NEJM Review: More Research, Treatments Needed for Endometriosis

By Alexa Josaphouitch, /alert Contributor
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According to a review in The New England Journal of Medicine, the diagnosis and treatment of endometriosis cannot advance until genetic and multidisciplinary research is facilitated. 

“Biomarkers are urgently needed, as are new therapeutics that target the varied physiological pathways related to the development and progression of endometriosis and the persistence of symptoms,” Krina T. Zondervan, University of Oxford Women’s Centre, and her colleagues wrote.

Although endometriosis is defined as the presence of endometrial tissue outside the uterus, the symptoms and presentation vary widely. The classification of severe endometriosis may not correlate with symptoms, treatment response, or prognosis. 

Since there are no biomarkers to detect or eliminate the status of endometriosis, the average delay between onset of symptoms and diagnosis is 7 years. Endometriomas can be identified reliably by transvaginal ultrasonography or MRI. Irrespective of treatment approach, approximately 50% of women with endometriosis have recurrent symptoms over a period of 5 years.

Hormonal treatment for endometriosis associated pain focuses on systemic or local estrogen suppression, inhibition of tissue proliferation and inflammation, or both. The oral contraceptive pill is used widely as first-line treatment for dysmenorrhea or chronic pelvic pain with or without presumed endometriosis.

Gonadotropin-releasing hormone (GnRH) agonists are second-line treatments that substantially suppress estrogen levels. The first GnRH antagonist, elagolix, is now available in North America. For individualized dose adjustment, oral administration is suggested. Oral GnRH antagonists such as linzagolix and relugolix are being evaluated in phase 3 clinical trials. Low-dose estrogen-replacement therapy is usually added to address menopause-like side effects such as bone loss.

For those with symptoms that are resistant to hormone therapy, there has been successful off-label use of aromatase inhibitors. This is not a long-term solution due to bone-density loss, vasomotor regulatory side effects such as hot flashes, and increased multiple-pregnancy rates.

Although it does not decrease pain in all women, surgical treatment can be considered for those with hormone-resistant pain. In studies of repeat surgeries, a high percentage of lesions regressed (42%), with equal percentage of progression and stability (29% in both cases). Endometriosis associated pain is the leading indication for hysterectomy among women 30-34 years old. However, post-hysterectomy pain is three times as likely among women with preoperative pain as among those without preoperative pain.

There are fertility concerns with surgery. The ovarian follicular reserve is affected by the removal of endometriomas. Surgical treatment of endometriosis in women without other identifiable infertility factors may improve rates of spontaneous pregnancy. It remains unclear whether surgery improves the likelihood of pregnancy with assisted reproductive technology or in vitro fertilization.

Due to the limitations of current hormonal and surgery treatment options, there is a need for nonhormonal therapeutic approaches that target the subphenotype of endometriosis. There are currently 15 registered clinical trials focused on nonhormonal treatments.

Zondervan and her colleagues believe that progress for endometriosis treatment “... can be achieved only through sufficiently powered, collaborative, multidisciplinary research, facilitated by funding bodies by means of the prioritization of endometriosis as an important public health issue.”

 

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