Treatment Options
No cure for endometriosis yet exists; primary treatment is directed toward relief of pain r6
Hormonal therapies do not eliminate endometriosis, and symptoms recur or worsen when treatment is discontinued
Empiric therapy is generally administered without surgical diagnosis; plan is based on clinical diagnosis
Initial therapy of NSAIDs is used for all patients who present with pelvic pain that is likely to be due to endometriosis, especially dysmenorrhea r2r4
If response to NSAIDs is inadequate and pregnancy is not desired, additional medical therapy includes the following: r4r11
- Combined hormonal contraceptives (oral, vaginal ring, or transdermal); combined hormonal contraceptive pill may be used cyclically or continuously
- Published guidelines typically recommend using a combined oral contraceptive pill as first line hormonal treatment of endometriosis; however, combined hormonal options may be less effective than progestin-dominant therapy r22
- Progestogens, including medroxy progesterone acetate, levonorgestrel-releasing intrauterine system, or an etonogestrel-releasing subdermal implant
- Progestin-dominant therapy may be the most effective means of controlling symptoms and suppressing disease progression r22
- GnRH (gonadotropin-releasing hormone) agonists (eg, leuprolide, goserelin) or GnRH antagonists (eg, Elagolix) may be prescribed as second line options if hormonal contraceptives or progestogens have been ineffective r33r34
- To prevent bone loss and hypoestrogenic complications with these agents, administer hormonal add-back therapy using estrogen and progestogen combination r4
- Aromatase inhibitors (eg letrozole) are an option for endometriosis-associated pain refractory to other medical or surgical treatment; these may be prescribed in combination with oral contraceptives, progestogens, GnRH agonists, or GnRH antagonists
- May be prescribed in combination with oral contraceptives, progestogens, GnRH agonists, or GnRH antagonists
- Danazol is no longer recommended as a medical treatment of endometriosis-associated pain due to its severe adverse effects r4
- May choose further medical therapies (second and third line agents) for those with inadequate response to medical therapy or may opt for an earlier surgical approach
If response to NSAIDs is inadequate and future pregnancy is desired, early referral to a gynecologist is recommended r11
Surgical therapy
- Laparoscopic removal of ectopic endometrial tissue r4
- Reserved for patients with medically refractory pain that limits function or causes significant emotional distress
- Removal of ectopic endometrial tissue may be achieved by excision, diathermy, or ablation/vaporisation r4r35
- In patients with ovarian endometrioma, ovarian cystectomy is preferred rather than drainage and coagulation r4r35
- CO₂ laser vaporization is an alternative to cystectomy. Early postsurgical recurrence rates may be lower after cystectomy; however, recurrence rates are similar beyond the first year after surgery r4
- Laparoscopic uterosacral nerve ablation offers no additional benefit over conventional laparoscopic surgery for endometriosis r4
- Presacral neurotomy is helpful as an adjunct to conventional laparoscopic surgery for the treatment of endometriosis-associated midline pain; however, it requires a high level of expertise and has risk of significant adverse effects r4
- Surgical removal of deep endometriosis nodule may reduce pain and improve quality of life but should be undertaken at centers of excellence. Colorectal involvement may require segmental bowel resection r4
- Hysterectomy r4
- Hysterectomy (with or without removal of the ovaries) including removal of all visible endometriosis lesions can be considered for females who do not wish to conceive and have failed to respond to more conservative treatments
- Relieves pain in 80% to 90% of patients with pain resistant to drug therapy and other surgical treatments r2
- 10% of patients experience pain recurrence within 1 to 2 years after surgery r2
- Combined estrogen/progestogen is recommended for patients with endometriosis after surgical menopause until the age of natural menopause r4
Adjunctive hormonal therapy after surgery
- Postoperative adjunctive hormone therapy (for less than 6 months after surgery) may be considered to improve the immediate outcome of surgery for endometriosis- associated pain in females not desiring immediate pregnancy r4
- Hormone treatment for secondary prevention of recurrence r4
- Consider use of a levonorgestrel-releasing intrauterine system or a combined hormonal contraceptive for at least 18 to 24 months for the secondary prevention of endometriosis-associated dysmenorrhea
- In patients who have undergone surgical treatment of ovarian endometrioma, offer long-term hormone treatment (eg, combined hormonal contraceptives) to prevent endometrioma and endometriosis-associated/related symptom recurrence
- Consider long-term postoperative hormone treatment for patients with deep endometriosis
Fertility-associated treatment options for infertile patients r2
- Laparoscopic excision or ablation of endometriotic lesions and adhesions generally improves chances of natural pregnancy r4
- Endometriosis Fertility Index can be used to identify patients that may benefit from assisted reproductive technologies after surgery
- No specific protocol is recommended r4
Drug therapy
- NSAIDs r4c65
- Ibuprofen c66
- Ibuprofen Oral tablet; Adults: 400 mg PO every 4 to 6 hours as needed. Max: 3,200 mg/day.
