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Sample records for endometriosis

  1. Endometriosis

    MedlinePlus

    ... a baby grows when a woman is pregnant. Endometriosis is a disease in which tissue that normally ... may be the first sign. The cause of endometriosis is not known. Surgery, usually a laparoscopy, is ...

  2. Endometriosis

    MedlinePlus

    Endometriosis is a problem affecting a woman's uterus - the place where a baby grows when she's pregnant. Endometriosis is when the kind of tissue that normally ... may be the first sign. The cause of endometriosis is not known. Pain medicines and hormones often ...

  3. Endometriosis

    MedlinePlus

    ... in the following places: • Peritoneum • Ovaries • Fallopian tubes • Outer surfaces of the uterus, bladder , ureters , intestines, and rectum • Cul-de-sac (the space behind the uterus) How does endometriosis cause problems? ...

  4. Endometriosis

    MedlinePlus

    ... want children in the future There are different treatment options. PAIN RELIEVERS If you have mild symptoms, you may be ... with: Exercise and relaxation techniques. Over-the-counter pain ... HORMONE THERAPY These medicines can stop endometriosis from getting worse. ...

  5. Endometriosis (For Teens)

    MedlinePlus

    ... How Can I Help a Friend Who Cuts? Endometriosis KidsHealth > For Teens > Endometriosis Print A A A ... doctor thought Anne might have endometriosis. What Is Endometriosis? When a woman has endometriosis, tissue that looks ...

  6. Living with endometriosis

    MedlinePlus

    Pelvic pain - living with endometriosis; Endometrial implant - living with endometriosis; Endometrioma - living with endometriosis ... counter pain relievers can reduce the pain of endometriosis. These include: Ibuprofen (Advil) Naproxen (Aleve) Acetaminophen (Tylenol) ...

  7. What Is Endometriosis?

    MedlinePlus

    ... NICHD Research Information Clinical Trials Resources and Publications Endometriosis: Condition Information Skip sharing on social media links Share this: Page Content What is endometriosis? Endometriosis is the term used to describe when ...

  8. [Intestinal endometriosis].

    PubMed

    González Rodríguez, C I; Cires, M; Jiménez, F J; Rubio, T

    2008-01-01

    Endometriosis is a chronic, benign gynaecological disorder that is frequent in women of a child-bearing age. It is estimated that there is some degree of endometriosis in as many as 15% of pre-menopausal women, associated with a history of infertility, caesarean antecedents, dysmenorrhoea and abnormality in uterine bleeding. It is believed to be due to the rise of menstrual contents through the Fallopian tubes (retrograde menstruation). In the intestinal affectation, the colon is the segment most frequently affected, above all at the rectosigmoidal level. The clinical features are unspecific, with abdominal pain the most frequent and/or pelvic pain of a cholic type that coincides with, or is exacerbated by, menstruation. Differential diagnosis includes intestinal inflammatory disease, diverticulitis, ischemic colitis and neoplastic processes, with the definitive diagnosis being anatomopathological. With respect to treatment, this will depend on the clinical features and the age of the patient, as well as her wishes with regard to pregnancy. PMID:18953367

  9. Microsurgery of ovarian endometriosis.

    PubMed

    Brosens, I A; Boeckx, W; Page, G

    1988-04-01

    A long-term follow-up study of 92 patients with ovarian endometriosis treated with microsurgical techniques showed that although endometriosis may persist in many patients, only seven patients required repeat ovarian surgery. Microsurgical techniques are to be recommended for the treatment of ovarian endometriosis and the prevention of postoperative adhesive disease of the ovaries. PMID:3372697

  10. Endometriosis still a challenge

    PubMed Central

    Mehedintu, C; Plotogea, MN; Ionescu, S; Antonovici, M

    2014-01-01

    Abstract Endometriosis is a debilitating disease with features of chronic inflammation. Endometriosis appears to be one of the most common benign gynecological proliferations in premenopausal women since it is estimated that 10–15% of reproductive aged women suffer from pelvic endometriosis. The biology of endometriosis is unclear. Despite its prevalence, this disease remains poorly understood and current studies prove that there is no relationship between the extent of the disease and its symptomatology. There is no blood test available for the diagnosis of endometriosis. Up to this point, there is no single very successful option for the treatment of endometriosis. Due to the relatively poor efficacy of hormonal therapy for endometriosis, several other experimental therapies are currently undergoing clinical trial. PMID:25408753

  11. Endometriosis: A Guide for Teens

    MedlinePlus

    ... Health Gynecology Medical Conditions Nutrition & Fitness Emotional Health Endometriosis: General Information Posted under Health Guides . Updated 29 ... can improve symptoms and preserve fertility. What is endometriosis? Endometriosis, pronounced, “end–o–me–tree–o–sis” ...

  12. Endometriosis-associated Malignancy

    PubMed Central

    Krawczyk, N.; Banys-Paluchowski, M.; Schmidt, D.; Ulrich, U.; Fehm, T.

    2016-01-01

    Endometriosis is a common condition in women of reproductive age. According to several epidemiological studies endometriosis may be associated with increased risk of various malignancies. However, endometriosis-associated malignancy (EAM) is defined by certain histological criteria. About 80 % of EAM have been found in the ovary, whereas 20 % are localized in extragonadal sites like intestine, rectovaginal septum, abdominal wall, pleura and others. Some authors suggest that EAM arise from atypical endometriosis as an intermediate lesion between endometriosis and cancer. Moreover, a number of genetic alterations, like loss of heterozygosity (LOH), PTEN, ARID1 A and p53 mutations have been found in both endometriosis and EAM. Endometriosis-associated ovarian cancer (EAOC) is mostly a well or intermediately differentiated tumor of endometrioid or clear cell histological sub-type. Women affected by EAOC are on average five to ten years younger than non-EAOC patients; in most of the cases EAOC is a low stage disease with favorable clinical outcome. Since EAM is a rare condition systematic data on EAM are still missing. A systematic retrospective study on endometriosis-associated malignancies (EAM study) is currently being conducted by the Endometriosis Research Foundation together with the study groups on ovarian and uterine tumors of the working group for gynecological oncology (AGO) (gyn@mlk-berlin.de). PMID:26941451

  13. Priorities for Endometriosis Research

    PubMed Central

    Rogers, Peter A. W.; D’Hooghe, Thomas M.; Fazleabas, Asgerally; Gargett, Caroline E.; Giudice, Linda C.; Montgomery, Grant W.; Rombauts, Luk; Salamonsen, Lois A.; Zondervan, Krina T.

    2009-01-01

    Endometriosis is an estrogen-dependent disorder where endometrial tissue forms lesions outside the uterus. Endometriosis affects an estimated 10% of women in the reproductive-age group, rising to 30% to 50% in patients with infertility and/or pain, with significant impact on their physical, mental, and social well-being. There is no known cure, and most current medical treatments are not suitable long term due to their side-effect profiles. Endometriosis has an estimated annual cost in the United States of $18.8 to $22 billion (2002 figures). Although endometriosis was first described more than 100 years ago, current knowledge of its pathogenesis, spontaneous evolution, and the pathophysiology of the related infertility and pelvic pain, remain unclear. A consensus workshop was convened following the 10th World Congress on Endometriosis to establish recommendations for priorities in endometriosis research. One major issue identified as impacting on the capacity to undertake endometriosis research is the need for multidisciplinary expertise. A total of 25 recommendations for research have been developed, grouped under 5 subheadings: (1) diagnosis, (2) classification and prognosis, (3) treatment and outcome, (4) epidemiology, and (5) pathophysiology. Endometriosis research is underfunded relative to other diseases with high health care burdens. This may be due to the practical difficulties of developing competitive research proposals on a complex and poorly understood disease, which affects only women. By producing this consensus international research priorities statement it is the hope of the workshop participants that researchers will be encouraged to develop new interdisciplinary research proposals that will attract increased funding support for work on endometriosis. PMID:19196878

  14. The history of endometriosis.

    PubMed

    Benagiano, Giuseppe; Brosens, Ivo; Lippi, Donatella

    2014-01-01

    A dispute has recently emerged whether early descriptions exist of the condition we name endometriosis. A first question is: 'Who identified endometriosis?' To respond, two non-complementary methods have been employed: searching for ancient descriptions of symptoms associated with endometriosis or, alternatively, identifying researchers who described pathological features we associate with the presence of endometriosis in its various forms. We opted for the latter and found no evidence that in older times anyone delineated the macroscopic features of endometriosis; descriptions of menstrual or cyclic pain cannot be taken as proof of knowledge of what caused it. During the mid-part of the 19th century, Rokitansky had a great intuition: endometrial glands and stroma can be present in ovarian and uterine neoplasias. However, using histological parameters of endometrial structure and activity, the first scientist to delineate peritoneal endometriosis under the name 'adenomyoma' was Cullen. On the other hand, Rokitansky was the first to describe a form of adenomyosis (an adenomatous polyp). Early descriptions of ovarian endometrioma as 'haematomas of the ovary' or 'chocolate cysts' date back to the end of the 19th century. The first mention of an 'ovary containing uterine mucosa' was published in 1899 by Russel, but Sampson was the first to demonstrate specific endometrial activities, such as desquamation at the time of menstruation and decidualization in pregnancy; subsequently, he presented a theory on its pathogenesis. PMID:24853333

  15. Seeking New Treatments for Endometriosis

    MedlinePlus

    ... Media Resources Interviews & Selected Staff Profiles Multimedia Seeking New Treatments for Endometriosis Skip sharing on social media ... genetic mechanisms of endometriosis may help in developing new prevention and treatment strategies. The NICHD’s extramural Gynecologic ...

  16. Endometriosis: Does It Cause Infertility?

    MedlinePlus

    ... Website of the American Society for Reproductive Medicine Endometriosis: Does It Cause Infertility? This fact sheet was ... with The Society of Reproductive Surgeons What is endometriosis? When tissue like the tissue that normally lines ...

  17. [Contraception and endometriosis].

    PubMed

    Brun, G

    1993-01-01

    Choosing a contraceptive method for a woman with endometriosis is an uncommon problem because endometriosis is relatively rare and because an estimated 30-50% of women with endometriosis are infertile. Uterine or internal endometriosis or adenomyosis is characterized by a congestive and pseudoinflammatory uterus slightly increased in volume. It must be distinguished from pelvic or external or peritoneo-ovarian endometriosis. Pelvic implants may involve destruction of the ovaries by cysts or their imprisonment in adhesions. They may cause stenosis in the proximal portion of the tubes or entrap them in adhesions. 4 stages of endometriosis have been distinguished according to the significance of the lesions and a scoring system. Stage 4 patients with scores over 70 or with a score over 50 for adhesions have been unable to conceive despite treatment. No contraception is necessary in these cases. The choice of a contraceptive for other patients is conditioned by the features of endometriosis. Endometriosis refers to the abnormal localization of a normal endometrium. The implants are sensitive to estrogen. Each implant behaves like a miniature uterus; the mucus proliferates and bleeds if estrogen secretions are present, or atrophies if not. Endometriosis may be completely asymptomatic, or cause sterility, or be accompanied by pain and metrorrhagia. Several earlier treatments of endometriosis have been abandoned because of side effects. The current treatment of choice is an LHRH analog administered by parenteral injections every 4 weeks to bring about a state of pseudomenopause. The treatment produces a rapid desensitization of the pituitary LHRH receptors and a diminution of gonadotrophins, estrogens, and progesterone. The secondary effects are those of hypoestrogenism: hot flashes, vaginal dryness, and increased bone loss after 6 months of treatment. It is also an expensive medication. Contraception is provided by the treatment itself for the first 6 months

  18. Recognising, understanding and managing endometriosis

    PubMed Central

    FRASER, IAN S.

    2008-01-01

    Endometriosis is defined as the presence of tissue lesions or nodules, histologically similar to the endometrium, at sites outside the uterus. It is a highly variable condition that has a wide spectrum of symptoms. The aetiology of endometriosis is probably multifactorial, with a strong familial component recognised. Women with endometriosis have multiple disturbances of function in the eutopic endometrium that women without the disease do not have. A firm diagnosis of endometriosis is rarely possible in general practice. The ‘gold standard’ for the diagnosis of pelvic endometriosis is currently a diagnostic laparoscopy. PMID:19562047

  19. Endocannabinoid involvement in endometriosis

    PubMed Central

    Dmitrieva, Natalia; Nagabukuro, Hiroshi; Resuehr, David; Zhang, Guohua; McAllister, Stacy L.; McGinty, Kristina A.; Mackie, Ken; Berkley, Karen J.

    2010-01-01

    Endometriosis is a disease common in women that is defined by abnormal extrauteral growths of uterine endometrial tissue and associated with severe pain. Partly because how the abnormal growths become associated with pain is poorly understood, the pain is difficult to alleviate without resorting to hormones or surgery, which often produce intolerable side effects or fail to help. Recent studies in a rat model and women showed that sensory and sympathetic nerve fibers sprout branches to innervate the abnormal growths. This situation, together with knowledge that the endocannabinoid system is involved in uterine function and dysfunction and that exogenous cannabinoids were once used to alleviate endometriosis-associated pain, suggests that the endocannabinoid system is involved in both endometriosis and its associated pain. Here, using a rat model, we found that CB1 cannabinoid receptors are expressed on both the somata and fibers of both the sensory and sympathetic neurons that innervate endometriosis’s abnormal growths. We further found that CB1 receptor agonists decrease, whereas CB1 receptor antagonists increase, endometriosis-associated hyperalgesia. Together these findings suggest that the endocannabinoid system contributes to mechanisms underlying both the peripheral innervation of the abnormal growths and the pain associated with endometriosis, thereby providing a novel approach for the development of badly-needed new treatments. PMID:20833475

  20. Immune interactions in endometriosis

    PubMed Central

    Herington, Jennifer L; Bruner-Tran, Kaylon L; Lucas, John A; Osteen, Kevin G

    2011-01-01

    Endometriosis is a common, complex gynecologic disorder characterized by the presence of endometrial glands and stroma at extrauterine (ectopic) sites. In women who develop this disease, alterations in specific biological processes involving both the endocrine and immune systems have been observed, which may explain the survival and growth of displaced endometrial tissue in affected women. In the past decade, a considerable amount of research has implicated a role for alterations in progesterone action at both eutopic and ectopic sites of endometrial growth which may contribute to the excessive inflammation associated with progression of endometriosis; however, it remains unclear whether these anomalies induce the condition or are simply a consequence of the disease process. In this article, we summarize current knowledge of alterations within the immune system of endometriosis patients and discuss how endometrial cells from women with this disease not only have the capacity to escape immunosurveillance, but also use inflammatory mechanisms to promote their growth within the peritoneal cavity. Finally, we discuss evidence that exposure to an environmental endocrine disruptor, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin, can mediate the development of an endometrial phenotype that exhibits both reduced progesterone responsiveness and hypersensitivity to proinflammatory stimuli mimicking the endometriosis phenotype. Future studies in women with endometriosis should consider whether a heightened inflammatory response within the peritoneal microenvironment contributes to the development and persistence of this disease. PMID:21895474

  1. [Psychosomatic aspects of endometriosis].

    PubMed

    Lütje, W; Brandenburg, U

    2003-01-01

    Endometriosis is a varied and unspecific disorder, which can be detected by way of subtle diagnostics in almost every woman. In one case it is a minor accidental finding, in another case it is a cancer-like, mostly incurable, chronic painful a disease, which often has sterility and aggressive therapies as subsequence. For the origin of endometriosis many causes are discussed. The theory of retrograde menstruation through an hyperperistaltic-dystocic uterus presents on one hand an organic explanation-concept. From the psychosomatic point of view this unphysiological menstruation could also be seen as the result of an unsolved conflict, which might be connected with the gender-role or personal, familiar and social attitudes about menstruation. The exo- and endogenic supply with hormones in a time with less pregnancies and therefore more menstruation is also a contributing factor to the origin and development of this disturbance. Beside the theory of endometriosis as an autoimmune disease also implicates psychosomatic thoughts. Though there is always a repeatedly talk the "cancer of the career-woman", there are however very few psychosomatic research projects regarding endometriosis. Therefore it is a characteristic of this disease, that finding and feeling are very often controversial. This emphasizes the importance of psychosomatic, psychosexual, social and biographical aspects in connection with endometriosis. This point of view makes a relative plausible and comfortable explanation for the CPPS and sterility uncertain. Without question diagnosis and therapy of endometriosis followed on one hand by stigmatization and on the other hand by often restriction of quality of life leads to a lot of subsequent psychosocial problems. PMID:14505264

  2. What Are the Symptoms of Endometriosis?

    MedlinePlus

    ... Resources and Publications What are the symptoms of endometriosis? Skip sharing on social media links Share this: ... symptoms, may cause these endometriosis symptoms to continue. Endometriosis-Related Pain Researchers know that pain is a ...

  3. Proton irradiation and endometriosis

    SciTech Connect

    Wood, D.H.; Yochmowitz, M.G.; Salmon, Y.L.; Eason, R.L.; Boster, R.A.

    1983-08-01

    Female rhesus monkeys given single total-body exposures of protons of varying energies developed endometriosis at a frequency significantly higher than that of nonirradiated animals of the same age. The minimum latency period was 7 years after exposure. The doses and energies of the radiation received were within the range that could be received by an aircrew member in near-earth orbit during a random solar flare event, leading to the conclusion that endometriosis should be a consideration in assessing the risk of delayed radiation effects in female crewmembers.

  4. Proton irradiation and endometriosis

    SciTech Connect

    Wood, D.H.; Yochmowitz, M.G.; Salmon, Y.L.; Eason, R.L.; Boster, R.A.

    1983-08-01

    It was found that female rhesus monkeys given single total-body exposures of protons of varying energies developed endometriosis at a frequency significantly higher than that of nonirradiated animals of the same age. The minimum latency period was determined to be 7 years after the proton exposure. The doses and energies of the radiation received by the experimental animals were within the range that could be received by an aircrew member in near-earth orbit during a random solar flare event. It is concluded that endometriosis should be a consideration in assessing the risk of delayed radiation effects in female crew members. 15 references.

  5. Art and Endometriosis.

    ERIC Educational Resources Information Center

    Berstein, Jane C.

    1995-01-01

    Relation of an art therapist's personal story concerning her struggle to overcome endometriosis, and how her artwork has played a vital role in coping with the disease. Illustrated with a chronology of artwork produced during a bout with the illness. (JPS)

  6. Endometriosis and infertility.

    PubMed

    Donnez, Jacques; Donnez, Olivier; Orellana, Renan; Binda, Maria M; Dolmans, Marie M

    2016-06-01

    Endometriosis remains a very enigmatic and perplexing disease. The exact mechanism by which endometriosis causes infertility is still unclear. In the present paper, we will review possible mechanisms leading to subfertility or infertility in women with endometriosis and examine them according to location. Endometriosis in the pelvic cavity is a pathology associated with a general inflammatory response and should therefore be considered an inflammatory disease. Inflammatory changes affect the peritoneal fluid and hence the intratubal milieu, since the ampulla (where fertilization takes place) is exposed to peritoneal fluid through the fimbria. Any inflammatory change at this level may therefore impact fertilization and natural conception. The relationship between ovarian endometriomas and infertility may, of course, be explained by the presence of periovarian endometriosis. In the ovary, fibrosis observed in some cortical areas is induced by the inflammatory reaction caused by the presence of endometriomas. The association between fibrosis and a reduced ovarian reserve was demonstrated. Upregulated recruitment and the subsequent demise of early follicles may result in focal exhaustion of primordial follicles. Burn-out of early follicles by a local pelvic inflammatory environment caused by endometriomas may therefore be suggested. However, intraovarian inflammation, subsequent fibrosis and depletion of the ovarian reserve constitute another reason that should also be given due consideration. In addition, surgery should not be ruled out as a possible cause of ovarian reserve depletion. In conclusion, potential mechanisms leading to infertility are numerous, and while some of them remain hypothetical for now, others are supported by clear evidence. These possible mechanisms were reviewed in the present paper. PMID:26837776

  7. Pathogenesis and Pathophysiology of Endometriosis

    PubMed Central

    Burney, Richard O.; Giudice, Linda C.

    2013-01-01

    Originally described over three hundred years ago, endometriosis is classically defined by the presence of endometrial glands and stroma in extrauterine locations. Endometriosis is an inflammatory, estrogen dependent condition associated with pelvic pain and infertility. This work reviews the disease process from theories regarding origin to the molecular basis for disease sequelae. A thorough understanding of the histopathogenesis and pathophysiology of endometriosis is essential toward the development of novel diagnostic and treatment approaches for this debilitating condition. PMID:22819144

  8. Novel therapies targeting endometriosis.

    PubMed

    Taylor, Hugh S; Osteen, Kevin G; Bruner-Tran, Kaylon L; Lockwood, Charles J; Krikun, Graciela; Sokalska, Anna; Duleba, Antoni J

    2011-09-01

    Endometriosis is an often painful disorder in which the endometrial glands and stroma grow outside the uterus. The disease affects women's quality of life and is a common cause of infertility. In this review, we describe promising new developments in the field based on in vitro assays and rodent models, each of which has the potential to be beneficial in the treatment of this disease. We will specifically describe the role of anti-inflammatory drugs, selective estrogen, or progesterone modulators, statins, antiangiogenic agents, and the potential for targeting stem cells as likely methods to hone in and eliminate endometriosis. The most promising of these potential therapies are currently slated for further testing in both rodent and nonhuman primate trials. PMID:21693775

  9. Urinary Tract Endometriosis.

    PubMed

    Kołodziej, Anna; Krajewski, Wojciech; Dołowy, Łukasz; Hirnle, Lidia

    2015-01-01

    Recently, occurrence of urinary tract endometriosis (UTE) is more frequently diagnosed. According to literature, it refers to approximately 0.3 to even 12% of all women with endometriosis. The pathogenesis of UTE has not been clearly explained so far. The actually proposed hypotheses include embryonic, migration, transplantation, and iatrogenic theory. Most frequently UTE affects bladder, less often ureters and kidneys. One-third of patients remains asymptomatic or exhibits only minor manifestations. In symptomatic patients main complaints include dysuria, urinary urgency, and/or frequency, painful micturition, and burning sensation in the urethra and discomfort in the retropubic area. Treatment of UTE is challenging and can be pharmacological, surgical or can be a combination of both methods. In this paper we present a review of the literature concerning the UTE, its diagnosis and treatment. PMID:26341760

  10. Novel Therapies Targeting Endometriosis

    PubMed Central

    Osteen, Kevin G.; Bruner-Tran, Kaylon L.; Lockwood, Charles J.; Krikun, Graciela; Sokalska, Anna; Duleba, Antoni J.

    2011-01-01

    Endometriosis is an often painful disorder in which the endometrial glands and stroma grow outside the uterus. The disease affects women’s quality of life and is a common cause of infertility. In this review, we describe promising new developments in the field based on in vitro assays and rodent models, each of which has the potential to be beneficial in the treatment of this disease. We will specifically describe the role of anti-inflammatory drugs, selective estrogen, or progesterone modulators, statins, antiangiogenic agents, and the potential for targeting stem cells as likely methods to hone in and eliminate endometriosis. The most promising of these potential therapies are currently slated for further testing in both rodent and nonhuman primate trials. PMID:21693775

  11. Extragenital endometriosis. A review.

    PubMed

    Bergqvist, A

    1992-01-01

    Extragenital endometriosis is common and may be found in any tissue. The most pronounced symptoms are pain and local bleeding that usually (at least initially) are cyclical and more pronounced at the time of menstruation. The lesions often infiltrate neighbouring organs, and cause considerable fibrosis together with increasing symptoms. The patients have often had pain for many years, have been investigated at different clinics, and been given conflicting diagnoses, often of mental instability, before the correct diagnosis is finally made. The disease is difficult to diagnose clinically, and must be verified histologically. Often the endometriosis responds to treatment with hormones to inactivate the ovaries, but, sometimes the lesions are resistant, or respond too slowly, to drugs, and local excision is required. A gynaecologist should be called if the diagnosis is made at laparotomy or laparoscopy, to establish the extension of the endometriotic lesion and should be consulted about complementary investigations and hormonal treatment. PMID:1348646

  12. DNA methylation in endometriosis (Review)

    PubMed Central

    KOUKOURA, OURANIA; SIFAKIS, STAVROS; SPANDIDOS, DEMETRIOS A.

    2016-01-01

    Endometriosis is defined by the presence and growth of functional endometrial tissue, outside the uterine cavity, primarily in the ovaries, pelvic peritoneum and rectovaginal septum. Although it is a benign disease, it presents with malignant characteristics, such as invasion to surrounding tissues, metastasis to distant locations and recurrence following treatment. Accumulating evidence suggests that various epigenetic aberrations may play an essential role in the pathogenesis of endometriosis. Aberrant DNA methylation represents a possible mechanism repsonsible for this disease, linking gene expression alterations observed in endometriosis with hormonal and environmental factors. Several lines of evidence indicate that endometriosis may partially be due to selective epigenetic deregulations influenced by extrinsic factors. Previous studies have shed light into the epigenetic component of endometriosis, reporting variations in the epigenetic patterns of genes known to be involved in the aberrant hormonal, immunologic and inflammatory status of endometriosis. Although recent studies, utilizing advanced molecular techniques, have allowed us to further elucidate the possible association of DNA methylation with altered gene expression, whether these molecular changes represent the cause or merely the consequence of the disease is a question which remains to be answered. This review provides an overview of the current literature on the role of DNA methylation in the pathophysiology and malignant evolution of endometriosis. We also provide insight into the mechanisms through which DNA methylation-modifying agents may be the next step in the research of the pharmaceutical treatment of endometriosis. PMID:26934855

  13. DNA methylation in endometriosis (Review).

    PubMed

    Koukoura, Ourania; Sifakis, Stavros; Spandidos, Demetrios A

    2016-04-01

    Endometriosis is defined by the presence and growth of functional endometrial tissue, outside the uterine cavity, primarily in the ovaries, pelvic peritoneum and rectovaginal septum. Although it is a benign disease, it presents with malignant characteristics, such as invasion to surrounding tissues, metastasis to distant locations and recurrence following treatment. Accumulating evidence suggests that various epigenetic aberrations may play an essential role in the pathogenesis of endometriosis. Aberrant DNA methylation represents a possible mechanism repsonsible for this disease, linking gene expression alterations observed in endometriosis with hormonal and environmental factors. Several lines of evidence indicate that endometriosis may partially be due to selective epigenetic deregulations influenced by extrinsic factors. Previous studies have shed light into the epigenetic component of endometriosis, reporting variations in the epigenetic patterns of genes known to be involved in the aberrant hormonal, immunologic and inflammatory status of endometriosis. Although recent studies, utilizing advanced molecular techniques, have allowed us to further elucidate the possible association of DNA methylation with altered gene expression, whether these molecular changes represent the cause or merely the consequence of the disease is a question which remains to be answered. This review provides an overview of the current literature on the role of DNA methylation in the pathophysiology and malignant evolution of endometriosis. We also provide insight into the mechanisms through which DNA methylation-modifying agents may be the next step in the research of the pharmaceutical treatment of endometriosis. PMID:26934855

  14. What Is Endometriosis? | NIH MedlinePlus the Magazine

    MedlinePlus

    ... of this page please turn JavaScript on. Feature: Endometriosis What Is Endometriosis? Summer 2016 Table of Contents A problem common ... to the location of the pain. What causes endometriosis? The exact cause of endometriosis is not known, ...

  15. Endometriosis-associated Lyme disease.

    PubMed

    Matalliotakis, I M; Cakmak, H; Ziogos, M D E; Kalogeraki, A; Kappou, D; Arici, A

    2010-02-01

    The aim of this study is to report three cases of patients with endometriosis and infertility, and associated with Lyme disease. The medical files of 405 women with endometriosis and 200 without endometriosis were studied retrospectively. We report 3 cases with endometriosis and Lyme disease. Of 405 patients with endometriosis treated in our study over a 6-year period, 3(0.8%) had Lyme disease. All cases presented with typical erythema migraines, fever and fatigue. The serological findings were positive for Borrelia burgdorferi, for 3 cases. Two out of 3 women underwent IVF-ET procedures and one of them conceived in the first cycle without complication during pregnancy or after childbirth recorded. We concluded that women with endometriosis are more likely to have chronic fatigue syndrome, systemic lupus erythematous, Sjögren's syndrome, rheumatoid arthritis, multiple sclerosis, and other autoimmune inflammatory and endocrine diseases. A review of the literature confirms the uniqueness of the co-existence of Lyme disease in women with endometriosis in these cases. PMID:20143981

  16. Laparoscopic management of intestinal endometriosis.

    PubMed

    Varol, N; Maher, P; Woods, R

    2000-08-01

    Intestinal involvement by endometriosis traditionally required open laparotomy for bowel resection and anastomosis. Operative laparoscopy may offer the most effective form of treatment for these women. Two women with endometriosis of the rectum and right hemicolon, respectively, underwent transvaginal resection of the rectum and laparotomy for hemicolectomy, assisted by laparoscopy. The only morbidity was postoperative ileus in the former patient. Both women were asymptomatic at the 6-week postoperative visit. PMID:10924638

  17. Imprinting genes associated with endometriosis

    PubMed Central

    Kobayashi, Hiroshi

    2014-01-01

    Purpose: Much work has been carried out to investigate the genetic and epigenetic basis of endometriosis and proposed that endometriosis has been described as an epigenetic disease. The purpose of this study was to extract the imprinting genes that are associated with endometriosis development. Methods: The information on the imprinting genes can be accessed publicly from a web-based interface at http://www.geneimprint.com/site/genes-by-species. Results: In the current version, the database contains 150 human imprinted genes derived from the literature. We searched gene functions and their roles in particular biological processes or events, such as development and pathogenesis of endometriosis. From the genomic imprinting database, we picked 10 genes that were highly associated with female reproduction; prominent among them were paternally expressed genes (DIRAS3, BMP8B, CYP1B1, ZFAT, IGF2, MIMT1, or MIR296) and maternally expressed genes (DVL1, FGFRL1, or CDKN1C). These imprinted genes may be associated with reproductive biology such as endometriosis, pregnancy loss, decidualization process and preeclampsia. Discussion: This study supports the possibility that aberrant epigenetic dysregulation of specific imprinting genes may contribute to endometriosis predisposition. PMID:26417259

  18. What Are the Treatments for Endometriosis?

    MedlinePlus

    ... in treating the symptoms of endometriosis. Additionally, our perception of pain may be altered by different hormones. ... minimal endometriosis may have changes in their pain perception that persist after the lesions are removed. 1 , ...

  19. ENVIRONMENTAL PCB EXPOSURE AND RISK OF ENDOMETRIOSIS

    EPA Science Inventory

    BACKGROUND: Hormonally active environmental agents recently have been associated with the development of endometriosis. METHODS: We undertook a study to assess the relation between endometriosis, an estrogen dependent gynecologic disease, and 62 individual polychlorinated biphe...

  20. Endometriosis and Infertility: Can Surgery Help?

    MedlinePlus

    ... Website of the American Society for Reproductive Medicine Endometriosis and Infertility: Can Surgery Help? This fact sheet ... with The Society of Reproductive Surgeons What is endometriosis? When tissue like the tissue that that normally ...

  1. Researchers Realize Major Breakthrough in Understanding Endometriosis

    MedlinePlus

    ... 16, 2014 Researchers Realize Major Breakthrough in Understanding Endometriosis Contact Jessica Meade nibibpress@mail.nih.gov 301- ... 10% of women, surprisingly little is known about endometriosis — a disorder that causes uterine tissue to grow ...

  2. The Association between Endometriosis and Chronic Endometritis

    PubMed Central

    Takebayashi, Akie; Kimura, Fuminori; Kishi, Yohei; Ishida, Mitsuaki; Takahashi, Akimasa; Yamanaka, Akiyoshi; Takahashi, Kentaro; Suginami, Hiroshi; Murakami, Takashi

    2014-01-01

    Objective To evaluate the association between endometriosis and chronic endometritis. Methods Endometrial specimens were obtained from 71 patients, 34 with endometriosis (endometriosis group) and 37 without endometriosis (non-endometriosis group), who underwent hysterectomy, and the specimens were immunostained for the plasmacyte marker CD138. The rate of chronic endometritis was compared between the endometriosis group and the non-endometriosis group. Furthermore, the 71 patients were also divided into two groups, 28 with chronic endometritis (chronic endometritis group) and 43 without chronic endometritis (non-chronic endometritis group). Logistic regression analysis was performed with variables including age, body mass index (BMI), gravidity and parity, and diagnoses of leiomyoma, adenomyosis, and endometriosis on pathology to examine the independent effect of each variable on chronic endometritis. Patients suffering from cervical invasive carcinoma, endometrial carcinoma, and endometrial polyps or treated with gonadotropin-releasing hormone agonists, progestins, or oral contraceptives before surgery were excluded. Results Chronic endometritis was identified in 52.94% of the endometriosis group and 27.02% of the non-endometriosis group (p<0.05). Logistic regression analysis revealed that endometriosis was associated with chronic endometritis. Conclusions This result suggests a strong association between endometriosis and chronic endometritis. PMID:24558386

  3. [Digestive endometriosis. Current concepts].

