Clinical Review

Endometriosis and pain: Expert answers to 6 questions targeting your management options

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Experts address the nuances of endometriosis-associated pain and describe a multipronged approach to keep it at bay

Endometriosis: 3 intraoperative videos
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Endometriosis has always posed a treatment challenge. Take the early 19th Century, for example, before the widespread advent of surgery, when the disease was managed by applying leeches to the cervix. In fact, as Nezhat and colleagues note in their comprehensive survey of the 4,000-year history of endometriosis, “leeches were considered a mainstay in treating any condition associated with menstruation.”1

Fast forward to the 21st Century, and the picture is a lot clearer, though still not crystal clear. The optimal approach to endometriosis depends on numerous factors, foremost among them the chief complaint of the patient—pain or infertility (or both).

In this article—Part 2 of a 3-part series on endometriosis—the focus is on medical and surgical management of pain. Six experts address such questions as when is laparoscopy indicated, who is best qualified to treat endometriosis, is excision or ablation of lesions preferred, what is the role of hysterectomy in eliminating pain, and what to do about the problem of recurrence.

In Part 3, to be published in the June 2015 issue of OBG Management, ­endometriosis-associated infertility will be the topic of discussion.

In Part 1, 7 experts answer crucial questions on the diagnosis of endometriosis.

For a detailed look at the pathophysiology of endometriosis-associated pain, see “Avoiding “shotgun” treatment: New thoughts on endometriosis-associated pelvic pain,” by Kenneth A. Levey, MD, MPH, in this issue.

1. What are the options for empiric therapy?
One reason for the diagnostic delay for endometriosis, which still averages about 6 years, is that definitive diagnosis is achieved only through laparoscopic investigation and histologic confirmation. For many women who experience pain thought to be associated with endometriosis, however, clinicians begin empiric treatment with medical agents as a way to avert the need for surgery, if at all possible.

“There is no cure for endometriosis,” says John R. Lue, MD, MPH, “but there are many ways that endometriosis can be treated” and the impact of the disease reduced in a patient’s life. Dr. Lue is Associate Professor and Chief of the Section of General Obstetrics and Gynecology and Medical Director of Women’s Ambulatory Services at the Medical College of Georgia and Georgia Regents University in Augusta, Georgia.

Among the medical and hormonal management options:

  • Nonsteroidal anti-inflammatory drugs (NSAIDs), often used with combined oral contraceptives (OCs). NSAIDs are not a long-term treatment option because of their effect on cyclo-oxygenase (COX) 1 and 2 enzymes, says Dr. Lue. COX-1 protects the gastrointestinal (GI) system, and prolonged use of NSAIDs can cause adverse GI effects.
  • Cyclic combined OCs “are recommended as first-line therapy in the absence of contraindications,” says Dr. Lue, and are often used in combination with NSAIDs. However, the failure rate may be as high as 20% to 25%.2 “If pain persists after a trial of 3 to 6 months of cyclic OCs, one can consider switching to continuous low-dose combined OCs for an additional 6 months,” says Dr. Lue. When combined OCs were compared with placebo in the treatment of dysmenorrhea, they reduced baseline pain scores by 45% to 52%, compared with 14% to 17% for placebo (P<.001).2 They also reduced the volume of endometriomas by 48%, compared with 32% for placebo (P = .04). According to Linda C. Giudice, MD, PhD, “In women with severe dysmenorrhea who have been treated with cyclic combined OCs, a switch to continuous combined OCs reduced pain scores by 58% within 6 months and by 75% at 2 years” (P<.001).2 Dr. Giudice is the Robert B. Jaffe, MD, Endowed Professor in the Reproductive Sciences and Chair of Obstetrics, Gynecology, and Reproductive Sciences at the University of California, San Francisco.
  • Depot medroxyprogesterone acetate (DMPA) or the ­levonor­gestrel-releasing intrauterine system (LNG-IUS). These agents suppress the hypothalamic-­pituitary-ovarian (HPO) axis to different degrees. DMPA suppresses the HPO completely, preventing ovulation. The LNG-IUS does not fully suppress the HPO but acts directly on endometrial tissue, with antiproliferative effects on eutopic and endometriotic implants, says Dr. Lue. The LNG-IUS also is effective at suppressing disease after surgical treatment, says Dr. Giudice.2
  • Gonadotropin-releasing hormone (GnRH) agonist therapy, with estrogen and/or progestin add-back therapy to temper the associated loss in bone mineral density, “may be effective—if only temporarily—as it inhibits the HPO axis and blocks ovarian function, thereby greatly reducing systemic estrogen levels and inducing artificial menopause,” says Dr. Lue.
  • Norethindrone acetate, a synthetic progestational agent, is occasionally used as empiric therapy for endometriosis because of its ability to inhibit ovulation. It has antiandrogenic and antiestrogenic effects.
  • Aromatase inhibitors. Dr. Lue points to considerable evidence that endometriotic implants are an autocrine source of estrogen.3 “This locally produced estrogen ­results from overexpression of the enzyme P450 aromatase by endometriotic tissue,” he says. Consequently, in postmenopausal women, “aromatase inhibitors may be used orally in a daily pill form to curtail endometriotic implant production of estrogen and subsequent implant growth.”4 In women of reproductive age, aromatase inhibitors are combined with an HPO-­suppressive therapy, such as norethindrone acetate. These strategies represent off-label use of aromatase inhibitors.
  • Danazol, a synthetic androgen, has been used in the past to treat dysmenorrhea and dyspareunia. Because of its severe androgenic effects, however, it is not widely used today.


Next Article:

Avoiding “shotgun” treatment: New thoughts on endometriosis-associated pelvic pain

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