- Naproxen c67
- Naproxen Oral tablet; Adults: 500 mg PO once, then 250 mg PO every 6 to 8 hours as needed. Max: 1,250 mg/day.
- Mefenamic acid c68
- Mefenamic Acid Oral capsule; Adults: 500 mg PO once at onset of menses, then 250 mg PO every 6 hours as needed for 2 to 3 days.
- Celecoxib c69
- Note: celecoxib may pose a reproductive risk by delaying or preventing prostaglandin-mediated rupture of ovarian follicles, which has been associated with reversible infertility. Consider withdrawal of celecoxib in females who have difficulties conceiving or who are undergoing infertility evaluation r36
- Celecoxib Oral capsule; Adults: 400 mg PO initially, then followed by an additional 200 mg PO on the first day, if needed. On subsequent days, 200 mg PO twice daily, as needed. Consider starting celecoxib at half the lowest recommended dose in patients who are poor CYP2C9 metabolizers.
- Cyclic oral contraceptives r2c70
- Norgestimate–ethinyl estradiol c71
- Inert Oral tablet, Norgestrel, Ethinyl Estradiol Oral tablet; Adult and Adolescent females: Follow dose as for routine contraception. Alternatively, the active tablets can be given continuously in selected patients.
- Norethindrone–ethinyl estradiol c72
- Ethinyl Estradiol, Norethindrone Oral tablet, Ethinyl Estradiol, Norethindrone Oral tablet, Inert Oral tablet; Adult and Adolescent females: 1 tablet PO once daily in the order indicated in the pack for 21 days, followed by a period of 7 days without drug. Phase 1 consists of 10 tablets, each containing 0.5 mg of norethindrone and 35 mcg of ethinyl estradiol. Phase 2 consists of 11 tablets, each containing 1 mg of norethindrone and 35 mcg of ethinyl estradiol.
- Cyclic vaginal ring c73
- Etonogestrel–ethinyl estradiol vaginal ring c74
- Ethinyl Estradiol, Etonogestrel Vaginal insert; Adult and Adolescent females: Follow dosage as for routine contraception.
- Continuous combined oral contraceptives r2c75
- Norgestimate–ethinyl estradiol c76
- Inert Oral tablet, Norgestimate, Ethinyl Estradiol Oral tablet; Adult and Adolescent females: Follow dose as for routine contraception for specific product; alternatively, the active tablets can be given continuously.
- Levonorgestrel-ethinyl estradiol c77
- Levonorgestrel, Ethinyl Estradiol Oral tablet; Adult and Adolescent females: Follow dose as for routine contraception for specific product; alternatively, the active tablets can be given continuously.
- Progestins (progestogens) r4c78
- Medroxyprogesterone acetate c79
- Medroxyprogesterone Acetate Oral tablet; Adult and Adolescent females: 10 mg PO once daily for 10 days a month (e.g., from day 16 to 25 of the menstrual cycle) for 3 months. Endometriosis treatment guidelines recommend medroxyprogesterone as an option for reducing endometriosis-associated pain.
- Levonorgestrel-releasing intrauterine system c80
- Levonorgestrel Vaginal insert; Adult and adolescent females: Insert 1 IUD into the uterus as per instructions. IUD delivers 20 mcg/day. Provides efficacy for up to 5 years, then remove and replace. Wait 6 weeks postpartum or until uterine involution occurs before inserting. Per endometriosis guidelines, may consider a levonorgestrel-releasing IUD as 1 of the options to reduce endometriosis-associated pain.
