Pharmacists Are Crucial in Managing Endometriosis Symptoms

Endometriosis affects between 2% and 10% of women aged 25 to 40 years in the United States, but as with many conditions, specifically affecting women, clinical research is woefully underfunded. In 2019, only $13 million of federal fudning was allocated to endometriosis research, accoeding to the Endometriosis Foundation of America, despite 1 in 10 women living with the disease.¹

The inflammatory disease causes the uterine lining to grow outside of the uterus due to estrogen, in places such as the ovaries, the fallopian tubes, and the pelvic cavity, and even in abdominal areas such as the bowel and the bladder.² Often painful, endometriosis can severely affect quality of life and cause infertility,^2,3 and it has been linked with a 34% increase in the risk of stroke.^4,5

Like research, available endometriosis treatment options are lacking. Treatment targets typically include pain management and reduction of endometrial growth; in some cases, surgery is required. The type of treatment depends on whether or not the patient wants to have children, the patient’s age, and the severity of the symptoms and the disease.²

Endometriosis and Autoimmune Disease

Although it is not considered an autoimmune disease, the association between endometriosis and autoimmune diseases was examined in a 2019 meta-analysis published in Human Reproduction Update.⁶ Study investigators identified associations between endometriosis and inflammatory bowel disase (IBD) systemic lupus erythematosus (SLE), Addison disease, Sjögren syndrome (SS), multiple sclerosis (MS), rheumatoid arthritis (RA), autoimmune thyroid disorder, and celiac disease⁶ but "only 5 of the 26 studies could provide high-quality evidence, and among these, 4 supported a statistically significant association between endometriosis and at least 1 autoimmune disease." The results of this research highlight the need for providers to remain aware of autoimmune disease as a comorbidity. Endometriosis is also associated with inflammation. A 2016 study published in Frontiers in Bioscience found that “inflammation is crucial in the pathogenesis of endometriosis.”⁷ One key cytokine, tumor necrosis factor-α, plays an important role in endome- trial inflammation, which can lead to endothelial dysfunction.⁷

Available Treatment Options

According to Veronica Vernon, PharmD, assistant professor of pharmacy practice at the Butler University College of Health Sciences and Pharmacy in Indianapolis, Indiana, pharmacists play a key role in helping patients manage endometriosis. For patients taking pharmacological treatment—including nonsteroidal anti-inflammatory drugs (NSAIDs), hormonal contraception, and gonadotropin-releasing hormone (GnRH) antagonists/agonists—pharmacists can help manage adverse effects and monitor symptoms.

“Pharmacists also...can bring awareness to the condition and advocate for patients,” Vernon added. “Many patients feel dismissed by family, friends, and health care providers when discussing their endometriosis symptoms.” Results of a survey conducted by the Alliance for Endometriosis, Vernon noted, found that as many as 90% of patients have been dismissed when discussing their pain, and 42% were dismissed by a health care provider.⁸

These patients may turn to pharmacists for pain relief recommendations. “Dysmenorrhea may be a common reason people seek self-care, and pharmacists can help identify if someone needs an evaluation for endometriosis or another secondary form of dysmenorrhea,” Vernon said.
NSAIDs such as ibuprofen or naproxen are often recommended as a first-line pain treatment, but sometimes prescription pain relievers are needed. NSAIDs should be used with caution due to cardiovascular and gastrointestinal risks.⁹ Using the lowest possible dosage is recommended, and patients allergic to aspirin should avoid taking NSAIDs.⁹ Pain management is also necessary for patients whose endometriosis requires surgery. Several hormone therapies can be used to treat pain and reduce symptoms. GnRH medications can signifi- cantly reduce pelvic pain¹⁰ and prevent ovulation. In 2018, Elagolix (Orilissa)—a GnRH antagonist¹¹—became the first FDA-approved oral treatment for moderate to severe pain associated with endometriosis in over a decade.¹² To prevent bone loss, the low-dose version (150 mg) should only be taken for 24 months; the high-dose version (200 mg) should be taken for no longer than 6 months.¹²

Oral contraceptives may also be used to treat endometriosis to reduce growth and assist with pain relief. However, pain relief often disappears when treatment is stopped, and adverse effects of this treatment include breakthrough bleeding, bloating, and weight gain.

In August 2022 the FDA approved relugolix 40 mg, estradiol 1 mg, and norethindrone acetate 0.5 mg (Myfem- bree),¹³ a once-daily pill to treat pain in moderate to severe endometriosis that can be used for 2 years. Its effec- tiveness was supported by 2 clinical studies whose results were published in The Lancet.¹⁴ Of note with this med- ication is the list of possible adverse effects, which include stroke and pulmonary embolism, mood disorders and suicidal ideation, elevated blood pressure, liver injury, alopecia, and more. Patients should not use hormonal contraceptives while taking this medication.¹³

A 2022 study published Cannabis and Cannabinoid Research found that during the COVID-19 pandemic, patients increasingly turned to cannabis consumption to treat endometriosis when access to health care was limited.¹⁵ Results of another study, published in PLOS One,¹⁶ found that cannabis can be effective for pelvic pain, mood, and gastrointestinal issues, “with effectiveness differing based on method of ingestion.”¹⁶ As more states legalizing cannabis products, pharmacists should ask patients if they are using this form of treatment on their own, which may have fewer risks than long-term use of NSAIDs and other drugs. Researchers from the study published in PLOS One urged additional study of this promising treatment.

