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Endometriosis: 5 Things to Know

A Spotlight on Endometriosis

What was once a common condition suffered largely in silence and out of public view has been making news in recent months. Celebrities have shared their experiences with this painful, debilitating, and often misunderstood condition. Advocates launched a hashtag on social media and held a protest at the Washington, DC, headquarters of the American College of Obstetricians and Gynecologists, demanding improved standards of care and resources for patients with endometriosis. On Worldwide Endometriosis Day, the annual EndoMarch took place to raise awareness of and demand more attention to the problem of endometriosis.

Fortunately, progress is being made, bit by bit. A new drug treatment for endometriosis-associated pain has just been approved. Researchers are working on a noninvasive diagnostic blood test. And the Australian Minister for Health released a national action plan to address endometriosis, because so many people „have never heard of the word.”

The Burden of Endometriosis

Endometriosis is a benign chronic inflammatory disease that affects up to 10% of women. The symptoms of endometriosis, including cyclic pelvic pain, dysmenorrhea, and dyspareunia, may significantly influence a woman’s quality of life, sexual relationships, and time away from work, costing billions in healthcare expenses at a national level.

Here are five things to know about endometriosis.

1. It’s thought to be the result of „retrograde menstruation.” Endometriosis occurs when endometrial glands and stroma migrate to extrauterine locations. Many theories, but no consensus, exist about the etiology of endometriosis. The most widely accepted is that of retrograde menstruation, in which fragments of endometrium are passed through the fallopian tubes into the peritoneal cavity. This mechanism does not explain all cases of endometriosis, especially those in which lesions are found in distant locations (such as the lungs). In another theory, endometrial tissue travels to ectopic sites through blood or lymphatic channels, similar to the way in which cancer cells spread.

Histopathologic analysis of tissue samples removed surgically is the gold standard for the diagnosis of endometriosis.

In some cases, endometriosis can be suspected in the presence of characteristic symptoms—dysmenorrhea, chronic pelvic pain, menstrual irregularities, dyspareunia, cyclic intestinal or urinary symptoms, and infertility. Imaging studies (ultrasound, MRI) may also reveal lesions typical of endometriosis (eg, endometriomas). Immobility of the pelvic organs, and palpation or direct visualization of lesions in the vaginal wall upon pelvic exam, may also suggest endometriosis. Some experts believe that a strong clinical suspicion supported by imaging findings is sufficient for starting therapy.

2. Endometriosis is estrogen-dependent. Endometriosis isn’t seen before menarche, and its symptoms improve after menopause. Endometriosis is known to proliferate in an estrogen-rich environment and undergoes atrophy when estrogen levels are low.

Thus, hormones that create a progesterone-dominant environment are used in the management of endometriosis. Drugs that suppress ovulation or the hypothalamic/pituitary axis, or increase progesterone availability (which induces atrophy or decidualization of endometrial implants), as well as nonhormonal agents that interfere with neovascularization can be considered for medical therapy. Hormone treatments, which include combined oral contraceptives, progestins, gonadotropin-releasing hormone (GnRH) agonists, and androgens, have demonstrated efficacy for the relief of pain associated with endometriosis. Nonsteroidal anti-inflammatory drugs (NSAIDs) also help by reducing the prostaglandin levels that play a key role in dysmenorrhea and chronic pelvic pain. An oral GnRH antagonist, elagolix, has recently been approved for endometriosis.

Surgical treatment of endometriosis is recommended when chronic pain does not respond to medical therapy, when deep infiltrating endometriosis results in significant bowel or ureter stenosis, or as part of infertility management. Surgery may be conservative or definitive. Surgical excision or coagulation of endometriotic lesions significantly improves pain associated with the condition. To reduce recurrence risk, surgery may be combined with postoperative medical treatment.Laparoscopic uterine nerve ablation and presacral neurectomy are other techniques to reduce chronic pelvic pain, but with limited efficacy.

3. Endometrial lesions and endometriomas can infiltrate nonreproductive organs, making treatment challenging. Endometriosis can infiltrate nearly every organ in the body, although the lesions are typically found in abdominal or pelvic sites, including the bladder, bowel, and rectum. Lesions that penetrate > 5 mm below the peritoneal surface are considered „deeply infiltrative endometriosis.”

Endometriomas (sometimes called „chocolate cysts”) are the cysts that develop in the ovaries of a woman with endometriosis. Asymptomatic endometriomas that do not display suspicious sonographic features may be followed expectantly with regular ultrasound. Medical management rarely induces regression of endometriomas. Cysts that are > 5 cm, appear suspicious on ultrasound (septated cyst, papillary projections), grow rapidly, or cause pain may require surgical intervention. For best long-term results, excision of the cyst wall is recommended over fenestration and coagulation. Cysts frequently recur after aspiration only.

Hysterectomy with or without bilateral salpingo-oophorectomy may be considered as definitive surgery in women who no longer desire fertility and/or are close to menopause. Long-term results are superior when the ovaries are removed as well. To avoid the complications of hypoestrogenism, combined hormone replacement therapy may be needed postoperatively.