    PubMed

    Caligaris, P; Ducassou, M J; Masselot, R; Maurin, B; Cardon, J M; Bricot, R

    1982-12-01

    Endometriosis involving the digestive tract accounts for 1% of all cases of the disease. There is a marked predominance in the recto-sigmoid and terminal ileal loops. Symptomatology is dominated by disturbances in intestinal transit, sub-occlusion or acute obstruction, pain worsening at the time of menstruation and by a haemorrhagic rectal discharge again accompanying menstruation. Apart from classical aetiopathogenic theories such as grafting onto the digestive tract by tubal, lymph vessel or venous propagation, it would appear that prostaglandins and in particular a change in the (formula; see text) ratio may play a large role. Operative resection of localised stenosis combined with oophorectomy, if the latter is possible in view of the patient's age, or prolonged medical treatment with progestational agents or even better Danazol results in cure and avoids recurrences. PMID:6891703

  4. Endometriosis and Chronic Pelvic Pain

    PubMed Central

    Bloski, Terri; Pierson, Roger

    2010-01-01

    Nurses often encounter patients with chronic pelvic pain associated with endometriosis, which is a puzzling and problematic gynecologic condition that has continued to plague women and baffle doctors and researchers worldwide since it was first identified by Dr. J. Sampson in the 1920s (Sampson, 1940). Endometriosis is defined as the growth, adhesion and progression of endometrial glands and stroma outside of the uterine cavity, with cellular activity evident in lesions, nodules, cysts or endometriomas (Audebert et al., 1992). Although it typically appears benign on histopathology, endometriosis has been likened to a malignant tumor since the lesions grow, infiltrate and adhere to adjacent tissues and interfere with physiologic processes (Kitawaki et al., 2002; Noble, Simpson, Johns, & Bulun, 1996). Ectopic endometriotic growths respond to cyclic changes of estrogen and proliferate and shed in a manner similar to eutopic endometrium. This cyclic ectopic activity results in internal bleeding, formation of scar tissue, inflammation and sometimes debilitating chronic pain (Kitawaki et al.). PMID:18837717

  5. Endometriosis, Angiogenesis and Tissue Factor

    PubMed Central

    Krikun, Graciela

    2012-01-01

    Tissue factor (TF), is a cellular receptor that binds the factor VII/VIIa to initiate the blood coagulation cascade. In addition to its role as the initiator of the hemostatic cascade, TF is known to be involved in angiogenesis via intracellular signaling that utilizes the protease activated receptor-2 (PAR-2). We now review the physiologic expression of TF in the endometrium and its altered expression in multiple cell types derived from eutopic and ectopic endometrium from women with endometriosis compared with normal endometrium. Our findings suggest that TF might be an ideal target for therapeutic intervention in endometriosis. We have employed a novel immunoconjugate molecule known as Icon and were able to eradicate endometrial lesions in a mouse model of endometriosis without affecting fertility. These findings have major implications for potential treatment in humans. PMID:24278684

  6. Confronting Endometriosis | NIH MedlinePlus the Magazine

    MedlinePlus

    ... of this page please turn JavaScript on. Feature: Endometriosis Confronting Endometriosis Summer 2016 Table of Contents left to right: ... condition. Would you share your personal history with endometriosis? My symptoms started with my first period when ...

  7. Nutritional aspects related to endometriosis.

    PubMed

    Halpern, Gabriela; Schor, Eduardo; Kopelman, Alexander

    2015-01-01

    This literature review analyzed the evidence on nutritional aspects related to the pathogenesis and progression of endometriosis. Diets deficient in nutrients result in changes in lipid metabolism, oxidative stress and promote epigenetic abnormalities, that may be involved in the genesis and progression of the disease. Foods rich in omega 3 with anti-inflammatory effects, supplementation with N-acetylcysteine, vitamin D and resveratrol, in addition to the increased consumption of fruits, vegetables (preferably organic) and whole grains exert a protective effect, reducing the risk of development and possible regression of disease. Dietary re-education seems to be a promising tool in the prevention and treatment of endometriosis. PMID:26841161

  8. [Thoracic endometriosis and catamenial pneumothorax].

    PubMed

    Voskresenskiĭ, O V; Smoliar, A N; Damirov, M M; Galankina, I E; Zhelev, I G

    2014-01-01

    It was analyzed own experience of diagnosis and treatment of catamenial (menstrual) pneumothorax and thoracic endometriosis and literature review. It is shown that catamenial pneumothorax has specific clinical and instrumental signs allowing to establish the diagnosis before surgery. It was proposed surgical treatment including the removal of trans diaphragmatic way of pneumothorax development, removal of thoracic endometriosis and the establishment of reliable pleurodesis. It was demonstrated that this volume of surgery can be successfully implemented by using of thoracoscopic access. Relapse prevention includes hormonal therapy for the 6 months after surgery under the supervision of an obstetrician-gynecologist. PMID:25484144

  9. Multifocal endometriosis. A case report.

    PubMed

    Vercellini, P; Vendola, N; Presti, M; Bolis, G

    1993-10-01

    Disseminated endometriosis of the urinary, genital and intestinal systems was treated successfully with conservative surgery. We hypothesize that this unusual presentation may have derived from retrograde menstruation, pooling of endometrial cells in the dependent anterior and posterior cul-de-sacs with subsequent passage across the peritoneal mesothelium, and dissemination by clockwise intraabdominal currents. PMID:8263874

  10. [Nasal endometriosis: apropos of 1 case].

    PubMed

    Laghzaoui, O; Laghzaoui, M

    2001-12-01

    The nasal mucosa is an exceptional localization for endometriosis. We report a case observed in a woman who developed nasal tumefaction associated with epistaxis that had followed a cyclic repetitive pattern since puberty. Surgical excision of the nasal nodule confirmed the diagnosis of endometriosis. Local and general evaluated identified other localizations. Outcome has been favorable at short and mid term. Endometriosis is a frequent condition although extra-pelvic localizations are uncommon. The nasal localization is highly exceptional. PMID:11917731

  11. Cathepsin Protease Inhibition Reduces Endometriosis Lesion Establishment.

    PubMed

    Porter, Kristi M; Wieser, Friedrich A; Wilder, Catera L; Sidell, Neil; Platt, Manu O

    2016-05-01

    Endometriosis is a gynecologic disease characterized by the ectopic presence of endometrial tissue on organs within the peritoneal cavity, causing debilitating abdominal pain and infertility. Current treatments alleviate moderate pain symptoms associated with the disorder but exhibit limited ability to prevent new or recurring lesion establishment and growth. Retrograde menstruation has been implicated for introducing endometrial tissue into the peritoneal cavity, but molecular mechanisms underlying attachment and invasion are not fully understood. We hypothesize that cysteine cathepsins, a group of powerful extracellular matrix proteases, facilitate endometrial tissue invasion and endometriosis lesion establishment in the peritoneal wall and inhibiting this activity would decrease endometriosis lesion implantation. To test this, we used an immunocompetent endometriosis mouse model and found that endometriotic lesions exhibited a greater than 5-fold increase in active cathepsins compared to tissue from peritoneal wall or eutopic endometrium, with cathepsins L and K specifically implicated. Human endometriosis lesions also exhibited greater cathepsin activity than adjacent peritoneum tissue, supporting the mouse results. Finally, we tested the hypothesis that inhibiting cathepsin activity could block endometriosis lesion attachment and implantation in vivo. Intraperitoneal injection of the broad cysteine cathepsin inhibitor, E-64, significantly reduced the number of attached endometriosis lesions in our murine model compared to vehicle-treated controls demonstrating that cathepsin proteases contribute to endometriosis lesion establishment, and their inhibition may provide a novel, nonhormonal therapy for endometriosis. PMID:26482207

  12. Endometriosis: A Disease That Remains Enigmatic

    PubMed Central

    Velasco, Irene

    2013-01-01

    Endometriosis, a gynecologic pathology, is defined by the presence of a tissue similar to uterine endometrium, which is located in places other than physiologically appropriate. These endometrial heterotopic islets contain glands and stroma and are functionally capable of responding to exogenous, endogenous, or local hormonal stimuli. Endometriosis affects 8%–10% of women of reproductive age; in 30% of the women, the condition is associated with primary or secondary infertility. In several instances, endometriosis persists as a minimal or mild disease, or it can resolve on its own. Other cases of endometriosis show severe symptomatology that ends when menopause occurs. Endometriosis can, however, reactivate in several postmenopausal women when iatrogenic or endogenous hormones are present. Endometriosis is occasionally accompanied by malignant ovarian tumors, especially endometrioid and clear cell carcinomas. Its pathogenesis is widely debated, and its variable morphology appears to represent a continuum of individual presentations and progressions. Endometriosis has no pathognomonic signs or symptoms; it is therefore difficult to diagnose. Because of its enigmatic etiopathogenesis, there is currently no satisfactory therapy for all patients with endometriosis. Treatments include medications, surgery, or combined therapies; currently, the only procedures that seem to cure endometriosis are hysterectomy and bilateral salpingo-oophorectomy. In this paper, we review the most controversial and enigmatic aspects of this disease. PMID:23956867

  13. Endometriosis mimicking colonic stromal tumor

    PubMed Central

    Wadhwa, Vaibhav; Slattery, Eoin; Garud, Sagar; Sethi, Saurabh; Wang, Helen; Poylin, Vitaliy Y.; Berzin, Tyler M.

    2016-01-01

    Endometriosis is defined as the presence of endometrial glands and stroma at extra-uterine sites; it is a common disease affecting women of reproductive age. Endometrial tissue can implant itself to various organs, including the gastrointestinal tract, and can cause significant gastrointestinal symptoms. These ectopic endometrial tissue implants are usually located in the pelvis but can be present almost anywhere in the body. Endometriosis seems to be the most frequent cause of chronic pelvic pain in women of reproductive age and may cause prolonged suffering and disability that negatively affect health-related quality of life. We report a case in a generally healthy young female patient who presented for evaluation of diarrhea. PMID:25725039

  14. Endometriosis in primary medical care.

    PubMed

    Bromham, D R

    1991-01-01

    The role of the family doctor in the management of endometriosis is considered in three phases. With the exception of a small minority of cases in which there are superficial endometriotic lesions, it will be difficult for the general practitioner to confirm the diagnosis without referral for laparoscopy or similar gynaecological investigation. In the majority of patients, clinical diagnosis based on symptomatology and physical findings on pelvic examination is not reliable enough to be a sound basis on which to initiate medical therapy. However, the early referral of patients with a suspicious history allows prompter confirmation of endometriosis, if present, and the establishment of a treatment regime, if required. Where medical therapy is instigated, this is usually by the gynaecological team, but, for the convenience of the patient, her surveillance during treatment is conducted jointly with the referring doctor. Compliance with and continuation of therapy will largely depend on the knowledge and skill of the general practitioner in assessing the significance of side-effects of medication. A significant proportion of endometriosis sufferers experience recurrence of their symptoms, and it may be possible for the general practitioner to initiate re-treatment, with the same or alternative medication, prior to a re-evaluation by the gynaecological team. PMID:1807362

  15. [Thoracic endometriosis: A difficult diagnosis].

    PubMed

    Hagneré, P; Deswarte, S; Leleu, O

    2011-09-01

    Thoracic endometriosis is a rare disease, which presents in women at a mean age of 35 years, later than for pelvic endometriosis. There are no known predisposing factors for the condition and its pathogenesis is not yet clearly established. The symptoms always appear in connection with the periods of the person affected by the condition, occurring within 24-48 h after the start of menstruation. Catamenial pneumothorax is the most common clinical entity. It is associated with pelvic endometriosis in 30-50% of cases. Thoracoscopy, preferably performed during menstruation, allows full inspection of the diaphragm and the pleural cavity for defects in the diaphragm, endometrial nodules and bullae. The level of CA 125 is often elevated but this is not a reliable or specific marker. Medical treatment is aimed at blocking the action of estrogen on the endometrium and ectopic endometrial implants. GnRH analogues or danazol are the preferred treatments. Surgery to repair and strengthen the diaphragm and/or resect nodules or bullae also has a role, supplemented by pleurodesis to prevent further pneumothorax or effusions. The main risk is recurrence, and thus the current usual practice is to combine surgery, immediately followed by hormone therapy focusing on GnRH analogues. PMID:21943537

  16. Aromatase inhibitors in the treatment of endometriosis.

    PubMed

    Słopień, Radosław; Męczekalski, Błażej

    2016-03-01

    Endometriosis is a chronic inflammatory condition in which foci of endometrial tissue grow outside of the uterine cavity. Endometriosis was estimated to affect 176 million women of childbearing potential all over the world in 2010. The presence of extrauterine endometrial tissue is associated with pain and infertility. Typical symptoms of endometriosis include dysmenorrhoea, dyspareunia, heavy menstrual periods (menorrhagia), pelvic pain that is not related to menstrual cycles, dysuria, and chronic fatigue. Medical treatments for endometriosis include combined oral contraceptive pills, danazol, gestrinone, medroxyprogesterone acetate, and gonadotropin-releasing hormone agonists (aGnRHs). A new class of medications called aromatase inhibitors has been identified in recent years as potential therapeutic agents for endometriosis. This article provides general information about aromatase inhibitors, their use in gynaecology, and their adverse effects. In particular, the paper discusses the use of aromatase inhibitors in the treatment of endometriosis in postmenopausal women. Unlike oral contraceptives, gestagens, aGnRHs, and danazol, which suppress ovarian oestrogen synthesis, aromatase inhibitors inhibit mainly extra-ovarian synthesis of oestrogens. Therefore, the use of aromatase inhibitors seems to be particularly relevant in older patients, as most of the body's oestrogen is produced outside the ovaries after menopause. The paper discusses also the use of aromatase inhibitors in the treatment of pain associated with endometriosis and infertility caused by endometriosis. PMID:27095958

  17. Advances in the genetics of endometriosis

    PubMed Central

    2010-01-01

    Endometriosis is a gynecological disease characterized by implantation of endometrial tissue outside of the uterus. Early familial aggregation and twin studies noted a higher risk of endometriosis among relatives. Studies on the roles of the environment, genetics and aberrant regulation in the endometrium and endometriotic lesions of women with endometriosis suggest that endometriosis arises from the interplay between genetic variants and environmental factors. Elucidating the hereditary component has proven difficult because multiple genes seem to produce a susceptibility to developing endometriosis. Molecular techniques, including linkage and genome-wide analysis, have identified candidate genes located near known loci related to development and regulation of the female reproductive tract. As new candidate genes are discovered and hereditary pathways identified using technologies such as genome-wide analysis, the possibility of prevention and treatment becomes more tangible for millions of women affected by endometriosis. Here, we discuss the advances of genetic research in endometriosis and describe technologies that have contributed to the current understanding of the genetic variability in endometriosis, variability that includes regulatory polymorphisms in key genes. PMID:20959029

  18. Aromatase inhibitors in the treatment of endometriosis

    PubMed Central

    Męczekalski, Błażej

    2016-01-01

    Endometriosis is a chronic inflammatory condition in which foci of endometrial tissue grow outside of the uterine cavity. Endometriosis was estimated to affect 176 million women of childbearing potential all over the world in 2010. The presence of extrauterine endometrial tissue is associated with pain and infertility. Typical symptoms of endometriosis include dysmenorrhoea, dyspareunia, heavy menstrual periods (menorrhagia), pelvic pain that is not related to menstrual cycles, dysuria, and chronic fatigue. Medical treatments for endometriosis include combined oral contraceptive pills, danazol, gestrinone, medroxyprogesterone acetate, and gonadotropin-releasing hormone agonists (aGnRHs). A new class of medications called aromatase inhibitors has been identified in recent years as potential therapeutic agents for endometriosis. This article provides general information about aromatase inhibitors, their use in gynaecology, and their adverse effects. In particular, the paper discusses the use of aromatase inhibitors in the treatment of endometriosis in postmenopausal women. Unlike oral contraceptives, gestagens, aGnRHs, and danazol, which suppress ovarian oestrogen synthesis, aromatase inhibitors inhibit mainly extra-ovarian synthesis of oestrogens. Therefore, the use of aromatase inhibitors seems to be particularly relevant in older patients, as most of the body's oestrogen is produced outside the ovaries after menopause. The paper discusses also the use of aromatase inhibitors in the treatment of pain associated with endometriosis and infertility caused by endometriosis. PMID:27095958

  19. [Diagnosis of internal endometriosis of the uterus].

    PubMed

    Kulakov, V I; Bakuleva, L P; Damirov, M M; Sarkisov, S E; Sliusar, N N

    1995-01-01

    The authors analyze the informative value of instrumental methods of examination (hysteroscopy, hysterosalpingography, ultrasonic scanning) and measurements of blood phosphatidyl inosites in 50 patients with internal endometriosis and come to a conclusion that it is in proportion with the disease severity, hysteroscopy being the most informative. A reliable reduction (p < 0.001) of blood phosphatidyl inosites were seen in endometriosis patients as against normal subjects. Combined examinations making use of instrumental methods and blood phosphatidylinosite measurements essentially improve the accuracy of internal endometriosis diagnosis and help develop a rational treatment strategy. PMID:7762750

  20. World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonisation Project: I. Surgical phenotype data collection in endometriosis research

    PubMed Central

    Becker, Christian M.; Laufer, Marc R.; Stratton, Pamela; Hummelshoj, Lone; Missmer, Stacey A.; Zondervan, Krina T.; Adamson, G. David; Adamson, G.D.; Allaire, C.; Anchan, R.; Becker, C.M.; Bedaiwy, M.A.; Buck Louis, G.M.; Calhaz-Jorge, C.; Chwalisz, K.; D'Hooghe, T.M.; Fassbender, A.; Faustmann, T.; Fazleabas, A.T.; Flores, I.; Forman, A.; Fraser, I.; Giudice, L.C.; Gotte, M.; Gregersen, P.; Guo, S.-W.; Harada, T.; Hartwell, D.; Horne, A.W.; Hull, M.L.; Hummelshoj, L.; Ibrahim, M.G.; Kiesel, L.; Laufer, M.R.; Machens, K.; Mechsner, S.; Missmer, S.A.; Montgomery, G.W.; Nap, A.; Nyegaard, M.; Osteen, K.G.; Petta, C.A.; Rahmioglu, N.; Renner, S.P.; Riedlinger, J.; Roehrich, S.; Rogers, P.A.; Rombauts, L.; Salumets, A.; Saridogan, E.; Seckin, T.; Stratton, P.; Sharpe-Timms, K.L.; Tworoger, S.; Vigano, P.; Vincent, K.; Vitonis, A.F.; Wienhues-Thelen, U.-H.; Yeung, P.P.; Yong, P.; Zondervan, K.T.

    2014-01-01

    Objective To standardize the recording of surgical phenotypic information on endometriosis and related sample collections obtained at laparoscopy, allowing large-scale collaborative research into the condition. Design An international collaboration involving 34 clinical/academic centers and three industry collaborators from 16 countries. Setting Two workshops were conducted in 2013, bringing together 54 clinical, academic, and industry leaders in endometriosis research and management worldwide. Patient(s) None. Intervention(s) A postsurgical scoring sheet containing general and gynecological patient and procedural information, extent of disease, the location and type of endometriotic lesion, and any other findings was developed during several rounds of review. Comments and any systematic surgical data collection tools used in the reviewers' centers were incorporated. Main Outcome Measure(s) The development of a standard recommended (SSF) and minimum required (MSF) form to collect data on the surgical phenotype of endometriosis. Result(s) SSF and MSF include detailed descriptions of lesions, modes of procedures and sample collection, comorbidities, and potential residual disease at the end of surgery, along with previously published instruments such as the revised American Society for Reproductive Medicine and Endometriosis Fertility Index classification tools for comparison and validation. Conclusion(s) This is the first multicenter, international collaboration between academic centers and industry addressing standardization of phenotypic data collection for a specific disease. The Endometriosis Phenome and Biobanking Harmonisation Project SSF and MSF are essential tools to increase our understanding of the pathogenesis of endometriosis by allowing large-scale collaborative research into the condition. PMID:25150390

  1. Endometriosis: bright future for a cloudy past?

    PubMed

    Nothnick, Warren B

    2015-01-21

    New estrogen receptor ligands arrest endometriotic implant survival but spare reproductive cycles in a mouse model of endometriosis, thus forging a path to new treatment options (Zhao et al., this issue). PMID:25609165

  2. Thoracic Endometriosis Syndrome: A Veritable Pandora's Box.

    PubMed

    Nair, Sobha S; Nayar, Jayashree

    2016-04-01

    Thoracic endometriosis syndrome is a rare disorder characterised by the presence of functioning endometrial tissue in pleura, lung parenchyma, airways, and/or encompasses mainly four clinical entities-catamenial pneumothorax, catamenial haemothorax, catamenial haemoptysis and lung nodules. The cases were studied retrospectively by reviewing the records at Amrita Institute of Medical Sciences, for duration of five years i.e., form March 2010-2014 and analysed for the clinical presentation and management of thoracic endometriosis syndrome. Catamenial breathlessness was the main symptom. Pneumothorax and pleural effusion were the findings on investigations. Histopathology report of endometriosis was present in three cases (50%). Conditions with excess oestrogen like endometriosis, fibroid, adenomyosis were diagnosed in these patients by pelvic scan. After the initial supportive treatment with hormones, pleurodesis, hysterectomy and lung decortication were the treatment modalities. Two cases that had multiple recurrences were diagnosed as disseminated TES. They underwent combined treatment of surgery and hormones. PMID:27190904

  3. How Do Health Care Providers Diagnose Endometriosis?

    MedlinePlus

    ... Information Clinical Trials Resources and Publications How do health care providers diagnose endometriosis? Skip sharing on social media ... under a microscope, to confirm the diagnosis. 1 Health care providers may also use imaging methods to produce ...

  4. Severe teenage acne and risk of endometriosis

    PubMed Central

    Xie, Jing; Kvaskoff, Marina; Li, Yunhui; Zhang, Mingfeng; Qureshi, Abrar A.; Missmer, Stacey A.; Han, Jiali

    2014-01-01

    STUDY QUESTION Is there a relationship between severe teenage acne and endometriosis? SUMMARY ANSWER Endometriosis is positively associated with severe teenage acne. WHAT IS KNOWN ALREADY No studies have specifically explored a possible association between severe acne in adolescence and risk of endometriosis. STUDY DESIGN, SIZE, DURATION This prospective cohort study used data collected from 88 623 female nurses from September 1989 to June 2009 as part of the Nurses' Health Study II (NHS II) cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS Regression models were used to calculate hazard ratios (HRs) and confidence intervals (CIs) for endometriosis among women with and without severe teenage acne. Multivariate models were adjusted for established risk factors of endometriosis. MAIN RESULTS AND THE ROLE OF CHANCE A total of 4 382 laparoscopically confirmed endometriosis cases were documented during 1 132 272 woman-years of follow-up. Compared with women without a history of severe teenage acne, women who had severe teenage acne had a 20% increased risk of endometriosis (HR = 1.20, 95% CI: 1.08–1.32). The association was not affected by adjusting for use of tetracycline or isotretinoin. LIMITATIONS AND REASONS FOR CAUTION The HR is likely to be underestimated since we only included endometriosis cases confirmed by laparoscopy. Although geographically diverse, the NHS II cohort is primarily Caucasian, which may limit generalization to more ethnically diverse populations. WIDER IMPLICATIONS OF THE STUDY The results of this study suggest that severe teenage acne is associated with an increased risk of endometriosis. As a visible and non-invasive clinical indicator, severe teenage acne may be useful for early detection of endometriosis. We bring this counter-intuitive association to the attention of clinicians for the benefit of the patient and an early diagnosis of endometriosis. STUDY FUNDING/COMPETING INTEREST This study was funded by research grant CA176726 from the

  5. Peripheral changes in endometriosis-associated pain

    PubMed Central

    Morotti, Matteo; Vincent, Katy; Brawn, Jennifer; Zondervan, Krina T.; Becker, Christian M.

    2014-01-01

    BACKGROUND Pain remains the cardinal symptom of endometriosis. However, to date, the underlying mechanisms are still only poorly understood. Increasing evidence points towards a close interaction between peripheral nerves, the peritoneal environment and the central nervous system in pain generation and processing. Recently, studies demonstrating nerve fibres and neurotrophic and angiogenic factors in endometriotic lesions and their vicinity have led to increased interest in peripheral changes in endometriosis-associated pain. This review focuses on the origin and function of these nerves and factors as well as possible peripheral mechanisms that may contribute to the generation and modulation of pain in women with endometriosis. METHODS We conducted a systematic search using several databases (PubMed, MEDLINE, EMBASE and CINAHL) of publications from January 1977 to October 2013 to evaluate the possible roles of the peripheral nervous system in endometriosis pathophysiology and how it can contribute to endometriosis-associated pain. RESULTS Endometriotic lesions and peritoneal fluid from women with endometriosis had pronounced neuroangiogenic properties with increased expression of new nerve fibres, a shift in the distribution of sensory and autonomic fibres in some locations, and up-regulation of several neurotrophins. In women suffering from deep infiltrating endometriosis and bowel endometriosis, in which the anatomical distribution of lesions is generally more closely related to pelvic pain symptoms, endometriotic lesions and surrounding tissues present higher nerve fibre densities compared to peritoneal lesions and endometriomas. More data are needed to fully confirm a direct correlation between fibre density in these locations and the amount of perceived pain. A better correlation between the presence of nerve fibres and pain symptoms seems to exist for eutopic endometrium. However, this appears not to be exclusive to endometriosis. No correlation between

  6. Defining Future Directions for Endometriosis Research

    PubMed Central

    D’Hooghe, Thomas M.; Fazleabas, Asgerally; Giudice, Linda C.; Montgomery, Grant W.; Petraglia, Felice; Taylor, Robert N.

    2013-01-01

    Endometriosis, defined as estrogen-dependent lesions containing endometrial glands and stroma outside the uterus, is a chronic and often painful gynecological condition that affects 6% to 10% of reproductive age women. Endometriosis has estimated annual costs of US $12 419 per woman (approximately €9579), comprising one-third of the direct health care costs with two-thirds attributed to loss of productivity. Decreased quality of life is the most important predictor of direct health care and total costs. It has been estimated that there is a mean delay of 6.7 years between onset of symptoms and a surgical diagnosis of endometriosis, and each affected woman loses on average 10.8 hours of work weekly, mainly owing to reduced effectiveness while working. To encourage and facilitate research into this debilitating disease, a consensus workshop to define future directions for endometriosis research was held as part of the 11th World Congress on Endometriosis in September 2011 in Montpellier, France. The objective of this workshop was to review and update the endometriosis research priorities consensus statement developed following the 10th World Congress on Endometriosis in 2008.1 A total of 56 recommendations for research have been developed, grouped under 6 subheadings: (1) diagnosis, (2) classification and prognosis, (3) clinical trials, treatment, and outcomes, (4) epidemiology, (5) pathophysiology, and (6) research policy. By producing this consensus international research priorities statement, it is the hope of the workshop participants that researchers will be encouraged to develop new interdisciplinary research proposals that will attract increased funding support for work on endometriosis. PMID:23427182

  7. Laparoscopic Surgical Techniques for Endometriosis and Adenomyosis

    PubMed Central

    Wood, C.; Maher, P.; Woods, R.

    2000-01-01

    The details of surgical techniques for laparoscopic removal of endometriosis and adenomyosis are described briefly in textbooks and gynaecological journal articles. We have described a wide variety of techniques for the various procedures required in the treatment of endometriosis and adenomyosis, excluding hysterectomy. The principles are based upon those used in removal of primary cancer lesions. The limitations of thermal ablation are discussed, and evidence of improved results after excision of lesions have been submitted for publication. PMID:18493534

  8. Dysmenorrhea and Endometriosis in Young Women

    PubMed Central

    Harada, Tasuku

    2013-01-01

    Dysmenorrhea is defined as symptoms associated with menstruation, such as abdominal pain, cramping and lumbago, that interfere with daily activity. Primary dysmenorrhea refers to menstrual pain without underlying pathology, whereas secondary dysmenorrhea is menstrual pain associated with underlying pathology. Endometriosis, one of the main causes of secondary dysmenorrhea, induces dysmenorrhea, pelvic pain and infertility, resulting in marked reduction of quality of life during reproductive age. This review article is a comprehensive overview of dysmenorrhea and endometriosis in young women. PMID:24574576

  9. Immune-endocrine interactions in endometriosis.

    PubMed

    Cakmak, Hakan; Guzeloglu-Kayisli, Ozlem; Kayisli, Umit Ali; Arici, Aydin

    2009-01-01

    Endocrine and immune systems are among the most essential regulators of endometrial physiology, and immune-endocrine interactions are likely to be involved in the pathogenesis of endometriosis. Endometriosis is an inflammatory, estrogen-dependent disease defined by the presence of viable endometrial tissue outside the uterine cavity. Impaired immune response that results in inadequate removal of refluxed menstrual debris has been proposed as a possible causative factor in the development of endometriosis. Moreover, decrease in spontaneous apoptosis of endometrium is the other theory proposed for the development of endometriosis. Endometriotic tissues respond to sex steroids aberrantly and behave differently compared to endometrium in addition to their ability to produce local estrogen. The effects of estrogen on distinct intracellular signaling pathways including MAPK, PI3K/AKT and NF-kappa B may take a role in enhanced endometrial cell survival, altered immune response, and differential cytokine and chemokine expression in endometriosis. Better understanding of immune-endocrine interactions will set the stage for effective immune-targeted therapies not only for endometriosis but also for other endometrial diseases such as adenomyosis, recurrent reproductive failure and implantation-related infertility. PMID:19482657

  10. Radiation-induced endometriosis in Macaca mulatta

    SciTech Connect

    Fanton, J.W.; Golden, J.G. )

    1991-05-01

    Female rhesus monkeys received whole-body doses of ionizing radiation in the form of single-energy protons, mixed-energy protons, X rays, and electrons. Endometriosis developed in 53% of the monkeys during a 17-year period after exposure. Incidence rates for endometriosis related to radiation type were: single-energy protons, 54%; mixed-energy protons, 73%; X rays, 71%; and electrons, 57%. The incidence of endometriosis in nonirradiated control monkeys was 26%. Monkeys exposed to single-energy protons, mixed-energy protons, and X rays developed endometriosis at a significantly higher rate than control monkeys (chi 2, P less than 0.05). Severity of endometriosis was staged as massive, moderate, and minimal. The incidence of these stages were 65, 16, and 19%, respectively. Observations of clinical disease included weight loss in 43% of the monkeys, anorexia in 35%, space-occupying masses detected by abdominal palpation in 55%, abnormal ovarian/uterine anatomy on rectal examination in 89%, and radiographic evidence of abdominal masses in 38%. Pathological lesions were endometrial cyst formation in 69% of the monkeys, adhesions of the colon in 66%, urinary bladder in 50%, ovaries in 86%, and ureters in 44%, focal nodules of endometrial tissue throughout the omentum in 59%, and metastasis in 9%. Clinical management of endometriosis consisted of debulking surgery and bilateral salpingo-oophorectomy combined in some cases with total abdominal hysterectomy. Postoperative survival rates at 1 and 5 years for monkeys recovering from surgery were 48 and 36%, respectively.

  11. Nerve Bundles and Deep Dyspareunia in Endometriosis.

    PubMed

    Williams, Christina; Hoang, Lien; Yosef, Ali; Alotaibi, Fahad; Allaire, Catherine; Brotto, Lori; Fraser, Ian S; Bedaiwy, Mohamed A; Ng, Tony L; Lee, Anna F; Yong, Paul J

    2016-07-01

    The etiology of deep dyspareunia in endometriosis is unclear. Our objective was to determine whether nerve bundle density in the cul-de-sac/uterosacrals (zone II) is associated with deep dyspareunia in women with endometriosis. We conducted a blinded retrospective immunohistochemistry study (n = 58) at a tertiary referral center (2011-2013). Patients were stringently phenotyped into a study group and 2 control groups. The study group (tender endometriosis, n = 29) consisted of patients with deep dyspareunia, a tender zone II on examination, and an endometriosis lesion in zone II excised at surgery. Control group 1 (nontender endometriosis, n = 17) consisted of patients without deep dyspareunia, a nontender zone II on examination, and an endometriosis lesion in zone II excised at surgery. Control group 2 (tender nonendometriosis, n = 12) consisted of patients with deep dyspareunia, a tender zone II on examination, and a nonendometriosis lesion (eg, normal histology) in zone II excised at surgery. Protein gene product 9.5 (PGP9.5) immunohistochemistry was performed to identify nerve bundles (nerve fibers surrounded by perineurium) in the excised zone II lesion. PGP9.5 nerve bundle density (bundles/high powered field [HPF]) was then scored by a pathologist blinded to the group. We found a significant difference in PGP9.5 nerve bundle density between the 3 groups (analysis of variance, F2,55 = 6.39, P = .003). Mean PGP9.5 nerve bundle density was significantly higher in the study group (1.16 ± 0.56 bundles/HPF [±standard deviation]) compared to control group 1 (0.65 ± 0.36, Tukey test, P = .005) and control group 2 (0.72 ± 0.56, Tukey test, P = .044). This study provides evidence that neurogenesis in the cul-de-sac/uterosacrals may be an etiological factor for deep dyspareunia in endometriosis. PMID:26711313

  12. Immunoresponsiveness in endometriosis: implications of estrogenic toxicants.

    PubMed Central

    Rier, S E; Martin, D C; Bowman, R E; Becker, J L

    1995-01-01

    Endometriosis is a reproductive disease characterized by the growth of endometrial cells at sites outside the uterus. This disease is a serious disorder associated with chronic pain and infertility, which may be present in 6 million women in this country. Traditional medical therapy has consisted of hormonal regimens that limit the action of endogenous estrogen. The etiology of endometriosis is unknown, but studies suggest that soluble factors known as cytokines play a role in disease pathogenesis. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD or dioxin) is an environmental toxicant that alters the action of estrogen in reproductive organs and adversely affects immunocompetence. The incidence of endometriosis was determined in rhesus monkeys that were chronically exposed to dioxin for a period of approximately 4 years. Ten years after termination of dioxin treatment, the presence and severity of endometriosis was assessed by surgical laparoscopy. The incidence of endometriosis correlated with dioxin exposure and disease severity was dependent upon the dose administered. Moderate to severe endometriosis was not found in control animals but was documented in three of seven animals exposed to 5 ppt dioxin (43%) and in five of seven animals exposed to 25 ppt dioxin (71%). The frequency of spontaneous disease in the control group was 33%, similar to an overall prevalence of 30% in 304 rhesus monkeys with no history of dioxin exposure. This study indicates that endometriosis may be associated with dioxin exposure in the rhesus. In view of overwhelming evidence that cytokines participate in the mediation of reproductive-endocrine phenomena and regulation of endometrial growth, future assessment of the effects of environmental toxicants on reproductive health may depend upon our understanding of the bidirectional cytokine network between the immune and endocrine systems. PMID:8593863

  13. Complement Pathway is Frequently Altered in Endometriosis and Endometriosis-Associated Ovarian Cancer

    PubMed Central

    Suryawanshi, Swati; Huang, Xin; Elishaev, Esther; Budiu, Raluca A.; Zhang, Lixin; Kim, SungHwan; Donnellan, Nicole; Mantia-Smaldone, Gina; Ma, Tianzhou; Tseng, George; Lee, Ted; Mansuria, Suketu; Edwards, Robert; Vlad, Anda M.

