Successful treatment of refractory endometriosis-related chronic pelvic pain with aromatase inhibitors in premenopausal patients

Objective

Not every patient with endometriosis responds to currently recommended conventional medical treatment regimens. The objective of this study was to determine the efficacy and side effects of aromatase inhibitors in the treatment of premenopausal patients with endometriosis associated with chronic pelvic pain refractory to conventional treatment.

Study design

Four premenopausal patients with documented refractory endometriosis and chronic pelvic pain were treated with aromatase inhibitors, either anastrazole (3) or letrozole (1), for 6 months. The treatment was combined with calcium 1.5 g per day and vitamin D 800 U per day. The main outcome measure was reduction in pelvic pain assessed by visual analogue scale. Side effects were documented and changes in serum LH, FSH and 17-β estradiol and bone density (Dexa scan) were measured before, during and after treatment.

Results

There was marked improvement in pelvic pain in the four patients. Their mean pain score fell from 9 prior to treatment to 4.5 at the end of treatment. One patient with infertility conceived immediately after completing the treatment. There were no changes in the hormone levels and bone scan scores. The most common side effect was irregular bleeding with anastrazole and joint pains with letrozole.

Conclusions

Aromatase inhibitors are beneficial in premenopausal women with chronic pelvic pain secondary to refractory endometriosis without compromising fertility and with minimal side effects. Further cohort and comparative studies are needed to confirm these observations.     

The influence of endometriosis-related symptoms on work life and work ability: a study of Danish endometriosis patients in employment

Objective

Little is known about the implications of endometriosis on women's work life. This study aimed at examining the relation between endometriosis-related symptoms and work ability in employed women with endometriosis.

Study design

In a cohort study, 610 patients with diagnosed endometriosis and 751 reference women completed an electronic survey based on the Endometriosis Health Profile 30-questionnaire and the Work Ability Index (short form). Percentages were reported for all data. Binary and multivariate logistic regression analyses were used to assess risk factors for low work ability. The level of statistical significance was set at p < 0.025 in all analyses.

Results

In binary analyses a diagnosis of endometriosis was associated with more sick days, work disturbances due to symptoms, lower work ability and a wide number of other implications on work life in employed women. Moreover, a higher pain level and degree of symptoms were associated with low work ability. Full regression analysis indicated that tiredness, frequent pain, a higher daily pain level, a higher number of sick days and feeling depressed at work were associated with low work ability. A long delay from symptom onset to diagnosis was associated with low work ability.

Conclusions

These data indicate a severe impact of endometriosis on the work ability of employed women with endometriosis and add to the evidence that this disease represents a significant socio-economic burden.     

Pronóstico y resultados en pacientes diagnosticadas de endometriosis a las que se les ha realizado por primera vez una cirugía conservadora por dolor o esterilidad

Objective

To analyze clinical outcomes in patients with suspected endometriosis undergoing conservative surgery. Pain reduction, pregnancy rates, and reinterventions were analyzed.

Material and methods

Patients with suspected endometriosis and symptoms of pain or infertility undergoing conservative surgery for the first time were included (n = 128). Exclusion criteria consisted of incomplete medical histories and interventions indicated for reasons other than pain or infertility.

Results

Surgery was indicated for pain in 70.3% and for infertility in 29.7%. A total of 32.5% of the patients had pain at the first postsurgical visit, 42.5% at 6 months and 58.3% at 1 year. Reintervention was performed in 11.29%. Among reinterventions for pain, there was a higher percentage of intestinal symptoms before surgery (P=.07), as well as episodes of abdominal pain requiring hospital care (P=.08); a higher proportion of these patients had pain in the first visit (P=.05) and at 1 year (P=.03) than patients not undergoing reintervention. Postsurgical medical treatment was less frequent in patients undergoing reintervention (P=.11). Among patients undergoing surgery for infertility, pregnancy was achieved in 65.8%.

Conclusions

Pain was less frequent in the first postsurgical visit than in subsequent visits. Among patients undergoing reintervention for pain, there was a higher percentage of intestinal symptoms and episodes of abdominal pain requiring hospital care prior to the intervention. Pain at the first visit and at 1 year are factors of poor prognosis for reintervention. Patients undergoing reintervention for pain less frequently required postsurgical medical treatment. More than half of patients with interfertility and endometriosis achieved spontaneous pregnancy after surgery.     

