Letrozole and norethisterone acetate in colorectal endometriosis

Objective

Up to now limited attention has been given to the medical treatment of bowel endometriosis. This study evaluates the efficacy of aromatase inhibitors and norethisterone acetate in treating pain and gastrointestinal symptoms caused by bowel endometriosis.

Study design

This prospective pilot study included six women with colorectal endometriosis; all women had intestinal nodules infiltrating at least the muscularis propria of the bowel and did not have a stenosis of the bowel lumen >60%; the patients suffered from pain and intestinal symptoms. The study subjects received letrozole (2.5 mg/day) and norethisterone acetate (2.5 mg/day) continuously for 6 months. The presence and intensity of symptoms were evaluated before starting the treatment, and after 3 and 6 months of treatment.

Results

The double-drug regimen improved pain, non-menstrual pelvic pain, deep dyspareunia, dyschezia, symptoms mimicking diarrhoea-predominant irritable bowel syndrome, intestinal cramping, abdominal bloating and passage of mucus in the stools, and 67% of the patients declared that the treatment improved their gastrointestinal symptoms.

Conclusions

The administration of letrozole and norethisterone acetate reduces pain and gastrointestinal symptoms of women with colorectal endometriosis, particularly when patients suffer from symptoms mimicking diarrhoea-predominant irritable bowel syndrome.     

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.     

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.     

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.     

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.     

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.     

Coagulation versus excision of primary superficial endometriosis: a 2-year follow-up

Objective

Even the common mild forms of endometriosis can strongly affect quality of life due to dysmenorrhea, dyspareunia, dyschezia, or subfertility. We compared the effectiveness of the two laparoscopic methods, coagulation versus excision, for intraperitoneal superficial endometriosis with regard to recurrence and symptom control.

Study design

In a retrospective analysis we evaluated the postoperative follow-up of 79 patients, aged 16–42, with superficial manifestation of endometriosis (median rASRM score 9.2) operated on in the Department of Gynecology and Obstetrics at the Jena University Hospital. Forty-three patients were treated by electrocoagulation and 36 underwent sharp excision. Therapy success was evaluated by using a questionnaire after a mean follow-up of 29 months. Patients were interviewed about pain associated with endometriosis such as dysmenorrhea, dyspareunia, dyschezia and possible medical treatment after surgery. We evaluated the number of surgically proven relapses and questionnaire results using a pain score on an ordinal scale (1–5) for the three categories dysmenorrhea, dyspareunia, and dyschezia.

Results

Both treatment methods resulted in a low number of endometriosis-related symptoms after surgical intervention and in recurrences of 2.8% in the coagulation group and 18.6% in the excision group. The recurrence rate in the coagulation group was lower (p = 0.001). The coagulation group was also presented with a significantly lower postoperative pain score at our long-term follow-up (p = 0.0067).

Conclusion

In cases of superficial endometriosis, laparoscopic surgery achieved low recurrence rates and good symptom control. Compared to sharp excision the use of bipolar electrocoagulation might result in fewer endometriosis-related symptoms as well as fewer relapses with need for surgical re-intervention after a more than 2-year interval. Due to the retrospective, non-randomized character of this study the results should be interpreted carefully. Further prospective studies are needed to assess the value of both surgical approaches in the treatment of endometriosis.     

Safety,efficacy, and prognostic factors in endovascular treatment of pelvic congestion syndrome

Objective

To evaluate the safety and effectiveness of transcatheter embolization using coils for treatment of pelvic congestion syndrome (PCS) and to elucidate prognostic factors for clinical success.

Methods

Data were retrospectively analyzed from 113 women with PCS who underwent endovascular embolization of ovarian and pelvic varicose veins at Hospital Clínico Universitario, Zaragoza, Spain between January 2001 and January 2011. Pain score was evaluated before and after the procedure via a visual analog scale (VAS). Associated symptoms (dysmenorrhea, dyspareunia, urinary urgency, and lower limb symptoms) were also evaluated. Patients were followed up for 12 months.

Results

The technical and clinical success was 100%. At 12 months, 53% of patients had no pelvic pain and 47% reported a reduction in pelvic pain. The average VAS was 7.34 before the procedure and 0.47 at 12 months. Complete relief of pain and associated symptoms was achieved for 37% of patients. Urinary urgency, lower limb symptoms, and vulvar and lower limbs varicosities were prognostic factors related to incomplete treatment success. The global complication rate was low (5/113, 4.4%).