    2014-01-01

    Purpose Mechanisms of immune dysregulation associated with advanced tumors are relatively well understood. Much less is known about the role of immune effectors against cancer precursor lesions. Endometrioid and clear cell ovarian tumors partly derive from endometriosis, a commonly diagnosed chronic inflammatory disease. We performed here a comprehensive immune gene expression analysis of pelvic inflammation in endometriosis and endometriosis-associated ovarian cancer (EAOC). Experimental design RNA was extracted from 120 paraffin tissue blocks comprising of normal endometrium (n=32), benign endometriosis (n=30), atypical endometriosis (n=15) and EAOC (n=43). Serous tumors (n=15) were included as non-endometriosis associated controls. The immune microenvironment was profiled using Nanostring and the nCounter® GX Human Immunology Kit, comprising probes for a total of 511 immune genes. Results One third of the endometriosis patients revealed a tumor-like inflammation profile, suggesting that cancer–like immune signatures may develop earlier, in patients classified as clinically benign. Gene expression analyses revealed the complement pathway as most prominently involved in both endometriosis and EAOC. Complement proteins are abundantly present in epithelial cells in both benign and malignant lesions. Mechanistic studies in ovarian surface epithelial (OSE) cells from mice with conditional (Cre-loxP) mutations show intrinsic production of complement in epithelia and demonstrate an early link between Kras- and Pten-driven pathways and complement upregulation. Downregulation of complement in these cells interferes with cell proliferation. Conclusions These findings reveal new characteristics of inflammation in precursor lesions and point to previously unknown roles of complement in endometriosis and EAOC. PMID:25294912

  14. Delivery after Operation for Deeply Infiltrating Endometriosis

    PubMed Central

    Allerstorfer, Christina; Enzelsberger, Simon H.; Shebl, Omar Josef; Mayer, Richard Bernhard

    2016-01-01

    Background. It has been suggested that, during pregnancy, endometriosis can cause a variety of disease-related complications. Objectives. The purpose of the study was to find out if women with histologically confirmed endometriosis do have a higher risk of adverse pregnancy outcome and if they suffer from a higher rate of complications during labor. Study Design. 51 women who underwent surgery because of deeply infiltrating endometriosis in the General Hospital Linz and the Women's General Hospital Linz and who gave birth in the Women's General Hospital Linz after the surgery were included in our survey. Results. 31 women (60.8%) had a spontaneous delivery and in 20 women (39.2%) a caesarean section was performed. There were no cases of third- and fourth-degree perineal lacerations. Collectively there were 4 cases (7.8%) of preterm delivery and one case (2.0%) of premature rupture of membranes. In two women (6.5%) a retained placenta was diagnosed. Conclusions. Our study is the first description on delivery modes after surgery for deeply infiltrating endometriosis. We did not find an elevated risk for perineal or vaginal laceration in women with a history of surgery for deeply infiltrating endometriosis, even when a resection of the rectum or of the posterior vaginal wall had been performed. PMID:27517050

  15. Delivery after Operation for Deeply Infiltrating Endometriosis.

    PubMed

    Allerstorfer, Christina; Oppelt, Peter; Enzelsberger, Simon H; Shamiyeh, Andreas; Schimetta, Wolfgang; Shebl, Omar Josef; Mayer, Richard Bernhard

    2016-01-01

    Background. It has been suggested that, during pregnancy, endometriosis can cause a variety of disease-related complications. Objectives. The purpose of the study was to find out if women with histologically confirmed endometriosis do have a higher risk of adverse pregnancy outcome and if they suffer from a higher rate of complications during labor. Study Design. 51 women who underwent surgery because of deeply infiltrating endometriosis in the General Hospital Linz and the Women's General Hospital Linz and who gave birth in the Women's General Hospital Linz after the surgery were included in our survey. Results. 31 women (60.8%) had a spontaneous delivery and in 20 women (39.2%) a caesarean section was performed. There were no cases of third- and fourth-degree perineal lacerations. Collectively there were 4 cases (7.8%) of preterm delivery and one case (2.0%) of premature rupture of membranes. In two women (6.5%) a retained placenta was diagnosed. Conclusions. Our study is the first description on delivery modes after surgery for deeply infiltrating endometriosis. We did not find an elevated risk for perineal or vaginal laceration in women with a history of surgery for deeply infiltrating endometriosis, even when a resection of the rectum or of the posterior vaginal wall had been performed. PMID:27517050

  16. Natural Killer Cells: Key Players in Endometriosis.

    PubMed

    Thiruchelvam, Uma; Wingfield, Mary; O'Farrelly, Cliona

    2015-10-01

    Endometriosis affects more than 10% of women, causing significant pain and morbidity. It is also a significant cause of infertility. The aetiology of the disease remains an enigma, and the mechanisms responsible for the associated infertility are unclear. A role for immune cells in endometriosis has been postulated, with attention directed towards natural killer (NK) cells and macrophages. NK cells kill tumours and infected cells but also have roles in tissue remodelling in several organs including the uterus and are key to successful pregnancy. Here, we explore evidence (from peer-reviewed published articles) of phenotypic and functional abnormalities in NK cell subpopulations of women with endometriosis. It is clear that peripheral blood NK cells and peritoneal NK cells have reduced cytotoxic function in women with endometriosis. Uterine NK cells have a vital role in infertility, but very little research has been carried out in this area. We propose that abnormal u NK cell activity may contribute to the pathogenesis of endometriosis and its associated infertility and that future research should focus on this complex area. PMID:26104509

  17. Endometriosis: alternative methods of medical treatment

    PubMed Central

    Muñoz-Hernando, Leticia; Muñoz-Gonzalez, Jose L; Marqueta-Marques, Laura; Alvarez-Conejo, Carmen; Tejerizo-García, Álvaro; Lopez-Gonzalez, Gregorio; Villegas-Muñoz, Emilia; Martin-Jimenez, Angel; Jiménez-López, Jesús S

    2015-01-01

    Endometriosis is an inflammatory estrogen-dependent disease defined by the presence of endometrial glands and stroma at extrauterine sites. The main purpose of endometriosis management is alleviating pain associated to the disease. This can be achieved surgically or medically, although in most women a combination of both treatments is required. Long-term medical treatment is usually needed in most women. Unfortunately, in most cases, pain symptoms recur between 6 months and 12 months once treatment is stopped. The authors conducted a literature search for English original articles, related to new medical treatments of endometriosis in humans, including articles published in PubMed, Medline, and the Cochrane Library. Keywords included “endometriosis” matched with “medical treatment”, “new treatment”, “GnRH antagonists”, “Aromatase inhibitors”, “selective progesterone receptor modulators”, “anti-TNF α”, and “anti-angiogenic factors”. Hormonal treatments currently available are effective in the relief of pain associated to endometriosis. Among new hormonal drugs, association to aromatase inhibitors could be effective in the treatment of women who do not respond to conventional therapies. GnRH antagonists are expected to be as effective as GnRH agonists, but with easier administration (oral). There is a need to find effective treatments that do not block the ovarian function. For this purpose, antiangiogenic factors could be important components of endometriosis therapy in the future. Upcoming researches and controlled clinical trials should focus on these drugs. PMID:26089705

  18. World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonization Project: III. Fluid biospecimen collection, processing, and storage in endometriosis research

    PubMed Central

    Rahmioglu, Nilufer; Fassbender, Amelie; Vitonis, Allison F.; Tworoger, Shelley S.; Hummelshoj, Lone; D'Hooghe, Thomas M.; Adamson, G. David; Giudice, Linda C.; Becker, Christian M.; Zondervan, Krina T.; Missmer, Stacey A.; Adamson, G.D.; Allaire, C.; Anchan, R.; Becker, C.M.; Bedaiwy, M.A.; Buck Louis, G.M.; Calhaz-Jorge, C.; Chwalisz, K.; D'Hooghe, T.M.; Fassbender, A.; Faustmann, T.; Fazleabas, A.T.; Flores, I.; Forman, A.; Fraser, I.; Giudice, L.C.; Gotte, M.; Gregersen, P.; Guo, S.-W.; Harada, T.; Hartwell, D.; Horne, A.W.; Hull, M.L.; Hummelshoj, L.; Ibrahim, M.G.; Kiesel, L.; Laufer, M.R.; Machens, K.; Mechsner, S.; Missmer, S.A.; Montgomery, G.W.; Nap, A.; Nyegaard, M.; Osteen, K.G.; Petta, C.A.; Rahmioglu, N.; Renner, S.P.; Riedlinger, J.; Roehrich, S.; Rogers, P.A.; Rombauts, L.; Salumets, A.; Saridogan, E.; Seckin, T.; Stratton, P.; Sharpe-Timms, K.L.; Tworoger, S.; Vigano, P.; Vincent, K.; Vitonis, A.F.; Wienhues-Thelen, U.-H.; Yeung, P.P.; Yong, P.; Zondervan, K.T.

    2014-01-01

    Objective To harmonize standard operating procedures (SOPs) and standardize the recording of associated data for collection, processing, and storage of fluid biospecimens relevant to endometriosis. Design An international collaboration involving 34 clinical/academic centers and 3 industry collaborators from 16 countries on 5 continents. Setting In 2013, 2 workshops were conducted, followed by global consultation, bringing together 54 leaders in endometriosis research and sample processing worldwide. Patient(s) None. Intervention(s) Consensus SOPs were based on: [1] systematic comparison of SOPs from 18 global centers collecting fluid samples from women with and without endometriosis on a medium/large scale (publication on >100 cases), [2] literature evidence where available, or consultation with laboratory experts otherwise, and [3] several global consultation rounds. Main Outcome Measure(s) Standard recommended and minimum required SOPs for biofluid collection, processing, and storage in endometriosis research. Result(s) We developed recommended standard and minimum required SOPs for the collection, processing, and storage of plasma, serum, saliva, urine, endometrial/peritoneal fluid, and menstrual effluent, and a biospecimen data-collection form necessary for interpretation of sample-derived results. Conclusion(s) The Endometriosis Phenome and Biobanking Harmonisation Project SOPs allow endometriosis research centers to decrease variability in biofluid sample results, facilitating between-center comparisons and collaborations. The procedures are also relevant to research into other female conditions involving biofluid samples subject to cyclic reproductive influences. The consensus SOPs are based on the best available evidence; areas with limited evidence are identified as requiring further pilot studies. The SOPs will be reviewed based on investigator feedback, and through systematic tri-annual follow-up. Updated versions will be made available at

  19. Endometriosis

    MedlinePlus

    ... the disease and leave your organs in place. Hysterectomy is surgery to remove your uterus, fallopian tubes, ... the uterus, fallopian tubes, and both ovaries (a hysterectomy) gives you the best chance for a cure.

  20. Endometriosis

    MedlinePlus

    ... National Institute on Alcohol Abuse and Alcoholism. (2003). Alcohol's Effects on Female Reproductive Function. Schliep, K., et al. ( ... National Institute on Alcohol Abuse and Alcoholism. (2003). Alcohol's Effects on Female Reproductive Function. Schliep, K., et al. ( ...

  1. Endometriosis

    MedlinePlus Videos and Cool Tools

    ... site at www.asrm.org Find a Health Care Provider Back to Top Home | About Us | Reproductive ... News & Publications | Resources Site endowed by Advanced Reproductive Care, Inc. (ARC, Inc.) ©1996 - 2016 ASRM, American Society ...

  2. Megestrol acetate for treatment of endometriosis.

    PubMed

    Schlaff, W D; Dugoff, L; Damewood, M D; Rock, J A

    1990-04-01

    Between 1977-1989, 29 women with symptomatic endometriosis were treated with megestrol acetate by the Johns Hopkins Division of Reproductive Endocrinology. All had previously received one or more alternative medical treatments for endometriosis, in each case discontinued because of poor response or development of unacceptable side effects. Treatment consisted of a daily dose of 40 mg megestrol acetate orally for up to 24 months. Disease-related symptoms (dysmenorrhea, noncyclic pelvic pain, and dyspareunia) were relieved in 86% of the subjects treated with an adequate course of therapy. Side effects were fairly well tolerated, although eight women discontinued treatment within 2 months and two others stopped the drug by 4 months. These preliminary findings suggest that megestrol acetate may be an effective treatment for patients with endometriosis, even those who have been unresponsive to other modes of therapy. PMID:2314784

  3. Pathogenetic Mechanisms of Deep Infiltrating Endometriosis.

    PubMed

    Tosti, Claudia; Pinzauti, Serena; Santulli, Pietro; Chapron, Charles; Petraglia, Felice

    2015-09-01

    Endometriosis is a benign gynecologic disease, affecting women of reproductive age associated with chronic pelvic pain, dysmenorrhea, dyspareunia and infertility. Ovarian endometrioma (OMA), superficial peritoneal endometriosis (SPE), and deep infiltrating endometriosis (DIE) are, till now, recognized as major phenotypes. The discussion is to know whether they share the same pathogenetic mechanisms. Till today, DIE is recognized as the most severe clinical form of endometriosis and has a complex clinical management. The DIE lesions have been considered in the present article, without distinguishing between the anterior (bladder) or the posterior (vagina, uterosacral ligaments, rectum, and ureter) compartment. The present knowledge indicates that hormonal function (estrogen and progesterone receptors) and immunological factors, such as peritoneal macrophages, natural killer cells, and lymphocytes, are critically altered in DIE. The aggressive behavior of DIE may be explained by the highly decreased apoptosis (nuclear factor kappa-light-chain-enhancer of activated B cells [NF-kB], B-cell lymphoma 2 [Blc-2], and anti-Mullerian hormone) and by the increased proliferation activity related to oxidative stress (NF-kB, reactive oxygen species, extracellular regulated kinase (ERK), advanced oxidation protein product). Invasive mechanisms are more expressed (matrix metalloproteinases and activins) in DIE in comparison to the OMA and SPE. Correlated with the increased invasiveness are the data on very high expression of neuroangiogenesis (nerve growth factor, vascular endothelial growth factor, and intercellular adhesion molecule) genes in DIE. Therefore, at the present time, several of the DIE pathogenetic features result specific in comparison to other endometriosis phenotypes, pleading for the existence of a specific entity. These evidence of specific pathogenetic features of DIE may explain the more severe symptomatology related to this form of endometriosis and suggest

  4. Cyclical rectal bleeding in colorectal endometriosis.

    PubMed

    Levitt, M D; Hodby, K J; van Merwyk, A J; Glancy, R J

    1989-12-01

    Three case reports of cyclical rectal bleeding in endometriosis affecting rectum and sigmoid colon emphasize the close relationship between such cyclical bleeding and intestinal endometriosis. The cause of bleeding, however, is still unclear. The predilection of endometriotic deposits for the outer layers of the bowel wall suggests that mucosal involvement is not a prerequisite for rectal bleeding. The frequent absence of identifiable intramural haemorrhage casts doubt on the premise that intestinal endometriotic deposits 'menstruate'. The cause may simply be a transient tear in normal mucosa due to swelling of an underlying endometriotic deposit at the time of menstruation. PMID:2597100

  5. World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonisation Project: IV. Tissue collection, processing, and storage in endometriosis research

    PubMed Central

    Fassbender, Amelie; Rahmioglu, Nilufer; Vitonis, Allison F.; Viganò, Paola; Giudice, Linda C.; D’Hooghe, Thomas M.; Hummelshoj, Lone; Adamson, G. David; Becker, Christian M.; Missmer, Stacey A.; Zondervan, Krina T.; Adamson, G.D.; Allaire, C.; Anchan, R.; Becker, C.M.; Bedaiwy, M.A.; Buck Louis, G.M.; Calhaz-Jorge, C.; Chwalisz, K.; D'Hooghe, T.M.; Fassbender, A.; Faustmann, T.; Fazleabas, A.T.; Flores, I.; Forman, A.; Fraser, I.; Giudice, L.C.; Gotte, M.; Gregersen, P.; Guo, S.-W.; Harada, T.; Hartwell, D.; Horne, A.W.; Hull, M.L.; Hummelshoj, L.; Ibrahim, M.G.; Kiesel, L.; Laufer, M.R.; Machens, K.; Mechsner, S.; Missmer, S.A.; Montgomery, G.W.; Nap, A.; Nyegaard, M.; Osteen, K.G.; Petta, C.A.; Rahmioglu, N.; Renner, S.P.; Riedlinger, J.; Roehrich, S.; Rogers, P.A.; Rombauts, L.; Salumets, A.; Saridogan, E.; Seckin, T.; Stratton, P.; Sharpe-Timms, K.L.; Tworoger, S.; Vigano, P.; Vincent, K.; Vitonis, A.F.; Wienhues-Thelen, U.-H.; Yeung, P.P.; Yong, P.; Zondervan, K.T.

    2014-01-01

    Objective To harmonize standard operating procedures (SOPs) and standardize the recording of associated data for collection, processing, and storage of human tissues relevant to endometriosis. Design An international collaboration involving 34 clinical/academic centers and three industry collaborators from 16 countries on five continents. Setting In 2013, two workshops were conducted followed by global consultation, bringing together 54 leaders in endometriosis research and sample processing from around the world. Patient(s) None. Intervention(s) Consensus SOPs were based on: 1) systematic comparison of SOPs from 24 global centers collecting tissue samples from women with and without endometriosis on a medium or large scale (publication on >100 cases); 2) literature evidence where available, or consultation with laboratory experts otherwise; and 3) several global consultation rounds. Main Outcome Measure(s) Standard recommended and minimum required SOPs for tissue collection, processing, and storage in endometriosis research. Result(s) We developed “recommended standard” and “minimum required” SOPs for the collection, processing, and storage of ectopic and eutopic endometrium, peritoneum, and myometrium, and a biospecimen data collection form necessary for interpretation of sample-derived results. Conclusion(s) The EPHect SOPs allow endometriosis research centers to decrease variability in tissue-based results, facilitating between-center comparisons and collaborations. The procedures are also relevant to research into other gynecologic conditions involving endometrium, myometrium, and peritoneum. The consensus SOPs are based on the best available evidence; areas with limited evidence are identified as requiring further pilot studies. The SOPs will be reviewed based on investigator feedback and through systematic triannual follow-up. Updated versions will be made available at: http://endometriosisfoundation.org/ephect. PMID:25256928

  6. DIOXINS AND ENDOMETRIOSIS: A PLAUSIBLE HYPOTHESIS

    EPA Science Inventory

    A potential connection exists between the increasing prevalence of endometriosis and exposure to organochlorine chemicals. There is evidence that dioxin (2,3,7,8-TCDD) can increase the incidence and severity of the disease in monkeys and can promote the growth or survival of end...

  7. Endometriosis Linked to Heart Disease in Study

    MedlinePlus

    ... epidemiologic research in reproductive medicine at Brigham and Women's Hospital in Boston. Missmer said the study found an association between endometriosis and the risk of heart disease, but can't prove a cause-and-effect relationship. She believes this is the first study to ...

  8. [Ileal and appendicular endometriosis (author's transl)].

    PubMed

    Thorbeck, R V

    1978-01-01

    A bibliographical review it's been made on the base of a double rara localization of endometriosis: ileal and appendicular, marking the diagnostic difficulties found appendicular, marking the diagnostic-difficulties found before and after surgery, emphasizing the interest of the histological integrity and motivity of intestinal mucosa. PMID:721916

  9. Bladder Endometriosis Mimicking TCC - A Case Report.

    PubMed

    Gupta, Asish; Bhatnagar, Atul; Seth, B N; Dang, Arbinder; Gupta, Vineeta

    2016-02-01

    Endometriosis is the ectopic presence of endometrial tissue outside the uterus. Though on its own endometriosis is not a rare lesion, the involvement of the urinary tract is rare but with the bladder being the most commonly affected organ. Endometriosis is usually seen in females between the ages of 30-40 years and may occur due to fluctuating levels of oestrogen and progesterone. Clinically the patient maybe asymptomatic or show symptoms of dysmenorrhea, irregular or heavy periods, pain in the pelvic area, lower abdomen or in the back. It has been suggested that ultrasonography should be done either before or during menstruation as the lesion becomes more evident and a biopsy taken during this period is a strong aid in reaching a final diagnosis. We report here an unusual case of bladder endometriosis where the patient came with severe pelvic pain and an endoluminal mass seen on the ultrasonographic report. Based on these findings a differential of transitional cell carcinoma was given which was ruled out based on the cystoscopic findings. PMID:27042525

  10. Novel three-dimensional in vitro models of ovarian endometriosis

    PubMed Central

    2014-01-01

    Background Endometriosis is characterized by the presence of functional endometrial tissue outside of the uterine cavity. It affects 1 in 10 women of reproductive age. This chronic condition commonly leads to consequences such as pelvic pain, dysmenorrhea, infertility and an elevated risk of epithelial ovarian cancer. Despite the prevalence of endometriosis and its impact on women’s lives, there are relatively few in vitro and in vivo models available for studying the complex disease biology, pathophysiology, and for use in the preclinical development of novel therapies. The goal of this study was to develop a novel three-dimensional (3D) cell culture model of ovarian endometriosis and to test whether it is more reflective of endometriosis biology than traditional two dimensional (2D) monolayer cultures. Methods A novel ovarian endometriosis epithelial cell line (EEC16) was isolated from a 34-year old female with severe endometriosis. After characterization of cells using in vitro assays, western blotting and RNA-sequencing, this cell line and a second, already well characterized endometriosis cell line, EEC12Z, were established as in vitro 3D spheroid models. We compared biological features of 3D spheroids to 2D cultures and human endometriosis lesions using immunohistochemistry and real-time semi-quantitative PCR. Results In comparison to normal ovarian epithelial cells, EEC16 displayed features of neoplastic transformation in in vitro assays. When cultured in 3D, EEC16 and EEC12Z showed differential expression of endometriosis-associated genes compared to 2D monolayer cultures, and more closely mimicked the molecular and histological features of human endometriosis lesions. Conclusions To our knowledge, this represents the first report of an in vitro spheroid model of endometriosis. 3D endometriosis models represent valuable experimental tools for studying EEC biology and the development of novel therapeutic approaches. PMID:24502583

  11. Endometriosis and Infertility: How and When to Treat?

    PubMed Central

    Fadhlaoui, Anis; Bouquet de la Jolinière, Jean; Feki, Anis

    2014-01-01

    Endometriosis is defined as the presence of endometrial-like tissue (glands or stroma) outside the uterus, which induces a chronic inflammatory reaction. Although endometriosis impairs fertility, it does not usually completely prevent conception. The question of evidence based-medicine guidelines in endometriosis-associated infertility is weak in many situations. Therefore, we will highlight in this issue where the challenges are. PMID:25593948

  12. Extragenital endometriosis: assessment with MR imaging. A pictorial review.

    PubMed

    Menni, Katiuscia; Facchetti, Luca; Cabassa, Paolo

    2016-04-01

    Endometriosis is a gynaecologic disease characterized by endometrial tissue outside the uterine cavity. Commonly it affects the pelvic organs. When endometrial nodules or plaques are localized in sites other than the uterus or ovaries, it is termed extragenital endometriosis. Adequate pre-operative assessment is essential for treatment planning. MRI is a non-invasive method with high spatial resolution that allows the multiplanar evaluation of genital and extragenital endometriosis. Herein, we present a pictorial review of a variety of extragenital endometriosis cases, all of which can be encountered in clinical practice. PMID:26846303

  13. [Is endometriosis a precancerous lesion? Perspectives and clinical implications].

    PubMed

    Chene, G; Caloone, J; Moret, S; Le Bail-Carval, K; Chabert, P; Beaufils, E; Mellier, G; Lamblin, G

    2016-02-01

    Epidemiological studies have shown a relationship between endometriosis and clear cell/endometrioid ovarian cancers (named "Endometriosis Associated Ovarian Cancer" or EAOC). The recent discovery of signaling pathways (especially the SWI/SNF and PI3K/AKT/mTOR pathways) that linked endometriosis and EAOC could lead to the development of specific biomarkers as ARID1A to screen benign to premalignant endometriosis and to new targeted treatment. Moreover, the better understanding of the pathogenesis of the epithelial ovarian cancer arising from the Fallopian tube could allow new early prevention strategies that will be described in this review. PMID:26850282

  14. Primary Umbilical Endometriosis: Unusual and Rare Clinical Presentation

    PubMed Central

    Taniguchi, Fuminori; Hirakawa, Eriko; Azuma, Yukihiro; Uejima, Chihiro; Ashida, Keigo; Harada, Tasuku

    2016-01-01

    Primary umbilical endometriosis is a rare disorder and is defined as the presence of ectopic endometrial tissue within the umbilicus. A patient with painful mass in the umbilicus during menstrual period is studied in this paper. The possibility of subcutaneous endometriosis should be considered when an umbilical mass is detected despite the absence of previous surgery. In this case, urachal cancer, urachal remnant, umbilical endometriosis, and its malignant transformation were among the diseases considered in the differential diagnosis. Complete excision and histology are necessary to obtain a definitive diagnosis and optimal treatment for umbilical subcutaneous endometriosis. PMID:27242939

  15. Intrinsic ureteral endometriosis as a cause of unilateral obstructive uropathy

    PubMed Central

    Mason, Ross J.; Alamri, Abdulaziz; Gusenbauer, Kaela; Kapoor, Anil

    2016-01-01

    Endometriosis is a common gynecological condition, but involvement of the urinary tract is rare. Ureteral endometriosis can present in a nonspecific fashion, and may mimic ureteral malignancy. This case report describes a 44-year-old woman who initially presented with chronic flank pain and was found to have left-sided renal dysfunction and a distal left ureteric mass. She was eventually diagnosed with ureteral endometriosis after undergoing nephroureterectomy for what was thought to be either a ureteral fibroepithelial polyp or transitional cell carcinoma. Ureteral endometriosis should be considered in the differential diagnosis for a woman presenting with obstructive uropathy in the presence of a ureteric mass. PMID:27330580

  16. Evaluation of Risk Factors Associated with Endometriosis in Infertile Women

    PubMed Central

    Ashrafi, Mahnaz; Sadatmahalleh, Shahideh Jahanian; Akhoond, Mohammad Reza; Talebi, Mehrak

    2016-01-01

    Background Endometriosis affects women’s physical and mental wellbeing. Symptoms include dyspareunia, dysmenorrhea, pelvic pain, and infertility. The purpose of this study is to assess the correlation between some relevant factors and symptoms and risk of an endometriosis diagnosis in infertile women. Materials and Methods A retrospective study of 1282 surgical patients in an infertility Institute, Iran between 2011 and 2013 were evaluated by laparoscopy. Of these, there were 341 infertile women with endometriosis (cases) and 332 infertile women with a normal pelvis (comparison group). Chi-square and t tests were used to compare these two groups. Logistic regression was done to build a prediction model for an endometriosis diagnosis. Results Gravidity [odds ratio (OR): 0.8, confidence interval (CI): 0.6-0.9, P=0.01], parity (OR: 0.7, CI: 0.6-0.9, P=0.01), family history of endometriosis (OR: 4.9, CI: 2.1-11.3, P<0.001), history of galactorrhea (OR: 2.3, CI: 1.5-3.5, P=0.01), history of pelvic surgery (OR: 1.9, CI: 1.3-2.7, P<0.001), and shorter menstrual cycle length (OR: 0.9, CI: 0.9-0.9, P=0.04) were associated with endometriosis. Duration of natural menstruation and age of menarche were not correlated with subsequent risk of endometriosis (P>0.05). Fatigue, diarrhea, constipation, dysmenorrhea, dyspareunia, pelvic pain and premenstrual spotting were more significant among late-stage endometriosis patients than in those with early-stage endometriosis and more prevalent among patients with endometriosis than that of the comparison group. In the logistic regression model, gravidity, family history of endometriosis, history of galactorrhea, history of pelvic surgery, dysmenorrhoea, pelvic pain, dysparaunia, premenstrual spotting, fatigue, and diarrhea were significantly associated with endometriosis. However, the number of pregnancies was negatively related to endometriosis. Conclusion Endometriosis is a considerable public health issue because it affects many

  17. Endometriosis: a high-risk population for major chronic diseases?

    PubMed Central

    Kvaskoff, Marina; Mu, Fan; Terry, Kathryn L.; Harris, Holly R.; Poole, Elizabeth M.; Farland, Leslie; Missmer, Stacey A.

    2015-01-01

    BACKGROUND Despite an estimated prevalence of 10% in women, the etiology of endometriosis remains poorly understood. Over recent decades, endometriosis has been associated with risk of several chronic diseases, such as cancer, autoimmune diseases, asthma/atopic diseases and cardiovascular diseases. A deeper understanding of these associations is needed as they may provide new leads into the causes or consequences of endometriosis. This review summarizes the available epidemiological findings on the associations between endometriosis and other chronic diseases and discusses hypotheses for underlying mechanisms, potential sources of bias and methodological complexities. METHODS We performed a comprehensive search of the PubMed/Medline and ISI Web of Knowledge databases for all studies reporting on the associations between endometriosis and other diseases published in English through to May 2014, using numerous search terms. We additionally examined the reference lists of all identified papers to capture any additional articles that were not identified through computer searches. RESULTS We identified 21 studies on the associations between endometriosis and ovarian cancer, 14 for breast cancer, 8 for endometrial cancer, 4 for cervical cancer, 12 for cutaneous melanoma and 3 for non-Hodgkin's lymphoma, as well as 9 on the links between endometriosis and autoimmune diseases, 6 on the links with asthma and atopic diseases, and 4 on the links with cardiovascular diseases. Endometriosis patients were reported to be at higher risk of ovarian and breast cancers, cutaneous melanoma, asthma, and some autoimmune, cardiovascular and atopic diseases, and at decreased risk of cervical cancer. CONCLUSIONS Increasing evidence suggests that endometriosis patients are at higher risk of several chronic diseases. Although the underlying mechanisms are not yet understood, the available data to date suggest that endometriosis is not harmless with respects to women's long-term health. If

  18. Common Genetic Influences Underlie Comorbidity of Migraine and Endometriosis

    PubMed Central

    Nyholt, Dale R.; Gillespie, Nathan G.; Merikangas, Kathleen R.; Treloar, Susan A.; Martin, Nicholas G.; Montgomery, Grant W.

    2009-01-01

    We examined the co-occurrence of migraine and endometriosis within the largest known collection of families containing multiple women with surgically confirmed endometriosis and in an independent sample of 815 monozygotic and 457 dizygotic female twin pairs. Within the endometriosis families, a significantly increased risk of migrainous headache was observed in women with endometriosis compared to women without endometriosis (odds ratio [OR] 1.57, 95% confidence interval [CI]: 1.12–2.21, P = 0.009). Bivariate heritability analyses indicated no evidence for common environmental factors influencing either migraine or endometriosis but significant genetic components for both traits, with heritability estimates of 69 and 49%, respectively. Importantly, a significant additive genetic correlation (rG = 0.27, 95% CI: 0.06–0.47) and bivariate heritability (h2 = 0.17, 95% CI: 0.08–0.27) was observed between migraine and endometriosis. Controlling for the personality trait neuroticism made little impact on this association. These results confirm the previously reported comorbidity between migraine and endometriosis and indicate common genetic influences completely explain their co-occurrence within individuals. Given pharmacological treatments for endometriosis typically target hormonal pathways and a number of findings provide support for a relationship between hormonal variations and migraine, hormone-related genes and pathways are highly plausible candidates for both migraine and endometriosis. Therefore, taking into account the status of both migraine and endometriosis may provide a novel opportunity to identify the genes underlying them. Finally, we propose that the analysis of such genetically correlated comorbid traits can increase power to detect genetic risk loci through the use of more specific, homogenous and heritable phenotypes. PMID:18636479

  19. Colorectal endometriosis: benefits of long-term follow-up in patients who underwent laparoscopic surgery.

    PubMed

    Stepniewska, Anna; Pomini, Paola; Guerriero, Massimo; Scioscia, Marco; Ruffo, Giacomo; Minelli, Luca

    2010-05-01

    In this retrospective cohort study, three groups of patients were included: 60 women who underwent endometriosis surgery with colorectal segmental resection, 40 women with surgical evidence of bowel endometriosis who underwent endometriosis removal without bowel resection, and 55 women affected by moderate or severe endometriosis with at least one endometrioma and deep infiltrating endometriosis but without bowel involvement. The results of a long-term ambulatory follow-up showed that if colorectal endometriosis was present, postoperative pain regression was more frequent, and among patients with bowel endometriosis the rate of recurrence was lower if segmental resection was performed. PMID:19836731

  20. [Prolegomena before any psychoanalytical approach to endometriosis].

