility. Treatment options include the following:
a.Observation alone.
b.Medical therapy or pharmacologic therapy.
c.Referral or consultation for laparoscopic therapy, including laser vaporization and removal of adhesions, if other treatment strategies are unsuccessful.
2.Continuation or recurrence of pelvic pain may necessitate assisting the woman to manage her chronic pelvic pain and dysmenorrhea with nonsteroidal antiinflammatory drugs (NSAIDs), hormonal options, and/or other nonnarcotic chronic pain therapies, such as visualization and biofeedback.
3.Hysterectomy and bilateral salpingo-oophorectomy are the only definitive cures for women who do not wish to conserve their reproductive capacity. This should be considered only as a last resort for failed conservative treatment.
C.Pharmaceutical therapy:
1.Mild endometriosis (which does not cause frequent interference with work or school):
a.NSAIDs and combined hormonal contraception is considered the first-line therapy. If the patient experiences pain during the week of withdrawal bleeding, she may take active pills/use ring continuously, omitting the placebo days. Avoid cyclooxygenase 2 (COX-2) inhibitors and hormonal contraceptives in patients who are trying to conceive.
b.Medroxyprogesterone acetate 10 mg/d for up to 6 months; a long-acting progestin (Depo-Provera) 150 mg by intramuscular (IM) injection every 3 months for 6 months.
2.Moderate to severe complaints:
a.Gonadotropin-releasing hormone (Gn-RH) agonist:
i.Elagolix (Orilissa): First Food and Drug Administration (FDA)-approved oral treatment for the management of moderate to severe pain associated with endometriosis was released in 2018. Initiation: 150 mg/d delivers a dosedependent partial suppression of estradiol production.
ii.Maximum treatment duration with no co-morbid conditions is 24 months. The maximum treatment duration with moderate hepatic impairment (Child-Pugh Class B) is 6 months.
iii.Maximum treatment duration with moderate hepatic impairment (Child-Pugh Class B) is 6 months.
iv.No dosage adjustment is required in women with mild hepatic impairment (Child-Pugh Class A).
b.200 mg twice/d (400 mg total daily) delivers almost full suppression of estradiol production and may be used with coexisting dyspareunia:
i.Maximum treatment duration is 6 months.
ii.Elagolix 200 mg twice/d is not recommended for moderate hepatic impairment.
c.The most common adverse reactions (>5%) in clinical trials included hot flushes and night sweats, headache, nausea, insomnia, amenorrhea, anxiety, arthralgia, depression-related adverse reactions, and mood changes:
i.Elagolix causes a dose-dependent decrease in bone mineral density (BMD), which is greater with increasing duration of use and may not be completely reversible after stopping treatment.
ii.Contraindications to elagolix use:
•Pregnancy.
•Known osteoporosis.
•Severe hepatic impairment.
•Concomitant use of strong organic anion transporting polypeptide (OATP) 1B1 inhibitors (e.g., cyclosporine and gemfibrozil).
iii.Leuprolide acetate (Lupron) 3.75 mg by IM injection every month or 11.25 mg IM injection every 3 months.
iv.Nafarelin (Synarel) nasal spray 200 mcg twice/d.
v.Consider adding oral norethindrone acetate 5 mg/d to minimize hypoestrogenic symptoms. This is called add-back therapy.
Use of Gn-RH agonist, which acts to suppress ovulation, can result in side effects, including hot flashes, mood changes, and other menopausal symptoms. Use is restricted to 6 months (or 12 months if using add-back therapy) to avoid decrease in bone density. Expense of this therapy may preclude its use.
d.Danazol 200 to 400 mg twice/d for up to 6 months:
i.Use of danazol, which acts to produce anovulation and hypogonadotropism, can result in androgenic side effects, including acne, hirsutism, weight gain, and voice changes that may not be reversible.
ii.Other side effects, which are reversible, include decreased breast size, atrophic vaginitis, dyspareunia, hot flashes, and emotional liability.
iii.Confirmation of diagnosis with laparoscopy is recommended prior to initiation of this treatment due to side effect profile.
e.Progestin therapy:
i.Levonorgestrel intrauterine system (LNG-IUS), etonogestrel implant, or medroxyprogesterone acetate (as noted earlier).
ii.Note: Only trained healthcare providers who carefully reviewed the selected device’s manufacturer’s package insert for indications and use as well as specific insertion instructions should place intrauterine devices (IUDs).
Follow-Up
A.Patients must return monthly while receiving Gn-RH agonist or danazol therapies to assess for symptom relief and side effect profile.
Consultation/Referral
A.The workup, evaluation, and medications for endometriosis are expensive. Consider referral to a women’s health specialist for initial management. A prudent approach is recommended with a conservative treatment option; evaluate the results before trying another.
B.Refer the patient for a surgical consultation for definitive diagnosis. Endometriosis may be suspected based on symptoms and physical examination. It cannot, however, be confirmed unless actually visualized by laparoscopy.
Individual Considerations
A.Pregnancy: Infertility may be a presenting symptom. Treatment focus may be on endometriosis abatement and fertility support.
Resource
Endometriosis Association: endometriosisassn.org