EXECUTIVE SUMMARY

The authors of a new scientific paper indicate that dichloroacetate, investigated as a potential cancer treatment, may be effective against endometriosis.

Endometriosis affects up to 10% of U.S. women between the ages of 25-40 years. Finding a new treatment option would augment current treatment strategies of hormone therapy and surgery, which involve significant side effects and recurrence after treatment.

Orilissa (elagolix) is an oral gonadotropin-releasing hormone antagonist specifically developed for treatment of women with moderate to severe endometriosis pain. Available in tablet form, Orilissa is manufactured in two strengths. The lower-strength tablet is taken once daily for no more than 24 months, while the higher-strength dosage is taken twice daily for no more than six months.


The authors of a new scientific paper indicate that dichloroacetate, investigated as a potential cancer treatment, may be effective against endometriosis.1 Endometriosis affects up to 10% of U.S. women between the ages of 25 and 40 years. Finding a new treatment option would augment current treatment strategies of hormone therapy and surgery, which involve significant side effects and recurrence after treatment.2

In many cases, endometriosis results from retrograde menstruation, where endometrial tissue flows backward through the fallopian tubes and into the pelvic cavity, rather than out through the cervix. The endometrial tissue attaches to organs in the abdominal and pelvic cavities, including the ovaries, the outside of the uterus, the intestines, and other organs or tissues. This abnormal tissue continues to follow the monthly menstrual cycle, with the resulting bleeding causing inflammation, scarring, and pain. Up to 30% to 50% of women with endometriosis may experience infertility.3

Researchers from the University of Edinburgh reported that cells from the pelvic walls of women with endometriosis exhibit different metabolism characteristics compared to women without the disease. Cells from the pelvic walls of affected women were found to produce higher amounts of lactate, which is similar to the behavior of cancer cells.

“We decided to investigate dichloroacetate because it had been used to treat lactate acidosis in children, and tested as a treatment for some cancers,” says lead author Andrew Horne, MB, ChB, PhD, FRCOG, professor of gynecology and reproductive sciences at the University of Edinburgh. “When the cells from women with endometriosis were treated with dichloroacetate, they were found to return to normal metabolic behavior.”

New Option Available, but Search Continues

In July 2018, the FDA approved Orilissa (elagolix), an oral gonadotropin-releasing hormone (GnRH) antagonist specifically developed for treatment of women with moderate to severe endometriosis pain.

Patients with endometriosis pain have been treated with various forms of pain management, such as nonsteroidal anti-inflammatory drugs (NSAIDs) including ibuprofen, naproxen sodium, and mefenamic acid. Clinicians also may use hormonal contraceptives, such as combined oral contraceptives, the contraceptive patch or vaginal ring, the single-rod contraceptive progestin implant, intramuscular or subcutaneous depot medroxyprogesterone
acetate, or the levonorgestrel IUD, for treatment of the estrogen-dependent condition.

The Orilissa tablet is manufactured in two strengths. The lower-strength tablet is taken once daily for no more than 24 months, while the higher-strength dosage is taken twice daily for no more than six months. Longer use is not recommended due to bone loss. In clinical trials, both strengths reduced pain during and between menstrual periods after three months of treatment.4

In 2019, a Society for Women’s Health Research working group published a review article highlighting areas of need to improve a woman’s diagnosis, treatment, and access to quality care for endometriosis, as well as specifying priorities for future research and care. According to the review, women with endometriosis can experience delays of seven to 12 years from the time they first experience symptoms to their diagnosis. The authors noted that the causes of endometriosis remain unknown, and the current gold standard for diagnosis is surgery to verify abnormal tissue growth. Endometriosis can negatively affect all aspects of a woman’s daily life; estimated healthcare expenditures for endometriosis come in at $69.4 billion per year in the United States.5

Clinicians who treat an adolescent population are familiar with endometriosis: It is the leading cause of secondary dysmenorrhea in adolescents. According to an American College of Obstetricians and Gynecologists committee opinion, endometriosis should be considered in adolescent patients with persistent, clinically significant dysmenorrhea despite treatment with hormonal agents and NSAIDs, particularly if no other etiology for chronic pelvic pain or secondary dysmenorrhea has been identified based on history, physical examination, and pelvic ultrasonography.6

“Despite its significant burden on women, their families, and society as a whole, endometriosis is underfunded and under-researched, greatly limiting understanding of the disease and slowing much-needed innovation in diagnostic and treatment options,” review co-author Rebecca Nebel, PhD, director of scientific programs at the Society for Women’s Health Research, said in a statement.7

REFERENCES

  1. Horne AW, Ahmad SF, Carter R, et al. Repurposing dichloroacetate for the treatment of women with endometriosis. Proc Natl Acad Sci USA 2019; doi:10.1073/pnas.1916144116.
  2. As-Sanie S, Black R, Giudice LC, et al. Assessing research gaps and unmet needs in endometriosis. Am J Obstet Gynecol 2019;221:86-94.
  3. Bulletti C, Coccia ME, Battistoni S, et al. Endometriosis and infertility. J Assist Reprod Genet 2010;27:441-447.
  4. Taylor HS, Giudice LC, Lessey BA, et al. Treatment of endometriosis-associated pain with elagolix, an oral GnRH antagonist. N Engl J Med 2017;377:28-40.
  5. As-Sanie S, Black R, Giudice LC, et al. Assessing research gaps and unmet needs in endometriosis. Am J Obstet Gynecol 2019;221:86-94.
  6. ACOG Committee Opinion No. 760 Summary: Dysmenorrhea and endometriosis in the adolescent. Obstet Gynecol 2018;132:1517-1518.
  7. Society for Women’s Health Research. Identifying barriers to care for women with endometriosis. Feb. 25, 2019. Available at: https://bit.ly/2E6rFJZ.