    PubMed

    Louka, J-M

    2007-04-01

    Endometriosis is a disease, which requires medication or surgery to be treated. However, it can be considered as a symptom psychoanalytically speaking. Before going further into the question from this point of view, let us examine some prolegomena--preliminary principles. The scientistic ideology of a La Mettrie's "Human Machine", the unconscious subject promoted by psychoanalysts for more than a century, the Anglo-American notion of post-traumatic stress disorder, and womanhood and the mental structure customarily called hysteria stand for the main prolegomena. English and French speaking psychopathological literature is reviewed to introduce our personal experience of women with endometriosis. Finally, a public consultation is considered to confirm or invalidate scientific data stemmed from psychoanalytical experience. PMID:17350875

  1. Jack in the box: inguinal endometriosis.

    PubMed

    Pandey, Deeksha; Coondoo, Ambika; Shetty, Jyothi; Mathew, Stanley

    2015-01-01

    A 39-year-old woman with a left-sided inguinal swelling was referred to us with a diagnosis of inguinal hernia. On asking leading questions, the patient gave a typical history of cyclical pain and increased swelling during menstruation. Fine-needle aspiration biopsy revealed endometrial glands. Preoperatively, the extent of the endometriotic lesion was delineated using MRI. The lesion was approached through the patient's caesarean scar for cosmetic reasons and excised in toto. Final diagnosis was round ligament endometriosis. The patient was asymptomatic at 3, 6 and 12 months' follow-up. This case re-emphasises the fact that endometriosis is an enigmatic disease and can be found anywhere in the body. Thus, a woman of reproductive age presenting with any cyclical symptom should be asked about its relation to her menstrual cycle. PMID:25827916

  2. Spontaneous endometriosis in a mandrill (Mandrillus sphinx).

    PubMed

    Nakamura, S; Ochiai, K; Ochi, A; Ito, M; Kamiya, T; Yamamoto, H

    2012-01-01

    A 25-year-old female mandrill (Mandrillus sphinx) died after exhibiting weakness and recumbency with serosanguineous ascites. Gross findings included haemoperitoneum and multifocal to diffuse serosal thickening with petechiae and ecchymoses throughout the peritoneum. The uterus was covered entirely with large blood clots and was adherent to the ovaries and pelvic wall. Microscopical and immunohistochemical examination revealed extra- and intra-uterine growth of ectopic endometrial tissue with marked fibrosis. The ectopic endometrial tissues predominantly consisted of stromal cells expressing CD10 and progesterone receptor and variably-sized glands lined by the epithelium with occasional slight expression of oestrogen receptor α. A diagnosis of endometriosis was made. This is the first report of naturally occurring endometriosis in a mandrill. PMID:22520805

  3. Theories on the pathogenesis of endometriosis.

    PubMed

    Sourial, Samer; Tempest, Nicola; Hapangama, Dharani K

    2014-01-01

    Endometriosis is a common, chronic inflammatory disease defined by the presence of extrauterine endometrial tissue. The aetiology of endometriosis is complex and multifactorial, where several not fully confirmed theories describe its pathogenesis. This review examines existing theories on the initiation and propagation of different types of endometriotic lesions, as well as critically appraises the myriad of biologically relevant evidence that support or oppose each of the proposed theories. The current literature suggests that stem cells, dysfunctional immune response, genetic predisposition, and aberrant peritoneal environment may all be involved in the establishment and propagation of endometriotic lesions. An orchestrated scientific and clinical effort is needed to consider all factors involved in the pathogenesis of this multifaceted disease and to propose novel therapeutic targets to reach effective treatments for this distressing condition. PMID:25763392

  4. Theories on the Pathogenesis of Endometriosis

    PubMed Central

    Sourial, Samer; Hapangama, Dharani K.

    2014-01-01

    Endometriosis is a common, chronic inflammatory disease defined by the presence of extrauterine endometrial tissue. The aetiology of endometriosis is complex and multifactorial, where several not fully confirmed theories describe its pathogenesis. This review examines existing theories on the initiation and propagation of different types of endometriotic lesions, as well as critically appraises the myriad of biologically relevant evidence that support or oppose each of the proposed theories. The current literature suggests that stem cells, dysfunctional immune response, genetic predisposition, and aberrant peritoneal environment may all be involved in the establishment and propagation of endometriotic lesions. An orchestrated scientific and clinical effort is needed to consider all factors involved in the pathogenesis of this multifaceted disease and to propose novel therapeutic targets to reach effective treatments for this distressing condition. PMID:25763392

  5. Endometriosis Mimicking an Advanced Malignant Tumor.

    PubMed

    Wang, Taisong; Xing, Yan; Zhao, Jinhua

    2016-08-01

    A 27-year-old woman with swelling left leg, groin pain, and increased serum CA125 level underwent FDG PET/CT to evaluate a pelvic mass revealed by an MRI performed from an outside hospital. A large hypermetabolic solid mass in the left pelvic wall and several lymph nodes with elevated FDG activity were noted, which indicated malignancy. However, histopathological examination demonstrated endometriosis. PMID:27187736

  6. [Catamenial rectal bleeding and sigmoid endometriosis].

    PubMed

    Kazadi Buanga, J; Alcazar, J L; Laparte, M C; Lopez Garcia, G

    1992-01-01

    We describe a case of menstrual rectal bleeding due to sigmoid endometriosis. The history led us to the diagnosis and since a small biopsy of the lesion and scanning could not help us to a conclusive diagnosis we carried out histological examination of a piece removed at operation. This case has led us to estimate the incidence, the difficulties of diagnosis and the present therapeutic measures. PMID:1469232

  7. Peripheral biomarkers of endometriosis: a systematic review

    PubMed Central

    May, K.E.; Conduit-Hulbert, S.A.; Villar, J.; Kirtley, S.; Kennedy, S.H.; Becker, C.M.

    2010-01-01

    BACKGROUND Endometriosis is estimated to affect 1 in 10 women during the reproductive years. There is often delay in making the diagnosis, mainly due to the non-specific nature of the associated symptoms and the need to verify the disease surgically. A biomarker that is simple to measure could help clinicians to diagnose (or at least exclude) endometriosis; it might also allow the effects of treatment to be monitored. If effective, such a marker or panel of markers could prevent unnecessary diagnostic procedures and/or recognize treatment failure at an early stage. METHODS We used QUADAS (Quality Assessment of Diagnostic Accuracy Studies) criteria to perform a systematic review of the literature over the last 25 years to assess critically the clinical value of all proposed biomarkers for endometriosis in serum, plasma and urine. RESULTS We identified over 100 putative biomarkers in publications that met the selection criteria. We were unable to identify a single biomarker or panel of biomarkers that have unequivocally been shown to be clinically useful. CONCLUSIONS Peripheral biomarkers show promise as diagnostic aids, but further research is necessary before they can be recommended in routine clinical care. Panels of markers may allow increased sensitivity and specificity of any diagnostic test. PMID:20462942

  8. Spontaneous External Endometriosis in a Gorilla (Gorilla gorilla)

    PubMed Central

    Doré, Monique; Lagacé, Andre

    1985-01-01

    The present report describes a case of external endometriosis in a 28 year old female gorilla (Gorilla gorilla). Microscopical examination of a pelvic mass observed at necropsy revealed ovarian tissue together with uterine glands and stroma, fibrous tissue and many siderophages. Theories of pathogenesis of external endometriosis are briefly reviewed. ImagesFigure 1 and 2. PMID:17422589

  9. Intraperitoneal inflammation decreases endometriosis in a mouse model

    PubMed Central

    Nowak, N.M.; Fischer, O.M.; Gust, T.C.; Fuhrmann, U.; Habenicht, U.-F.; Schmidt, A.

    2008-01-01

    BACKGROUND The role of the immune system in the pathogenesis of endometriosis remains elusive. It has been shown that patients have an altered peritoneal environment with increased levels of inflammatory cytokines, activated macrophages and reduced clearance of retrogradely transported endometrial fragments. However, it is not known if this unique inflammatory situation is cause or consequence of endometriosis. This study investigates the impact of a pre-existing peritoneal inflammation on endometriosis establishment in a mouse model. METHODS Endometriosis was induced by intraperitoneal injection of enhanced green fluorescent protein (EGFP)-expressing endometrium in mice. In parallel, a peritonitis model was established via intraperitoneal injection of thioglycolate medium (TM). Finally, endometriosis was induced in the inflamed peritoneal cavity and lesion establishment as well as morphological and histological characteristics were analysed. RESULTS Induction of endometriosis in an inflamed peritoneal cavity resulted in fewer lesions and significantly lower sum of lesion surface area per mouse in the TM-treated group. Additionally, a higher amount of non-attached debris could be detected in the peritoneal cavity of TM-treated mice. CONCLUSIONS An intraperitoneal inflammation decreases endometriosis establishment in this mouse model. Thus, a pre-existing peritoneal inflammation might not be a factor favouring the development of endometriosis. PMID:18653673

  10. Rectus abdominis muscle endometriosis after cesarean section--case report.

    PubMed

    Dordević, Momcilo; Jovanović, Bozidar; Mitrović, Slobodanka; Dordević, Gordana; Radovanović, Dragce; Sazdanović, Predrag

    2009-09-01

    Endometriosis is defined by the presence of functional endometrial tissue outside the uterus, where it is normally located. Endometriosis is one of the most common gynecologic entities affecting 8%-18% of menstrual women. Endometriosis can occur at intra- and extrapelvic localizations. The most common intrapelvic localizations are those involving the ovaries, Douglas' area, pelvic peritoneum, uterus, bladder and rectum. Abdominal endometriosis is the most common localization of extrapelvic endometriosis and usually develops in connective tissue. Extra-pelvic implantation of endometrial tissue may develop in any organ including the skin, lungs, liver, extremities, brain and stomach. Three years after cesarean section, a 35-year-old female was operated on for suspected anterior abdominal hernia at the site of previous section. An egg-sized tumor was removed from the rectus abdominis muscle and referred for histopathologic and immunohistochemical analyses. The results showed endometriosis of the muscle with positive estrogen and progesterone receptors. A year after the procedure, treatment with gonadotropin-releasing hormone analogs was continued due to recurrent pain in the scar area, along with ultrasonography and biochemical marker (carbohydrate antigen 125) follow-up. Clinical diagnosis of scar endometriosis can be made by thorough history and physical, ultrasonography and biochemical examinations. Scar endometriosis should always be considered when the symptoms occur in a cyclic and hormone-dependent pattern, mostly after gynecologic operations, and worsening during menstruation. Definitive diagnosis is based on histopathologic analysis. PMID:20405641

  11. Length of Menstrual Cycle and Risk of Endometriosis

    PubMed Central

    Wei, Ming; Cheng, Yanfei; Bu, Huaien; Zhao, Ye; Zhao, Wenli

    2016-01-01

    Abstract Endometriosis is a complex disease that affects a large number of women worldwide and may cause pain and infertility. To systematically review published studies evaluating the relationship between menstrual cycle length and risk of endometriosis. We searched the Cochrane Library, PubMed, Web of Science, and EMBASE in databases in July 2014 using the keywords “case–control studies,” “epidemiologic determinants,” “risk factors,” “menstrual cycle,” “menstrual length,” “menstrual character,” and “endometriosis.” We included case–control studies published in English that investigated cases of surgically confirmed endometriosis and examined the relationship between endometriosis risk and menstrual cycle. Eleven articles that met the inclusion criteria included data of 3392 women with endometriosis and 5006 controls. Fixed-effects and random-effects models were used for the evaluation. For the association of risk of endometriosis and menstrual cycle length shorter than or equal to 27 days (SEQ27) or length longer than or equal to 29 days (LEQ29), the odds ratio was 1.22 (95% confidence interval [CI]: 1.05–1.43) and 0.68 (95% CI: 0.48–0.96), respectively. In conclusion, this meta-analysis suggests that menstrual cycle length SEQ27 increase the risk of endometriosis and cycle length LEQ29 decrease the risk. PMID:26945395

  12. [Colorectal cancer endometriosis resembling stenosing extrapelvic: report of two cases].

    PubMed

    Gallardo Arteaga, Josué; Marin Calderón, Luis; Barboza Beraun, Aurelio; Rivas Wong, Luz; Frisancho Velarde, Oscar

    2012-01-01

    We present two women of 40 and 42 years with colorectal endometriosis, both with a history of pelvic endometriosis and simultaneous episodes of rectal bleeding with menstruation. In endoscopic evaluations detected a sigmoid tumor and rectosigmoid tumor respectively, which apparently corresponds to stenosing colorectal cancer of epithelial origin. PMID:23307093

  13. Do we need a robot in endometriosis surgery?

    PubMed

    Hickman, Lisa C; Kotlyar, Alexander; Luu, Thanh H; Falcone, Tommaso

    2016-06-01

    Since the initial approval of robotic surgery for gynecologic procedures in 2005, its use has been widely adopted, and its application has been expanded beyond hysterectomies and myomectomies. The role of robotics in endometriosis surgery remains controversial, as no randomized control trials have been conducted to evaluate its use over conventional laparoscopy, the current gold standard for diagnosis and treatment. The advantage of robotic surgery in early stage endometriosis remains unclear, whereas several case reports and retrospective studies have suggested a role for robotics in treating advanced stage and deep infiltrating endometriosis. Advantages in advanced stage endometriosis include lower blood loss and possible reduction in length of hospital stay, compared to conventional laparoscopy; however, operative times are consistently longer in robotic surgery with no differences in quality of life and fertility outcomes. Randomized control trials comparing robotic to conventional laparoscopy for endometriosis surgery are needed to more clearly define the role for this promising technology. PMID:26658115

  14. Phosphoproteomics Analysis of Endometrium in Women with or without Endometriosis

    PubMed Central

    Xu, Hong-Mei; Deng, Hai-Teng; Liu, Chong-Dong; Chen, Yu-Ling; Zhang, Zhen-Yu

    2015-01-01

    Background: The molecular mechanisms underlying the endometriosis are still not completely understood. In order to test the hypothesis that the approaches in phosphoproteomics might contribute to the identification of key biomarkers to assess disease pathogenesis and drug targets, we carried out a phosphoproteomics analysis of human endometrium. Methods: A large-scale differential phosphoproteome analysis, using peptide enrichment of titanium dioxide purify and sequential elution from immobilized metal affinity chromatography with linear trap quadrupole-tandem mass spectrometry, was performed in endometrium tissues from 8 women with or without endometriosis. Results: The phosphorylation profiling of endometrium from endometriosis patients had been obtained, and found that identified 516 proteins were modified at phosphorylation level during endometriosis. Gene ontology annotation analysis showed that these proteins were enriched in cellular processes of binding and catalytic activity. Further pathway analysis showed that ribosome pathway and focal adhesion pathway were the top two pathways, which might be deregulated during the development of endometriosis. Conclusions: That large-scale phosphoproteome quantification has been successfully identified in endometrium tissues of women with or without endometriosis will provide new insights to understand the molecular mechanisms of the development of endometriosis. PMID:26415800

  15. Knowledge of, and treatment strategies for, endometriosis among general practitioners.

    PubMed

    van der Zanden, Moniek; Nap, Annemiek W

    2016-05-01

    Endometriosis is the most common benign gynaecological disorder. The general practitioner (GP) plays an important role in identifying women at early stages of the disease. This study was conducted to acquire information about awareness and knowledge of endometriosis among Dutch GPs, and clinical strategies taken. A total of 101 GPs completed a questionnaire either by email or at a local education meeting. The GPs annually encounter 2.8 women they suspect of having endometriosis. The estimated time to diagnosis was 65.7 months (39.1 months patient delay and 26.6 months doctors delay); 56.7% of GPs primarily refer to a gynaecologist for consultation or diagnostic tests. The GPs answered on average 16.6 out of 28 knowledge questions correctly. Seventy-six out of 87 GPs stated that they needed further education. The results of this study indicate that if a GP considers endometriosis as a diagnosis, adequate action is undertaken. As only limited numbers of women with endometriosis are encountered in their practice, GPs do not recognize immediately the symptoms that may be caused by endometriosis, leading to diagnostic delay. Our findings may help to set up teaching programmes and awareness strategies for first-line medical professionals to enhance timely diagnosis and treatment of endometriosis. PMID:26947452

  16. Bowel endometriosis: colorectal surgeon's perspective in a multidisciplinary surgical team.

    PubMed

    Wolthuis, Albert M; Meuleman, Christel; Tomassetti, Carla; D'Hooghe, Thomas; de Buck van Overstraeten, Anthony; D'Hoore, André

    2014-11-14

    Endometriosis is a gynecological condition that presents as endometrial-like tissue outside the uterus and induces a chronic inflammatory reaction. Up to 15% of women in their reproductive period are affected by this condition. Deep endometriosis is defined as endometriosis located more than 5 mm beneath the peritoneal surface. This type of endometriosis is mostly found on the uterosacral ligaments, inside the rectovaginal septum or vagina, in the rectosigmoid area, ovarian fossa, pelvic peritoneum, ureters, and bladder, causing a distortion of the pelvic anatomy. The frequency of bowel endometriosis is unknown, but in cases of bowel infiltration, about 90% are localized on the sigmoid colon or the rectum. Colorectal involvement results in alterations of bowel habits such as constipation, diarrhea, tenesmus, dyschezia, and, rarely, rectal bleeding. Differential diagnosis must be made in case of irritable bowel syndrome, solitary rectal ulcer syndrome, and a rectal tumor. A precise diagnosis about the presence, location, and extent of endometriosis is necessary to plan surgical treatment. Multidisciplinary laparoscopic treatment has become the standard of care. Depending on the size of the lesion and site of involvement, full-thickness disc excision or bowel resection needs to be performed by an experienced colorectal surgeon. Long-term outcomes, following bowel resection for severe endometriosis, regarding pain and recurrence rate are good with a pregnancy rate of 50%. PMID:25400445

  17. Endometriosis: where are we and where are we going?

    PubMed

    Greene, Alexis D; Lang, Stephanie A; Kendziorski, Jessica A; Sroga-Rios, Julie M; Herzog, Thomas J; Burns, Katherine A

    2016-09-01

    Endometriosis currently affects ~5.5 million reproductive-aged women in the U.S. with symptoms such as painful periods (dysmenorrhea), chronic pelvic pain, pain with intercourse (dyspareunia), and infertility. It is defined as the presence of endometrial tissue outside the uterine cavity and is found predominately attached to sites within the peritoneal cavity. Diagnosis for endometriosis is solely made through surgery as no consistent biomarkers for disease diagnosis exist. There is no cure for endometriosis and treatments only target symptoms and not the underlying mechanism(s) of disease. The nature of individual predisposing factors or inherent defects in the endometrium, immune system, and/or peritoneal cavity of women with endometriosis remains unclear. The literature over the last 5 years (2010-2015) has advanced our critical knowledge related to hormones, hormone receptors, immune dysregulation, hormonal treatments, and the transformation of endometriosis to ovarian cancer. In this review, we cover the aforementioned topics with the goal of providing the reader an overview and related references for further study to highlight the progress made in endometriosis research, while concluding with critical areas of endometriosis research that are urgently needed. PMID:27165051

  18. Bisphenol A and Phthalates and Endometriosis, The ENDO Study

    PubMed Central

    Buck Louis, Germaine M.; Peterson, C. Matthew; Chen, Zhen; Croughan, Mary; Sundaram, Rajeshwari; Stanford, Joseph; Varner, Michael W.; Kennedy, Anne; Giudice, Linda; Fujimoto, Victor Y.; Sun, Liping; Wang, Lei; Guo, Ying; Kannan, Kurunthachalam

    2013-01-01

    Objective To explore the relation between bisphenol A and 14 phthalate metabolites and endometriosis. Design Matched cohort design. Setting 14 clinical centers in Salt Lake City, Utah or San Francisco, California, 2007–2009. Patients The operative cohort comprised 495 women undergoing laparoscopy/laparotomy, while the population cohort comprised 131 women matched on age and residence. Interventions None Main Outcome Measure(s) Surgically visualized or pelvic magnetic resonance imaging (MRI) diagnosed endometriosis in the two cohorts, respectively. Results Odds ratios (OR) and 95% confidence intervals (CIs) were estimated using logistic regression adjusting for age, body mass index and creatinine. In the population cohort, six phthalate metabolites (mBP, mCMHP, mECPP, mEHP, mEHHP, and mEOHP) were significantly associated with approximately a twofold increase in the odds of an endometriosis diagnosis. Two phthalates were associated with endometriosis in the operative cohort when restricting to visualized and histologic endometriosis (mOP; OR=1.38; 95% CI 1.10, 1.72), or when restricting comparison women to those with a postoperative diagnosis of a normal pelvis (mEHP; OR=1.35; 95% CI 1.03, 1.78). Conclusions Select phthalates were associated with higher odds of an endometriosis diagnosis for women with MRI diagnosed endometriosis. The lack of consistency of findings across cohorts underscores the impact of methodology on findings. PMID:23579005

  19. GPs have key role in early diagnosis of endometriosis.

    PubMed

    Coleman, Laura; Overton, Caroline

    2015-03-01

    Endometriosis is defined as the presence of endometrial-like tissue outside the uterus. Deposits are commonly distributed on the ovaries, uterosacral ligaments, pouch of Douglas, rectum and sigmoid colon, bladder and ureter. Endometriosis is common, affecting 10% of the female adult population and up to 50% of women with infertility. Risk factors include early menarche, late menopause, delayed childbearing, vaginal outflow obstruction and a first-degree relative affected. Women commonly present to their GP with pelvic pain, painful intercourse or subfertility. Classically the pain starts several days before the period which is extremely painful. After the period, symptoms tend to improve until mid-cycle when the pattern repeats again. Patients also complain of fatigue. Abdominal palpation, bimanual and speculum examination are important to identify signs of endometriosis, but also to exclude alternative diagnoses such as fibroid uterus, infection or pregnancy. However, a normal examination does not exclude a diagnosis of endometriosis. Serum CA125 can be raised in endometriosis but is not specific or sensitive for the condition and is therefore not recommended as a screening test. A normal pelvic ultrasound scan does not exclude a diagnosis of endometriosis. The gold standard investigation for endometriosis is laparoscopy and biopsy with histological confirmation. Referral should be considered if pain is not controlled with simple analgesia or the diagnosis is suspected in a woman who is actively trying to conceive. Early referral should be considered in women with abnormal examination findings, or an abnormal ultrasound result. PMID:26062268

  20. Circulating microRNAs as potential biomarkers for endometriosis

    PubMed Central

    Cho, SiHyun; Mutlu, Levent; Grechukhina, Olga; Taylor, Hugh S.

    2015-01-01

    Objectives To evaluate whether micrRNAs associated with endometriosis are detectable in the circulation and could serve as potential noninvasive biomarkers for endometriosis. Design Case-control study. Setting University hospital. Patient(s) Twenty-four women with endometriosis and 24 women without the disease (controls). Interventions Serum samples were collected from women undergoing laparoscopy for endometriosis and other benign gynecologic disease. Main Outcome Measure(s) Total RNA was extracted from serum and qRT-PCR was used to determine levels of miRNA let-7a–f and miR-135a,b. Result(s) Levels of circulating let-7b and miR-135a were significantly decreased in women with endometriosis compared with controls, while let-7d and 7f showed a trend toward down-regulation. Let-7b expression strongly correlated with serum CA-125 levels and showed the highest AUC curve of 0.691. When the subjects were analyzed according to the phase of the menstrual cycle, expression of let-7b, 7c, 7d, and 7e were significantly lower in women with endometriosis during the proliferative phase. Using a logistic regression model, the diagnostic power of differently expressed miRNAs were evaluated, and the combination of let-7b, let-7d and let-7f during the proliferative phase yielded the highest ACU curve value of 0.929 in discriminating endometriosis from controls. Conclusions Several circulating miRNAs are differentially expressed in sera of patients with endometriosis compared to controls. Combination of serum let-7b, 7d and 7f levels during the proliferative phase may serve as a diagnostic marker for endometriosis. PMID:25772772

  1. Priorities for endometriosis research: recommendations from an international consensus workshop.

    PubMed

    Rogers, Peter A W; D'Hooghe, Thomas M; Fazleabas, Asgerally; Gargett, Caroline E; Giudice, Linda C; Montgomery, Grant W; Rombauts, Luk; Salamonsen, Lois A; Zondervan, Krina T

    2009-04-01

    Endometriosis is an estrogen-dependent disorder where endometrial tissue forms lesions outside the uterus. Endometriosis affects an estimated 10% of women in the reproductive-age group, rising to 30% to 50% in patients with infertility and/or pain, with significant impact on their physical, mental, and social well-being. There is no known cure, and most current medical treatments are not suitable long term due to their side-effect profiles. Endometriosis has an estimated annual cost in the United States of $18.8 to $22 billion (2002 figures). Although endometriosis was first described more than 100 years ago, current knowledge of its pathogenesis, spontaneous evolution, and the pathophysiology of the related infertility and pelvic pain, remain unclear. A consensus workshop was convened following the 10th World Congress on Endometriosis to establish recommendations for priorities in endometriosis research. One major issue identified as impacting on the capacity to undertake endometriosis research is the need for multidisciplinary expertise. A total of 25 recommendations for research have been developed, grouped under 5 subheadings: (1) diagnosis, (2) classification and prognosis, (3) treatment and outcome, (4) epidemiology, and (5) pathophysiology. Endometriosis research is underfunded relative to other diseases with high health care burdens. This may be due to the practical difficulties of developing competitive research proposals on a complex and poorly understood disease, which affects only women. By producing this consensus international research priorities statement it is the hope of the workshop participants that researchers will be encouraged to develop new interdisciplinary research proposals that will attract increased funding support for work on endometriosis. PMID:19196878

  2. Functional MicroRNA Involved in Endometriosis

    PubMed Central

    Creighton, Chad J.; Han, Derek Y.; Zariff, Azam; Anderson, Matthew L.; Gunaratne, Preethi H.; Matzuk, Martin M.

    2011-01-01

    Endometriosis is a common disease seen by gynecologists. Clinical features involve pelvic pain and unexplained infertility. Although endometriosis is pathologically characterized by endometrial tissue outside the normal uterine location, endometriosis is otherwise not easily explained. Endometriomas, endometriotic cysts of the ovary, typically cause pain and distortion of pelvic anatomy. To begin to understand the pathogenesis of endometriomas, we describe the first transcriptome-microRNAome analysis of endometriomas and eutopic endometrium using next-generation sequencing technology. Using this approach, we generated a total of more than 54 million independent small RNA reads from our 19 clinical samples. At the microRNA level, we found 10 microRNA that were up-regulated (miR-202, 193a-3p, 29c, 708, 509-3-5p, 574-3p, 193a-5p, 485-3p, 100, and 720) and 12 microRNA that were down-regulated (miR-504, 141, 429, 203, 10a, 200b, 873, 200c, 200a, 449b, 375, and 34c-5p) in endometriomas compared with endometrium. Using in silico prediction algorithms, we correlated these microRNA with their corresponding differentially expressed mRNA targets. To validate the functional roles of microRNA, we manipulated levels of miR-29c in an in vitro system of primary cultures of human endometrial stromal fibroblasts. Extracellular matrix genes that were potential targets of miR-29c in silico were significantly down-regulated using this biological in vitro system. In vitro functional studies using luciferase reporter constructs further confirmed that miR-29c directly affects specific extracellular matrix genes that are dysregulated in endometriomas. Thus, miR-29c and other abnormally regulated microRNA appear to play important roles in the pathophysiology of uterine function and dysfunction. PMID:21436257

  3. Endometriosis of the Terminal Ileum: A Diagnostic Dilemma

    PubMed Central

    Karaman, Kerem; Pala, Emel Ebru; Bayol, Umit; Akman, Ozlem; Olmez, Mustafa; Unluoglu, Saime; Ozturk, Safak

    2012-01-01

    Endometriosis is characterized by the presence of endometrial tissue consisting of glands and/or stroma located outside the uterus. Involvement of the terminal ileum is extremely rare. Preoperative distinction of ileal endometriosis from other diseases of the ileocecal region is difficult in terms of clinical presentation, symptomatology, radiological appearance, and surgical and pathological findings. We report a case initially diagnosed as Crohn's disease due to a longstanding diarrhea with subsequent intestinal obstruction, but finally diagnosed as ileal endometriosis by histopathological evaluation after resection of the involved segment. PMID:22997597

  4. Cutaneous endometriosis: non-invasive analysis by epiluminescence microscopy.

    PubMed

    De Giorgi, V; Massi, D; Mannone, F; Stante, M; Carli, P

    2003-05-01

    The clinical appearance of cutaneous endometriosis can share some features with malignant melanoma, thus representing a possible cause for concern in both patient and clinician. In recent years, the use of epiluminescence microscopy (ELM, dermoscopy) has proved useful in improving the accuracy of diagnosis of pigmented skin lesions. The purpose of this study was to analyse the dermoscopic features of cutaneous endometriosis with histopathological correlation. We studied a case which showed homogeneous reddish pigmentation, regularly distributed. Within this typical pigmentation there were small red globular structures, but more defined and of a deeper hue, which we called 'red atolls'. ELM thus revealed a distinctive pattern in cutaneous endometriosis. PMID:12780722

  5. [New data on the pathogenesis of endometriosis interna].

    PubMed

    Damirov, M M; Kulakov, V I; Bakuleva, L P; Shabanov, A M; Sliusar', N N; Sarkisov, S E

    1993-01-01

    Eighty-six patients with histologically verified internal endometriosis were examined using histochemical, morphometric methods, and measurements of blood and myometrial tissue phosphatidyl inosites. Blood levels of phosphatidyl inosites were found reliably decreased in the patients vs. normal subjects, whereas their levels in myometrial tissue were significantly increased. Increased counts of tissue basophils, microcirculation disorders, lymphostasis and membranogenic stromal edema development were observed round endometriosis foci. Changes in the basic substance and fibrous structures of myometrial connective tissue complex were revealed, most marked in the areas adjacent to the endometrium. A possible mechanism of the development of pathologic shifts in internal endometriosis is discussed. PMID:8250133

  6. Endometriosis-associated Maternal Pregnancy Complications – Case Report and Literature Review

    PubMed Central

    Petresin, J.; Wolf, J.; Emir, S.; Müller, A.; Boosz, A. S.

    2016-01-01

    The incidence of endometriosis is increasing. Particularly during pregnancy and labour, clinicians should be alert to possible endometriosis-associated complications or complications of previous endometriosis treatment, despite a low relative risk. In addition to an increased rate of early miscarriage, complications such as spontaneous bowel perforation, rupture of ovarian cysts, uterine rupture and intraabdominal bleeding from decidualised endometriosis lesions or previous surgery are described in the literature. Unfavourable neonatal outcomes have also been discussed. We report on an irreducible ovarian torsion in the 16th week of pregnancy following extensive endometriosis surgery, and an intraabdominal haemorrhage due to endometriosis of the bowel in the 29th week of pregnancy. PMID:27570252

  7. Autoimmunity to endometrium and ovary in endometriosis.

    PubMed Central

    Mathur, S; Peress, M R; Williamson, H O; Youmans, C D; Maney, S A; Garvin, A J; Rust, P F; Fudenberg, H H

    1982-01-01

    Antibody titres to whole ovary, theca cells, granulosa cells and endometrium were determined by passive haemagglutination and immunofluorescence assays in sera and in cervical and vaginal secretions from 13 patients with endometriosis. Antibody titres to endometrium (mean log2 +/- s.e.m., 7.08 +/- 0.80; P less than 0.0001), ovary (3.58 +/- 0.87; P = 0.0092), theca cells (4.42 +/- 0.73; P less than 0.0001) and granulosa cells (3.33 +/- 0.63; P = 0.0024) were significantly higher in the patients' sera than in sera from 15 normal non-pregnant females. Antibody titres to granulosa cells were elevated (7.97 +/- 1.46; P = 0.0424) in their cervical secretions. Antibody titres to all tissues tested were similar in vaginal secretions of patients and controls. Immunofluorescent antibody assay of biopsied endometrial tissue and sera from the patients revealed the antibodies to be primarily IgG and IgA. The results suggest that autoantibodies to endometrium and ovary are present in patients with endometriosis. Images Fig. 1 Fig. 2 Fig. 3 PMID:6759000

  8. [Endometriosis in the abdominal wall (author's transl)].