“Understanding the medications used to treat endometriosis will equip pharmacists to better care for patients,” Vernon said. “It is essential that pharmacists advocate for their patients with endometriosis by acknowledging their symptoms and validating them.”

References

1. Endometriosis Foundation of American: Our commitment to research. Endometriosis Foundation of American. Accessed February 13, 2023. https://www.endofound.org/research

2. Fourquet J, Sinaii N, Stratton P, et al. Characteristics of women with endometriosis from the USA and Puerto Rico. J Endometr Pelvic Pain Disord. 2015;7(4):129-135. doi:10.5301/je.5000224

3. Endometriosis. National Institute of Child Health and Human Development at the National Institutes of Health (NIH). Updated February 21, 2020. Accessed February 2, 2023. https://www.nichd.nih.gov/health/topics/endometriosis

4. Science update: Endometriosis linked to higher stroke risk, NIH-funded study suggests. Eunice Kennedy Shriver National Institute of Child Health and Human Development. Published July 27, 2022. Accessed February 13, 2023. https://www.nichd.nih.gov/newsroom/news/072722-endometriosis-stroke

5. Farland LV, Degnan WJ 3rd, Bell ML, et al. Laparoscopically confirmed endometriosis and risk of incident stroke: a prospective cohort study. Stroke. 2022;53(10):3116-3122. doi:10.1161/STROKEAHA.122.039250

6. Shigesi N, Kvaskoff M, Kirtley S, et al. The association between endometriosis and autoimmune diseases: a systematic review and meta-analysis. Hum Reprod Update. 2019;25(4):486-503. doi:10.1093/humupd/dmz014
7. Jiang L, Yan Y, Liu Z, Wang Y. Inflammation and endometriosis. Front Biosci(Landmark Ed). 2016;21(5):941-948. doi:10.2741/4431

8. The Alliance for Endometriosis Survey Reveals Actions Needed to Iprove the Endometriosis Patient Experience. News release. The Alliance for Endometriosis. November 30, 2021. Accessed February 13, 2023. https://www.prnewswire.com/news-releases/the-alliance-for-endometriosis-survey-reveals-actions-needed-to-improve-the-endometriosis-patient-experience-301431226.html

9. Vonkeman HE, van de Laar MA. Nonsteroidal anti-inflammatory drugs: adverse effects and their prevention. Semin Arthritis Rheum. 2010;39(4):294-312. doi:10.1016/j.semarthrit.2008.08.001

10. Rafique S, DeCherney AH. Medical management of endometriosis. Clin Obstet Gynecol. 2017;60(3):485-496. doi:10.1097/GRF.000000000000029211. Features to consider. Orilissa. Accessed February 13, 2023.

11. Features to consider. Orilissa. Accessed February 13, 2023. https://www.orilissa.com/hcp/about-orilissa/mechanism-of-action

12. AbbVie receives US FDA approval of Orilissa (elagolix) for the management of moderate to severe pain associated with endometriosis. News release. AbbVie. July 24, 2018. Accessed February 13, 2023. https://news.abbvie.com/news/abbvie-receives-us-fda-approval-orilissa-elagolix-for-management-moderate-to-severe-pain-associated-with-endometriosis.htm

13. Myovant Sciences and Pfizer receive U.S. FDA approval of MYFEMBREE, a once-daily treatment for the management of moderate to severe pain associated with endometriosis. News release. Myovant Sciences. August 5, 2022. Accessed February 2, 2023. https://investors.myovant.com/news-releases/news-release-details/myovant-sciences-and-pfizer-receive-us-fda-approval-myfembreer

14. Giudice LC, As-Sanie S, Arjona Ferreira JC, et al. Once daily oral relugolixcombination therapy versus placebo in patients with endometriosis-associated pain: two replicate phase 3, randomised, double-blind, studies (SPIRIT 1 and 2). Lancet. 2022;399(10343):2267-2279. doi:10.1016/S0140-6736(22)00622-5

15. Armour M, Sinclair J, Cheng J, et al. Endometriosis and cannabis consumption during the COVID-19 pandemic: an international cross-sectional survey. Cannabis Cannabinoid Res. 2022;7(4):473-481. doi:10.1089/can.2021.0162

16. Sinclair J, Collett L, Abbott J, Pate DW, Sarris J, Armour M. Effects of cannabis ingestion on endometriosis-associated pelvic pain and related symptoms. PLoS One. 2021;16(10):e0258940. doi:10.1371/journal.pone.0258940