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Preventing endometriosis recurrence postsurgery
The postoperative recurrence of disease and/or pain remain formidable challenges in clinical practice, but increasing options for long-term medical management help to optimize outcomes for many patients
BY KATHLEEN KRAFTON
Perspectives on Endometriosis Management
Endometriosis is a complex disease that arises, at least in part, from cellular proliferation, invasion, neoangiogenesis, and chronic inflammation—the same mechanisms that have been implicated in its postoperative reoccurrence. Exactly how often the disease recurs following surgery remains unknown. “That’s a hard question to answer,” said Stephanie Estes, MD, Associate Professor of Reproductive Endocrinology and Infertility and Director of Robotic Surgical Services at Penn State Hershey Obstetrics and Gynecology in Hershey, Pennsylvania.
“It’s really throughout the woman’s life that this has to be managed,” she said. “We want to make sure that we look at it with the whole person in mind and not just the surgical viewpoint,” added Dr. Estes.
In this article, Estes shares her expert guidance on the long-term prevention of pain and disease recurrence following surgical intervention for endometriosis, including the role of hormonal therapy.
1. What is the risk of endometrioma recurrence after surgery without any treatment?
“Endometriomas do not resolve without surgery, so that is one of the indications for surgical intervention,” said Dr. Estes.
Similar to postoperative endometriosis, divergent rates of postsurgical endometrioma recurrence have been reported. "Typically at about 12 months after initial surgery, approximately 30% of patients have disease progression, about 30% are doing better, and the rest of the patients are unchanged," said Dr. Estes.
The technique of the endometrioma removal is the most important prognostic factor, said Dr. Estes. "For those whose endometriomas are just aspirated, we know the recurrence risk is 80% or higher. If you actually remove the cyst wall, then this decreases recurrences. Good surgical technique can preserve ovarian function."
Women with more advanced disease are known to have a higher rate of endometrioma recurrence, and the risk for recurrence increases with length of time from surgery. Other identified prognostic factors include prior surgery for endometriosis; the presence of pelvic adhesions; high disease scores according to the American Society for Reproductive Medicine; and use of ovarian-stimulating drugs.4,5 Conversely, postoperative pregnancy has been shown to exert a significant protective effect on both pain and endometrioma recurrences.4
How to best manage recurrent endometriomas is still a matter of debate, as few studies have been conducted. Efforts to excise the cyst while preserving ovarian function have been met with mixed results. Laparoscopic techniques, notably the stripping technique, are controversial due to the loss of healthy ovarian tissue and decrease in ovarian egg supply that ensue. 6
Given the risks and lack of clear benefits, repeat surgeries for endometrioma are best avoided whenever possible, particularly in women who may wish to conceive.7 Moreover, recurrent endometriomas often present an increased surgical challenge due to the development of postsurgical adhesions, a result of the chronic inflammatory process associated with endometriosis.8 Medical management, therefore, is the preferred treatment to reduce recurrence risk whenever feasible.
2. What is the risk of pain recurrence after surgery without any treatment?
“Usually, pain recurrence varies from 20% to 40%, which is similar to a primary surgery. So a fair number of patients do have a return of pain,” said Dr. Estes.
“I try to explain to patients, let’s look to the ultimate goal. Give me 6 months to 1 year to work with you, and we will find some therapy that provides relief of your pain symptoms, but it’s not going to be an overnight treatment plan,” she said.
3. What is first-line medical therapy after surgery to combat disease and pain recurrence?
For women who do not wish to become pregnant, oral contraceptives are usually the first-line choice, often in combination with nonsteroidal anti-inflammatory drugs for pain relief. "Oral contraceptive pills have a very high acceptability to women and a low side effect profile, and the cost is usually very reasonable," said Dr. Estes.
Progesterone-only pills are another option. "They are quite effective," said Dr. Estes. "There are no data supporting superiority of one therapy over another, so when you go through these options, you have to talk to the patients about their preferences, what have they used in the past, what side effects have they had, how available are the treatments, and the cost."
The choice of administration route is also largely driven by patient preference and ease of use, said Estes. In addition to oral contraceptives, available contraceptive options include vaginal administration with NuvaRing (etonogestrel/ethinyl estradiol vaginal ring) and patches, with the latter options being good choices for patients who are not adherent with oral administration.
Progestin-containing IUDs are another option. "An IUD can be placed usually for 3 to 5 years," said Dr. Estes. “That is something that is not patient-dependent to be effective and you can get a really good response. Oftentimes, if you find endometriosis at the time of the surgery, you can place a progestin IUD right in the operating room and the patient won’t even need a separate visit for IUD insertion."
Data specific to recurrence or pain scores for IUDs in that setting are limited. "That's something that is newer," noted Dr. Estes. "We know that the IUD reduces painful periods in women with endometriosis. I can’t tell you that it officially reduces endometrioma recurrence, but we suspect that it does."
For patients who wish to become pregnant, the clinical pathway differs.
4. When oral contraceptives fail, what are the hormonal therapy options?
Progestin-only therapy provides an estrogen-free option. “Progestins cause decidualization and atrophy of endometrial tissue and are superior to placebo in treating endometriosis pain. Most frequently utilized are norethindroneacetate or medroxyprogesterone acetate,” said Dr. Estes.
The testosterone derivate danazol is also available, although it is not used as frequently today as it once was due to the availability of other options with fewer adverse effects. However, Dr. Estes does not rule out use of danazol.
“So danazol could be that option.”
Some women respond more favorably to danazol, and using the lowest effective dosage may help to reduce adverse effects.
5. What are the adverse effects of medical therapies?
For any long-term treatment plan to be successful, tolerability and management of adverse effects are essential. "We try to modify symptoms, but sometimes they aren’t all modifiable," said Dr. Estes.
Side effects with progestin treatment can include abnormal uterine bleeding/spotting, mood disturbances, amenorrhea or weight gain.
"With the aromatase inhibitors, there are surprisingly not many side effects at all actually," she continued. "The GnRH agonists make people feel menopausal, so women have hot flashes, vaginal dryness, mood swings, headaches, and they can have decrease in their bone mineral density."
"It's called the estrogen threshold hypothesis," Dr. Estes explained. "Basically, you want people in the middle."
“With careful monitoring and subspecialty expertise, you can have patients on [Lupron Depot] longer [than the recommended 12 months] if they have had successful control of their symptoms,” said Dr. Estes.
Dr. Estes pointed to research that is currently underway on an oral GnRH antagonist. “I think in the future we are looking toward treating endometriosis as a chronic medical disease, and many more treatments will be available—we just haven’t quite gotten there yet. But the oral GnRH antagonist is a very exciting new treatment option that’s coming soon.” Other opportunities may exist, such as treatments as selective progesterone/estrogen receptor modulators, immunomodulators, or neuromodulators.
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Kathleen Krafton is a contributing writer for OBG Management.
Stephanie Estes reports no financial relationships relevant to this article.