    PubMed

    Caligaris, P; Masselot, R; Ducassou, M J; Le Treut, Y; Bricot, R

    1981-01-01

    The authors give 9 case histories of endometriosis localised to the abdominal wall : 3 of them in the umbilicus, 3 in laparotomy incisions (2 of those were Caesareans), 2 of them in the round ligaments at the external opening of the inguinal canal and 1 of them in the right rectus muscle sheath in the abdomen. The functional symptomatology is rhythmical according to menstruation; it is associated with a burning type of pain, a tumour and blood loss. Over and above the theories of aetiology that are now classical, namely tubal retrograde spill, and lymphatic or venous spread, it would seem that prostaglandins and in particular the ratio of P.G.E. divided by P.D.F2 alpha can play a big role. Although Danazol is an effective treatment for endometriosis, the treatment of choice is, in these lesions that are superficial in localisation and easily accessible, to cut them out surgically. This makes it possible on the one hand to look for other intra-abdominal lesions and also on the other hand to confirm the anatomy and pathology (this was done in 7 out of 9 of our cases). PMID:6459361

  9. Update on Biomarkers for the Detection of Endometriosis

    PubMed Central

    Fassbender, Amelie; Burney, Richard O.; O, Dorien F.; D'Hooghe, Thomas; Giudice, Linda

    2015-01-01

    Endometriosis is histologically characterized by the displacement of endometrial tissue to extrauterine locations including the pelvic peritoneum, ovaries, and bowel. An important cause of infertility and pelvic pain, the individual and global socioeconomic burden of endometriosis is significant. Laparoscopy remains the gold standard for the diagnosis of the condition. However, the invasive nature of surgery, coupled with the lack of a laboratory biomarker for the disease, results in a mean latency of 7–11 years from onset of symptoms to definitive diagnosis. Unfortunately, the delay in diagnosis may have significant consequences in terms of disease progression. The discovery of a sufficiently sensitive and specific biomarker for the nonsurgical detection of endometriosis promises earlier diagnosis and prevention of deleterious sequelae and represents a clear research priority. In this review, we describe and discuss the current status of biomarkers of endometriosis in plasma, urine, and endometrium. PMID:26240814

  10. The impact of endometriosis on work and social participation.

    PubMed

    Gilmour, Jean A; Huntington, Annette; Wilson, Helen V

    2008-12-01

    Endometriosis is a debilitating chronic disease that can affect many aspects of everyday life owing to symptoms such as pain and fatigue. This paper reports the findings of a study exploring the impact of symptomatic endometriosis on women's social and working life. The study used a feminist approach. Eighteen women were interviewed and a thematic approach used to analyse the data. The analysis is structured around three themes focusing on issues around disclosure of symptoms in the work place; the impact of symptoms on work, education and social participation; and the strategies used by women in the study to manage endometriosis. A range of health and employment implications are discussed in this paper. In particular, nurses can provide useful support to women by careful assessment and prompt referral for diagnostic procedures and by providing timely and comprehensive information, including information about the lifestyle and nutritional factors recommended by women with endometriosis. PMID:19126072

  11. Neuroendocrine–immune disequilibrium and endometriosis: an interdisciplinary approach

    PubMed Central

    Tariverdian, Nadja; Theoharides, Theoharis C.; Siedentopf, Friederike; Gutiérrez, Gabriela; Jeschke, Udo; Rabinovich, Gabriel A.; Blois, Sandra M.

    2007-01-01

    Endometriosis, a chronic disease characterized by endometrial tissue located outside the uterine cavity, affects one fourth of young women and is associated with chronic pelvic pain and infertility. However, an in-depth understanding of the pathophysiology and effective treatment strategies of endometriosis is still largely elusive. Inadequate immune and neuroendocrine responses are significantly involved in the pathophysiology of endometriosis, and key findings are summarized in the present review. We discuss here the role of different immune mechanisms particularly adhesion molecules, protein–glycan interactions, and pro-angiogenic mediators in the development and progression of the disease. Finally, we introduce the concept of endometrial dissemination as result of a neuroendocrine-immune disequilibrium in response to high levels of perceived stress caused by cardinal clinical symptoms of endometriosis. PMID:17621704

  12. Neonatal uterine bleeding as antecedent of pelvic endometriosis.

    PubMed

    Brosens, Ivo; Brosens, Jan; Benagiano, Giuseppe

    2013-11-01

    We elaborate on a new theory to explain pelvic endometriosis, including endometriosis in premenarcheal girls, based on the finding that the neonatal endometrium can display secretory activity immediately after birth and, in some cases, changes analogous to those seen at menstruation in adults. The neonatal uterus is therefore capable of shedding its endometrium. Indeed, occult vaginal bleeding occurs in a majority of neonates, although overt bleeding is estimated to occur in only 5% of neonates. This may be due to functional plugging of the endocervical canal in the neonate, which in turn would promote retrograde flux of endometrial cells contained in menstrual debris. Ectopic endometrial implantation in a newborn with hydrometrocolpos has been documented. These data, coupled with the observation of a significantly increased risk of endometriosis in adolescents with cervical outflow obstruction and patent Fallopian tubes, indicate that endometriosis, especially in children and young adolescents, may originate from retrograde uterine bleeding soon after birth. PMID:24048011

  13. Thoracic Endometriosis Syndrome: A Veritable Pandora’s Box

    PubMed Central

    Nayar, Jayashree

    2016-01-01

    Thoracic endometriosis syndrome is a rare disorder characterised by the presence of functioning endometrial tissue in pleura, lung parenchyma, airways, and/or encompasses mainly four clinical entities–catamenial pneumothorax, catamenial haemothorax, catamenial haemoptysis and lung nodules. The cases were studied retrospectively by reviewing the records at Amrita Institute of Medical Sciences, for duration of five years i.e., form March 2010-2014 and analysed for the clinical presentation and management of thoracic endometriosis syndrome. Catamenial breathlessness was the main symptom. Pneumothorax and pleural effusion were the findings on investigations. Histopathology report of endometriosis was present in three cases (50%). Conditions with excess oestrogen like endometriosis, fibroid, adenomyosis were diagnosed in these patients by pelvic scan. After the initial supportive treatment with hormones, pleurodesis, hysterectomy and lung decortication were the treatment modalities. Two cases that had multiple recurrences were diagnosed as disseminated TES. They underwent combined treatment of surgery and hormones. PMID:27190904

  14. Primary ovarian and pararectal hydatid cysts mimicking pelvic endometriosis.

    PubMed

    Bozkurt, Murat; Bozkurt, Duygu Kara; Çil, Ahmet Said; Karaman, Mehmet

    2012-01-01

    We report a case of 48-year-old woman with multiple hydatid cysts in pararectal region and right paraovarian localization with an unusual sonographic and computed tomographic presentation mimicking a pelvic endometriosis. During laparotomy, multiple pararectal and right ovarian cysts resembling endometriosis were resected. Pathologic examination gives the diagnosis of hydatid cysts. Retrospectively, we investigate the primary infection but the patient had no history of hepatic and liver involvement, it is a case of primary infection. PMID:23456529

  15. MANAGEMENT OF ENDOMETRIOSIS IN TWO CAPTIVE MANDRILLS (MANDRILLUS SPHINX).

    PubMed

    Okeson, Danelle M; Higbie, Christine T; Mylniczenko, Natalie D; Haynes, April; Bennett, Suzanne; Klocke, Emily; Carpenter, James W

    2016-06-01

    Endometriosis has been reported in humans, great apes, and Old World monkeys. Although cases are noted anecdotally in Mandrillus spp., and a previously reported case was noted on postmortem examination, to the authors' knowledge, no previous reports of case management have been published in the peer-reviewed literature. This paper describes the medical and surgical management of endometriosis in two mandrills (Mandrillus sphinx). PMID:27468036

  16. Interplay between Endometriosis and Pregnancy in a Mouse Model

    PubMed Central

    Bilotas, Mariela Andrea; Olivares, Carla Noemí; Ricci, Analía Gabriela; Baston, Juan Ignacio; Bengochea, Tatiana Soledad; Meresman, Gabriela Fabiana; Barañao, Rosa Inés

    2015-01-01

    Objectives To evaluate the effect of endometriosis on fertility and the levels of the IL-2 and IFN-γ in the peritoneal fluid in a mouse model; to evaluate the effect of pregnancy on endometriotic lesion growth, apoptosis and cell proliferation. Study Design Two month old C57BL/6 female mice underwent either a surgical procedure to induce endometriosis or a sham surgery. Four weeks after surgery mice were mated and sacrificed at day 18 of pregnancy. Number of implantation sites, fetuses and fetal weight were recorded. Endometriotic lesions were counted, measured, excised and fixed. Apoptosis and cell proliferation were evaluated in lesions by TUNEL and immunohistochemistry for PCNA respectively. Levels of IL-2 and IFN-γ were assessed by ELISA in the peritoneal fluid. Results Pregnancy rate (i.e. pregnant mice/N) decreased in mice with endometriosis. However there were no significant differences in resorption rate, litter size and pup weight between groups. IFN-γ augmented in endometriosis mice independently of pregnancy outcome. Additionally IFN-γ increased in pregnant endometriosis mice compared to pregnant sham animals. While IFN-γ increased in non pregnant versus pregnant mice in the sham group, IL-2 was increased in non pregnant mice in the endometriosis group. The size of endometriotic lesions increased in pregnant mice while apoptosis increased in the stroma and cell proliferation decreased in the epithelium of these lesions. Additionally, leukocyte infiltration, necrosis and decidualization were increased in the same lesions. Conclusions Pregnancy rate is reduced in this mouse model of endometriosis. Levels of IL-2 are increased in the peritoneal fluid of mice with endometriosis suggesting a role of this cytokine in infertility related to this disease. The size of endometriotic lesions is increased in pregnant mice; however pregnancy has a beneficial effect on lesions by decreasing cell proliferation and by increasing apoptosis, decidualization and

  17. Oxidation Sensitive Nociception Involved in Endometriosis Associated Pain

    PubMed Central

    Ray, Kristeena; Fahrmann, Johannes; Mitchell, Brenda; Paul, Dennis; King, Holly; Crain, Courtney; Cook, Carla; Golovko, Mikhail; Brose, Stephen; Golovko, Svetlana; Santanam, Nalini

    2015-01-01

    Endometriosis is a disease characterized by the growth of endometrial tissue outside the uterus and is associated with chronic pelvic pain. Peritoneal fluid (PF) of women with endometriosis is a dynamic milieu, rich in inflammatory markers and pain-inducing prostaglandins PGE2/PGF2α and lipid peroxides, and the endometriotic tissue is innervated with nociceptors. Our clinical study showed the abundance of oxidatively-modified lipoproteins in the PF of women with endometriosis and the ability of antioxidant supplementation to alleviate endometriosis-associated pain. We hypothesized that oxidatively-modified lipoproteins present in the PF are the major source of nociceptive molecules that play a key role in endometriosis-associated pain. In this study, PF obtained from women with endometriosis or control women were used for (i) the detection of lipoprotein derived oxidation-sensitive pain molecules, (ii) the ability of such molecules to induce nociception, and (iii) the ability of antioxidants to suppress this nociception. LC-MS/MS showed the generation of eicosanoids by oxidized-lipoproteins similar to that seen in the PF. The oxidatively-modified lipoproteins induced hypothermia (intra-cerebroventricular) in CD-1 mice and nociception in the Hargreaves paw-withdrawal latency assay in Sprague-Dawley rats. Antioxidants, vitamin-E and N-acetylcysteine and the NSAID, indomethacin suppressed the pain inducing ability of oxidatively-modified lipoproteins. Treatment of human endometrial cells with oxidatively-modified lipoproteins or PF from women with endometriosis showed up-regulation of similar genes belonging to the opioid and inflammatory pathways. Our finding that oxidatively-modified lipoproteins can induce nociception has a broader impact not only in the treatment of endometriosis-associated pain but also in other diseases associated with chronic pain. PMID:25599233

  18. Fetal programming theory: implication for the understanding of endometriosis.

    PubMed

    Kobayashi, Hiroshi; Iwai, Kana; Niiro, Emiko; Morioka, Sachiko; Yamada, Yuki

    2014-03-01

    Comparison of the transcriptomes and proteomes of the decidualization-specific genes that express high vs low levels of the eutopic and ectopic endometrium of women with endometriosis compared with controls, could be useful in understanding the pathogenesis of endometriosis. Genome-wide comparison between decidual tissue and non-decidual tissue identified many genes significantly modulated in the process of decidualization. Comparison of eutopic endometrium and endometriotic sites also revealed up- and down-regulated genes. A combined analysis of the experimental data showed specific genes up-regulated both at the endometriotic site and in the decidualization process, representing a broad diversity of molecular functions, including cell cycle regulation, angiogenesis and adhesion molecules. In contrast, down-regulated genes identified in endometriosis among genes overexpressed in decidualization encode Müllerian embryogenesis, which includes transcription factors, hormonal regulation and cytokine expression. The mechanism responsible for insufficient decidualization in endometriosis may be mediated through down-regulation of the Müllerian embryogenesis-related genes. In conclusion, a range of decidualization resistance has been associated with endometriosis. Future study will identify the putative mechanisms relating epigenetic changes of decidualization susceptibility genes in early life to the risk of developing endometriosis in adulthood. PMID:24374047

  19. MAST scores, alcohol consumption, and gynecological symptoms in endometriosis patients.

    PubMed

    Perper, M M; Breitkopf, L J; Breitstein, R; Cody, R P; Manowitz, P

    1993-04-01

    Alcohol consumption (quantity, frequency, and pattern) and alcohol-related problems were determined in endometriosis patients (n = 137), patients with other gynecological disorders (n = 91), and normal control subjects (n = 98). Participants completed a self-administered questionnaire, including the Michigan Alcoholism Screening Test (MAST), questions to determine the quantity and frequency of alcohol use, and questions regarding the relationship between gynecological symptoms and alcohol intake. The percentage of endometriosis patients with MAST scores greater than five or seven was significantly greater than that of normal control subjects (p = 0.045 and p = 0.009, respectively), but did not differ from that for patients with other gynecological disorders. Endometriosis patients with high MAST scores (> or = 5) tended to consume more alcohol on a yearly basis than normal control subjects with high MAST scores (p = 0.07). Among participants who experienced gynecological symptoms and were not abstainers, 31% of endometriosis patients, 9.5% of normal control subjects, and 14.3% of patients with other gynecological disorders reported increasing their alcohol consumption when experiencing gynecological symptoms. Endometriosis patients tended to differ in this regard from normal control subjects (p = 0.058) and were significantly different from patients with other gynecological disorders (p = 0.039). The evidence suggests that the gynecological problems of endometriosis may be a major medical correlative of alcoholism in women. PMID:8488967

  20. The role of inflammation and matrix metalloproteinases in equine endometriosis

    PubMed Central

    Benali, Silvia; Giannuzzi, Diana; Mantovani, Roberto; Castagnaro, Massimo; Falomo, Maria Elena

    2012-01-01

    Equine endometriosis is a multifactorial disease considered to be a major cause of equine infertility. The purpose of this study was to evaluate the reliability of histomorphological grading for biopsy-like samples compared to entire uterine wall samples, to examine the association between the degree of endometriosis with animal age, and to investigate the role of inflammation in endometriosis and the expression of different matrix metalloproteinases in equine endometrium. Histomorphological lesions in 35 uterine samples were examined while comparing biopsy-like samples and entire-wall samples. Seventeen uterine samples were stained with antibodies against MMP-2, MMP-9, MMP-14, and TIMP-2. The morphologic evaluation results of the biopsy-like tissue and entire-wall samples were significantly correlated. Endometriosis in older mares (>12 years of age) was more severe than in young mares (2~4 years of age), confirming the positive correlation between animal age and disease severity, while inflammation was poorly related to the degree of endometriosis. MMP-2 and MMP-14 were detected in stromal cells, while MMP-9 and TIMP-2 were both found in stromal and glandular epithelial cells. There were no significant differences in MMPs expression between the two groups (young vs. old mares). Additional studies on the activity of MMPs could further define the role of these enzymes in equine endometriosis. PMID:22705739

  1. To Your Health: NLM update transcript - Endometriosis linked to heart disease

    MedlinePlus

    ... transcript052316.html To Your Health: NLM update Transcript Endometriosis linked to heart disease : 05/23/2016 To ... use MedlinePlus to follow up on weekly topics. Endometriosis significantly increases the risk of developing heart disease ...

  2. Endometriosis and Ovarian Cancer: A Review of Clinical, Pathologic, and Molecular Aspects

    PubMed Central

    Wei, Jian-Jun; William, Josette; Bulun, Serdar

    2014-01-01

    Summary Endometriosis is a chronic disease that affects millions of reproductive-age women. Despite the destructive and invasive nature of endometrioses, most cases are perpetually benign or eventually regress; however, atypical endometriosis is a precursor lesion and can lead to certain types of ovarian cancer. Endometriosis induced inflammation and auto- and paracrine production of sex steroid hormones contribute to ovarian tumorigenesis. These changes provide microenvironment necessary to accumulate enough genetic alterations for endometriosis associated malignant transformation. It takes years for endometriosis to undergo the pathophysiological progression that begins with atypical epithelial proliferation (atypical endometriosis and metaplasia), and then is followed by the formation of well-defined borderline tumors, and finally culminates in fully malignant ovarian cancer. This study is a review of the natural history of endometriosis and the role of microenvironments that favor the accumulation of genetic alterations and endometriosis-associated ovarian cancer progression. PMID:21979592

  3. How Many People Are Affected by or at Risk for Endometriosis?

    MedlinePlus

    ... people are affected by or at risk for endometriosis? Skip sharing on social media links Share this: ... menstruates. Factors that May Increase the Risk of Endometriosis Studies show that women are at higher risk ...

  4. Bronchial Artery Embolization in the Management of Pulmonary Parenchymal Endometriosis with Hemoptysis

    SciTech Connect

    Kervancioglu, Selim Andic, Cagatay; Bayram, Nazan; Telli, Cumali; Sarica, Akif; Sirikci, Akif

    2008-07-15

    Pulmonary parenchymal endometriosis is extremely rare and usually manifests itself with a recurrent hemoptysis associated with the menstrual cycle. The therapies proposed for women with endometriosis consist of medical treatments and surgery. Bronchial artery embolization has become a well-established and minimally invasive treatment modality for hemoptysis, and to the best of our knowledge, it has not been reported in pulmonary endometriosis. We report a case of pulmonary parenchymal endometriosis treated with embolotheraphy for hemoptysis.

  5. Clear Cell Adenocarcinoma Arising from Adenofibroma in a Patient with Endometriosis of the Ovary.

    PubMed

    Cho, Inju; Lim, Sung-Chul

    2016-03-01

    Ovarian clear cell adenocarcinomas (CCACs) are frequently associated with endometriosis and, less often with clear cell adenofibromas (CCAFs). We encountered a case of ovarian CCAC arising from benign and borderline adenofibromas of the clear cell and endometrioid types with endometriosis in a 53-year-old woman. Regions of the adenofibromas showed transformation to CCAC and regions of the endometriosis showed atypical endometriotic cysts. This case demonstrates that CCAC can arise from CCAF or endometriosis. PMID:26498012

  6. Successful laparoscopic treatment of ileo-cecal endometriosis producing bowel obstruction.

    PubMed

    Fujimoto, A; Osuga, Y; Tsutsumi, O; Fujii, T; Okagaki, R; Taketani, Y

    2001-08-01

    Bowel endometriosis manifesting with ileus is difficult to diagnose, often requiring laparotomy for diagnosis and treatment. We report here a case of ileo-cecal endometriosis causing bowel obstruction. A diagnosis of intestinal endometriosis with menstruation-associated bowel symptoms was made, and the patient was successfully treated by laparoscopic ileo-cecal resection. PMID:11721734

  7. [Differential-diagnostic symptoms of endometriosis and cancer of the rectum].

    PubMed

    Klur, V Iu; Tsvelev, Iu V; Gur'ev, A V; Stoĭko, Iu M

    1990-06-01

    93 patients aged from 21 to 52 years were examined and operated upon. Endometriosis was diagnosed in 31 patients, carcinoma of the rectum--in 62 patients. Endometriosis had two forms: superficial (noninvasive) and deep (invasive) forms. The necessary components of diagnostics should be rectal and rectovaginal examinations, endoscopy, histological verification. Differential symptoms of endometriosis and rectal carcinoma are described. PMID:2175485

  8. [Extragenital endometriosis leading to piriformis syndrome].

    PubMed

    Hettler, A; Böhm, J; Pretzsch, M; von Salis-Soglio, G

    2006-04-01

    We report on a 44-year-old woman with a history of sciatica fluctuating with her menstrual cycle and going back over 10 years; ultimately it was present continuously and became disabling. Over the years the patient developed ipsilateral foot-drop, a sensory disorder in the lateral aspect of the lower limb and back of the foot, and atrophy of the gluteus muscle. MRI confirmed the suspicion of extragenital endometriosis, which had caused piriformis syndrome by compression with consequent damage to the sciatic and inferior gluteal nerves. After hormonal therapy had been tried without success, the endometrioma was excised to relieve the pressure on the nerves, and the diagnosis was confirmed histopathologically. The motor deficit remained up to the 15 months since surgery, but the patient is now free of pain. PMID:16425055

  9. Pelvic Endometriosis Presenting as a Supralevator Abscess

    PubMed Central

    Anderson, Bernard B.; Tuckson, Wayne B.

    1988-01-01

    A 32-year-old woman presented with sepsis nine days after a transrectal incision and drainage of a recurrent supralevator abscess. The findings included a large mass arising from the pelvis containing multiple, leaking, and infected endometrial cysts. After a supracervical hysterectomy, bilateral salpingo-oophorectomy, sigmoid loop colostomy, appendectomy, and extensive irrigation and debridement, her condition improved with no recurrence at two-year follow-up. This case illustrates the varied presentations of endometriosis, the importance of identifying the source of a perirectal or perianal abscess, and that when a supralevator abscess develops from an intraabdominal process, the process must be addressed to prevent recurrence, fistulization, or other complications. ImagesFigure 1Figure 2 PMID:3246707

  10. Endometriosis and breast cancer: A survey of the epidemiological studies

    PubMed Central

    PONTIKAKI, A.; SIFAKIS, S.; SPANDIDOS, D. A.

    2016-01-01

    Endometriosis is a chronic gynecological disease with a wide spectrum of clinical manifestations that affects approximately 10% of women of reproductive age. Recent reviews have demonstrated the connection between endometriosis and breast cancer, which represents the most frequently diagnosed female cancer and the most common cause of cancer-related mortality among women worldwide. The aim of this study was to conduct a survey of available published epidemiological studies indicating the association between endometriosis and breast cancer, and simultaneously to categorize the results based on the strength of the association, with the intention of the critical evaluation of the existing data. We performed a rigorous search of the PubMed/Medline database, using the key words ‘endometriosis’ and ‘breast cancer’ for all studies published in the English language until September 2015. We found 4 retrospective cohort studies, 4 case-control studies and 3 case-cohort studies that demonstrated a notable risk for developing breast cancer among women with endometriosis. By contrast, we also found 5 case-control studies, 1 prospective cohort study, 1 case-cohort study and 1 cross-sectional study that demonstrated a negative association between endometriosis and breast cancer. In conclusion, as regards the clarification of a ‘robust’ or ‘weak’ association between endometriosis and breast cancer, no definite conclusions could be drawn, due to the limited number of studies and the limitations of each of these studies. New well-designed, prospective cohort or randomized control trials with long-term follow-up are warranted in order to provide evidence-based clinical recommendations for proper counseling, screening and treatment strategies for patients with endometriosis, and hence to improve public health. PMID:26870162

  11. Molecular Changes in Endometriosis-Associated Ovarian Clear Cell Carcinoma

    PubMed Central

    Worley, Michael J.; Liu, Shubai; Hua, Yuanyuan; Kwok, Jamie Sui-Lam; Samuel, Anicka; Hou, Lei; Shoni, Melina; Lu, Shi; Sandberg, Evelien M.; Keryan, Anna; Wu, Di; Ng, Shu-Kay; Kuo, Winston P.; Parra-Herran, Carlos E.; Tsui, Stephen KW; Welch, William; Crum, Christopher; Berkowitz, Ross S.; Ng, Shu-Wing

    2015-01-01

    BACKGROUND Endometriosis is frequently associated with and thought of having propensity to develop into ovarian clear cell carcinoma (OCCC), although the molecular transformation mechanism is not completely understood. METHODS We employed immunohistochemical (IHC) staining for marker expression along the potential progression continuum. Expression profiling of microdissected endometriotic and OCCC cells from patient-matched formalin-fixed, paraffin-embedded samples was performed to explore the carcinogenic pathways. Function of novel biomarkers was confirmed by knockdown experiments. RESULTS PTEN was significantly lost in both endometriosis and invasive tumor tissues, while estrogen receptor (ER) expression was lost in OCCC relative to endometriosis. XRCC5, PTCH2, eEF1A2, and PPP1R14B were significantly overexpressed in OCCC and associated endometriosis, but not in benign endometriosis (p≤0.004). Knockdown experiments with XRCC5 and PTCH2 in a clear cell cancer cell line resulted in significant growth inhibition. There was also significant silencing of a panel of target genes with histone H3 lysine 27 trimethylation, a signature of polycomb chromatin-remodeling complex in OCCC. IHC confirmed the loss of expression of one such polycomb target gene, the serous ovarian cancer lineage marker WT1 in OCCC, while endometriotic tissues showed significant co-expression of WT1 and ER. CONCLUSIONS Loss of PTEN expression is proposed as an early and permissive event in endometriosis development, while the loss of ER and polycomb-mediated transcriptional reprogramming for pluripotency may play an important role in the ultimate transformation process. Our study provides new evidence to redefine the pathogenic program for lineage-specific transformation of endometriosis to OCCC. PMID:26059197

  12. Shared genetics underlying epidemiological association between endometriosis and ovarian cancer.

    PubMed

    Lu, Yi; Cuellar-Partida, Gabriel; Painter, Jodie N; Nyholt, Dale R; Morris, Andrew P; Fasching, Peter A; Hein, Alexander; Burghaus, Stefanie; Beckmann, Matthias W; Lambrechts, Diether; Van Nieuwenhuysen, Els; Vergote, Ignace; Vanderstichele, Adriaan; Doherty, Jennifer Anne; Rossing, Mary Anne; Wicklund, Kristine G; Chang-Claude, Jenny; Eilber, Ursula; Rudolph, Anja; Wang-Gohrke, Shan; Goodman, Marc T; Bogdanova, Natalia; Dörk, Thilo; Dürst, Matthias; Hillemanns, Peter; Runnebaum, Ingo B; Antonenkova, Natalia; Butzow, Ralf; Leminen, Arto; Nevanlinna, Heli; Pelttari, Liisa M; Edwards, Robert P; Kelley, Joseph L; Modugno, Francesmary; Moysich, Kirsten B; Ness, Roberta B; Cannioto, Rikki; Høgdall, Estrid; Jensen, Allan; Giles, Graham G; Bruinsma, Fiona; Kjaer, Susanne K; Hildebrandt, Michelle A T; Liang, Dong; Lu, Karen H; Wu, Xifeng; Bisogna, Maria; Dao, Fanny; Levine, Douglas A; Cramer, Daniel W; Terry, Kathryn L; Tworoger, Shelley S; Missmer, Stacey; Bjorge, Line; Salvesen, Helga B; Kopperud, Reidun K; Bischof, Katharina; Aben, Katja K H; Kiemeney, Lambertus A; Massuger, Leon F A G; Brooks-Wilson, Angela; Olson, Sara H; McGuire, Valerie; Rothstein, Joseph H; Sieh, Weiva; Whittemore, Alice S; Cook, Linda S; Le, Nhu D; Gilks, C Blake; Gronwald, Jacek; Jakubowska, Anna; Lubiński, Jan; Gawełko, Jan; Song, Honglin; Tyrer, Jonathan P; Wentzensen, Nicolas; Brinton, Louise; Trabert, Britton; Lissowska, Jolanta; Mclaughlin, John R; Narod, Steven A; Phelan, Catherine; Anton-Culver, Hoda; Ziogas, Argyrios; Eccles, Diana; Gayther, Simon A; Gentry-Maharaj, Aleksandra; Menon, Usha; Ramus, Susan J; Wu, Anna H; Dansonka-Mieszkowska, Agnieszka; Kupryjanczyk, Jolanta; Timorek, Agnieszka; Szafron, Lukasz; Cunningham, Julie M; Fridley, Brooke L; Winham, Stacey J; Bandera, Elisa V; Poole, Elizabeth M; Morgan, Terry K; Risch, Harvey A; Goode, Ellen L; Schildkraut, Joellen M; Webb, Penelope M; Pearce, Celeste L; Berchuck, Andrew; Pharoah, Paul D P; Montgomery, Grant W; Zondervan, Krina T; Chenevix-Trench, Georgia; MacGregor, Stuart

    2015-10-15

    Epidemiological studies have demonstrated associations between endometriosis and certain histotypes of ovarian cancer, including clear cell, low-grade serous and endometrioid carcinomas. We aimed to determine whether the observed associations might be due to shared genetic aetiology. To address this, we used two endometriosis datasets genotyped on common arrays with full-genome coverage (3194 cases and 7060 controls) and a large ovarian cancer dataset genotyped on the customized Illumina Infinium iSelect (iCOGS) arrays (10 065 cases and 21 663 controls). Previous work has suggested that a large number of genetic variants contribute to endometriosis and ovarian cancer (all histotypes combined) susceptibility. Here, using the iCOGS data, we confirmed polygenic architecture for most histotypes of ovarian cancer. This led us to evaluate if the polygenic effects are shared across diseases. We found evidence for shared genetic risks between endometriosis and all histotypes of ovarian cancer, except for the intestinal mucinous type. Clear cell carcinoma showed the strongest genetic correlation with endometriosis (0.51, 95% CI = 0.18-0.84). Endometrioid and low-grade serous carcinomas had similar correlation coefficients (0.48, 95% CI = 0.07-0.89 and 0.40, 95% CI = 0.05-0.75, respectively). High-grade serous carcinoma, which often arises from the fallopian tubes, showed a weaker genetic correlation with endometriosis (0.25, 95% CI = 0.11-0.39), despite the absence of a known epidemiological association. These results suggest that the epidemiological association between endometriosis and ovarian adenocarcinoma may be attributable to shared genetic susceptibility loci. PMID:26231222

  13. Nanoparticle-Assisted Combinatorial Therapy for Effective Treatment of Endometriosis.

    PubMed

    Singh, Abhay Kumar; Chakravarty, Baidyanath; Chaudhury, Koel

    2015-05-01

    Endometriosis is characterized by the presence of endometrial glands and stroma outside the uterine cavity. Conventional treatment modalities for endometriosis are unsatisfactory; therefore, there is a need to treat the underlying causes and mechanism. Oxidative stress, extracellular matrix degradation, and angiogenesis are associated with the pathogenesis of endometriosis. The anti-angiogenic and antioxidant properties of epigallocatechin gallate and the matrix metalloproteinase inhibitory activity of the antibiotic doxycycline are well established. However, epigallocatechin gallate and doxycycline have several limitations when used in their native forms. This motivated us to synthesize dual drug-loaded (epigallocatechin gallate and doxycycline) nanoparticles and check their therapeutic efficacy in mice with induced endometriosis. The synthesized nanoparticles displayed features of a promising drug-delivery system, such as small size, high encapsulation efficiency, controlled drug release, and low toxicity. The serum of endometriosis-induced mice and controls was assessed for various oxidative stress markers, matrix-degrading enzymes, and angiogenic markers before and after nanoparticle administration. Endometrial glands, stroma, and new microvessels were determined using histochemistry and immunohistochemistry. Treatment with dual drug-loaded nanoparticles markedly decreased oxidative stress, matrix metalloproteinase activity, and angiogenesis, as well as endometrial gland presence and microvessel density. Mitigation of endometriosis-related adverse effects further produced an improvement in the quality of oocytes, which is critical for successful pregnancy outcomes. Our observations suggest that owing to their combinatorial effect, poly(lactic-co-glycolic) acid nanoparticles loaded with epigallocatechin gallate and doxycycline in a single vehicle appear to be promising for the treatment of endometriosis. PMID:26349392

  14. Retinoic acid biosynthesis is impaired in human and murine endometriosis.

    PubMed

    Pierzchalski, Keely; Taylor, Robert N; Nezhat, Ceana; Jones, Jace W; Napoli, Joseph L; Yang, Guixiang; Kane, Maureen A; Sidell, Neil

    2014-10-01

    Endometriosis is characterized by the presence of endometrial glands and stroma in extrauterine sites. Our objective was to determine whether endometriotic lesions (ELs) from women with endometriosis have altered retinoid levels compared with their eutopic endometrium, and to test the hypothesis that defects in all-trans retinoic acid (ATRA) biosynthesis in EL is related to reduced expression of cellular retinol-binding protein type 1 (RBP1). Retinoids were evaluated by liquid chromatography-tandem mass spectrometry and high-performance liquid chromatography in eutopic endometrial biopsies (EBs) and ELs from 42 patients with pathologically confirmed endometriosis. The ATRA levels were reduced, whereas the retinol and retinyl ester concentrations were elevated in EL compared with EB tissue. Similar results were found in a mouse model of endometriosis that used green fluorescent protein-positive endometrial tissue injected into the peritoneum of syngeneic hosts to mimic retrograde menses. The ATRA biosynthesis in vitro in retinol-treated primary human endometrial stromal cell (ESC) cultures derived from ELs was reduced compared with that of ESCs derived from patient-matched EBs. Correspondingly, RBP1 expression was reduced in tissue and ESCs derived from EL versus EB. Rbp1(-/-) mice showed reduced endometrial ATRA concentrations compared with wild type, associated with loss of tissue organization and hypercellularity. These findings provide the first quantitative measurements of ATRA in human endometrium and endometriosis, demonstrating reduced ATRA in ectopic tissue and corresponding ESC cultures. Quantitation of retinoids in murine endometriosis and in Rbp1(-/-) mice supports the contention that impaired ATRA synthesis caused by reduced RBP1 promotes an "endometriosis phenotype" that enables cells to implant and grow at ectopic sites. PMID:25143356

  15. Medical Treatments for Endometriosis-Associated Pelvic Pain

    PubMed Central

    Luppi, Stefania; Ricci, Giuseppe

    2014-01-01

    The main sequelae of endometriosis are represented by infertility and chronic pelvic pain. Chronic pelvic pain causes disability and distress with a very high economic impact. In the last decades, an impressive amount of pharmacological agents have been tested for the treatment of endometriosis-associated pelvic pain. However, only a few of these have been introduced into clinical practice. Following the results of the controlled studies available, to date, the first-line treatment for endometriosis associated pain is still represented by oral contraceptives used continuously. Progestins represent an acceptable alternative. In women with rectovaginal lesions or colorectal endometriosis, norethisterone acetate at low dosage should be preferred. GnRH analogues may be used as second-line treatment, but significant side effects should be taken into account. Nonsteroidal anti-inflammatory drugs are widely used, but there is inconclusive evidence for their efficacy in relieving endometriosis-associated pelvic pain. Other agents such as GnRH antagonist, aromatase inhibitors, immunomodulators, selective progesterone receptor modulators, and histone deacetylase inhibitors seem to be very promising, but there is not enough evidence to support their introduction into routine clinical practice. Some other agents, such as peroxisome proliferator activated receptors-γ ligands, antiangiogenic agents, and melatonin have been proven to be efficacious in animal studies, but they have not yet been tested in clinical studies. PMID:25165691

