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.     

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.     

Symptomatology and Surgical Perspective of Scar Endometriosis: A Case Series of 16 Women

Aim

The prevalence of scar endometriosis is increasing with the increasing caesarean deliveries and laparoscopic procedures done for pelvic endometriosis. To analyse the symptomatology and surgical perspective of scar endometriosis.

Materials and methods

Retrospective review of 16 women who underwent surgery for scar endometriosis in the period of 4 years in Amrita institute of medical sciences.

Results

Mean age of the patients is 35.19 years. Mean interval from the index surgery to the presentation is 4.56 years. Mean size of the swelling is 2.84 cm. In 68.8% of the patients, caesarean section was the inciting surgery. 18.7% had port site endometriosis. Cyclical pain and swelling at the scar site was present in 93.8% of the women. 18.9% had concurrent pelvic endometriosis. All women had involvement of the subcutaneous tissue followed by 11 women with the involvement of rectus sheath. There was no recurrence of the lesion in the operated patients in the mean follow-up period of 11.91 months.

Conclusion

In all women presenting with cyclical scar site pain and swelling, scar endometriosis should be considered. It commonly follows caesarean section and laparoscopic surgeries done for endometriosis. Wide local excision with or without reconstruction is the method of choice for this condition. Role of tumescent solution during surgery and postoperative medical management to reduce recurrence needs further prospective studies.

     

Polymorphic variants of DNMT3A and the risk of endometriosis

Objective

Overexpression of DNA methyltransferase 3A (DNMT3A) and aberrant methylation of various genes in eutopic endometrium have been demonstrated in women with endometriosis. We aimed to study whether DNMT3A polymorphisms could be a genetic risk factor for endometriosis and endometriosis-related infertility.

Study design

We studied 5 SNPs (rs2289195, rs7590760, rs13401241, rs749131 and rs1550117) located in the DNMT3A gene in 357 women with endometriosis and 640 controls.

Results

We did not observe significant differences between genotype and allele frequencies of rs2289195, rs7590760, rs13401241, rs749131 and rs1550117 SNPs in women with endometriosis, endometriosis-related infertility, and controls. The lowest p values of the trend test were observed for DNMT3A rs1550117 in endometriosis and endometriosis-related infertility (p_trend = 0.049 and p_trend = 0.055, respectively).

Conclusions

Our results did not supply evidence for the contribution of SNPs located in DNMT3A to either endometriosis or endometriosis-related infertility.     

Possible effects of endometriosis-related immune events on reproductive function

Purpose

To examine possible effects of endometriosis-related immune events on reproductive function.

Methods

The synthesis and review of the relevant current literature in English language.

Results

The endometriosis-related immune events may have a negative impact on almost all components of the reproductive function including fallopian tube function, oocyte quality, sperm function, fertilization, embryo quality, endometrial receptivity, implantation and placentation.

Conclusions

An important portion of the cases of infertility or miscarriage seen in women with endometriosis may be due to some immunological alterations associated with endometriosis.     

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.     

Recurrence of Ovarian Endometrioma in Adolescents after Conservative,Laparoscopic Cyst Enucleation

Study Objective

To evaluate the cumulative recurrence rate of endometriomas after a laparoscopic endometriotic cyst enucleation in adolescents and to find the factors associated with recurrence.

Long-term treatment of endometriosis with dienogest: retrospective analysis of efficacy and safety in clinical practice

Purpose

Endometriosis is a debilitating disease with high recurrence rates requiring long-term management. Progestins such as dienogest are used empirically when first symptoms occur and post-surgery to reduce recurrence. This retrospective, practice-based study assessed the efficacy and safety of dienogest in women with endometriosis treated for at least 60 months.

Methods

37 women (age 39?±?8 years) with laparoscopically diagnosed endometriosis received dienogest 2 mg orally once daily. Endometriosis-associated pelvic pain (EAPP) was measured on a 0–100 mm visual analog scale at baseline and every 12 months. Laboratory measures of lipid and liver metabolism, hemostatic and hormonal parameters were investigated in a subgroup of 15 women. Adverse events including bleeding disturbances and depressive symptoms were recorded.