Long-term follow-up and recurrence rate after mesorectum-sparing bowel resection among women with rectovaginal endometriosis

Objective

To demonstrate the quality of a combined vaginal–abdominal surgical approach to rectovaginal endometriosis by analyzing long-term outcome and recurrence rates.

Methods

In a prospective cohort study in Berlin, Germany, women with endometriosis of the rectovaginal septum were enrolled between September 2004 and December 2012. Bowel infiltration was verified intraoperatively and treated by a nerve-sparing, mesentery-preserving vaginal–abdominal operative approach. Operative results were evaluated by assessing short- and long-term complications and recurrence rates.

Results

During the study period, 110 women underwent surgery. For 71 (64.5%) patients, bowel infiltration was confirmed intraoperatively. Overall, 15% of the patients had peri- or postoperative complications. No long-term complications occurred. After a median follow-up of 64 months, no recurrence in the rectovaginal septum was observed among the study patients. The recurrence of pelvic endometriosis was 15%.

Conclusion

The surgical nerve-sparing approach to rectovaginal endometriosis was confirmed to facilitate precise diagnosis and treatment with minimal morbidity and a long-term complication rate of 0%.     

Biopsychosocial correlates of persistent postsurgical pain in women with endometriosis

Objective

To examine pain and biopsychosocial correlates over time for women with persistent postsurgical pain after surgery for endometriosis.

Methods

Cross-sectional study of women who underwent any endometriosis surgery between 2003 and 2006. Following surgery, patients completed validated questionnaires (Short-Form McGill Pain Questionnaire, 12-item Short-Form Health Survey, Beck Depression Inventory, Coping Strategies Questionnaire catastrophizing subscale). The primary outcome was pelvic pain intensity, measured by the McGill total pain score. Bivariate comparisons between each potential predictor and pain intensity were performed using the χ² and t tests, 1-way analysis of variance, and simple linear regression.

Results

In total, 79 completed the questionnaires and were included in the present analysis. The McGill affective pain score was negatively correlated with age (β-coefficient –0.12, P = 0.002) and positively correlated with catastrophization (β-coefficient 0.66, P = 0.01). Women with a history of dyspareunia scored significantly higher on the McGill total pain score (P < 0.001); there was no association between pain intensity and endometriosis severity.

Conclusion

Younger age and catastrophization are correlated with persistent pain following surgery for endometriosis. The severity of endometriosis does not predict persistent pain. Further evaluation of psychosocial factors may identify patients who are least likely to benefit from surgeries for endometriosis-associated pelvic pain.     

A retrospective review of patient-reported outcomes on the impact on quality of life in patients undergoing total abdominal hysterectomy and bilateral salpingo-oophorectomy for endometriosis

Objective

The Endometriosis Health Profile-30 (EHP-30), an endometriosis-specific health-related quality of life (HRQoL) questionnaire, forms part of our service evaluation of all women undergoing total abdominal hysterectomy and bilateral salpingo-oophorectomy for endometriosis in our reproductive medicine unit. We used the EHP-30 to investigate patient-reported outcomes in all patients undergoing this procedure.

Study design

Retrospective review of 16 women with endometriosis undergoing total abdominal hysterectomy and bilateral salpingo-oophorectomy for debilitating symptoms after other modalities of treatment had failed. Patients completed EHP-30 questionnaires before the operation and again three months after surgery.

Results

Total abdominal hysterectomy and bilateral salpingo-oophorectomy for endometriosis results in a significant improvement in HRQoL. The impact was greatest in the core domains – control and powerlessness, emotional wellbeing and social support. There was a 100% response rate for the core domains whereas in the modular domains, missing response rates ranged from 12.5% to 62.5%, with the percentage of missing data being greatest in the concern on infertility and relationship with children domains. Pain was significantly positively correlated with control and powerlessness, emotional wellbeing, work life and relationship with children. After multiple regression analyses, only control and powerlessness and emotional wellbeing were found to be predictive of pain. Additionally, changes in pain before and after total abdominal hysterectomy and bilateral salpingo-oophorectomy were significantly positively correlated with the changes in the core domains – control and powerlessness, emotional wellbeing and self image. After multiple regression analyses, change in pain was found to be predictive of ΔControl and powerlessness in our study subjects.

Conclusion

Total abdominal hysterectomy and bilateral salpingo-oophorectomy significantly improves HRQoL in patients debilitated by symptoms attributable to endometriosis and in whom other modalities of treatment have failed.     

