Endometriosis care: Women’s health nurse practitioners share perspectives

in statistically significant reductions in endometriosis- related pain and improved quality of life.20,21 Although more data are available on combined oral contra- ceptives, vaginal and transdermal CHCs demonstrated efficacy in endometriosis-related pain reduc- tion in both systematic reviews. A Table 2. Medications for endometriosis-related pain management 5,12,15 Medication ESRHE (2022) NICE (2017) CNGOF/HAS (2018) NSAIDs Weak recommendation Consider short trial (3 months) alone or in combination with other treatments Long-term use not recommended due to gastric and renal side effects CHCs Strong recommendation Oral, vaginal, transdermal Cyclic or continuous Offer combined oral contraceptive pill in suspected or confirmed endometriosis CHC recommended as first-line hormonal therapy Progestins Strong recommendation 52-mg LNG-IUS ENG implant DMPA Offer progestin in suspected or confirmed endometriosis 52-mg LNG-IUS recommended first-line hormonal therapy *Grade C desogestrel low-dose progestin contraception, ENG implant, and dienogest recommended second- line therapy GnRH agonists Strong recommendation Prescribe if CHCs or progestins ineffective No recommendation *Grade C recommended second-line therapy GnRH antagonists Recommendation based on data from phase 3 trials of elagolix Prescribe if CHCs or progestins ineffective No recommendation *Grade C Data available when guidelines established did not justify recommendation for use outside clinical trial setting Aromatase inhibitors Strong recommendation in those with endometriosis- associated pain refractory to other medical or surgical treatment No recommendation *Grade C In absence of data, aromatase inhibitors are not recommended Danazol Danazol no longer recommended No recommendation No recommendation CHC, combination hormonal contraceptive; DMPA, depot medroxyprogesterone acetate; ENG, etonogestrel; GnRH, gonadotropin-releasing hormone; LNG-IUS, levonorgestrel-releasing intrauterine system; NSAIDs, nonsteroidal anti-inflammatory drugs. *Grade C CNGOF/HAS recommendations could be revised once results of ongoing clinical trials available.15 NPWomenshealthcare.COM December 2022 Women’s Healthcare 9 continuous-use regimen appears to be more efficacious in regard to dysmenorrhea, with nonsignificant differences between continuous and cyclic regimens for chronic pelvic pain and dyspareunia.22 Progestins A systematic review including progestin-only pills, the 52-mg levonorgestrel intrauterine system (LNG-IUS), etonogestrel (ENG)- releasing subdermal implant, and depot medroxyprogesterone acetate found all to be effective in reducing endometriosis-related pain.19 A recent randomized controlled trial reported that both the ENG implant and LNG-IUS significantly reduced endometriosis- related pain, dysmenorrhea, and chronic pelvic pain.23 GnRH agonists Gonadotropin-releasing hormone agonists have demonstrated efficacy in relieving endometriosis-related pain.5,12,15,24 They bind to GnRH receptors on the anterior pituitary, causing a down-regulation of the pituitary-ovarian axis and profound but reversible hypoestrogenism.24 Commonly used GnRH agonists that are FDA approved for up to 12 months for treatment of endome- triosis-related pain are goserelin SC, leuprolide IM, and nafarelin depot via nasal spray.1 There has been no demonstrated difference in efficacy or reported side effects related to route of administration.24 The most reported side effects are vaginal dryness, hot flushes, headaches, and joint pain.1 The use of GnRH agonists is contraindicated during pregnancy. Reduction of BMD is a major concern with GnRH agonist treat- ment continuing for longer than 6 months. The addition of add-back therapy prevents bone loss and does not affect the efficacy of the GnRH agonist treatment.25 Commonly used add-back regimens include the progestins medroxyprogester- one acetate and norethindrone, a low-dose estrogen-progestin com- bination, and bisphosphonates.25 Considering the possible impact on BMD, GnRH agonists should only be used after careful consideration in young women and adolescents if first-line treatments are ineffective.12 GnRH antagonists Two oral GnRH antagonists have been FDA approved for the man- agement of moderate-to-severe pain associated with endometriosis. Elagolix, which is available in two dosages, was approved in 2018.26 Relugolix combined with estradiol and norethindrone acetate was approved in 2022.27 GnRH antag- onists suppress follicle-stimulating hormone, luteinizing hormone, and estrogen and may have a quicker symptom relief profile than GnRH agonists as well as the advantage of oral administration. The most frequently reported side effects across both medications include hot flushes, night sweats, and irreg- ular bleeding.26,27 The use of GnRH antagonists is contraindicated in pregnancy. Like GnRH agonists, reduction of BMD is a concern with long-term GnRH antagonist use. Prescribing information recommends limiting duration of use to 24 months for elagolix 150 mg and relugolix com- bined with estradiol and norethin- drone acetate.26,27 The higher dose of elagolix (200 mg twice daily), while more effective in pain relief, is associated with more bone loss than the lower dose with recommended use limited to 6 months.26 Consid- ering the possible impact on BMD, GnRH antagonists should only be used after careful consideration in young women and adolescents if first-line treatments are ineffective.12 Other considerations Neuromodulators such as tricyclic antidepressants, selective reuptake inhibitors, and anticonvulsants have shown promise as a component of the management of endometrio- sis-related pain but are associated with dose-limiting side effects. Pel- vic physical therapy and cognitive behavioral therapy also may be of benefit to some women.2 It has been suggested that pain syndromes such as endometrio- sis may interact with other pain syndromes (eg, irritable bowel syndrome, fibromyalgia, migraine headaches) and that this interaction may feature increased pain sensi- tivity stemming from the effects of nociceptive inputs on the nervous system. Perceptual responses to pain can become exaggerated, prolonged, and widely spread (central sensitiza- tion).28 If central sensitization is sus- pected, further pain evaluation and pain management is recommended. This often requires a multidisciplinary team that includes a pain specialist, physical therapist, psychologist, and primary healthcare provider.15 For patients who have undergone laparoscopic surgery, postoper- ative use of a CHC or progestin is recommended to prevent the risk of disease recurrence when preg- nancy is not desired.12,15 Hormone replacement therapy can be offered to postmenopausal women who have undergone surgical treatment, although endometriosis symptoms could recur.12,15 Endometriosis-related infertility management should consider cur- rent pain as well as the results of the pretreatment infertility evalua- tion.5,15 The benefits and risks of sur- gery prior to assisted reproductive therapy should be discussed to in- clude the potential negative impact on ovarian reserve.12 There is insuffi- cient evidence to support extended GnRH agonist, CHC, or progestin use 10 December 2022 Women’s Healthcare NPWomenshealthcare.COM prior to assisted reproductive thera- pies to increase live birth rates.12,15 Implications for NP practice Nurse practitioners can play a key role in the early diagnosis and treat- ment of endometriosis. Comprehen- sive knowledge of endometriosis that includes risk factors, symptoms, potential physical examination findings, and current imaging mo- dalities empower the NP to clinically diagnose endometriosis and to recognize when consultation or collaboration is beneficial. Special considerations should be given to adolescent assessment. Providing patient education about normal menses and symptoms that require healthcare attention can be incor- porated into the patient history. A patient-centered approach to endometriosis treatment considers the patient’s individual goals, HRQL, and follow-up to evaluate for any needed adjustment based on treat- ment efficacy, patient satisfaction, and change in reproductive goals. �

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