  16. Potential role of estrogen in maintaining the imbalanced sympathetic and sensory innervation in endometriosis.

    PubMed

    Liang, Yanchun; Yao, Shuzhong

    2016-03-15

    Endometriosis, one of the most common benign gynecological diseases, affects millions of women of childbearing age. Endometriosis-associated pain is a major cause of disability and compromised quality of life in women. Neuropathic mechanisms are believed to play an important role. An imbalanced sympathetic and sensory innervation (reduced sympathetic innervation, with unchanged or increased sensory innervation in endometriotic lesions) has been demonstrated in endometriosis in recent studies. And it is believed to contribute to the pathogenesis of endometriosis-associated pain. It is primarily considered to be a natural adaptive program to endometriosis-associated inflammation. However, it is important to further clarify whether other potential modulating factors are involved in this dysregulation. It is generally accepted that endometriosis is an estrogen dependent disease. Higher estrogen biosynthesis and lower estrogen inactivation in endometriosis can lead to an excess of local estrogen in endometriotic lesions. In addition to its proliferative and anti-inflammatory actions, local estrogen in endometriosis also exerts potential neuromodulatory effects on the innervation in endometriosis. The aim of this review is to highlight the role of estrogen in mediating this imbalanced sympathetic and sensory innervation in endometriosis, through direct and indirect mechanisms on sympathetic and sensory nerves. Theoretical elaboration of the underlying mechanisms provides new insights in supporting the therapeutic role of estrogen in endometriosis-associated pain. PMID:26777300

  17. Somatic Stem Cells and Their Dysfunction in Endometriosis

    PubMed Central

    Djokovic, Dusan; Calhaz-Jorge, Carlos

    2015-01-01

    Emerging evidence indicates that somatic stem cells (SSCs) of different types prominently contribute to endometrium-associated disorders such as endometriosis. We reviewed the pertinent studies available on PubMed, published in English language until December 2014 and focused on the involvement of SSCs in the pathogenesis of this common gynecological disease. A concise summary of the data obtained from in vitro experiments, animal models, and human tissue analyses provides insights into the SSC dysregulation in endometriotic lesions. In addition, a set of research results is presented supporting that SSC-targeting, in combination with hormonal therapy, may result in improved control of the disease, while a more in-depth characterization of endometriosis SSCs may contribute to the development of early-disease diagnostic tests with increased sensitivity and specificity. Key message: Seemingly essential for the establishment and progression of endometriotic lesions, dysregulated SSCs, and associated molecular alterations hold a promise as potential endometriosis markers and therapeutic targets. PMID:25593975

  18. Endometriosis Gene Expression Heterogeneity and Biosignature: A Phylogenetic Analysis

    PubMed Central

    Abu-Asab, Mones; Zhang, Ming; Amini, Dennis; Abu-Asab, Nihad; Amri, Hakima

    2011-01-01

    Endometriosis is a multifactorial disease with poorly understood etiology, and reflecting an evolutionary nature where genetic alterations accumulate throughout pathogenesis. Our objective was to characterize the heterogeneous pathological process using parsimony phylogenetics. Gene expression microarray data of ovarian endometriosis obtained from NCBI database were polarized and coded into derived (abnormal) and ancestral (normal) states. Such alterations are referred to as synapomorphies in a phylogenetic sense (or biomarkers). Subsequent gene linkage was modeled by Genomatix BiblioSphere Pathway software. A list of clonally shared derived (abnormal) expressions revealed the pattern of heterogeneity among specimens. In addition, it has identified disruptions within the major regulatory pathways including those involved in cell proliferation, steroidogenesis, angiogenesis, cytoskeletal organization and integrity, and tumorigenesis, as well as cell adhesion and migration. Furthermore, the analysis supported the potential central involvement of ESR2 in the initiation of endometriosis. The pathogenesis mapping showed that eutopic and ectopic lesions have different molecular biosignatures. PMID:22203846

  19. Endometriosis in Adolescence: Practical Rules for an Earlier Diagnosis.

    PubMed

    Zannoni, Letizia; Forno, Simona Del; Paradisi, Roberto; Seracchioli, Renato

    2016-09-01

    Dysmenorrhea, cyclic pelvic pain, and acyclic pelvic pain are common in adolescent girls, and at least 10% of these girls are at risk for subsequent development of endometriosis. In this article we highlight practical tips for the management of dysmenorrhea and chronic pelvic pain and how to diagnose endometriosis as early as possible and detect patients at risk for developing the disease in the future. We suggest five practical rules for managing adolescents with dysmenorrhea and chronic pelvic pain: (1) Never underestimate the pain; (2) Always consider endometriosis as a possible cause of severe cyclic pain; (3) Obtain a detailed and accurate history before performing clinical evaluation and pelvic sonography; (4) Treat the pain with hormonal therapies (combined oral contraceptives or progestogen-only pill) and analgesics (acetaminophen and nonsteroidal anti-inflammatory drugs); and (5) Plan frequent follow-up visits to re-evaluate the patient. [Pediatr Ann. 2016;45(9):e332-e335.]. PMID:27622918

  20. Transanal endoscopic microsurgery in the management of rectal wall endometriosis.

    PubMed

    Banky, Balazs; Saleki, Mahsa; Gill, Talvinder S

    2016-01-01

    A 29-year-old woman with known history of endometriosis was referred to colorectal outpatient clinic from gynaecology with a history of intermittent rectal bleeding and no associated bowel symptoms. Flexible sigmoidoscopy in concordance with pelvic MRI revealed a 3×2×2 cm sessile lesion in the anterior rectal wall. The lesion was also palpable as a firm mass on digital rectal examination. From the gynaecological point of view no intra-abdominal exploration was required; the sole rectal wall lesion was removed with the minimally invasive surgical technique of transanal endoscopic microsurgery. Full thickness rectal wall excision sample was reported to be histologically complete and confirmed endometriosis. No recurrence was detected at endoscopic follow-up at 6 months. The patient remained symptom free. Therefore, we demonstrated a case of minimally invasive removal of a rectal wall large endometriosis nodule in a fertile woman with a complete, symptomatic, uneventful recovery. PMID:27495176

  1. Pathogenesis of Endometriosis: Roles of Retinoids and Inflammatory Pathways.

    PubMed

    Taylor, Robert N; Kane, Maureen A; Sidell, Neil

    2015-07-01

    Endometriosis is a nonmalignant, but potentially metastatic, gynecological condition manifested by the extrauterine growth of inflammatory endometrial implants. Ten percent of reproductive-age women are affected and commonly suffer pelvic pain and/or infertility. The theories of endometriosis histogenesis remain controversial, but retrograde menstruation and metaplasia each infer mechanisms that explain the immune cell responses observed around the ectopic lesions. Recent findings from our laboratories and others suggest that retinoic acid metabolism and action are fundamentally flawed in endometriotic tissues and even generically in women with endometriosis. The focus of our ongoing research is to develop medical therapies as adjuvants or alternatives to the surgical excision of these lesions. On the basis of concepts put forward in this review, we predict that the pharmacological actions and anticipated low side-effect profiles of retinoid supplementation might provide a new treatment option for the long-term management of this chronic and debilitating gynecological disease. PMID:26132929

  2. Diagnosis and surgical treatment of isolated rectal endometriosis: long term complication of incomplete treatment for pelvic endometriosis.

    PubMed

    Kwack, Jae-Young; You, Seul Ki; Kwon, Yong-Soon

    2016-01-01

    A 40-year-old woman visited our hospital with cyclic hematochezia for four months. The patient had the history of laparoscopic-assisted vaginal hysterectomy because of severe dysmenorrhea two years ago at another tertiary hospital. According to the medical records, the past surgical treatment was incomplete excision of pelvic endometriotic lesions, especially in rectal serosal lesions. A colonoscopy and abdominopelvic computed tomography showed an isolated tumor mimicking neoplasm, in which a biopsy under colonoscopy was performed and the lesion was endometriosis pathologically. Laparoscopic anterior resection (LAR) was performed. There were no complications during intraoperative and postoperative period and the patient was discharged 7 days after the LAR. It is important for reducing of long-term complication like rectal endometriosis that complete and safe excision of pelvic endometriosis with expert surgical strategy. PMID:27375735

  3. Diagnosis and surgical treatment of isolated rectal endometriosis: long term complication of incomplete treatment for pelvic endometriosis

    PubMed Central

    Kwack, Jae-Young; You, Seul Ki; Kwon, Yong-Soon

    2016-01-01

    A 40-year-old woman visited our hospital with cyclic hematochezia for four months. The patient had the history of laparoscopic-assisted vaginal hysterectomy because of severe dysmenorrhea two years ago at another tertiary hospital. According to the medical records, the past surgical treatment was incomplete excision of pelvic endometriotic lesions, especially in rectal serosal lesions. A colonoscopy and abdominopelvic computed tomography showed an isolated tumor mimicking neoplasm, in which a biopsy under colonoscopy was performed and the lesion was endometriosis pathologically. Laparoscopic anterior resection (LAR) was performed. There were no complications during intraoperative and postoperative period and the patient was discharged 7 days after the LAR. It is important for reducing of long-term complication like rectal endometriosis that complete and safe excision of pelvic endometriosis with expert surgical strategy. PMID:27375735

  4. Effect of rapamycin on endometriosis in mice

    PubMed Central

    REN, XU; WANG, YIFENG; XU, GANG; DAI, LIBING

    2016-01-01

    The aims of the present study were to investigate the impact of rapamycin (RAPA) on the endometriosis (EMS) lesions in severe combined immunodeficiency (SCID) mice, and to examine the possible mechanism involved in a novel therapy in EMS. Following the successful establishment of an EMS-SCID mouse model, the mice were randomly assigned into the RAPA, control and saline treatment groups. Subsequent to treatment for 2 weeks, the serum hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) were detected using ELISA. The levels of HIF-1α and VEGF, as well as the size of EMS lesions, were compared among the three groups. In addition, the HIF-1α, VEGF and CD34 protein expression levels, and the microvessel density (MVD) of the lesions were determined by immunohistochemical analysis. Compared with the control and saline groups, the volume of EMS lesions in the RAPA-treated SCID mice was significantly reduced. Furthermore, the serum level and protein expression of VEGF, and the MVD in the lesions of the RAPA-treated group were significantly reduced when compared with the other two groups. These parameters were comparable in the control and saline groups. In conclusion, RAPA may inhibit the growth of endometriotic lesions, most possibly through the inhibition of the expression of VEGF in lesions, thereby inhibiting angiogenesis. PMID:27347023

  5. Correlation between matrix metalloproteinase-9 and endometriosis.

    PubMed

    Liu, Haiping; Wang, Jianye; Wang, Haiyu; Tang, Ning; Li, Yunfei; Zhang, Yan; Hao, Tianyu

    2015-01-01

    Endometrial implantation is the major cause of endometriosis (EMS). Matrix metalloproteinase (MMPs) can degrade multiple extracellular matrix and has been postulated to be related with EMC occurrence. This study thus investigated serum and ascites levels of MMP-9 in EMS patients, in an attempt to discuss the correlation between MMP-9 and EMS. A total of 100 EMS patients, including eutopic endometrium and ectopic endometrium, were recruited in this study along with hysteromyoma patients as the control group. Peripheral blood and ascites samples were collected and tested for MMP-9 levels using gelatin zymogram and enzyme-linked immunosorbent assay (ELISA). In EMS patients, MMP-9 levels in serum and ascites were 6.24 ± 0.53 mM and 38.57 ± 4.93 mM, respectively. Both of them were significantly higher than those in control group (P<0.05). Eutopic endometrium group had higher MMP-9 levels compared to those in ectopic endometrium ones (P<0.05). With advancement of disease stage, EMS patients had progressively elevated MMP-9 levels (P<0.05). Patients at proliferative stage had higher MMP-9 secretion (P<0.05). In summary, site of endometrium, clinical stage and proliferative cycle were independent risk factors for EMS. The elevation of serum and ascites MMP-9 existed in EMS patients, of which those had ectopic endometrium, advanced stage and at proliferative stage had higher MMP-9 expression. PMID:26722547

  6. Correlation between matrix metalloproteinase-9 and endometriosis

    PubMed Central

    Liu, Haiping; Wang, Jianye; Wang, Haiyu; Tang, Ning; Li, Yunfei; Zhang, Yan; Hao, Tianyu

    2015-01-01

    Endometrial implantation is the major cause of endometriosis (EMS). Matrix metalloproteinase (MMPs) can degrade multiple extracellular matrix and has been postulated to be related with EMC occurrence. This study thus investigated serum and ascites levels of MMP-9 in EMS patients, in an attempt to discuss the correlation between MMP-9 and EMS. A total of 100 EMS patients, including eutopic endometrium and ectopic endometrium, were recruited in this study along with hysteromyoma patients as the control group. Peripheral blood and ascites samples were collected and tested for MMP-9 levels using gelatin zymogram and enzyme-linked immunosorbent assay (ELISA). In EMS patients, MMP-9 levels in serum and ascites were 6.24±0.53 mM and 38.57±4.93 mM, respectively. Both of them were significantly higher than those in control group (P<0.05). Eutopic endometrium group had higher MMP-9 levels compared to those in ectopic endometrium ones (P<0.05). With advancement of disease stage, EMS patients had progressively elevated MMP-9 levels (P<0.05). Patients at proliferative stage had higher MMP-9 secretion (P<0.05). In summary, site of endometrium, clinical stage and proliferative cycle were independent risk factors for EMS. The elevation of serum and ascites MMP-9 existed in EMS patients, of which those had ectopic endometrium, advanced stage and at proliferative stage had higher MMP-9 expression. PMID:26722547

  7. Endometriosis Impairs Bone Marrow-Derived Stem Cell Recruitment to the Uterus Whereas Bazedoxifene Treatment Leads to Endometriosis Regression and Improved Uterine Stem Cell Engraftment

    PubMed Central

    Sakr, Sharif; Naqvi, Hanyia; Komm, Barry

    2014-01-01

    Endometriosis is a disease defined by the ectopic growth of uterine endometrium. Stem cells contribute to the generation of endometriosis as well as to repair and regeneration of normal endometrium. Here we demonstrate that the selective estrogen receptor modulator bazedoxifene (BZA), administered with conjugated estrogens (CEs), leads to regression of endometriosis lesions as well as reduction in stem cell recruitment to the lesions. Female mice underwent transplantation of male bone marrow. Endometrium was transplanted in the peritoneal cavity of half to create experimental endometriosis. Mice with or without experimental endometriosis were randomized to BZA/CE or vehicle treatment. Endometriosis lesions, bone marrow-derived mesenchymal stem cell engraftment of the lesions, and eutopic endometrium as well as ovarian stimulation were assessed. BZA treatment significantly reduced lesion size, gland number, and expression of proliferation marker proliferating cell nuclear antigen. Ovarian weight was not affected. Stem cells were recruited to the endometriosis lesions, and this recruitment was dramatically reduced by BZA/CE treatment. Stem cell engraftment was reduced in the uterus of animals with endometriosis; however the number of stem cells engrafting the uterus was completely restored by treatment with BZA/CE. Competition between endometriosis and the eutopic endometrium for a limited supply of stem cells and depletion of normal stem cells flux to the uterus is a novel mechanism by which endometriosis interferes with endometrial function and fertility. BZA/CE not only treats lesions of endometriosis, it also dramatically reduces stem cell recruitment to the lesions and restores stem cell engraftment of the uterine endometrium. PMID:24484171

  8. Chronic common femoral vein occlusion secondary to endometriosis

    PubMed Central

    Ju, Mila H.; Keldahl, Mark L.; Rodriguez, Heron E.

    2016-01-01

    Venous occlusion is sometimes caused by external compression due to adjacent masses. Endometriosis, the presence of functioning endometrial tissue outside the uterine cavity, is a rare cause of venous occlusion. We report a case of chronic common femoral vein occlusion due to endomctrioma causing severe leg edema and groin pain that was treated with resection and venous bypass. PMID:26993188

  9. Case study of a rare form of endometriosis

    PubMed Central

    Cirstoiu, M; Bodean, O; Secara, D; Munteanu, O; Cirstoiu, C

    2013-01-01

    Endometriosis is a common, benign, chronic, estrogen-dependent disorder. The endometrial tissue implants itself outside the uterus and can be usually found in the pelvis or, in rare cases, it can be found nearly anywhere in the body. There are no pathognomonic symptoms of this disease, therefore, in some cases the tumors are incidentally discovered during surgery. Deep infiltrative endometriosis (DIE) is a rare form of this condition, which mostly affects the uterosacral ligaments, the rectovaginal space, and the upper third of the posterior vaginal wall, the bowel, and the urinary tract. We present the case of a 29-year-old pregnant female who was diagnosed with infiltrative endometriosis during the cesarean section at 38 weeks of gestation. The tumors involving the vesicouterine peritoneum had a tendency of infiltrating the urinary bladder, but the patient had been completely asymptomatic prior to this incidental discovery. As cited by literature, the discovery and management of urinary endometriosis, as well as that of other localizations of DIE, is not based on high-level evidence data, but rather on case-series reported by surgical teams working in different centers worldwide. PMID:23599823

  10. A baboon model for endometriosis: implications for fertility

    PubMed Central

    Hastings, Julie M; Fazleabas, Asgerally T

    2006-01-01

    Endometriosis is one of the most common causes of chronic pelvic pain and infertility in women in the reproductive age group. Although the existence of this disease has been known for over 100 years our current knowledge of its pathogenesis and the pathophysiology of its related infertility remains unclear. Several reasons contribute to our lack of knowledge, the most critical being the difficulty in carrying out objective long-term studies in women. Thus, we and others have developed a model of this disease in the non-human primate, the baboon (Papio anubis). Intraperitoneal inoculation of autologous menstrual endometrium results in the development of endometriotic lesions with gross morphological characteristics similar to those seen in the human. Multiple factors have been implicated in endometriosis-associated infertility. We have described aberrant levels of factors involved in multiple pathways important in the establishment of pregnancy, in the endometrium of baboons induced with endometriosis. Specifically, we have observed dysregulation of proteins involved in invasion, angiogenesis, methylation, cell growth, immunomodulation, and steroid hormone action. These data suggest that, in an induced model of endometriosis in the baboon, an increased angiogenic capacity, decreased apoptotic potential, progesterone resistance, estrogen hyper-responsiveness, and an inability to respond appropriately to embryonic signals contribute to the reduced fecundity associated with this disease. PMID:17118171

  11. [Tumoriform endometriosis of the urinary bladder in advanced pregnancy].

    PubMed

    Zavadil, M; Feyreisl, J; Krofta, L; Jarolím, L

    2006-04-01

    A case of tumoriform endometriosis of urinary bladder immitating a tumor of the bladder during the first pregnancy of a 25-year-old patient was successfully treated by partial cystectomy allowing continuation of the pregnancy, a normal term delivery and after 5 months a second pregnancy with term delivery. PMID:16715635

  12. Clinical Outcome after Colonic Resection in Women with Endometriosis

    PubMed Central

    Klugsberger, Bettina; Shamiyeh, Andreas; Oppelt, Peter; Jabkowski, Christina; Schimetta, Wolfgang; Haas, Dietmar

    2015-01-01

    Background. In severe forms of endometriosis, the colon or rectum may be involved. This study evaluated the functional results and long-term outcome after laparoscopic colonic resection for endometriosis. Patients and Methods. Questionnaire survey with 24 women who had experienced typical symptoms, including pelvic pain, infertility, and endometriotic lesions in the bowel and undergone laparoscopic surgery, including low anterior resection, from 2009 to 2012, was conducted. Results. Information about the postoperative outcome was obtained from 22 women and was analyzed statistically. Twenty-one had undergone low anterior resection; one patient required a primary Hartmann procedure due to a rectovaginal fistula. The conversion rate was 4.5%. Major complications occurred in one patient, including an anastomotic leakage, and a Hartmann procedure was carried out subsequently in this patient. The symptoms of pain during defecation, pelvic pain, dyspareunia, dysmenorrhea, and hematochezia showed clear improvement one year after the operation and at the time of the questionnaire. Conclusion. Laparoscopic low anterior resection for deeply infiltrative endometriosis is technically demanding but feasible and safe, and it improves the clinical symptoms of endometriosis in the bowel. PMID:26258139

  13. ENVIRONMENTAL PCB AND PESTICIDE EXPOSURE AND RISK OF ENDOMETRIOSIS

    EPA Science Inventory

    Environmental PCB and Pesticide Exposure and Risk of Endometriosis

    Germaine M. Buck1, John M. Weiner2, Hebe Greizerstein3, Brian Whitcomb1, Enrique Schisterman1, Paul Kostyniak3, Danelle Lobdell4, Kent Crickard5, and Ralph Sperrazza5

    1Epidemiology Branch, Division o...

  14. Diagnosis, management, and long-term outcomes of rectovaginal endometriosis

    PubMed Central

    Moawad, Nash S; Caplin, Andrea

    2013-01-01

    Rectovaginal endometriosis is the most severe form of endometriosis. Clinically, it presents with a number of symptoms including chronic pelvic pain, dysmenorrhea, deep dyspareunia, dyschezia, and rectal bleeding. The gold standard for diagnosis is laparoscopy with histological confirmation; however, there are a number of options for presurgical diagnosis, including clinical examination, transvaginal/transrectal ultrasound, magnetic resonance imagining, colonoscopy, and computed tomography colonography. Treatment can be medical or surgical. Medical therapies include birth control pills, oral progestins, gonadotropin-releasing hormone agonists, danazol, and injectable progestins. Analgesics are often used as well. Surgery improves up to 70% of symptoms. Surgery is either ablative or excisional, and is conducted via transvaginal, laparoscopic, laparotomy, or combined approaches. Common surgical techniques involve shaving of the superficial rectal lesion, laparoscopic anterior discoid resection, and low anterior bowel resection and reanastomosis. Outcomes are generally favorable, but postoperative complications may include intra-abdominal bleeding, anastomotic leaks, rectovaginal fistulas, strictures, chronic constipation, and the need for reoperation. Recurrence of rectal endometriosis is a possibility as well. Other outcomes are improved pain-related symptoms and fertility. Long-term outcomes vary according to the management strategy used. This review will provide the most recent approaches and techniques for the diagnosis and treatment of rectovaginal endometriosis. PMID:24232977

  15. Diagnostic accuracy of urinary cytokeratin 19 fragment for endometriosis.

    PubMed

    Lessey, B A; Savaris, R F; Ali, S; Brophy, S; Tomazic-Allen, S; Chwalisz, K

    2015-05-01

    Endometriosis affects up to 10% of women of reproductive age and 176 million women worldwide. The prevalence in women with infertility is between 30% and 50% but may be higher in women with pelvic pain, interstitial cystitis, or irritable bowel syndrome. Cytokeratin 19 has been suggested as a potential biomarker in urine for the diagnosis of this condition. The objective of this study was to prospectively determine the accuracy and the performance of a urinary cytokeratin 19 (uCYFRA 21-1) test for diagnosing endometriosis. Ninety-eight consecutive women who underwent laparoscopy had a urinary sample obtained before surgery and were included in the study. Endometriosis was diagnosed by laparoscopy and pathology in 64.3% (63 of 98 women). The estimates and 95% confidence intervals for sensitivity, specificity, positive and negative predictive values, and likelihood ratios were 11.1% (4.5%-21.5%), 94.3% (80.8%-99.3%), 77.7% (39.9-97.1), 37% (27-47.9), 1.94 (0.43-8.86), and 0.94 (0.84-1.06), respectively. Despite the high specificity, the uCYFRA 21-1 test has limited value for clinical practice to discriminate between women with and without endometriosis. PMID:25296695

  16. Presentation of endometriosis to general surgeons: a 10-year experience.

    PubMed

    Singh, K K; Lessells, A M; Adam, D J; Jordan, C; Miles, W F; Macintyre, I M; Greig, J D

    1995-10-01

    The presentation and management of 24 patients with endometriosis (median age 34 (range 21-68)years) presenting to general surgeons over a period of 10 years (1985-1994) was reviewed. Patients presented with an abdominal wall swelling related to a previous Pfannenstiel incision (seven patients), umbilical swelling (four), inguinal canal swelling (two), incidentally following appendicectomy (five), terminal ileal obstruction (two), rectal bleeding (two) and urinary symptoms (two). Endometriosis was not suspected in most patients but was confirmed by surgical excision or resection with minimal morbidity. No recurrence occurred during a median follow-up of 53 (range 9-113) months. Endometriosis is a disease rarely seen by general surgeons and is often diagnosed incidentally or on histological examination. Cyclical symptoms associated with menstruation are present in 50 per cent of patients and should suggest the diagnosis in those presenting with scar-related and/or subcutaneous swellings. Simple excision or resection of the presenting lesion provides adequate treatment but, since pelvic endometriosis may be present, referral to a gynaecologist is recommended in every case. PMID:7489161

  17. Genes Downregulated in Endometriosis Are Located Near the Known Imprinting Genes

    PubMed Central

    Higashiura, Yumi; Koike, Natsuki; Akasaka, Juria; Uekuri, Chiharu; Iwai, Kana; Niiro, Emiko; Morioka, Sachiko; Yamada, Yuki

    2014-01-01

    There is now accumulating evidence that endometriosis is a disease associated with an epigenetic disorder. Genomic imprinting is an epigenetic phenomenon known to regulate DNA methylation of either maternal or paternal alleles. We hypothesize that hypermethylated endometriosis-associated genes may be enriched at imprinted gene loci. We sought to determine whether downregulated genes associated with endometriosis susceptibility are associated with chromosomal location of the known paternally and maternally expressed imprinting genes. Gene information has been gathered from National Center for Biotechnology Information database geneimprint.com. Several researchers have identified specific loci with strong DNA methylation in eutopic endometrium and ectopic lesion with endometriosis. Of the 29 hypermethylated genes in endometriosis, 19 genes were located near 45 known imprinted foci. There may be an association of the genomic location between genes specifically downregulated in endometriosis and epigenetically imprinted genes. PMID:24615936

  18. Human endometriosis is associated with plasma cells and overexpression of B lymphocyte stimulator

    PubMed Central

    Hever, Aniko; Roth, Richard B.; Hevezi, Peter; Marin, Maria E.; Acosta, Jose A.; Acosta, Hector; Rojas, Jose; Herrera, Rosa; Grigoriadis, Dimitri; White, Evan; Conlon, Paul J.; Maki, Richard A.; Zlotnik, Albert

    2007-01-01

    Endometriosis affects 10–20% of women of reproductive age and is associated with pelvic pain and infertility, and its pathogenesis is not well understood. We used genomewide transcriptional profiling to characterize endometriosis and found that it exhibits a gene expression signature consistent with an underlying autoimmune mechanism. Endometriosis lesions are characterized by the presence of abundant plasma cells, many of which produce IgM, and macrophages that produce BLyS/BAFF/TNFSF13B, a member of the TNF superfamily implicated in other autoimmune diseases. B lymphocyte stimulator (BLyS) protein was found elevated in the serum of endometriosis patients. These observations suggest a model for the pathology of endometriosis where BLyS-responsive plasma cells interact with retrograde menstrual tissues to give rise to endometriosis lesions. PMID:17640886

  19. Abdominal Wall Endometriosis on the Right Port Site After Laparoscopy: Case Report and Literature Review

    PubMed Central

    Cozzolino, Mauro; Magnolfi, Stefania; Corioni, Serena; Moncini, Daniela; Mattei, Alberto

    2015-01-01

    Background Endometriosis can be intrapelvic or, rarely, extrapelvic. Endometriosis involving the rectus abdominis muscle on the trocar port site is a rare event; until now, only 16 cases have been reported in the literature. The majority of cases were associated with previous abdominal surgery such as diagnostic laparoscopy, cyst excision, appendectomy, myomectomy, or cholecystectomy. We review all the reported cases of this unusual form of extrapelvic endometriosis. Case Report We report a new case of abdominal wall endometriosis at the trocar port site in the rectus abdominis muscle in a woman who had undergone 2 laparoscopies for endometriosis in the 3 years before coming to our attention. The diagnosis was made by sonography. We performed a surgical resection of the lesion with a free macroscopic margin of 5-10 mm. Conclusion Endometriosis should be considered in the differential diagnosis of any abdominal swelling. In our experience, surgery is the treatment of choice. PMID:26412997

  20. Catamenial pneumothorax due to solitary localization of diaphragmatic endometriosis

    PubMed Central

    Elia, Stefano; De Felice, Laura; Varvaras, Dimitrios; Sorrenti, Giuseppe; Mauriello, Alessandro; Petrella, Giuseppe

    2015-01-01

    Introduction Catamenial pneumothorax (CP) is a spontaneous recurrent pneumothorax occurring in women in reproductive age. The etiology of CP has been associated with thoracic endometriosis and is its most common presentation. Presentation of case A case of right catamenial pneumothorax in a 38 year old woman is presented in which three episodes of CP occurred within 72 h of menses in a 6 month period. The patient underwent videothoracoscopy that revealed a solitary localization of diaphragmatic endometriosis. After surgical pleurodesis and based on final pathology of resected lesion, hormonal treatment was started. The outcome was uneventful and the patients is symptom-free at 6 months. Discussion Catamenial pneumothorax (CP) is a rare clinical entity characterized by lung collapse during menstruation, believed to be secondary to pleural endometriosis. Nearly all catamenial pneumothorax occur on the right side as pleural lesions are almost exclusively right-sided. Diagnostic imaging is based on high resolution computed tomography (HRCT) and, preferably, magnetic resonance imaging (MRI) since it is able to detect the blood products in the endometrial deposits. However the lack of macroscopic findings at surgery makes this condition still under-diagnosed. Based on the solitary diaphragmatic localization of endometriosis in our case we preferred to limit surgery to videothoracoscopic pleurodesis and start hormonal treatment with successful outcome. Conclusion Catamenial pneumothorax is the most common presentation of thoracic endometriosis syndrome and should always be suspected in women in childbearing age. Treatment option are still debated but best results are achieved by videothoracoscopic pleurodesis combined with hormonal therapy. PMID:25981153

  1. Cadherin expression in gastrointestinal tract endometriosis: possible role in deep tissue invasion and development of malignancy.

    PubMed

    Van Patten, Katy; Parkash, Vinita; Jain, Dhanpat

    2010-01-01

    Cadherins are cell surface proteins crucial for cell adhesion and tissue integrity. The mechanism of deep tissue invasion in gastrointestinal endometriosis is unknown and may be related to the altered expression of these cell surface proteins. The goal of this study was to evaluate the expression of N-cadherin, E-cadherin, and beta-catenin in peritoneal endometriotic implants, gastrointestinal endometriosis, and carcinoma arising in gastrointestinal endometriosis. Cases of peritoneal endometriosis, gastrointestinal endometriosis, and carcinoma arising in gastrointestinal endometriosis were identified from our pathology database. Immunohistochemistry was performed using antibodies against N-cadherin, E-cadherin, and beta-catenin on representative tissue sections. Cases of normal proliferative and secretory endometrium and adenomyosis were included in the study for comparison. The intensity and extent of staining for each marker was scored semiquantitatively. Appropriate positive and negative controls were used. A total of 38 cases (peritoneal endometriosis (n=14), gastrointestinal endometriosis (n=21: 11 colon, 8 appendix, 2 small bowel), and 3 cases of endometrioid carcinoma arising in colonic endometriosis (n=3)) were included in the study. Compared with normal proliferative endometrium, N-cadherin expression was decreased in intensity and extent in secretory endometrium. Peritoneal and gastrointestinal endometriosis also showed markedly decreased expression of N-cadherin compared with proliferative endometrium. All three cases of carcinoma arising in colonic endometriosis showed a total loss of N-cadherin in the tumor, but preserved E-cadherin and beta-catenin expression. In these cases, areas of benign endometriotic glands near the tumor showed weak and focal N-cadherin expression that was gradually lost. Moderate-to-strong membranous staining for beta-catenin expression and variable intensity of E-cadherin expression was seen diffusely in normal endometrium and

  2. CYP19 gene variant confers susceptibility to endometriosis-associated infertility in Chinese women

    PubMed Central

    Wang, Ledan; Lu, Xiaosheng; Wang, Danhan; Qu, Wanglei; Li, Wenju; Xu, Xiaowen; Huang, Qiusui; Han, Xueying; Lv, Jieqiang

    2014-01-01

    An aromatase encoded by the CYP19 gene catalyzes the final step in the biosynthesis of estrogens, which is related to endometriosis development. To assess the association of CYP19 gene polymorphisms with the risks of endometriosis, chocolate cysts and endometriosis-related infertility, a case–control study was conducted in Chinese Han women by recruiting 225 healthy control females, 146 patients with endometriosis, 94 endometriosis women with chocolate cyst and 65 women with infertility resulting from endometriosis, as diagnosed by both pathological and laparoscopic findings. Individual genotypes at rs2236722:T>C, rs700518:A>G, rs10046:T>C and [TTTA]n polymorphisms were identified. Allelic and genotypic frequencies were compared between the control group and case groups by chi-square analysis. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were determined by logistic regression analysis to predict the association of CYP19 gene polymorphisms with the risk of endometriosis, the related chocolate cysts and infertility. The genotype distributions of the tested CYP19 gene polymorphisms were not significantly different between the healthy control group and the endometriosis/endometriosis with the chocolate cyst group. However, the CYP19 rs700518AA genotype was significantly associated with an increased risk of endometriosis-related infertility (55.4% in the infertility group vs 25.3% in the control group, P<0.001; OR (95% CI): 3.66 (2.06–6.50)) under the recessive form of the A allele. Therefore, we concluded that in Chinese Han females CYP19 gene polymorphisms are not associated with susceptibility to endometriosis or chocolate cysts, whereas CYP19 rs700518AA genotype confers genetic susceptibility to endometriosis-related infertility. PMID:24968701

  3. Study of experimental endometriosis using fluorescence of eosin-tamoxifen association

    NASA Astrophysics Data System (ADS)

    Brogniez, A.; Mordon, Serge R.; Devoisselle, Jean-Marie; Querleu, Denis; Brunetaud, Jean Marc

    1993-08-01

    The main problem of endometriosis is the detection of microscopic and atypical lesions. The successful destruction of these endometriotic sites depends on their detection. This study aimed to develop a spectrofluorometric method to increase the sensitivity of detection of endometriosis. A surgical-induced endometriosis was performed in ten rabbits. Five weeks later, the fluorescence of these endometriotic lesions was studied after injection of tamoxifen and local application of eosin. This fluorescence was compared with that of healthy broad ligament and that obtained without tamoxifen and without eosin. A spectral analysis showed a specific fluorescence of eosin-tamoxifen association, more intense than autofluorescence and selectively observed within endometriosis.