Results

In 22 women, dienogest was begun after laparoscopy; median EAPP score was 70 mm pre-surgery and 10, 10, 20, 20, and 20 mm, respectively, after 12, 24, 36, 48, and 60 months of dienogest treatment. Another 15 women began dienogest without prior surgery; median EAPP score was 80 mm pretreatment and 20, 20, 30, 30, and 30 mm, respectively, after 12, 24, 36, 48, and 60 months. All laboratory parameters remained within the normal range. Mean serum estradiol was 28?±?12 pg/ml after 60 months. Seven women experienced spotting episodes and four women presented with phases of depressed mood, which could all be clinically managed.

Conclusions

Long-term (60-month) treatment with dienogest 2 mg once-daily in women with endometriosis effectively reduced EAPP and avoided pain recurrence post-surgery. Dienogest was well tolerated and adverse effects were clinically managed.

     

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%.     

Vaginal danazol for women with rectovaginal endometriosis and pain symptoms persisting after insertion of a levonorgestrel-releasing intrauterine device

Objective

To evaluate the effectiveness of treatment with vaginal danazol in improving the pain symptoms caused by rectovaginal endometriosis that persist after insertion of a levonorgestrel-releasing intrauterine device (LNG-IUD).

Methods

This pilot observational study included 15 women with rectovaginal endometriosis and pain symptoms persisting after LNG-IUD insertion. Vaginal danazol (100 mg per day) was self-administered for 6 months. The intensity of pain symptoms and the volume of rectovaginal endometriotic nodules were evaluated.

Results

Twelve women were satisfied or very satisfied with the treatment. After treatment with vaginal danazol for 3 months, there was a significant decrease in the intensity of pain symptoms compared with their intensity before the administration of danazol. The intensity of pain symptoms decreased further at 6-month follow-up. The volume of the rectovaginal nodules decreased after treatment with vaginal danazol for 6 months (1.7 ± 0.8 cm³) compared with the baseline volume (2.3 ± 0.9 cm³; P < 0.001). Adverse effects of the treatment were minimal and well tolerated.

Conclusion

Although a placebo effect cannot be excluded, the results indicate that vaginal danazol decreases the severity of endometriosis-related pain symptoms after LNG-IUD insertion.     

Long-term follow-up after laparoscopic treatment for endometriosis: multivariate analysis of predictive factors for recurrence of endometriotic lesions and pain

Objective

To investigate factors that might influence the recurrence of both painful symptoms and endometriotic lesions following laparoscopic treatment of endometriosis.

Study design

Retrospective cohort study in a University teaching hospital. We reviewed data from patients referred for laparoscopy between March 1993 and November 2007. We selected women who were followed up throughout Transvaginal-ultrasound (TV-US) after a first conservative laparoscopy for endometriosis. After laparoscopy, all patients were followed up according to an internal protocol: a standard gynaecologic examination, the assessment of painful symptoms and a TV-US scan that were repeated at 3, 6, and 12 months, and subsequently on a yearly basis. Sixteen factors were assessed by univariable and multivariable Cox proportional hazards models to evaluate their associations with recurrence of endometriotic lesions and pain related-endometriosis.

Results

401 women were enrolled. A total of 154 (38.4%) experienced moderate or severe pain after laparoscopy; endometriotic lesions were observed by TV-US in 74 (18.4%) patients. In the multivariable model, age at menarche, severity of chronic pelvic pain (CPP) and dysmenorrhoea prior to surgery were significant risk factors for recurrence/occurrence of pain. Age at the first laparoscopy, stage of disease, pre-operative severity of CPP, and pregnancy were predictive factors of the recurrence for such lesions.

Conclusion

The severity of CPP prior to the first laparoscopy showed the only significant factor in the overall prediction of recurrence of pain and endometriotic lesions. Patients with severe CPP at the time of their first surgery might represent a sub-group of women with a more aggressive form of endometriosis.     

The impact of IVF procedures on endometriosis recurrence

Objective

In infertile women with endometriosis requiring an in vitro fertilization (IVF) procedure, the potential risk of an IVF-related progression of the disease remains a matter of debate. Thus, since available data on this issue are scanty and controversial, an observational study has been herein conducted in order to clarify this issue.