- Gonadotropin-releasing hormone agonists r4c81
- Females at high risk for osteoporosis are not good candidates for the use of gonadotropin-releasing hormone agonists
- Leuprolide c82
- Leuprolide Acetate Suspension for injection; Adult females: Initially, 3.75 mg IM once monthly OR 11.25 mg IM once every 3 months with or without norethindrone acetate 5 mg/day PO for 6 months. For recurrence of symptoms, leuprolide must be given with norethindrone acetate 5 mg/day PO for 6 months; the total duration of therapy with leuprolide plus norethindrone acetate should not exceed 12 months. Assess bone density before retreatment.
- Gonadotropin-releasing hormone antagonists
- Elagolix r33r37r38c83
- Elagolix Oral tablet; Adult Females: Initiate at 150 mg PO once daily; Max duration: 24 months. WOMEN WITH CO-EXISTING DYSPAREUNIA: Consider 200 mg PO twice daily initially; Max duration at this dose: 6 months. Use the lowest effective dose. Limit the duration of use as recommended to reduce risk of bone loss.
- Aromatase inhibitors r2c84
- Letrozole c85
- Letrozole Oral tablet; Adults: 2.5 mg PO once daily for up to 6 months, with or without other hormonal therapies, has been studied; guidelines recommend letrozole in combination with oral contraceptive pills, progestogens, or gonadotropin-releasing hormone analogs for endometrioses-associated pain refractory to other medical or surgical treatment.
Nondrug and supportive care
Procedures
Laparoscopic treatment of endometriosis c86
General explanation- Minimally invasive abdominal surgery to remove ectopic endometrial tissue r2r4
- Highly effective at reducing pain and improving fertility, but the recurrence rate is 40% to 50% at 5 years after surgery r6
- Any of 3 methods of endometrial tissue removal may be chosen based on symptoms and disease severity r2
- Superior pain relief when combining presacral neurectomy with lesion ablation
- Denervation of uterus and part of bladder is accomplished by electrosurgical destruction of nerve bundle within interiliac triangle
Indication- Excision (preferredr39) or drainage and ablation of ectopic endometrial tissue r2
- First line therapy for patients with endometrioma larger than 3 cm in diameter and chronic pelvic pain, and for infertile patients
- Fulguration, ablation, and excision of ectopic endometrial tissue r2
- Second line therapy for patients with dysmenorrhea, dyspareunia, or chronic pelvic pain resistant to pharmaceutical therapy
- First line therapy for patients with pelvic mass
- Laparoscopic presacral neurectomy r2
- Third line therapy for patients with dysmenorrhea, dyspareunia, and deep central abdominal pain poorly responsive to first or second line surgical therapies
Contraindications- Presence of dense pelvic adhesions that: r27
- Render accurate evaluation of pelvic pathosis impossible
- Prevent safe access to abdominopelvic cavity
Complications- Complications associated with laparoscopic removal of endometrial tissue include risk of 1 or more of the following: r2
- Infection
- Internal organ damage
- Hemorrhage
- New adhesion formation
- Complications associated with laparoscopic presacral neurectomy include: r2
- Hemorrhage of adjacent venous plexus
- No pain during first-stage labor
- Constipation
- Urinary urgency
Hysterectomy with or without bilateral salpingo-oophorectomy r4c87
General explanation- Surgical removal of uterus, fallopian tubes, and both ovaries r2
Indication- Fourth line therapy for noncyclic chronic pelvic pain resistant to all other therapies r2
Contraindications- Desire to maintain fertility r4
Complications- Persistent or recurrent pain r2
- Bowel injury or bladder injury
- Infection (greatest risk with vaginal hysterectomy) r40
Comorbidities
- Patients may have coexistent polycystic ovary syndrome, which can cause irregular cycles, as well as manifestations encountered in patients with endometriosis, such as menorrhagia and infertility c88c89c90d5
- In addition to oral contraceptives, these patients may require statins to control high cholesterol, hormones to increase fertility, and metformin to prevent diabetes r41
Special populations
- Females who may be pregnant or are breastfeeding
- Do not administer combined oral contraceptives r42
- Do not start or continue progestin therapy
- Stop administering gonadotropin-releasing hormone agonists