  4. Hypoxia-inducible factor-1alpha: A promising therapeutic target in endometriosis.

    PubMed

    Zhan, Lei; Wang, Wenyan; Zhang, Yu; Song, Enxue; Fan, Yijun; Wei, Bing

    2016-04-01

    Endometriosis is a common gynecologic disease defined as the presence of ectopic endometrial tissues on the ovaries and pelvic peritoneum, and it is a significant cause of pelvic pain, dysmenorrhea and infertility of women in their reproductive age. However, the etiology of endometriosis remains obscure. In recent years, a growing body of evidence validated that hypoxia developed a close relationship with endometriosis and the expression of hypoxia-inducible factor-1alpha (HIF-1α) was increased significantly in the development of endometriosis. Furthermore, inhibiting the expression of HIF-1α contributed to suppress endometriosis progression, suggesting HIF-1α plays a critical function in endometriosis. Nevertheless, the mechanisms by which HIF-1α associates with endometriosis are still undefined. In this brief review, we had a general understanding of HIF-1α firstly, and then we tried to sum up the collective knowledge of HIF-1α in endometriosis. Finally, we will discuss kinds of novel therapeutic approaches to endometriosis based on the functions of HIF-1α. PMID:26898675

  5. Endometriosis of the appendix presenting as acute appendicitis: a case report and literature review.

    PubMed

    Uwaezuoke, Stanley; Udoye, Ezenwa; Etebu, Ebitimitula

    2013-03-01

    Endometriosis is a common disease generally, but appendiceal endometriosis causing acute appendicitis is a very uncommon clinical phenomenon and a few cases have been reported. The authors aim to highlight the rarity of such clinical entity in Nigeria. A 29 year old nulliparous woman presented with severe right iliac fossa pains, tenderness and rebound tenderness on her second day of menstruation. She subsequently had appendicectomy and a histopathological diagnosis of appendiceal endometriosis causing acute appendicitis. Appendiceal endometriosis causing acute appendicitis is rare, and definitive diagnosis is performed through histopathological evaluation. Post-operative gynaecological follow-up is highly recommended. PMID:23559841

  6. Repetitive surgery for recurrent symptomatic endometriosis: what to do?

    PubMed

    Vercellini, Paolo; Barbara, Giussy; Abbiati, Annalisa; Somigliana, Edgardo; Viganò, Paola; Fedele, Luigi

    2009-09-01

    In spite of the increasing number of operative laparoscopies performed for endometriosis associated pelvic pain, postoperative symptomatic recurrences are very common. Reoperation is often considered the best treatment option, but the extent and duration of the effect of second-line surgery is still unclear. The best available evidence has been reviewed in order to define the results of repetitive conservative surgery, the effects of pelvic denervating procedures and postoperative medical treatments, as well as the long-term outcome of definitive surgery. Because of the paucity of published data, estimating the real risk of symptomatic recurrence and need for reoperation after repetitive conservative surgery for endometriosis is very difficult. Based on the limited information available, the long-term outcome appears suboptimal, with a cumulative probability of pain recurrence between 20% and 40%, and of a further surgical procedure between 15% and 20%. These figures are probably an underestimate related to drawbacks in study design, exclusions of dropouts, and publication bias and should be considered with caution. Systematic complementary performance of denervating procedures in addition to reoperation cannot be recommended, as only a few symptomatic patients complain of predominantly midline, hypo-gastric pain. The outcome of hysterectomy for endometriosis-associated pain at medium-term follow-up seems quite satisfactory. Nevertheless, about 15% of patients had persistent symptoms, and 3-5% experienced worsening of pain. Concomitant bilateral oophorectomy reduced the risk of reoperation due to recurrent pelvic pain by six times. However, at least one gonad should be preserved in young women, especially in those with objections to the use of oestrogen-progestogens. Medical treatment appears to have limited and inconsistent effects when used for only a few months after conservative procedures. Data on the benefit of prolonged drug regimens with oral contraceptives

  7. A cross-study gene set enrichment analysis identifies critical pathways in endometriosis

    PubMed Central

    Zhao, Hongbo; Wang, Qishan; Bai, Chunyan; He, Kan; Pan, Yuchun

    2009-01-01

    Background Endometriosis is an enigmatic disease. Gene expression profiling of endometriosis has been used in several studies, but few studies went further to classify subtypes of endometriosis based on expression patterns and to identify possible pathways involved in endometriosis. Some of the observed pathways are more inconsistent between the studies, and these candidate pathways presumably only represent a fraction of the pathways involved in endometriosis. Methods We applied a standardised microarray preprocessing and gene set enrichment analysis to six independent studies, and demonstrated increased concordance between these gene datasets. Results We find 16 up-regulated and 19 down-regulated pathways common in ovarian endometriosis data sets, 22 up-regulated and one down-regulated pathway common in peritoneal endometriosis data sets. Among them, 12 up-regulated and 1 down-regulated were found consistent between ovarian and peritoneal endometriosis. The main canonical pathways identified are related to immunological and inflammatory disease. Early secretory phase has the most over-represented pathways in the three uterine cycle phases. There are no overlapping significant pathways between the dataset from human endometrial endothelial cells and the datasets from ovarian endometriosis which used whole tissues. Conclusion The study of complex diseases through pathway analysis is able to highlight genes weakly connected to the phenotype which may be difficult to detect by using classical univariate statistics. By standardised microarray preprocessing and GSEA, we have increased the concordance in identifying many biological mechanisms involved in endometriosis. The identified gene pathways will shed light on the understanding of endometriosis and promote the development of novel therapies. PMID:19735579

  8. [Treatment of endometriosis with removing blood stasis and purgation method].

    PubMed

    Wang, D Z; Wang, Z Q; Zhang, Z F

    1991-09-01

    According to the method of differentiation of symptom complexes of traditional Chinese medicine (TCM), endometriosis is a disease of blood stasis and mass in the lower portion of abdomen. 76 cases were treated by TCM prescription named endometriotic pill No 1 with rhubarb as the main ingredient. The chief functions of the rhubarb were removing blood stasis, disintegrating mass and purgation. The total effective rate was 80.26%. Among them, the effective rate of dysmenorrhea was 88.89%, that of pelvic pain was 66.72%, that of intercourse pain 72.12%, and diminishing in size of mass or nodule 22.15%; 3 cases of 22 infertility got pregnant (13.63%). The results revealed that the endometriotic pill No 1 yielded distinct improvement in the treatment of endometriosis, including clinical symptoms and signs, laboratory assay of blood rheology, serum Ig, subgroup of T lymphocyte (OKT system) and PG. PMID:1773464

  9. Abdominal Wall Endometrioma after Laparoscopic Operation of Uterine Endometriosis.

    PubMed

    Vukšić, Tihomir; Rastović, Pejana; Dragišić, Vedran

    2016-01-01

    Endometriosis is presence of functional endometrium outside of uterine cavum. As a pluripotent tissue, endometrium has the possibility of implanting itself almost everywhere; even implantation in abdominal wall was described, but it is not common site. This case report presents implantation of functional endometrium in abdominal wall, inside scar tissue, and after insertion of a laparoscopic trocar port. Final diagnosis was confirmed by pathohistological examination. PMID:27340586

  10. Abdominal Wall Endometrioma after Laparoscopic Operation of Uterine Endometriosis

    PubMed Central

    Vukšić, Tihomir; Rastović, Pejana; Dragišić, Vedran

    2016-01-01

    Endometriosis is presence of functional endometrium outside of uterine cavum. As a pluripotent tissue, endometrium has the possibility of implanting itself almost everywhere; even implantation in abdominal wall was described, but it is not common site. This case report presents implantation of functional endometrium in abdominal wall, inside scar tissue, and after insertion of a laparoscopic trocar port. Final diagnosis was confirmed by pathohistological examination. PMID:27340586

  11. Danazol in the management of ureteral obstruction secondary to endometriosis

    SciTech Connect

    Rivlin, M.E.; Krueger, R.P.; Wiser, W.L.

    1985-08-01

    A case is reported in which a woman was diagnosed with ureteral obstruction secondary to endometriosis after cystourethrogram, retrograde pyelogram and a renal scan. After unsuccessful treatment with danazol, a retroperitoneal ureteroneocystotomy was performed. The ureter was found to be obstructed by dense fibrous tissue that contained endometrial glands. It was concluded that danazol is unlikely to relieve endometriotic ureteric obstruction once dense fibrosis has occurred. 8 references, 2 figures.

  12. Chronic Pain Syndromes in Gynaecological Practice: Endometriosis and Fibromyalgia

    PubMed Central

    Siedentopf, F.

    2012-01-01

    As gynaecologists frequently function as “general practitioners” for women, gynaecologists are frequently confronted with questions which initially appear to have only a tenuous connection to their field. Chronic pain syndromes represent a particular challenge, especially as pain syndromes are often associated with severe psychosocial stress for the affected woman. This article discusses some of the psychometric aspects of chronic pain in endometriosis and fibromyalgia together with practical therapeutic approaches. PMID:26640283

  13. Clear cell ovarian cancer and endometriosis: is there a relationship?

    PubMed Central

    Suzin, Jacek; Obirek, Katarzyna; Sochacka, Amanda; Łoszakiewicz, Marta

    2016-01-01

    Introduction Ovarian clear cell carcinoma is a rare type of ovarian cancer. In recent years, issues of the common genetic origin of endometriosis and ovarian clear cell carcinoma have been raised. Aim of this study Aim of this study was to evaluate the prevalence of this type of cancer, risk factors, prognosis and its potential aetiological association with endometriosis. Material and methods In a retrospective study, we analysed histopathological data of patients operated in the First Department of Gynaecology and Obstetrics (MU, Lodz) due to ovarian cancer in 2004-2014. Among the 394 patients operated on for ovarian cancer, clear cell carcinoma was found in 0.02% (9/394). Menstrual history, parity, comorbidities, data from physical examination, operational protocols and histopathological diagnoses were analysed. Follow-up was obtained from 77.8% of patients. Statistical analysis was performed using Microsoft Excel 2013. Results The mean age of patients at diagnosis was 57.6 years; the BMI in the study group was 27.2; the majority of patients were multiparous (77.8%). Clear cell carcinoma was detected mostly at stage Ia (n = 4). The concentration of Ca125 in the study group had an average of 142.75 U/ml and a median of 69.3 U/ml. The coexistence of endometriosis could not be clinically or histologically confirmed amongst our patients. The most common comorbidity in the study group was hypertension. Conclusions In our clinical material, ovarian clear cell carcinoma is a rare histopathological specimen with a prognostic value comparable to that of serous ovarian cancer. Due to the rarity of this histopathological subtype, proving a cause-and-effect relationship between it and endometriosis can only be elucidated through statistical studies of the entire population. PMID:27582682

  14. Molecular aspects of development and regulation of endometriosis

    PubMed Central

    2014-01-01

    Endometriosis is a common and painful condition affecting women of reproductive age. While the underlying pathophysiology is still largely unknown, much advancement has been made in understanding the progression of the disease. In recent years, a great deal of research has focused on non-invasive diagnostic tools, such as biomarkers, as well as identification of potential therapeutic targets. In this article, we will review the etiology and cellular mechanisms associated with endometriosis as well as the current diagnostic tools and therapies. We will then discuss the more recent genomic and proteomic studies and how these data may guide development of novel diagnostics and therapeutics. The current diagnostic tools are invasive and current therapies primarily treat the symptoms of endometriosis. Optimally, the advancement of “-omic” data will facilitate the development of non-invasive diagnostic biomarkers as well as therapeutics that target the pathophysiology of the disease and halt, or even reverse, progression. However, the amount of data generated by these types of studies is vast and bioinformatics analysis, such as we present here, will be critical to identification of appropriate targets for further study. PMID:24927773

  15. Colorectal endometriosis and pregnancy wish: why doing primary surgery.

    PubMed

    Roman, Horace

    2015-01-01

    One of the most interesting debates surrounding deep endometriosis concerns the management of patients with colorectal lesions and pregnancy intention, for which no strong first level of evidence data exists to recommend performing surgical excision of colorectal endometriosis or ART. Studies assessing the policy of primary IVF have recorded pregnancy rates inferior to 45% and estimated cumulative pregnancy rates after up to 3 cycles or IVF as high as 68%. Other authors have reported pregnancy rates over 60% in patients undergoing primary surgery for colorectal endometriosis, with spontaneous conception representing up to 60% of pregnancies. Although overall pregnancy rates appear roughly comparable in patients undergoing either IVF followed by surgery or surgery followed if required by IVF, questions remain as to whether delaying surgery for months or years impairs health. Delaying surgery may lead to bowel occlusion, higher rates of radical colorectal procedures, increased postoperative morbidity and prolonged painful complaints. To provide definitive answers requires a randomized trial on an international scale with a sample size exceeding 400 patients and follow up averaging 4 years. PMID:25961688

  16. Endometriosis and ovarian cancer: links, risks, and challenges faced

    PubMed Central

    Pavone, Mary Ellen; Lyttle, Brianna M

    2015-01-01

    Endometriosis is a benign gynecological condition characterized by specific histological, molecular, and clinical findings. It affects 5%–10% of premenopausal women, is a cause of infertility, and has been implicated as a precursor for certain types of ovarian cancer. Advances in technology, primarily the ability for whole genome sequencing, have led to the discovery of new mutations and a better understanding of the function of previously identified genes and pathways associated with endometriosis associated ovarian cancers (EAOCs) that include PTEN, CTNNB1 (β-catenin), KRAS, microsatellite instability, ARID1A, and the unique role of inflammation in the development of EAOC. Clinically, EAOCs are associated with a younger age at diagnosis, lower stage and grade of tumor, and are more likely to occur in premenopausal women when compared with other ovarian cancers. A shift from screening strategies adopted to prevent EAOCs has resulted in new recommendations for clinical practice by national and international governing bodies. In this paper, we review the common histologic and molecular characteristics of endometriosis and ovarian cancer, risks associated with EAOCs, clinical challenges and give recommendations for providers. PMID:26170722

  17. Aromatase inhibition for refractory endometriosis-related chronic pelvic pain

    PubMed Central

    Abushahin, Fadi; Goldman, Kara N.; Barbieri, Elizabeth; Milad, Magdy; Rademaker, Alfred; Bulun, Serdar E.

    2014-01-01

    Objective To evaluate the use of an aromatase inhibitor for the treatment of endometriosis-related chronic pelvic pain. Design Retrospective analysis. Setting Academic medical center outpatient reproductive endocrinology clinic. Patient (s) Sixteen patients with endometriosis and chronic pelvic pain who previously failed conventional medical and/or surgical therapy. Intervention (s) Treatment with the aromatase inhibitor letrozole (2.5 mg/d) plus a gonadotropin suppressor (norethindrone acetate, 2.5 mg/d, or a combination oral contraceptive [OC]) for an average of 6 months. Main Outcome Measure (s) Pain scores were reported at each visit using a visual analogue scale from 0 to 10 (0: no pain, 10: maximum pain). Result (s) Sixteen patients were treated with an aromatase inhibitor for 180 ± 31days. The median pain score at the start of therapy was 7, and at the end of therapy it was 1.5. In the nine patients who were evaluated after discontinuing therapy, pain scores returned to pretreatment levels. We did not find any correlation between the length of treatment and the overall improvement in pain score. Conclusion (s) Letrozole plus a gonadotropin suppressor substantially improved pain symptoms in patients with endometriosis refractory to conventional therapies; however, pain recurred after treatment was completed. PMID:21868006

  18. An efficient model of human endometriosis by induced unopposed estrogenicity in baboons.

    PubMed

    Nair, Hareesh B; Baker, Robert; Owston, Michael A; Escalona, Renee; Dick, Edward J; VandeBerg, John L; Nickisch, Klaus J

    2016-03-01

    Endometriosis is a chronic estrogen-dependent disease that occurs in approximately 10% of reproductive age women. Baboons offer a clear benefit for studying the initiation and progression of endometriosis since baboon is very close to humans phylogenetically. Progestins are used in the treatment of endometriosis. The therapeutic window of progestins depends on the ratio of its affinity towards progesterone receptor agonism verses antagonism. The present study is to determine the role of pure antiprogestin in baboon endometriosis. We hypothesize that pure antiprogestin will induce unopposed estrogenicity and spontaneous endometriosis in baboons. The rate of endometrial invasion and attachment through modeled peritoneum in the presence and absence of progesterone and antiprogestin was evaluated in this study. A baboon model of endometriosis induced by unopposed estrogenicity using progesterone receptor antagonist (EC304) was used in this study. We observed EC304 has induced unopposed estrogenicity that deregulated proteins involved in attachment, invasion, cell growth, and steroid hormone receptors in this model. Our data suggest that depleting progesterone levels in the endometrium will increase estrogen hyper-responsiveness that leads to increased endometriotic lesion progression in the baboon (Papio anubis) model. This study reports a refined model of human endometriosis in baboons that could potentially be used to develop new diagnostic and therapeutic strategies for the benefit of women suffering from endometriosis. PMID:26908459

  19. Induction of Endometriosis in Mice: A New Model Sensitive to Estrogen

    EPA Science Inventory

    Endometriosis consists of the growth of endometrial tissue outside the uterus. A rat model of endometriosis is available to evaluate the potential for environmental chemicals to promote the disease but may he relatively insensitive for the evaluation of the hazard of certain comp...

  20. The migrating adenomyoma: past views on the etiology of adenomyosis and endometriosis.

    PubMed

    Hudelist, Gernot; Keckstein, Joerg; Wright, Jeremy T

    2009-11-01

    This article discusses the history surrounding the debate on the etiopathology of endometriosis, specifically deep infiltrating endometriosis, and traces the controversies in its management that are as pertinent today as they were when the disease was first described in the late 19th and early 20th centuries. PMID:18976757

  1. Serum and Peritoneal Fluid Levels of Vascular Endothelial Growth Factor in Women with Endometriosis

    PubMed Central

    Kianpour, Maryam; Nematbakhsh, Mehdi; Ahmadi, Sayad Mehdi; Jafarzadeh, Mehrangiz; Hajjarian, Masomeh; Pezeshki, Zahra; Safari, Tahereh; Eshraghi-Jazi, Fatemeh

    2013-01-01

    Background: Endometriosis is known as one of the most common disease in women of reproductive age. Due to important role of vascular endothelial growth factor (VEGF) in neo-vascularization for the implantation of endometrial cell, and also presence of different studies reported VEGF level in the serum and peritoneal fluid (PF) in endometriosis patients, this study was designed to determine the serum and PF levels of VEGF in endometriosis patients, and to compare with normal subjects. Materials and Methods: In this descriptive study, 179 women subjected to laparoscopy for the evaluation of infertility or pelvic pain were allocated into the following two groups: group I: different types of endometriosis patients (n=90) and group II: non-endometriosis patients (n=89). The PF from pelvis and venous blood samples were obtained. The VEGF concentration of the serum and PF were measured using enzyme immunoassay kit and were compared using t test. Results: The level of VEGF in serum was significantly less than that in PF in both groups (p=0.00). However, endometriosis patients had significantly higher level of VEGF in peritoneal fluid than non-endometriosis patients (p=0.043). Conclusion: According to our findings, endometriosis is not associated with change in the level of circulating VEGF. PMID:24520470

  2. An efficient model of human endometriosis by induced unopposed estrogenicity in baboons

    PubMed Central

    Nair, Hareesh B.; Baker, Robert; Owston, Michael A.; Escalona, Renee; Dick, Edward J.; VandeBerg, John L.; Nickisch, Klaus J.

    2016-01-01

    Endometriosis is a chronic estrogen-dependent disease that occurs in approximately 10% of reproductive age women. Baboons offer a clear benefit for studying the initiation and progression of endometriosis since baboon is very close to humans phylogenetically. Progestins are used in the treatment of endometriosis. The therapeutic window of progestins depends on the ratio of its affinity towards progesterone receptor agonism verses antagonism. The present study is to determine the role of pure antiprogestin in baboon endometriosis. We hypothesize that pure antiprogestin will induce unopposed estrogenicity and spontaneous endometriosis in baboons. The rate of endometrial invasion and attachment through modeled peritoneum in the presence and absence of progesterone and antiprogestin was evaluated in this study. A baboon model of endometriosis induced by unopposed estrogenicity using progesterone receptor antagonist (EC304) was used in this study. We observed EC304 has induced unopposed estrogenicity that deregulated proteins involved in attachment, invasion, cell growth, and steroid hormone receptors in this model. Our data suggest that depleting progesterone levels in the endometrium will increase estrogen hyper-responsiveness that leads to increased endometriotic lesion progression in the baboon (Papio anubis) model. This study reports a refined model of human endometriosis in baboons that could potentially be used to develop new diagnostic and therapeutic strategies for the benefit of women suffering from endometriosis. PMID:26908459

  3. Epidemiology of Endometriosis in France: A Large, Nation-Wide Study Based on Hospital Discharge Data

    PubMed Central

    von Theobald, Peter; Cottenet, Jonathan; Iacobelli, Silvia; Quantin, Catherine

    2016-01-01

    We aimed to assess the prevalence of hospitalization for endometriosis in the general population in France and in each French region and to describe temporal trends, rehospitalization rates, and prevalence of the different types of endometriosis. The analyses were carried out on French hospital discharge data and covered the period 2008–2012 and a population of 14,239,197 women of childbearing age. In this population, the prevalence of hospitalization for endometriosis was 0.9%, ranging from 0.4% to 1.6% between regions. Endometriosis affected 1.5% of hospitalized women of childbearing age, ranging from 1.0% to 2.4% between regions. The number of patients hospitalized for endometriosis significantly increased over the study period (p < 0.01). Of these, 4.2% were rehospitalized at least once at one year: ranging from 2.7% to 6.3% between regions. The cumulative rehospitalization rate at 3 years was 6.9%. The types of endometriosis according to the procedures performed were as follows: ovarian (40–50%), peritoneal (20–30%), intestinal (10–20%), and ureteral or bladder (<10%), with significant differences between regions. This is the first detailed epidemiological study of endometriosis in France. Further studies are needed to assess the reasons for the increasing prevalence of endometriosis and for the significant differences in regional prevalence of this disease. PMID:27148550

  4. Chronic pelvic pain and endometriosis: translational evidence of the relationship and implications

    PubMed Central

    Stratton, Pamela; Berkley, Karen J.

    2011-01-01

    BACKGROUND Many clinicians and patients believe that endometriosis-associated pain is due to the lesions. Yet causality remains an enigma, because pain symptoms attributed to endometriosis occur in women without endometriosis and because pain symptoms and severity correlate poorly with lesion characteristics. Most research and reviews focus on the lesions, not the pain. This review starts with the recognition that the experience of pain is determined by the central nervous system (CNS) and focuses on the pain symptoms. METHODS Comprehensive searches of Pubmed, Medline and Embase were conducted for current basic and clinical research on chronic pelvic pain and endometriosis. The information was mutually interpreted by a basic scientist and a clinical researcher, both in the field of endometriosis. The goal was to develop new ways to conceptualize how endometriosis contributes to pain symptoms in the context of current treatments and the reproductive tract. RESULTS Endometriotic lesions can develop their own nerve supply, thereby creating a direct and two-way interaction between lesions and the CNS. This engagement provides a mechanism by which the dynamic and hormonally responsive nervous system is brought directly into play to produce a variety of individual differences in pain that can, in some women, become independent of the disease itself. CONCLUSIONS Major advances in improving understanding and alleviating pain in endometriosis will likely occur if the focus changes from lesions to pain. In turn, how endometriosis affects the CNS would be best examined in the context of mechanisms underlying other chronic pain conditions. PMID:21106492

  5. A Pilot Feasibility Multicenter Study of Patients After Excision of Endometriosis

    PubMed Central

    Tu, Frank; Bajzak, Krisztina; Lamvu, Georgine; Guzovsky, Olga; Agnelli, Rob; Peavey, Mary; Winer, Wendy; Albee, Robert; Sinervo, Ken

    2013-01-01

    Objective: To serve as a pilot feasibility study for a randomized study of excision versus ablation in the treatment of endometriosis by (1) estimating the magnitude of change in symptoms after excision only at multiple referral centers and (2) determining the proportion of women willing to participate in a randomized trial. Methods: We performed a multicenter prospective study of women undergoing excision for endometriosis (Canadian Task Force class II-3) at Duke University Center for Endometriosis Research & Treatment (currently the Saint Louis University Center for Endometriosis), Center for Endometriosis Care, Northshore University Health System, Memorial University (Canada), and Florida Hospital. The study comprised 100 female patients, aged 18 to 55 years, with endometriosis-suspected pelvic pain. The intervention was laparoscopic excision only of the abnormal peritoneum suspicious for endometriosis. The main outcome measures were quality of life, pelvic pain, dysmenorrhea, dyspareunia, and bowel and bladder symptoms. Results: The mean follow-up period was 8.5 months. Excision of endometriosis showed a significant reduction in all pain scores except bowel symptoms, as well as significant improvement in quality of life. Of the patients, 84% were willing to participate in a randomized study. Conclusions: Quality of life is a needed primary outcome for any randomized study comparing excision versus ablation. A multicenter comparative trial is feasible, although quality assurance would have to be addressed. Patients were willing to be randomized even at surgical referral centers. PMID:23743377

  6. Anxiety, coping skills and hypothalamus-pituitary-adrenal (HPA) axis in patients with endometriosis

    PubMed Central

    Quiñones, Maria; Urrutia, Rebecca; Torres-Reverón, Annelyn; Vincent, Katy; Flores, Idhaliz

    2015-01-01

    Background Endometriosis is an inflammatory disease that is defined by growth of endometrial tissue outside the uterus, resulting in pain, infertility, and emotional distress. Previous studies have shown that the HPA axis is compromised in patients with chronic, painful diseases, including endometriosis. However, the underlying mechanisms and the physiological and emotional consequences of dysfunctions in the HPA axis in these patients are largely unknown. We aimed to understand whether diurnal circulating cortisol levels in women with endometriosis are affected and how this impacts their emotional and behavioral responses. Methods Thirty-two patients with endometriosis and 36 healthy control women provided saliva samples and completed a series of psychological questionnaires. Salivary cortisol levels were measured in duplicate using a colorimetric immunoassay. Results There were significant differences in average cortisol levels between endometriosis patients and controls. A negative correlation was found between cortisol levels and infertility and dyspareunia. Furthermore, incapacitating pain was found to be a strong predictor of hypocortisolism. Women with endometriosis reported higher levels of trait anxiety, but showed no differences in perceived stress or in coping styles compared to the control group. Conclusions This study supports previous reports of hypocortisolism as a biomarker of aberrant HPA responses in women with endometriosis. Moreover, it provides further insight into the link between HPA axis dysregulation, emotional responses, and the high comorbidity between endometriosis and other inflammatory conditions. PMID:26900480

  7. Effect of Helixor A on Natural Killer Cell Activity in Endometriosis

    PubMed Central

    Jeung, In-Cheul; Chung, Youn-Jee; Chae, Boah; Kang, So-Yeon; Song, Jae-Yen; Jo, Hyun-Hee; Lew, Young-Ok; Kim, Jang-Heub; Kim, Mee-Ran

    2015-01-01

    Background and Aim: NK cells are one of the major immune cells in endometriosis pathogenesis. While previous clinical studies have shown that helixor A to be an effective treatment for endometriosis, little is known about its mechanism of action, or its relationship with immune cells. The aim of this study is to investigate the effects of helixor A on Natural killer cell (NK cell) cytotoxicity in endometriosis Materials and Methods: We performed an experimental study. Samples of peritoneal fluid were obtained from January 2011 to December 2011 from 50 women with endometriosis and 50 women with other benign ovarian cysts (control). Peritoneal fluid of normal control group and endometriosis group was collected during laparoscopy. Baseline cytotoxicity levels of NK cells were measured with the peritoneal fluid of control group and endometriosis group. Next, cytotoxicity of NK cells was evaluated before and after treatment with helixor A. NK-cell activity was determined based upon the expression of CD107a, as an activation marker. Results: NK cells cytotoxicity was 79.38±2.13% in control cells, 75.55±2.89% in the control peritoneal fluid, 69.59±4.96% in endometriosis stage I/II endometriosis, and 63.88±5.75% in stage III/IV endometriosis. A significant difference in cytotoxicity was observed between the control cells and stage III/IV endometriosis, consistent with a significant decrease in the cytotoxicity of NK cells in advanced stages of endometriosis; these levels increased significantly after treatment with helixor A; 78.30% vs. 86.40% (p = 0.003) in stage I/II endometriosis, and 73.67% vs. 84.54% (p = 0.024) in stage III/IV. The percentage of cells expressing CD107a was increased significantly in each group after helixor A treatment; 0.59% vs. 1.10% (p = 0.002) in stage I/II endometriosis, and 0.79% vs. 1.40% (p = 0.014) in stage III/IV. Conclusions: Helixor A directly influenced NK-cell cytotoxicity through direct induction of CD107a expression. Our results

  8. Video-assisted laparoscopy for the detection and diagnosis of endometriosis: safety, reliability, and invasiveness

    PubMed Central

    Schipper, Erica; Nezhat, Camran

    2012-01-01

    Endometriosis is a highly enigmatic disease with multiple presentations ranging from infertility to severe pain, often causing significant morbidity. Video-assisted laparoscopy (VALS) has now replaced laparotomy as the gold standard for the diagnosis and management of endometriosis. While imaging has a role in the evaluation of some patients, histologic examination is needed for a definitive diagnosis. Laboratory evaluation currently has a minor role in the diagnosis of endometriosis, although studies are underway investigating serum markers, genetic studies, and endometrial sampling. A high index of suspicion is essential to accurately diagnose this complex condition, and a multidisciplinary approach is often indicated. The following review discusses laparoscopic diagnosis of endometriosis from the pre-operative evaluation of patients suspected of having endometriosis to surgical technique for safe and adequate laparoscopic diagnosis of the condition and postsurgical care. PMID:22927769

  9. Endometrial nerve fibers in women with endometriosis, adenomyosis, and uterine fibroids.

    PubMed

    Zhang, Xinmei; Lu, Bangchun; Huang, Xiufeng; Xu, Hong; Zhou, Caiyun; Lin, Jun

    2009-11-01

    To determine whether nerve fibers in the functional layer endometrium are caused by an endometriosis itself or a common symptom of pain, endometrial tissues from 30 women with endometriosis, 40 women with adenomyosis, 41 women with uterine fibroids, and 47 endometriosis women with adenomyosis were stained immunohistochemically using the highly specific polyclonal rabbit antiprotein gene product 9.5 (PGP9.5) and monoclonal mouse antineurofilament protein. We demonstrated PGP9.5-immunoactive nerve fibers in the functional layer of endometrium in women with pain symptoms, but not in women without pain symptoms, whether the women had endometriosis, adenomyosis, uterine fibroids, or endometriosis with adenomyosis, suggesting a role of PGP9.5-immunoactive nerve fibers in the functional layer of the endometrium playing in pain generation in these disorders. PMID:19535047

  10. Endometriosis in a Patient with Mayer-Rokitansky-Küster-Hauser Syndrome

    PubMed Central

    Troncon, Júlia Kefalás; Zani, Ana Carolina Tagliatti; Vieira, Andrea Duarte Damasceno; Poli-Neto, Omero Benedicto; Nogueira, Antônio Alberto; Rosa-e-Silva, Júlio César

    2014-01-01

    Objective. To report a case of Mayer-Rokitansky-Küster-Hauser syndrome (MRKH) in which there were two nonfunctional rudimentary uteruses with the presence of ovarian endometrioma, corroborating that there are valid alternative theories to the existence of endometriosis, rather than Sampson's theory alone, such as the coelomic metaplasia theory. Design. A case report. Setting. A tertiary referral center, which is also a university hospital. Patient. A fifteen-year-old patient with MRKH syndrome and endometriosis. Intervention. Laparoscopic approach for diagnostic confirmation and treatment of the endometrioma. Results. Evidence of endometriosis in a patient with no functional uterus. Conclusions. This case report and a few others that are available in the literature reinforce the possibility that coelomic metaplasia could be the origin of endometriosis. Patients with müllerian agenesis and pelvic pain should be carefully evaluated, and the presence of pelvic endometriosis should not be excluded. PMID:25610677

  11. Genetic burden associated with varying degrees of disease severity in endometriosis

    PubMed Central

    Sapkota, Yadav; Attia, John; Gordon, Scott D.; Henders, Anjali K.; Holliday, Elizabeth G.; Rahmioglu, Nilufer; MacGregor, Stuart; Martin, Nicholas G.; McEvoy, Mark; Morris, Andrew P.; Scott, Rodney J.; Zondervan, Krina T.; Montgomery, Grant W.; Nyholt, Dale R.