Study design

We recruited 233 women with endometriosis who underwent IVF cycles in our unit. Patients were contacted to assess whether they experienced recurrences of the disease after IVF. The main outcome was to evaluate the impact of the number of IVF cycles and the responsiveness to ovarian hyperstimulation on the likelihood of recurrence. Clinical characteristics of women who did and did not have a recurrence were compared.

Results

One hundred and eighty-nine women were included, 41 of whom (22%) had a diagnosis of endometriosis recurrence. The 36 months cumulative recurrence rate was 20%. The number of IVF cycles and the responsiveness to ovarian hyperstimulation were not associated with the risk of disease recurrence. The adjusted OR for recurrences according to the number of started cycles was 0.92 (95% CI: 0.77–1.10) per cycle (p = 0.35). The adjusted OR for recurrences in women with intact versus compromised ovarian reserve was 0.80 (95% CI: 0.40–1.58) (p = 0.52).

Conclusions

IVF procedures do not seem to influence the likelihood of endometriosis recurrence.     

Research development of a new GnRH antagonist (Elagolix) for the treatment of endometriosis: a review of the literature

Purpose

Limitated studies have reported the efficacy of GnRH antagonist on endometriosis symptoms. The aim of our study was to review all available trials to investigate the medical treatment of endometriosis with only GnRH antagonists, with special attention to pharmacodynamic activity, safety, and efficacy.

Methods

Pub Med and Sciencedirect database were searched using terms of “endometriosis treatment”, “GnRH antagonist”, and “Elagolix”. The search was limited to clinical studies published in English. Title and abstract were screened to identify relevant articles.

Results

Five studies covering use of GnRH antagonist were found. A phase 1 study evaluated the safety, pharmacokinetics, and inhibitory effects on gonadotropins and estradiol of single dose and 7 day elagolix administration to healthy premenopausal women; two phase II studies evaluated efficacy in patient with endometriosis. Moreover, there are two Phase III clinical trials just completed.

Conclusion

GnRH antagonists may have the advantage of oral administration and lower incidence of adverse events. Currently, only Phase II studies have been published demonstrating promising results in terms of efficacy, safety, and tolerability. From the results of the phase III studies, elagolix may become a valuable addition to the armamentarium of pharmacological agents to treat endometriosis-related pain.

     

Molecular evaluation of proliferative-phase endometrium may provide insight about the underlying causes of infertility in women with endometriosis

Purpose

To determine if endometrial gene expression is different in women with endometriosis-related infertility and fertile women.

Methods

Prospective study of mid-follicular phase endometrium in 47 subjects in two phases: microarray study of 10 infertile women with endometriosis and five fertile controls, and a quantitative real-time PCR (qRT-PCR) study of 27 infertile women with endometriosis and 15 fertile controls. Gene expression was determined by DNA microarray, and qRT-PCR used for 12 “promising” genes based on the microarray analysis.

Results

Compared to fertile controls, women with stage I–II endometriosis had 23, and women with stage III–IV had 35 genes that were significantly up- or down-regulated by microarray. However, using qRT-PCR, only chemokine ligand (CXCL) 13 was significantly down-regulated and somatostatin was significantly up-regulated with early endometriosis, and only CXCL 14 was significantly down-regulated with advanced endometriosis compared to fertile controls.

Conclusions

Our findings indicate that the pattern of gene expression in proliferative-phase endometrium is different when comparing tissue from patients with endometriosis versus fertile controls. Recognition of these endometrial alterations could be helpful to diagnose and stage endometriosis, and may provide insight to explain why conception rates are low in women with endometriosis.     

Caesarean section greatly increases risk of scar endometriosis

Objective

To estimate the incidence of scar endometriosis after different surgical procedures.

Study design

A retrospective study of 72 patients diagnosed with scar endometriosis between 1978 and 2003 was performed. Patient age, site of endometriosis, previous operations, time-gap between last surgery and onset of symptoms, nodule characteristics, and recurrence were evaluated.