Guidelines for the management of painful endometriosis

Objectives

To establish guidelines for the medical and surgical management of painful endometriosis.

Material and Methods

An exhaustive review on Medline and Cochrane Database between 1980 and 2006 was performed.

Results

GnRH agonists, progestins, continuous monophasic oral contraceptives and danazol have a suppressive effect on dysmenorrhoea, nonmenstrual pain and dyspareunia (grade A). Surgical treatment is effective in painful endometriosis (grade B). Complete surgical excision of deep endometriotic lesions with conservation of uterus and ovaries has a limited term efficacy on pain relief (grade C). A multidisciplinary approach is recommended (grade C). The use of the psychotherapy improves the management of chronic pain (grade A). There is a lack of information concerning the therapeutic strategy able to prevent recurrences. Whether endometriosis recurrences occur, medical treatment should be the first line approach (expert opinion). A hysterectomy with salpingo-oophorectomy and complete excision of the lesions is efficient in women with pain recurrence who no longer desire pregnancy (grade C).

Conclusion

Medical and surgical treatments have a limited term efficacy on painful endometriosis (grade A). The benefit/risk relationship, depending on secondary effect therapy, should be assessed on a case to case basis.     

Ileocecal endometriosis: diagnosis and management

Objective

Ileocecal endometriosis is rare. Symptoms range from no symptoms, cramps, vomiting, to acute intestinal obstruction. Our objective was to review our cases, clarify, and resume its most appropriate management focusing on the factors to determine diagnosis. This is a retrospective study by revision of medical charts of all ileal endometriosis cases of our unit from 2006 to 2014.

Factors Associated with Severity of Irritable Bowel Syndrome Symptoms in Patients with Endometriosis

Objective

This study sought to examine factors associated with severity of irritable bowel syndrome (IBS) by using the Birmingham IBS symptom scale in patients presenting with endometriosis to a tertiary referral centre.

Letrozole and norethisterone acetate in rectovaginal endometriosis

This open-label prospective study evaluated the efficacy of letrozole (2.5 mg/day) combined with norethisterone acetate (2.5 mg/day) in the treatment of pain symptoms related to the presence of rectovaginal endometriosis. The treatment significantly and quickly decreased the intensity of symptoms, but pain recurred at 3-month follow-up; five women underwent surgery during the follow-up, and histologic examination of rectovaginal nodules revealed the presence of active endometriotic lesions.     

Responsiveness of the Dutch Endometriosis Health Profile-30 (EHP-30) questionnaire

Objective

To evaluate the responsiveness to change and the minimal clinical important difference (MCID) of the Dutch Endometriosis Health Profile-30 (EHP-30) questionnaire.

Study design

Prospective cohort study among endometriosis patients attending the Radboud University Nijmegen Medical Centre and members of the Dutch endometriosis patient-support group. EHP-30 was measured at baseline and after 6 months. Changes in treatment were recorded, as well as the subjective change in symptoms. Effect sizes and index of responsiveness were evaluated as appropriate. The MCID was estimated with use of the change in scores in women reporting to feel ‘somewhat better’ after 6 months.

Results

228 women were included. Effect sizes varied from 0.1 to 0.5 in the complete group and from 0.3 to 1.1 in the group of women who reported improvement. Index of responsiveness ranged from 0.1 to 0.7 on the eleven dimensions of the questionnaire. MCID was 3.2–17.5 depending on the dimension.

Conclusions

The Dutch EHP-30 is sensitive to change and represents a useful tool in future research on the effect of endometriosis treatment on health status.     

Decreased expression of pigment epithelium-derived factor and increased microvascular density in ovarian endometriotic lesions in women with endometriosis

Objectives

To determine whether women with endometriosis have altered expression of pigment epithelium-derived factor (PEDF) in ovarian endometriotic lesions as compared to women without endometriosis.

Study design

Ectopic and eutopic and normal endometrial tissues were sampled from 40 women with ovarian endometriosis and 20 control women, respectively. Endometrial PEDF expression and microvascular density (MVD) using an antibody to von Willebrand factor (vWF) and alpha-smooth muscle actin (α-SMA) were evaluated by using immunohistochemical staining.

