Editorial
The importance of treating pain in endometriosis Expert Rev. Obstet. Gynecol. 8(5), 393–395 (2013)
Michele Morelli Department of Obstetrics & Gynecology, “Magna Graecia” University, Gynecologic Oncology Unit, “Tommaso Campanella” Cancer Center of Germaneto, viale Europa, loc. Germaneto, 88100 Catanzaro
Roberta Venturella Author for correspondence: Department of Obstetrics & Gynecology, “Magna Graecia” University, Gynecologic Oncology Unit, “Tommaso Campanella” Cancer Center of Germaneto, viale Europa, loc. Germaneto, 88100 Catanzaro Tel.: +39 096 188 3234 Fax: +39 096 188 3234
[email protected]
Fulvio Zullo Department of Obstetrics & Gynecology, “Magna Graecia” University, Gynecologic Oncology Unit, “Tommaso Campanella” Cancer Center of Germaneto, viale Europa, loc. Germaneto, 88100 Catanzaro
“It is important to emphasize that in women undergoing surgery for endometriosis and not desiring pregnancy, a medical treatment is also extremely useful, if not mandatory, to prevent both pain relapse and disease recurrence rate.” As probably every gynecologist knows, chronic pelvic pain (CPP) is the uppermost aspect referred by patients with endometriosis. The importance of adequately managing this symptom is obvious considering that as many as 15% of female population is affected by CPP in the United States, with direct costs estimated at $2.8 billion and indirect costs at $555 million [1]. Due to the lack of noninvasive diagnostic testing for endometriosis, the average time between onset of symptoms and a definitive diagnosis is 7–8 years and patients with CPP often choose to undergo surgery to try to solve their symptoms. That is why 40% of gynecologic laparoscopies are performed to discern a gynecological etiology for CPP versus other genitourinary, gastrointestinal and musculoskeletal pathologies [2]. By the way, it is known that a cause of pain is not found by laparoscopy in 40% of women with CPP, and hysterectomy for treatment of CPP leaves up to 40% of patients with unsolved symptoms after surgery, suggesting a nongynecologic cause of their pain [2]. These are the reasons why we always say to our students and residents that the delay in diagnosis of endometriosis leads to a delay in surgical treatment which often means protection for our patients. We strongly think that time for a complete revolution about the role of surgery in endometriosis has come. As surgeons caring about patients, we now have to
reach two main goals: avoid unnecessary surgeries, particularly if inadequate and develop effective long-term medical treatment to delay first surgery and to reduce re-intervention risk. Specifically, ovarian endometrioma, among the four subtypes of endometriosis (superficial, deep, adenomyosis and endometrioma), has the most controversial and debated relationship with pelvic pain. Since ovarian endometriomas are often an occasional ultra-sonographic finding it is very important to carefully evaluate the entity and the pathogenetic correlations of the associated pelvic pain before opting for a surgical indication [3,4]. This evaluation is of prominent relevance. On the one hand, indeed, all visceral pain must be managed as early as possible to avoid severe chronicization [5]. It has been recognized that if the nociceptive stimulation lasts over time, modifications in the neural circuits are created with specific pattern of functional brain activation and brain anatomical reorganization, able to contribute to the chronicity of the pain and even to an increase in its intensity [6]. As a consequence, it may happen that a stimulus that is not perceived, in normal condition, as hurting, it becomes painful (allodynia), or that one little painful stimulus is perceived as much more intense (hyperalgesia). On the other hand, however, a too early indication to surgery in young women involves a high risk of recurrence of endometriosis, that is a chronic disease
KEYWORDS: DIE • endometriosis management • endometrioma • ex adiuvantibs strategy • GnRh-a • laparoscopic excision
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10.1586/17474108.2013.825467
Ó 2013 Informa UK Ltd
ISSN 1747-4108
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Editorial
Morelli, Venturella & Zullo
by definition. This is a cornerstone for handling all the decisions about surgical management of endometriosis, since nowadays it is clear that at the time of the second surgery for ovarian endometriosis the reproductive chances for such a patient are reduced by half [7]. In this context a shared idea is that a reliable nonsurgical and noninvasive tool for early diagnosis of endometriosis is strongly needed in clinical practice [8] since it could allow to early start an appropriate medical management of pain and to postpone the laparoscopic treatment as close as possible to patient reproductive desire [9]. We have a very good experience with the ‘ex adiuvantibus strategy’ of confirming the diagnosis of endometriosis or adenomyosis-related CPP by a combined assessment of delta CA125 between the menstrual and luteal phases and between the menstrual phase and following gonadotrophin-releasing hormone analog (GnRH-a) [8], and by evaluating the CPP reduction after GnRH-a, in endometriosis and adenomyosis patients [10], respectively. This strategy allows at the same time a very early and effective reduction of inflammation and pain coming from the superficial lesions often associated to endometriosis [11,12]. The ex adiuvantibus approach helps also to discriminate those very common situations in which the associated visceral pain caused by irritable bowel syndrome or interstitial cystitis/painful bladder syndrome (IC/PBS) are predominant and which could benefit from a different nongynecological management [13,14]. In patients with mild to moderate pain, once diagnosis of gynecological etiology is made and until reproductive desire is reached, medical treatment of endometriosis should be the first choice. In this regard, combined oral contraceptive (COCP) and progestins are the preferred tools, due to their longterm tolerability and low cost. Other alternatives, including