4. The right diet can impede the progress of endometriosis.

Lifestyle changes are often considered in the management of chronic diseases. Dietary changes and the use of supplements have been evaluated for their effects on endometriosis-associated pain. These changes may affect the immune system, thereby interfering with disease progression. The available data on these interventions are considered low-quality, mainly owing to small study sample sizes.

Limited evidence supports some benefit from certain supplements (fenugreek, fish oil, vitamin B1, ginger, valerian, and zinc) compared with no treatment or treatment with NSAIDs. According to a 2014 meta-analysis, coffee/caffeine intake does not influence endometriosis.

The consumption of certain dietary fats can have an impact on endometriosis; long-chain omega-3 fatty acids seem to lower the risk. It has been suggested that adequate vitamin D supplementation and higher dairy food intake can lower the risk for endometriosis as well. Furthermore, at least in one study, pain associated with endometriosis seemed to respond well to a gluten-free diet.

On the basis of the currently available data, fruits and vegetables (for their antioxidant effects), dairy products, certain types of fats, and a gluten-free diet may improve symptomatic endometriosis. A diet rich in red meat and ham should be avoided, however.

It must be acknowledged that the literature on the impact of diet on the symptoms of endometriosis are limited, and studies are needed for evidence-based recommendations. However, with a low risk for harm, these lifestyle modifications can be discussed with the patient in addition to offering standard medical and/or surgical therapies.

5. Endometriosis increases risk for some cancers. The lifetime risk for ovarian cancer, the sixth most common cancer in women, is 0.5%-1%. Ovarian cancer, which has genetic and reproductive risk factors, is associated with poor long-term survival because it typically is diagnosed at an advanced stage.

Women with endometriosis have about a 50% increased risk for epithelial ovarian cancer (especially clear cell, endometrioid, or low-grade squamous cell cancers). The altered inflammatory response of endometriosis may explain this increased risk. Genetic studies have also reported a link between endometriosis and ovarian cancer risk. The use of combined oral contraceptives has been shown to reduce this risk, and oophorectomy (both uni- and bilateral) has been shown to carry a protective effect.

One more thing: Infertility is common. Endometriosis may be diagnosed in about one half of women with infertility. In the presence of dense adhesions that distort the pelvic pathology, a clear association with infertility can be established. An adverse impact on oocyte quality, tubal function, or altered endometrial receptivity may be the link in other cases.

Infertility cannot be managed with medical therapy of endometriosis alone, because medical therapies interfere with ovulation. Laparoscopic treatment of early-stage endometriosis (I or II) improves the chance of spontaneous pregnancy. Considering the incidence of endometriosis and its impact on fertility, it is estimated that 30-40 laparoscopies must be done in asymptomatic women to achieve one additional pregnancy. Therefore, although laparoscopy is not recommended primarily to look for endometriosis in asymptomatic infertile women, when endometriosis is found during laparoscopy, it should be excised (the „see and treat” approach). Expectant management after surgery for stage III or IV endometriosis is believed by some experts to be associated with pregnancy rates as high as 50%, but this has not been confirmed in randomized controlled trials.

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FDA Clears Elagolix (Orilissa) for Endometriosis Pain

FDA Clears Elagolix (Orilissa) for Endometriosis Pain

The US Food and Drug Administration (FDA) has approved elagolix (Orilissa, AbbVie), the first oral gonadotropin-releasing hormone antagonist specifically developed for the treatment of moderate to severe pain associated with endometriosis, the company has announced.

The FDA approved elagolix under priority review. It is expected to be available in the United States next month.

Elagolix represents a „significant advancement for women with endometriosis and physicians who need more options for the medical management of this disease,” Michael Severino, MD, chief scientific officer at AbbVie, said in a news release.

Data from two studies involving nearly 1700 women with moderate to severe endometriosis pain supported FDA approval.

Elagolix, at a dose of 150 mg once daily or 200 mg twice daily, significantly reduced the three most common types of endometriosis pain: daily menstrual pelvic pain, nonmenstrual pelvic pain, and pain with sex, the company said.

The recommended duration of use of elagolix is up to 24 months for the 150-mg once-daily dose and up to 6 months for the 200-mg twice-daily dose, as it causes a dose-dependent decrease in bone mineral density (BMD), the company said.

Loss of BMD is greater with increasing duration of use and may not be completely reversible after stopping treatment, the company noted. For women with moderate hepatic impairment, the recommended dosage is 150 mg once daily for up to 6 months. The drug should be taken orally at roughly the same time each day, with or without food.

„Endometriosis is often characterized by chronic pelvic pain that can impact women’s daily activities,” Hugh Taylor, MD, study investigator from Yale University School of Medicine in New Haven, Connecticut, said in the release. „Women with endometriosis may undergo multiple medical treatments and surgical procedures seeking pain relief, and this approval gives physicians another option for treatment based on a woman’s specific type and severity of endometriosis pain.”

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