Conclusion

Transcatheter embolization was a safe and effective treatment for PCS. Lower limb symptoms, urinary urgency, and varicosities were associated with incomplete clinical success.     

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.     

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.     

Prevalence and incidence of diagnosed endometriosis and risk of endometriosis in patients with endometriosis-related symptoms: findings from a statutory health insurance-based cohort in Germany

Objective

The objectives were: (a) to determine the administrative prevalence and incidence of endometriosis and (b) to assess the risk of endometriosis associated with endometriosis-related symptoms.

Study design

The study is based on inpatient and outpatient data from a statutory health insurance fund in Germany. For prevalence and incidence definition 62,323 women aged 15-54 continuously insured in 2007 were identified. The prevalence and incidence of endometriosis in 2007 were calculated standardized to the age distribution in Germany. In a further prospective cohort study based within the health insurance sample 2095 patients with endometriosis-related symptoms and 8380 age-matched asymptomatic controls were identified. Endometriosis follow-up was from 2004 to 2008. Cox proportional hazard regression was used to examine the risk of endometriosis associated with endometriosis-related symptoms, such as pelvic pain, dysmenorrhoea, dyspareunia, menorrhagia, post-coital bleeding, inter-menstrual pain and ovarian cysts. Relative risks (RR) and 95% confidence intervals (CI) were calculated.

Results

Standardized prevalence and incidence rates were 8.1 and 3.5 per 1000 women, respectively. The highest prevalence was observed in women aged 35-44 with 12.8 per 1000 women. Median follow-up was 4.5 years. Risk of endometriosis associated with endometriosis-related symptomatology was RR (95% CI) = 4.95 (3.67-6.68); 4.5% of all symptomatic women were diagnosed with endometriosis in a median follow-up of 4.5 years. The highest risk was observed in women aged 35-44 [RR (95% CI) = 6.29 (4.00-9.90)] with 7.6% of all symptomatic women receiving a diagnosis of endometriosis during the follow-up.

Conclusion

Prevalence estimates based on population-based administrative data were lower than described in the literature. Risk of endometriosis was increased in women with endometriosis-related symptoms. However, those symptoms were of limited predictive value for endometriosis as only a small proportion of symptomatic patients were diagnosed with endometriosis in the follow-up.     

The V109G polymorphism in the p27 gene is associated with endometriosis

Objective

To investigate the prevalence of the p27 gene polymorphism in women with endometriosis.

Study design

Transversal case–control study. Genomic DNA was extracted from cells collected from buccal swabs. The p27 V109G polymorphism was investigated using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in a hospital-based Brazilian population.

Results

We analysed the 104 patients and 109 control subjects. The distribution of genotype and allele frequencies of p27 V109G polymorphism was significantly different between the endometriosis cases and healthy women (p = 0.016 and 0.002). Women who had at least one mutated allele presented twofold chances for endometriosis development (OR = 1.9; 95% CI, 1.120–3.343).

Conclusion

The polymorphic variant at codon 109 of the p27 gene seems to be associated with higher risk of endometriosis development.     

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.     

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.     

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.     

Perineal pain following childbirth: prevalence, effects on postnatal recovery and analgesia usage

Objective

to establish the prevalence of perineal pain, the effects of pain on postnatal recovery, analgesia used to relieve pain and the perceived effectiveness of such analgesia at the Royal Women's Hospital, Victoria, Australia.

Design, setting and participants

we conducted structured interviews of 215 women in the postnatal ward of a tertiary hospital, within 72 hours of a vaginal birth.

Findings

the structured interviews revealed that 90% of women reported some perineal pain, with 37% reporting moderate or severe pain. The degree of perineal trauma predicted women's ratings of perineal pain on a visual analogue scale, with more severe trauma related to higher pain scores. Over a third of women experienced moderate or severe perineal pain, particularly when walking (33%) or sitting (39%), while 45% noted that pain interfered with their ability to sleep. Women reported moderate or severe perineal pain when they undertook activities involving feeding their infant (12%) or caring for their infant (12%). Women used a range of analgesia, including a combination of ice packs (69%), oral analgesia (75%), narcotic analgesia (4%) and anti-inflammatory suppositories (25%). The majority of women rated these forms of analgesia as effective and identified very few side effects.

Key conclusions

following vaginal birth, women commonly reported pain from perineal trauma. This pain affected women's ability to mobilise and was relieved by a variety of agents. Side effects from analgesia were rare.

Implications for practice

the prevalence of perineal pain and the associated impact on women's recovery from childbirth warrants midwives' proactive care in offering a range of effective pain relief options to women.     

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.