Endometriosis is the focus of new scientific research

Endometriosis is the focus of new scientific research

Scientific efforts are being aimed at understanding and treating endometriosis, one of the most common health problems for women. Research has just provided a first step toward providing a more informed way of classifying endometriosis based on the underlying biological cause of the disease.¹

Endometriosis is a condition in which the type of tissue that forms the endometrium is found outside the uterus. It occurs in about one in 10 women of reproductive age and is most often diagnosed in women in their 30s and 40s.² Because pain associated with the condition might be mistaken for normal menstrual cramping, younger women have particularly high rates of misdiagnosis.³ Thirty percent to 50% of women with endometriosis might experience infertility.⁴

With endometriosis, endometrial tissue most often is found in such areas as the peritoneum, ovaries, Fallopian tubes, outer surfaces of the uterus, bladder, ureters, intestines, rectum, and cul-de-sac. In endometriosis, the tissue (known as implants) responds to changes in estrogen and might grow and bleed such as the uterine lining does during the menstrual cycle. Surrounding tissue can become irritated, inflamed, and swollen. The breakdown and bleeding of implants each month also can cause formation of adhesions, which can cause organs to stick together. The bleeding, inflammation, and scarring of implants often result in pain, especially before and during menstruation.

Scientists at the Massachusetts Institute of Technology (MIT) in Cambridge, MA, and Newton-Wellesley Hospital Center for Minimally Invasive Gynecologic Surgery in Newton, MA, have identified a pattern of immune system signaling molecules that correlates with certain symptoms of endometriosis. They also have been able to determine the underlying cellular activity that produces this signature. By using this signature, scientists might be able to develop a patient stratification system similar to that used for breast cancer patients, whose treatments are tailored to the molecular profile of their tumors. In the future, such a signature also might provide a mechanistic endpoint for assessing efficacy of new agents aimed at curtailing inflammatory mechanisms that drive disease progression, researchers note.

"Endometriosis patients report symptoms of infertility and pain, and beyond that, it’s just kind of a guessing game," said Linda Griffith, PhD, MIT School of Engineering Professor of Teaching Innovation in the biological engineering and mechanical engineering departments in a release accompanying the study’s publication. "There are few molecular mechanisms known."

Check treatment options

The contraceptive injection subcutaneous depot medroxyprogesterone acetate (DMPA-SC, Depo-SubQ Provera 104, Pfizer, New York City) was given Food and Drug Administration approval in 2005 for treatment of pain related to endometriosis after research indicated it was as effective as leuprolide acetate, a gonadotropin-releasing hormone (GnRH) analog, for such use.⁵

According to Contraceptive Technology, combined oral contraceptives also decrease the menstrual pain suffered by women with endometriosis. This benefit is enhanced by use extended-cycle pills, which reduce the number of painful episodes women have.⁶ The contraceptive implant (Nexplanon, Merck, Whitehouse Station, NJ) also might be effective in reducing pelvic pain associated with endometriosis.⁷

In 2012 Abbott (now Abbvie, North Chicago, IL), in cooperation with Neurocrine Biosciences in San Diego, announced the initiation of a pivotal Phase 3 clinical trial designed to evaluate the safety and efficacy of elagolix in female patients with endometriosis. Early studies indicate that elagolix, an oral GnRH antagonist, might be effective in treating pain associated with endometriosis.⁸

Scientists expect to have initial data from the first of two Phase 3 clinical trials of elagolix in endometriosis treatment in the second half of 2014, says Abbvie spokesperson David Freundel. The compound also is being evaluated in a Phase 2b clinical trial as a potential treatment option for women with uterine fibroids, he notes.

Swiss-based pharmaceutical company Gedeon Richter PregLem is looking at an oral, once-a-week steroid sulfatase inhibitor for the management of endometriosis. Steroid sulfatases are enzymes expressed in tissues whose growth is estrogen-dependent; in these tissues, these enzymes convert inactive estrogens and androgens into their corresponding biologically active forms. Scientists are studying the drug, PGL5001, in hopes to reduce endometriotic lesions by targeting the inflammatory pathway of the disease and restoring progesterone sensitivity. If the drug proves successful in its current proof of concept testing, it has the potential to cause regression of the disease rather than simply alleviating symptoms.⁹

REFERENCES

1. Beste MT, Pfäffle-Doyle N, Prentice EA, et al. Molecular network analysis of endometriosis reveals a role for c-Jun-regulated macrophage activation. Sci Transl Med 2014; doi: 10.1126/scitranslmed.3007988.
2. American College of Obstetricians and Gynecologists. Endometriosis. Accessed at http://bit.ly/1gkVWTK.
3. Janssen EB, Rijkers AC, Hoppenbrouwers K, et al. Prevalence of endometriosis diagnosed by laparoscopy in adolescents with dysmenorrhea or chronic pelvic pain: a systematic review. Hum Reprod Update 2013; 19(5):570-582.
4. American Society for Reproductive Medicine. Endometriosis: Does it cause infertility? Accessed at http://bit.ly/1g9MOgo.
5. Schlaff WD, Carson SA, Luciano A, et al. Subcutaneous injection of depot medroxyprogesterone acetate compared with leuprolide acetate in the treatment of endometriosis-associated pain. Fertil Steril 2006; 85(2):314-325.
6. Nelson AL, Cwiak C. Combined oral contraceptives. In: Hatcher RA, Trussell J, Nelson AL, et al. Contraceptive Technology: 20th revised edition. New York: Ardent Media; 2011.
7. Walch K, Unfried G, Huber J, et al. Implanon versus medroxyprogesterone acetate: effects on pain scores in patients with symptomatic endometriosis — a pilot study. Contraception 2009; 79(1):29-34.
8. Diamond MP(1), Carr B, Dmowski WP, et al Elagolix treatment for endometriosis-associated pain: results from a phase 2, randomized, double-blind, placebo-controlled study. Reprod Sci 2014; 21(3):363-371.
9. Colette S, Defrère S, Lousse JC, et al. Inhibition of steroid sulfatase decreases endometriosis in an in vivo murine model. Hum Reprod 2011; 26(6):1,362-1,370.