Results

Age ranged from 16 to 48 years. Location varied according to the previous surgery: 46 caesarean section, one hysterectomy, one in abdominal surgery, 19 episiotomy, one was a relapse and two pelvic floor procedures, two women with no previous surgery. The incidence of scar endometriosis after caesarean section was significantly higher than after episiotomy (0.2 and 0.06%, respectively: p < 0.00001) with a relative risk of 3.3. Pain was the most frequent symptom. The mean time between surgery and onset of symptoms was 3.7 years.

Conclusion

Our findings confirm that scar endometriosis is a rare condition and indicate, probably for the first time, that caesarean section greatly increases the risk of developing scar endometriosis.     

Endometriosis is the independent prognostic factor for survival in Chinese patients with epithelial ovarian carcinoma

Background

Clinico-pathological characteristics and possible prognostic factors among women with epithelial ovarian carcinoma (EOC) with or without concurrent endometriosis were explored.

Method

We retrospectively identified 304 patients with EOC treated primarily at Peking Union Medical College Hospital with median follow-up time of 60 months.

Results

Of 304 patients with EOC, concurrent endometriosis was identified in 69 (22.7%). The patients with concurrent endometriosis were younger and more probably post-menopausal at onset, were less likely to have abdominal distension, with significantly lower level of pre-surgery serum Ca125 and less possibility of having the history of tubal ligation. The women with concurrent endometriosis group were more likely to have early stage tumors (88.41% versus 52.77%), receive optimal cytoreductive surgery (92.75% versus 71.06%), and less likely to have lymph node metastasis or to develop platinum resistance disease (7.25% versus 14.89%, and 7.35% versus 20%), when compared with women without coexisting endometriosis. The univariate analysis showed that concurrent endometriosis was a prognostic factor for overall survival (OS) and disease-free survival (DFS), but this association just remained in the DFS by multivariate analysis. Besides, multivariate analysis also showed that FIGO stage, residual disease, chemotherapy cycles, chemotherapy resistance and concomitant hypertension were the independent impact factors of OS for EOC patients; whereas FIGO stage, lymphadenectomy, residual disease, coexisting endometriosis and chemoresistance were independent impact factors of DFS for those patients.

Conclusions

EOC patients with concurrent endometriosis showed distinct characteristics and had longer overall survival and disease-free survival when compared with those without endometriosis. Endometriosis was the independent prognostic factor for DFS for patients in this series.

     

Postoperative Hormonal Suppression for Prevention of Deeply Infiltrative Endometriosis Recurrence After Surgery

Purpose of Review

The long-term management of deeply infiltrative endometriosis (DIE) remains debatable. Surgical excision improves pain and fertility in patients with endometriosis, however recurrence is common. In this article, we present an evidence-based approach of recurrence and postoperative hormonal suppression in DIE.

Recent Findings

A clear understanding of recurrence patterns and methods for prevention of DIE are lacking. Repeat surgery in DIE patients is associated with increased morbidity. Older data has suggested the limited utility of short-term postoperative hormonal suppression for the prevention of pain or disease recurrence for patients with endometriosis (Yap et al., Cochrane Database Syst Rev. (3):CD003678, 2004). More recent studies suggest that long-term medical therapy with oral contraceptive pills (OCPs) or progesterone only pills (POPs) reduces recurrence of superficial disease and endometriomas. Limited data, however, exists for DIE.

Summary

This article reviews the literature of hormonal suppression for the prevention of postoperative recurrence of DIE. Despite the dearth of data, the current evidence suggests the utility of long-term postoperative hormonal suppression after surgery especially in those who underwent incomplete excision of DIE. Longer follow-up studies are greatly needed.

     

The clinical profile of young and adolescent women with laparoscopically diagnosed endometriosis in a Singapore tertiary hospital

Objective

Endometriosis has been increasingly recognized as the cause of severe dysmenorrhea among younger women including adolescents, often with significant delay from time of presentation to diagnosis. Data on the South East Asian women is scarce. This study aims to describe the disease pattern in a group of young Asian women with histological diagnosis of endometriosis in our center.