Results

We detected decreased PEDF expression and increased MVD using anti-vWF and -α-SMA in ovarian endometriotic lesions in women with endometriosis compared with the control group. In women with endometriosis, the MVD using anti-vWF and -α-SMA but not PEDF expression in ovarian endometriotic lesions correlated with the size of ovarian endometriotic cysts and the severity of the disease. Moreover, the MVD using anti-vWF was negatively correlated with PEDF expression in control endometrium but not in ovarian endometriotic lesions.

Conclusions

Our results suggest that decreased PEDF expression and increased MVD in ovarian endometriotic lesions might play an important role in the pathogenesis of ovarian endometriosis.     

Tratamiento de la endometriosis con 5 mg o 25 mg diarios de mifepristona durante 6 meses. Ensayo clínico aleatorizado,doble ciego

Objectives

To evaluate the safety and efficacy of 5 mg and 25 mg doses of mifepristone for the treatment of endometriosis.

Design

Randomized double-blind study.

Setting

Eusebio Hernández Hospital, Havana, Cuba.

Subjects

Twenty-six women laparoscopically diagnosed with endometriosis were included.

Treatment

Group I received one tablet of 25 mg mifepristone daily and group II received one tablet of 5 mg mifepristone daily for 6 months. Laparoscopy and endometrial biopsy were performed before and after treatment.

Variable to evaluate efficacy

Reduction in the intensity of dysmenorrhea measured by a visual analogue scale.

Results

In both groups reductions in the intensity of dysmenorrhea and dyspareunia were highly significant compared with initial values (P <.001). All the women were amenorrheic after 45 days of treatment.

Conclusions

At doses of 5 mg or 25 mg, mifepristone could be an alternative for the treatment of endometriosis.     

Histopathology-based combined surgical approach to rectovaginal endometriosis

Objective

To describe a new surgical approach to rectovaginal endometriosis. Rectovaginal endometriosis can be infiltrative or superficial involving the bowel. Only infiltrative disease should be treated by intestinal resection. However, infiltration of endometriosis cannot be confirmed by preoperative imaging techniques.

Methods

A total of 48 women with infiltrative rectovaginal endometriosis were included in this prospective study. Surgery was performed using a newly developed technique. All bowel resections were indicated according to operative findings and not on the basis of preoperative imaging technique results.

Results

The decision for rectosigmoidal resection was based on the results of the intraoperative dissection of the rectovaginal septum. Histologically, infiltration of the ventral bowel wall was confirmed in all cases.

Conclusion

This new surgical technique for the treatment of rectovaginal endometriosis allows precise diagnosis and treatment with low morbidity. A resection of the mesorectum is not necessary because the endometriotic nodules are always located on the antimesenteric surface of the bowel.     

Regression of the inflammatory microenvironment of the peritoneal cavity in women with endometriosis by GnRHa treatment

Objective

To investigate the effect of gonadotropin-releasing hormone analogues (GnRHa) on the peritoneal fluid microenvironment in women with endometriosis.

Study design

Peritoneal fluid was collected from 85 women with severe endometriosis (rAFS stage III and IV) during laparoscopic surgery during the proliferative phase. Prior to surgery clinical data were collected. The concentrations of specific markers for endometriosis in the peritoneal fluid were determined using an ELISA and a comparison between peritoneal fluid markers in women using GnRHa and no hormonal treatment was performed using a non-parametric Mann–Whitney U test.

Results

The study included peritoneal fluid from 39 patients who had been administered GnRHa (Zoladex^®) in the three months prior to surgery and 46 from women with no hormonal treatment in this period. Concentrations of IL-8, PAPP-A, glycodelin-A and midkine were significantly reduced in the GnRHa treatment group compared to women receiving no hormonal treatment. RANTES, MCP-1, ENA-78, TNF-α, OPG, IP-10 and defensin showed no significant change between the two groups.

Conclusions

GnRHa mediate a significant regression in the inflammatory nature of the peritoneal microenvironment in women with endometriosis.     

Increased levels of oxidative stress markers in the peritoneal fluid of women with endometriosis

Objective

To evaluate 8-hydroxy-2-deoxyguanosine (8-OHdG) and 8-isoprostane levels in the peritoneal fluid (PF) of women with endometriosis.

Study design

One hundred and ten women with laparoscopically and histopathologically confirmed endometriosis and, as reference groups, 119 patients with simple serous (n = 78) and dermoid (n = 41) ovarian cysts were studied. Peritoneal fluid 8-OHdG and 8-isoprostane concentrations were evaluated by enzyme-linked immunosorbent assays.