androgens such as danazol and GnRH-a, can be proposed to patients, but their use is limited by duration of activity, costs and side effects such as acne, greasy skin and the development of iatrogenic menopausal symptoms and the loss of bone mineral density for Danazol and GnRH-a, respectively. Future development of new drugs, such as selective estrogen receptor modulators, antiprogestogens and antiangiogenic agents may provide further medical treatment options with low morbidity or side effects. Recently, a selective progestin that combines the pharmacologic properties of 19-norprogestins and progesterone derivatives, Dienogest, has been marketed in Italy. It offers a potent progestogenic effect at the endometrium and seems to provide effective pain relief equivalent to GnRH-a, together with a significant reduction of endometriotic lesions and a good safety and tolerability profile [15,16]. It is important to emphasize that in women undergoing surgery for endometriosis and not desiring pregnancy, a medical treatment is also extremely useful, if not mandatory, to prevent both pain relapse and disease recurrence rate. In our experience [16], combined oral contraceptive containing Dienogest seems to be more effective in the control of these outcomes, compared to levonorgestrel-releasing intrauterine device, even if 394
the latter has significantly higher patient satisfaction, that is an aspect not to be underestimated, as adherence to treatment is crucial in long-term therapy. Obviously, when pain is unresponsive to medical treatment, or when endometriomas are associated to deep infiltrating endometriosis (DIE) with severe, site-specific catamenial pain and bleeding, the immediate surgical management remains the most effective treatment [17]. In this context, again, another important change in clinical practice is needed, because surgery for endometriosis has been for too long a ‘gym’ for laparoscopic surgeons. A large body of data, however, established a significant reduction in complications with high-volume surgeons compared to lower-volume surgeons in many areas of surgery, including gynecology [18], and considering the high difficulty of endometriosis surgery, inexperienced surgeons should always send their patients to more expert colleagues. Focusing on the best surgical technique for treating endometriosis-related pain, no significant difference in reduction in overall pain VAS scores has been demonstrated when comparing ablation and excision for superficial endometriosis [19], even if choosing excision of all the visible lesions is probably advisable to confirm the diagnosis by histology. Similarly, excisional surgery is the standard surgical procedure for treating ovarian endometrioma. Laparoscopic excision of the cyst wall, indeed, is associated with a reduced rate of recurrence of the endometrioma (odds ratio: 0.41, 95% CI: 0.18–0.93) and with a reduced requirement for further surgery (odds ratio: 0.21, 95% CI: 0.05–0.79) compared with surgery to ablate the endometrioma [20]. More debated is the best surgical technique for the treatment of DIE. We agree with Cornillie, and more recently Koninckx, that DIE, defined as adenomyosis externa, is a rarely a progressive and recurrent disease [17]. Pain relief after surgery is excellent and excision is feasible in over 90% of cases. Due to high risk of severe complications, such as leakage, recto-vaginal and ureterovaginal fistulas, infection and bladder, sexual and bowel dysfunctions, segmental bowel resections should be avoided, except for sigmoid and multiple, deep and large rectal nodules [17]. Once again, it is time that ethics guides medical decisions, and surgeons should take care of their patients and avoid defensive medicine (bowel resection makes bowel surgeons co-responsible for any complications) or profit surgery (reimbursement for resection is 5–10 times higher than discoid excision). In conclusion we strongly suggest that a ‘superficial’ evaluation of pelvic pain as related to endometriosis and an ‘easy’ indication to surgery do not guarantee an effective and definitive treatment of pain and expose patient to significant reproductive risks. On the contrary, a careful assessment of pain by anamnesis and ex adiuvantibus tools, being helpful to determine its correlation with both endometriosis subtypes or irritable bowel syndrome and interstitial cystitis/painful bladder syndrome, allows an early and effective medical treatment of the pain syndrome and a proper timing for laparoscopic surgery close to reproductive desire. Expert Rev. Obstet. Gynecol. 8(5), (2013)
The importance of treating pain in endometriosis
Financial disclosure
The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This
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Chapron C, Santulli P, de Ziegler D et al. Ovarian endometrioma: severe pelvic pain is associated with deeply infiltrating endometriosis. Hum. Reprod. 27, 702–711 (2012).
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Sikandar S, Dickenson AH. Visceral pain: the ins and outs, the ups and downs. Curr. Opin. Support. Palliat. Care 6, 17–26 (2012).
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Farmer MA, Chanda ML, Parks EL, Baliki MN, Apkarian AV, Schaeffer AJ. Brain functional and anatomical changes in chronic prostatitis/chronic pelvic pain syndrome. J. Urol. 186, 117–124 (2011).
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Vercellini P, Crosignani PG, Abbiati A, Somigliana E, Vigano` P, Fedele L. The effect of surgery for symptomatic endometriosis: the other side of the story. Hum. Reprod. Update 15, 177–188 (2009).
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Venturella R, D’Alessandro P, Gallo F, Morelli M, Zullo F. CA 125 modifications
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includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript.
throughout menstrual cycle and following GnRH-analog administration to diagnose endometriosis as cause of chronic pelvic pain. A prospective controlled study. J. Endometriosis 3, 151–158 (2011).
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