Results

8-OHdG and 8-isoprostane levels in peritoneal fluid were significantly higher in patients with endometriosis compared with the reference groups. Higher PF 8-OHdG and 8-isoprostane concentrations were observed in patients with advanced stages of endometriosis. A statistically significant positive correlation was found between 8-OHdG and 8-isoprostane levels in peritoneal fluid.

Conclusion

Endometriosis induces greater oxidative stress and frequent DNA mutations in peritoneal fluid than nonendometriotic ovarian cysts. The most severe oxidative stress occurs in the peritoneal cavity of women with more advanced stages of the disease.     

Complete loss of unilateral renal function secondary to endometriosis: a report of three cases

Objectives

To report the impact that urinary tract endometriosis may have on renal function. Ureteral endometriosis is an uncommon and silent cause of renal injury. It is therefore very important to be highly suspicious in order to be able to make an early diagnosis and thus prevent renal failure.

Study design

Case reports of the management and outcome of three cases of premenopausal women with deep endometriosis affecting the ureter, associated with secondary unilateral complete loss of renal function.

Results and conclusions

Ureteral involvement by endometriosis is a rare and often silent disease which is capable of producing significant morbidity, as it can lead to hydronephrosis and ultimately to renal failure. Because of the lack of specific symptoms and the limitations of imaging methods, a high index of suspicion is necessary to obtain an early diagnosis. On diagnosis of deep infiltrating endometriosis, urinary tract ultrasound is a screening tool to detect ureterohydronephrosis due to ureteral obstruction. MRI is of value to map the extent of disease. Surgery is the treatment of choice to remove endometriotic lesions and relieve ureteral obstruction if the kidney is still functional, or to perform a nephrectomy if there is a complete loss of renal function.     

What do midwives need to know about approaches of women towards labour pain management? A qualitative interview study into expectations of management of labour pain for pregnant women receiving midwife-led care in the Netherlands

Objective

to investigate factors important to women receiving midwife-led care with regard to their expectations for management of labour pain.

Design

semi-structured ante partum interviews and analyses using constant comparison method.

Participants

fifteen pregnant women between 36 and 40 weeks gestation receiving midwife-led care.

Setting

five midwifery practices across the Netherlands between June 2009 and July 2010.

Main outcome

women's expectations regarding management of labour pain.

Results

we found three major themes to be important in women's expectations for management of labour pain: preparation, support and control and decision-making. In regards to all these themes, three distinct approaches towards women's planning for pain management in labour were identified: the ‘pragmatic natural’, the ‘deliberately uninformed’ and the ‘planned pain relief’ approach.

Conclusion

midwives need to recognise that women take different approaches to pain management in labour in order to adapt care to the individual woman.     

Effect of palmitoylethanolamide–polydatin combination on chronic pelvic pain associated with endometriosis: Preliminary observations

Objective

Endometriosis is a chronic oestrogen-dependent gynaecological disorder, the most common symptom of which is pain. Inflammation can be considered one of the major causes of pain in endometriosis. In particular, degranulating mast cells have been found in significantly greater quantities in endometriotic lesions than in unaffected tissues. The increase in activated and degranulating mast cells is closely associated with nerve structures in painful endometriotic lesions. These observations indicate that inflammation due to mast cells may contribute to the development of pain and hyperalgesia in endometriosis. Controlling mast-cell activation may therefore relieve the pain associated with endometriotic lesions.

Study design

Four patients presenting an endometriosis-related pain intensity ≥5 (visual analogue scale for pain, or VAS) were enrolled and monitored during 3 months of the following treatment: oral palmitoylethanolamide 400 mg and polydatin 40 mg, twice daily for 90 days. Deep dyspareunia, dyschezia, dysuria, dysmenorrhoea and analgesic drug use during the 3-month follow-up period were also monitored, with the aim of demonstrating a reliable reduction in chronic pelvic pain.

Results

The preliminary results indicate that all patients enrolled experienced pain relief as early as 1 month after starting treatment. Furthermore, a reduction in the analgesic drugs usually employed for pain control was observed in all subjects treated. Additionally, some improvements in endometriotic lesions seemed to be demonstrated by imaging.

Conclusions

The palmitoylethanolamide–polydatin combination seems to be very useful in controlling chronic pelvic pain associated with endometriosis. As a result of these findings we have initiated a multi-centre pilot study to verify the effectiveness of this treatment in controlling the chronic pelvic pain associated with endometriosis.