    2015-01-01

    Endometriosis is primarily characterized by the presence of tissue resembling endometrium outside the uterine cavity and is usually diagnosed by laparoscopy. The most commonly used classification of disease, the revised American Fertility Society (rAFS) system to grade endometriosis into different stages based on disease severity (I to IV), has been questioned as it does not correlate well with underlying symptoms, posing issues in diagnosis and choice of treatment. Using two independent European genome-wide association (GWA) datasets and top-level classification of the endometriosis cases based on rAFS [minimal or mild (Stage A) and moderate-to-severe (Stage B) disease], we previously showed that Stage B endometriosis has greater contribution of common genetic variation to its aetiology than Stage A disease. Herein, we extend our previous analysis to four endometriosis stages [minimal (Stage I), mild (Stage II), moderate (Stage III) and severe (Stage IV) disease] based on the rAFS classification system and compared the genetic burden across stages. Our results indicate that genetic burden increases from minimal to severe endometriosis. For the minimal disease, genetic factors may contribute to a lesser extent than other disease categories. Mild and moderate endometriosis appeared genetically similar, making it difficult to tease them apart. Consistent with our previous reports, moderate and severe endometriosis showed greater genetic burden than minimal or mild disease. Overall, our results provide new insights into the genetic architecture of endometriosis and further investigation in larger samples may help to understand better the aetiology of varying degrees of endometriosis, enabling improved diagnostic and treatment modalities. PMID:25882541

  12. Coping with Endometriosis Eckersley Jill and Aziz Zara Coping with Endometriosis 128pp £9.99 Sheldon Press 9781847093523 1847093523 [Formula: see text].

    PubMed

    2016-02-10

    The powerful foreword by award-winning author Dame Hilary Mantel, who has endometriosis, gives the stamp of authority to this book for women who have the condition and for those who have symptoms but are undiagnosed. PMID:26860163

  13. Association between endometriosis and the interleukin 1A (IL1A) locus

    PubMed Central

    Sapkota, Yadav; Low, Siew-Kee; Attia, John; Gordon, Scott D.; Henders, Anjali K.; Holliday, Elizabeth G.; MacGregor, Stuart; Martin, Nicholas G.; McEvoy, Mark; Morris, Andrew P.; Takahashi, Atsushi; Scott, Rodney J.; Kubo, Michiaki; Zondervan, Krina T.; Montgomery, Grant W.; Nyholt, Dale R.

    2015-01-01

    STUDY QUESTION Are single-nucleotide polymorphisms (SNPs) at the interleukin 1A (IL1A) gene locus associated with endometriosis risk? SUMMARY ANSWER We found evidence for strong association between IL1A SNPs and endometriosis risk. WHAT IS KNOWN ALREADY Genetic factors contribute substantially to the complex aetiology of endometriosis and the disease has an estimated heritability of ∼51%. We, and others, have conducted genome-wide association (GWA) studies for endometriosis, which identified a total of nine independent risk loci. Recently, two small Japanese studies reported eight SNPs (rs6542095, rs11677416, rs3783550, rs3783525, rs3783553, rs2856836, rs1304037 and rs17561) at the IL1A gene locus as suggestively associated with endometriosis risk. There is also evidence of a link between inflammation and endometriosis. STUDY DESIGN, SIZE, DURATION We sought to further investigate the eight IL1A SNPs for association with endometriosis using an independent sample of 3908 endometriosis cases and 8568 controls of European and Japanese ancestry. The study was conducted between October 2013 and July 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS By leveraging GWA data from our previous multi-ethnic GWA meta-analysis for endometriosis, we imputed variants in the IL1A region, using a recent 1000 Genomes reference panel. After combining summary statistics for the eight SNPs from our European and Japanese imputed data with the published results, a fixed-effect meta-analysis was performed. An additional meta-analysis restricted to endometriosis cases with moderate-to-severe (revised American Fertility Society stage 3 or 4) disease versus controls was also performed. MAIN RESULTS AND THE ROLE OF CHANCE All eight IL1A SNPs successfully replicated at P < 0.014 in the European imputed data with concordant direction and similar size to the effects reported in the original Japanese studies. Of these, three SNPs (rs6542095, rs3783550 and rs3783525) also showed association with

  14. Looking for Celiac Disease in Italian Women with Endometriosis: A Case Control Study

    PubMed Central

    Campo, Sebastiano; D'Onofrio, Ferruccio; Gallo, Antonella; Campo, Vincenzo; Palombini, Guglielmo; Santoliquido, Angelo; Gasbarrini, Giovanni

    2014-01-01

    In the last years, a potential link between endometriosis and celiac disease has been hypothesized since these disorders share some similarities, specifically concerning a potential role of oxidative stress, inflammation, and immunological dysfunctions. We investigated the prevalence of celiac disease among Italian women with endometriosis with respect to general population. Consecutive women with a laparoscopic and histological confirmed diagnosis of endometriosis were enrolled; female nurses of our institution, without a known history of endometriosis, were enrolled as controls. IgA endomysial and tissue transglutaminase antibodies measurement and serum total IgA dosage were performed in both groups. An upper digestive endoscopy with an intestinal biopsy was performed in case of antibodies positivity. Presence of infertility, miscarriage, coexistence of other autoimmune diseases, and family history of autoimmune diseases was also investigated in all subjects. Celiac disease was diagnosed in 5 of 223 women with endometriosis and in 2 of 246 controls (2.2% versus 0.8%; P = 0.265). Patients with endometriosis showed a largely higher rate of infertility compared to control group (27.4% versus 2.4%; P < 0.001). Our results confirm that also in Italian population an increased prevalence of celiac disease among patients with endometriosis is found, although this trend does not reach the statistical significance. PMID:24804204

  15. How to Develop an Electronic Clinical Endometriosis Research File Integrated in Clinical Practice

    PubMed Central

    Vanhie, A.; Fassbender, A.; O, D.; Tomassetti, C.; Meuleman, C.; Peeraer, K.; Debrock, S.; D'Hooghe, Th.

    2015-01-01

    Endometriosis is associated with a range of pelvic-abdominal pain symptoms and infertility. It is a chronic disease that can have a significant impact on various aspects of women's lives, including their social and sexual relationships, work, and study. Despite several international guidelines on the management of endometriosis, there is a wide variety of clinical practice in the management of endometriosis, resulting in many women receiving delayed or suboptimal care. In this paper we discuss the possibilities and benefits of using electronic health records for clinical research in the field of endometriosis. The development of a wide range of clinical software for electronic patient records has made the registration of large datasets feasible and the integration of research files and clinical files possible. Integration of global standards on registration of endometriosis care in electronic health records could improve reporting of research data and facilitate the execution of large, multicentre randomized trials on the management of endometriosis. These highly needed trials could bring us the evidence needed for the optimisation of management of women with endometriosis. PMID:26240823

  16. Association of interleukin-16 polymorphisms with disease progression and susceptibility in endometriosis.

    PubMed

    Azimzadeh, P; Khorram Khorshid, H R; Akhondi, M M; Shirazi, A

    2016-10-01

    Interleukin-16 (IL-16) is a multifunctional pro-inflammatory cytokine that was previously found in association with complex disorders, and it is now cleared that this cytokine plays a critical role in regulation of cellular functions such as homoeostasis. Due to the complexity of endometriosis and its resemblance to cancer, we designed present case-control study to determine the effects of genetic polymorphisms of the human IL-16 gene on Iranian women's susceptibility to endometriosis. A total of 126 patients with endometriosis (stages I-IV) and 144 healthy women as control group were recruited to the study. We genotyped four single nucleotide polymorphisms of IL-16 gene (rs11556218 T>G, rs4778889 T>C, rs4072111 C>T and rs1131445 C>T). Genotyping was performed using PCR and restriction fragment length polymorphism. Our results showed that genotype distribution in two exonic polymorphisms including rs11556218 and rs4072111 was significantly different between Endometriosis patients and healthy individuals (P < 0.05). We have also found an association between rs4072111 and rs1131445 with progression to the severe stages (III-IV) of endometriosis (P < 0.05). Finally, we may conclude that IL-16 gene polymorphisms are highly associated with increased risk of endometriosis and could be considered as a susceptibility factor for endometriosis. PMID:27484651

  17. Potential involvement of the immune system in the development of endometriosis

    PubMed Central

    Kyama, Cleophas M; Debrock, Sophie; Mwenda, Jason M; D'Hooghe, Thomas M

    2003-01-01

    This article presents an overview of immunological factors and their role in the development of endometriosis, with emphasis on inflammatory cytokines, growth and adhesion factors. Although retrograde menstruation is a common phenomenon among women of reproductive age, not all women who have retrograde menstruation develop endometriosis. The development of endometriosis is hypothesised to be a complex process, which may be facilitated by several factors, including the quantity and quality of endometrial cells in peritoneal fluid (PF), increased inflammatory activity in PF, increased endometrial-peritoneal adhesion and angiogenesis, reduced immune surveillance and clearance of endometrial cells, and increased production of autoantibodies against endometrial cells. Potential biomarkers like cytokines and autoantibodies upregulated during development of endometriosis may be useful in the development of a non-surgical diagnostic tool. Although endometriosis can be treated using hormonal suppression, there is need for non-hormonal drugs, which can inhibit the development of endometriosis and alleviate pain or infertility without inhibition of ovulation. New molecules that modulate immune function in endometriosis should be the targets for future research. PMID:14651748

  18. Functional genetic polymorphisms and female reproductive disorders: Part II—endometriosis

    PubMed Central

    Tempfer, C.B.; Simoni, M.; Destenaves, B.; Fauser, B.C.J.M.

    2009-01-01

    BACKGROUND Endometriosis has a strong genetic component, and numerous genetic studies have been reported. METHODS We have systematically reviewed these studies and included 114 in our final selection. RESULTS We found no consistent evidence linking endometriosis with specific polymorphisms in genes encoding inflammatory mediators, proteins involved in sex steroid metabolism, vascular function and tissue remodelling. Although a number of polymorphisms have been associated with endometriosis in selected populations, the associations have not been independently confirmed, either because only single studies were carried out on these markers/genes or because other studies reported no association. The most solid evidence linking specific polymorphisms to endometriosis came from studies investigating glutathione-S-transferase, a phase II detoxification enzyme. Carriage of the GSTT1 null deletion variant showed consistent association with endometriosis with a 29% increased risk; however, it cannot be excluded that this result was due to publication bias, and this association should be independently confirmed in large-scale, well-designed case–control studies. CONCLUSIONS The evidence of an association between genetic polymorphisms and endometriosis is weak. Carriage of the GSTT1 null deletion may moderately increase the risk of this disease. We suggest that the methodology of association studies should be improved in order to identify and validate associations in endometriosis. PMID:18805939

  19. Use of Neutral Argon Plasma in the Laparoscopic Treatment of Endometriosis

    PubMed Central

    Kho, Kimberly A.; Morozov, Vadim

    2009-01-01

    Background and Objectives: To report the feasibility and safety of the use of a novel energy source that uses an electrically neutral beam of pure argon plasma for the laparoscopic management of endometriosis. Methods: In this prospective pilot study, 20 patients undergoing laparoscopic treatment of endometriosis were included. Characteristic endometriotic lesions throughout the pelvis were vaporized or resected using neutral argon plasma. Specimens were evaluated for the presence of endometriosis and thermal effects on tissue. The bases of the treated lesions were biopsied to determine whether residual endometriosis was present. Results: Neutral argon plasma was used in 18 of the 20 patients for laparoscopic treatment of pelvic endometriosis. All biopsies confirmed complete vaporization or re-section with no residual endometriosis at the base. Endometriosis was identified on pathology in all lesions excised. Thermal effects did not interfere with histologic analysis in any of the lesions. No complications occurred. Conclusion: Neutral argon plasma can be utilized as a multi-functional device that has vaporization, coagulation, and superficial cutting capacities with minimal thermal spread and acceptable outcomes. The use of neutral argon plasma appears to be efficacious and safe for the complete treatment of endometriotic implants. PMID:20202387

  20. How to Develop an Electronic Clinical Endometriosis Research File Integrated in Clinical Practice.

    PubMed

    Vanhie, A; Fassbender, A; O, D; Tomassetti, C; Meuleman, C; Peeraer, K; Debrock, S; D'Hooghe, Th

    2015-01-01

    Endometriosis is associated with a range of pelvic-abdominal pain symptoms and infertility. It is a chronic disease that can have a significant impact on various aspects of women's lives, including their social and sexual relationships, work, and study. Despite several international guidelines on the management of endometriosis, there is a wide variety of clinical practice in the management of endometriosis, resulting in many women receiving delayed or suboptimal care. In this paper we discuss the possibilities and benefits of using electronic health records for clinical research in the field of endometriosis. The development of a wide range of clinical software for electronic patient records has made the registration of large datasets feasible and the integration of research files and clinical files possible. Integration of global standards on registration of endometriosis care in electronic health records could improve reporting of research data and facilitate the execution of large, multicentre randomized trials on the management of endometriosis. These highly needed trials could bring us the evidence needed for the optimisation of management of women with endometriosis. PMID:26240823

  1. Expression of vascular endothelial growth factor C and anti-angiogenesis therapy in endometriosis

    PubMed Central

    Song, Wei-Wei; Lu, Huan; Hou, Wen-Jing; Xu, Guang-Xu; Zhang, Ji-Hong; Sheng, You-Hua; Cheng, Ming-Jun; Zhang, Rong

    2014-01-01

    Angiogenesis is an important pathogenesis of Endometriosis. Vascular endothelial growth factor C (VEGF-C) is one of the most important factor in the regulation of both normal and abnormal angiogenesis. Anti-angiogenic treatment of endometriosis is still in the exploratory stage. In this study, we investigate the relationship between VEGF-C and endometriosis, the therapeutic effects of Endostar in the rat endometriosis model. We then demonstrated that Immunohistochemical expression of VEGF-C was higher in endometriotic tissues than in control normal ovary tissues (P < 0.01) and higher in the endomertriosis grade III-IV than in endomertriosis grade I-II (P=0.013). In rat endometriosis model, we observed a significant reduction in the mean volume and weight of the endometriotic implants per rat in the treatment group as compared with the control group. By immunohistochemical evaluation, there was a significant reduction in VEGF-C expression after treatment in all areas examined. VEGF-C may be involved in the pathogenesis of endomertriosis by regulating the angiogenesis. Endostar has therapeutic effects of endometriosis lesions in the rat endometriosis model. PMID:25550812

  2. Oocyte quality is decreased in women with minimal or mild endometriosis

    PubMed Central

    Xu, Bo; Guo, Nan; Zhang, Xiao-min; Shi, Wei; Tong, Xian-hong; Iqbal, Furhan; Liu, Yu-sheng

    2015-01-01

    Endometriosis, a pathological condition in which the endometrium grows outside the uterus, is one of the most common causes of female infertility; it is diagnosed in 25–40% of infertile women. The mechanism by which endometriosis affects the fertility of females remains largely unknown. We examined the ultrastructure of oocytes from patients with minimal or mild endometriosis and control females undergoing in vitro fertilization (IVF) treatment by transmission electron microscopy (TEM) to investigate the physiological significance of oocyte quality for patients with minimal or mild endometriosis. The TEM results revealed that the oocytes from women with minimal or mild endometriosis exhibited abnormal mitochondrial structure and decreased mitochondria mass. Quantitative real time PCR analysis revealed that the mitochondrial DNA copy number was significantly reduced in the oocytes from women with minimal or mild endometriosis compared with those of the control subjects. Our results suggest that decreased oocyte quality because of impaired mitochondrial structure and functions probably an important factor affecting the fertility of endometriosis patients. PMID:26022105

  3. Potential role of endometrial stem/progenitor cells in the pathogenesis of early-onset endometriosis.

    PubMed

    Gargett, C E; Schwab, K E; Brosens, J J; Puttemans, P; Benagiano, G; Brosens, I

    2014-07-01

    The pathogenesis of early-onset endometriosis has recently been revisited, sparked by the discovery of endometrial stem/progenitor cells and their possible role in endometriosis, and because maternal pregnancy hormone withdrawal following delivery induces uterine bleeding in the neonate. The neonatal uterus has a large cervix to corpus ratio which is functionally blocked with mucous, supporting the concept of retrograde shedding of neonatal endometrium. Only 5% show overt bleeding. Furthermore, the presence of endometriosis in pre-menarcheal girls and even in severe stage in adolescents supports the theory that early-onset endometriosis may originate from retrograde uterine bleeding soon after birth. Endometrial stem/progenitor cells have been identified in menstrual blood suggesting that they may also be shed during neonatal uterine bleeding. Thus, we hypothesized that stem/progenitor cells present in shedding endometrium may have a role in the pathogenesis of early-onset endometriosis through retrograde neonatal uterine bleeding. During the neonatal and pre-pubertal period, shed endometrial stem/progenitor cells are postulated to survive in the pelvic cavity in the absence of circulating estrogens supported by niche cells also shed during neonatal uterine bleeding. According to this hypothesis, during thelarche, under the influence of rising estrogen levels, endometrial stem/progenitor cells proliferate and establish ectopic endometrial lesions characteristic of endometriosis. This New Research Horizon review builds on recent discussions on the pathogenesis of early-onset endometriosis and raises new avenues for research into this costly condition. PMID:24674992

  4. Patients With Chronic Pelvic Pain: Endometriosis or Interstitial Cystitis/Painful Bladder Syndrome?

    PubMed Central

    2007-01-01

    Background: Endometriosis and interstitial cystitis/painful bladder syndrome share similar symptoms. Interstitial cystitis was once considered rare, but it is now recognized as more common than previously thought. This review examines evidence that patients presenting with symptoms typically attributed to endometriosis or with unresolved pelvic pain after treatment for endometriosis may, in fact, have interstitial cystitis, and suggests approaches for appropriate diagnosis. Methods: A MedLine search using “chronic pelvic pain,” “endometriosis,” “interstitial cystitis,” and “bladder origin pain” as key words was performed for the most recent English-language articles. Additional references were obtained through cross-referencing the bibliography cited in each publication. Discussion: The symptoms of endometriosis and inter-stitial cystitis frequently overlap, and these 2 conditions may even coexist in the same patient. In cases of unresolved endometriosis and persistent pelvic pain, patients may have interstitial cystitis. A variety of tools are available to aid in identifying interstitial cystitis. Conclusion: Gynecologists should be alert to the possible presence of interstitial cystitis in patients who present with chronic pelvic pain typical of endometriosis. PMID:17761077

  5. Bowel endometriosis: Colorectal surgeon’s perspective in a multidisciplinary surgical team

    PubMed Central

    Wolthuis, Albert M; Meuleman, Christel; Tomassetti, Carla; D’Hooghe, Thomas; de Buck van Overstraeten, Anthony; D’Hoore, André

    2014-01-01

    Endometriosis is a gynecological condition that presents as endometrial-like tissue outside the uterus and induces a chronic inflammatory reaction. Up to 15% of women in their reproductive period are affected by this condition. Deep endometriosis is defined as endometriosis located more than 5 mm beneath the peritoneal surface. This type of endometriosis is mostly found on the uterosacral ligaments, inside the rectovaginal septum or vagina, in the rectosigmoid area, ovarian fossa, pelvic peritoneum, ureters, and bladder, causing a distortion of the pelvic anatomy. The frequency of bowel endometriosis is unknown, but in cases of bowel infiltration, about 90% are localized on the sigmoid colon or the rectum. Colorectal involvement results in alterations of bowel habits such as constipation, diarrhea, tenesmus, dyschezia, and, rarely, rectal bleeding. Differential diagnosis must be made in case of irritable bowel syndrome, solitary rectal ulcer syndrome, and a rectal tumor. A precise diagnosis about the presence, location, and extent of endometriosis is necessary to plan surgical treatment. Multidisciplinary laparoscopic treatment has become the standard of care. Depending on the size of the lesion and site of involvement, full-thickness disc excision or bowel resection needs to be performed by an experienced colorectal surgeon. Long-term outcomes, following bowel resection for severe endometriosis, regarding pain and recurrence rate are good with a pregnancy rate of 50%. PMID:25400445

  6. New Horizons in the Etiopathogenesis and Non-Invasive Diagnosis of Endometriosis.

    PubMed

    Zubrzycka, A; Zubrzycki, M; Janecka, A; Zubrzycka, M

    2015-01-01

    Endometriosis is one of the most common gynecological inflammatory diseases, occurring in adolescents and women in the reproductive age group and leading to infertility. The precise etiopathogenesis of endometriosis is unknown, but several theories concerning the phenomena involved in its development have been proposed. Beside classic retrograde menstruation, these include lymphatic and vascular metastases, iatrogenic direct implantation, coelomic metaplasia, embryonic remnants and mesenchymal cell differentiation or induction; the persistence of a form of embryonic endometriosis may also be involved, as well as the theory of the possible role of endometrial stem/progenitor cells. This paper deals with other risk factors which may be potentially involved in the etiopathogenesis of endometriosis, including the immune, inflammatory, endocrine, genetic, anatomical and environmental factors. At present, endometriosis can only be diagnosed with surgery, where laparoscopy is considered a gold standard. Therefore, there is an urgent need for a test allowing to detect non-invasive molecular biomarkers to identify the symptoms of endometriosis early on in disease development. A thorough understanding of the etiopathogenesis of endometriosis is essential toward the development of novel diagnostic assays and effective treatments of the disease. PMID:26391550

  7. Diagnostics and Therapy for Malignant (Degenerate) Colon Endometriosis – Three Case Reports

    PubMed Central

    Schutz, R.; Woziwodzki, J.; Schweppe, K.-W.

    2016-01-01

    Malignant degeneration of colon endometriosis is a very rare event. We report here on three cases. A 48-year-old woman with a 10-year history of endometriosis was treated for a rectal adenocarcinoma, a 61-year-old G1P1, who was operated at the age of 40 years for ovarian endometriosis and again at the age of 53 years for an endometriosis-associated endometroid ovarian carcinoma, presented for therapy for a lymph node recurrence of the ovarian cancer and, secondly, due to a malignantly degenerated rectum-sigmoid colon endometriosis; furthermore a 54-year old woman with a 21-year history of endometriosis was operated for malignant colon endometriosis. The tumour occurred during an adjuvant anti-oestrogen treatment with an aromatase inhibitor following surgical and radiotherapy for breast cancer. In all cases a radical cancer operation was followed by adjuvant chemotherapy and in one case with an additional radiotherapy. In the follow-up periods of 18 months, 2 and 5 years, respectively, all women remained free of recurrences. Although this is not a randomised controlled study due to the rare occurrence of such cases, a radical operation followed by individualised adjuvant therapy appears to be the treatment of choice. PMID:27134299

  8. The Role of Placental Protein 14 in the Pathogenesis of Endometriosis

    PubMed Central

    Wang, Ping; Zhu, Libo

    2013-01-01

    Placental protein 14 (PP-14) is the principal secretory phase product of endometrium and has been shown to inhibit cell immune function. But its role in the pathogenesis of endometriosis is controversy. The objective of this study is to determine the concentrations of PP-14 in peritoneal fluid (PF) and serum and PP-14 protein expression in endometriotic lesions in women with ovarian endometriosis (n = 75) when compared to women without endometriosis (n = 49) between day 7 and day 20 of their menstrual cycle. Concentrations of PP-14 in PF and serum as well as PP-14 protein expression in endometriotic lesions in women with and without endometriosis were evaluated by using enzyme-linked immunosorbent assay and immunohistochemical staining, respectively. Serum PP-14 concentrations were significantly increased in women with endometriosis (7.5 ± 1.4 ng/mL) compared to those in women without endometriosis (5.8 ± 0.9 ng/mL; P < .05) and statistically decreased after surgery and further reduced by using gonadotropin-releasing hormone agonist therapy (P < .05). However, the concentrations of PP-14 in PF did not reach a significant difference between women with and without endometriosis (P > .05). In women with endometriosis, scores of PP-14 protein expression in the lesions (n = 50, 2.2 [0∼5.8]) were significantly correlated with serum PP-14 concentrations (n = 50, 7.6 ± 1.3 ng/mL; P < .01). Our results suggest that PP-14 may play an important role in the pathogenesis of endometriosis. PMID:23670949

  9. Elevated Systemic Levels of Endocannabinoids and Related Mediators Across the Menstrual Cycle in Women With Endometriosis.

    PubMed

    Sanchez, Ana Maria; Cioffi, Raffaella; Viganò, Paola; Candiani, Massimo; Verde, Roberta; Piscitelli, Fabiana; Di Marzo, Vincenzo; Garavaglia, Elisabetta; Panina-Bordignon, Paola

    2016-08-01

    Cannabinoids and modulators of the endocannabinoid system affect specific mechanisms that are critical to the establishment and development of endometriosis. The aim of this study was to measure the systemic levels of endocannabinoids and related mediators in women with and without endometriosis and to investigate whether such levels correlated with endometriosis-associated pain. Plasma and endometrial biopsies were obtained from women with a laparoscopic diagnosis of endometriosis (n = 27) and no endometrial pathology (n = 29). Plasma levels of endocannabinoids (N-arachidonoylethanolamine [AEA] and 2-arachidonoylglycerol [2-AG]) and related mediators (N-oleoylethanolamine [OEA] and N-palmitoylethanolamine [PEA]), messenger RNA expression of some of their receptors (cannabinoid receptor type 1 [CB1], CB2, transient receptor potential vanilloid type [TRPV1]), and the enzymes involved in the synthesis (N-acyl-phosphatidylethanolamine-hydrolyzing phospholipase D [NAPE-PLD]) and degradation (fatty acid amide hydrolase 1 [FAAH]) of AEA, OEA, and PEA were evaluated in endometrial stromal cells. The systemic levels of AEA, 2-AG, and OEA were elevated in endometriosis in the secretory phase compared to controls. The expression of CB1 was higher in secretory phase endometrial stromal cells of controls versus endometriosis. Similar expression levels of CB2, TRPV1, NAPE-PLD, and FAAH were detected in controls and endometriosis. Patients with moderate-to-severe dysmenorrhea and dyspareunia showed higher AEA and PEA levels than those with low-to-moderate pain symptoms, respectively. The association of increased circulating AEA and 2-AG with decreased local CB1 expression in endometriosis suggests a negative feedback loop regulation, which may impair the capability of these mediators to control pain. These preliminary data suggest that the pharmacological manipulation of the action or levels of these mediators may offer an alternative option for the management of endometriosis

  10. Effect of hydroxychloroquine and characterization of autophagy in a mouse model of endometriosis

    PubMed Central

    Ruiz, A; Rockfield, S; Taran, N; Haller, E; Engelman, R W; Flores, I; Panina-Bordignon, P; Nanjundan, M

    2016-01-01

    In endometriosis, the increased survival potential of shed endometrial cells (which normally undergo anoikis) is suggested to promote lesion development. One mechanism that may alter anoikis is autophagy. Using an autophagic flux inhibitor hydroxychloroquine (HCQ), we identified that it reduces the in vitro survival capacity of human endometriotic and endometrial T-HESC cells. We also identified that HCQ could decrease lesion numbers and disrupt lesion histopathology, as well as increase the levels of peritoneal macrophages and the IP-10 (10 kDa interferon-γ-induced protein) chemokine in a mouse model of endometriosis. We noted that RNA levels of a subset of autophagic markers were reduced in lesions relative to uterine horns from endometriosis-induced (untreated) mice. In addition, the RNA levels of autophagic markers were decreased in uterine horns of endometriosis-induced mice compared with those from controls. However, we noted that protein expression of LC3B (microtubule-associated protein 1 light-chain 3β; an autophagic marker) was increased in uterine horns of endometriosis-induced mice compared with uterine horns of controls. By immunohistochemical staining of a human endometriosis-focused tissue microarray, we observed LC3B expression predominantly in epithelial relative to stromal cells in both eutopic and ectopic endometria. Via transmission electron microscopy, cells from eutopic endometria of endometriosis-induced mice contained more lipid droplets (rather than autophagosomes) compared with uterine horns from controls. Collectively, our findings indicate that the autophagic pathway is dysregulated in both ectopic and eutopic endometrium in a murine model of endometriosis and that HCQ has potential as a therapeutic agent for women afflicted with endometriosis. PMID:26775710

  11. Diet and risk of endometriosis in a population-based case–control study

    PubMed Central

    Trabert, Britton; Peters, Ulrike; De Roos, Anneclaire J.; Scholes, Delia; Holt, Victoria L.

    2012-01-01

    Diet plausibly has a role in the aetiology of endometriosis through effects on steroid hormone levels; however, few published studies have examined the diet and endometriosis risk. We evaluated dietary risk factors for endometriosis in a population-based case–control study. Cases were 284 Group Health (GH) enrollees aged 18–49 years with newly diagnosed, surgically confirmed endometriosis between 1996 and 2001. Controls were 660 randomly selected age-matched female GH enrollees without a history of endometriosis. Nutrients and selected food groups were assessed using the Women’s Health Initiative FFQ. OR of endometriosis risk associated with dietary exposures were estimated using unconditional logistic regression and adjusted for identified covariates. Increased total fat consumption was associated with decreased endometriosis risk (fourth quartile v. lowest: OR 0·5, 95% CI 0·2, 1·0, P-trend=0·12). Increased β-carotene consumption and servings/d of fruit were associated with increased risk (β-carotene third quartile v. lowest: OR 1·7, 95% CI 1·1, 2·6; fourth quartile v. lowest: OR 1·6, 95% CI 1·0, 2·5, P-trend 0·16; fruit >2 servings/d v. <1: OR 1·5, 95% CI 1·0, 2·3, P -trend=0·04). We also found a suggestion of decreased endometriosis risk associated with the consumption of dairy products (2 servings/d v. ≤1: OR 0·6, >2 servings/d v. ≤1: OR 0·7), but this association was not statistically significant for the highest tertile. The present study suggests that specific dietary components may be associated with endometriosis risk. PMID:20875189

  12. Evaluation of the endometriosis treatment success rate by the laparoscopic-pharmacological method

    NASA Astrophysics Data System (ADS)

    Mutrynowski, Andrzej; Zabielska, Renata; Smolarczyk, Roman

    1996-03-01

    The study aimed at evaluating the success rate of the operative laparoscopy assisted by electrocoagulation and laser as well as danazol and lynestrenol in the endometriosis treatment. One-hundred-ninety women with the recognized endometriosis were included into the study. In the I degree(s) endometriosis the operative or hormonal therapy was applied, in the II-IV degree(s) the combined therapy was used. The complete cure was achieved in 159 of the patients (84%): 28 women conceived, in 131 of the cases remission was recognized during the second laparoscopy. Eighteen women found improvement (9%) while 13 women (7%) reported the lack of improvement.

  13. The Impact of Endometriosis across the Lifespan of Women: Foreseeable Research and Therapeutic Prospects

    PubMed Central

    Hughes, C. L.; Foster, W. G.

    2015-01-01

    In addition to estrogen dependence, endometriosis is characterized by chronic pelvic inflammation. The impact of the chronic pelvic inflammatory state on other organ systems and women's health is unclear. Endometriosis associated chronic inflammation and potential adverse health effects across the lifespan render it imperative for renewed research vigor into the identification of novel biomarkers of disease and therapeutic options. Herein we propose a number of opportunities for research and development of new therapeutics to address the unmet needs in the treatment of endometriosis per se and its ancillary risks for other diseases in women across the lifespan. PMID:26064879

  14. A case of advanced-stage endometrial stromal sarcoma of the ovary arising from endometriosis

    PubMed Central

    Back, Ju A; Choi, Myeong Gyune; Ju, U Chul; Kang, Woo Dae

    2016-01-01

    Endometrial stromal sarcoma (ESS) is a rare malignancy. Development of extrauterine ESS form endometriosis is particularly rare. The majority of extrauterine ESS occurs in areas with preexisting endometriosis. The most common site is the ovary. We experienced a case of ESS of the ovary that arose from endometriosis with multiple disseminated lesions. This disease was managed by total abdominal hysterectomy, bilateral salpingo-oophorectomy, both pelvic lymph nodes dissection, omentectomy, and appendectomy followed by postoperative high-dose progesterone therapy. Here, we report this case with literature review. PMID:27462602

  15. Reversal of fortune: estrogen receptor-β in endometriosis.

    PubMed

    Simmen, Rosalia C M; Kelley, Angela S

    2016-08-01

    Enhanced inflammation and reduced apoptosis sustain the growth of endometriotic lesions. Alterations in the expression of estrogen receptor-alpha (ERα) and estrogen receptor-beta (ERβ) accompany the conversion of resident endometrial cells within the normal uterine environment to ectopic lesions located in extrauterine sites. Recent studies highlighted in this focused review linked ERβ to dysregulation of apoptotic and inflammatory networks involving novel interacting partners in endometriosis. The elucidation of these nongenomic actions of ERβ using human cells and mouse models is an important step in understanding key regulatory pathways that are disrupted leading to disease establishment and progression. PMID:27272520

  16. Is acupuncture effective in the treatment of pain in endometriosis?

    PubMed Central

    Lund, Iréne; Lundeberg, Thomas

    2016-01-01

    Introduction Endometriosis is a multifactorial, estrogen-dependent, inflammatory gynecological condition – often with long-lasting visceral pelvic pain of different origin, and infertility among women. Current management options for patients’ are often inadequate, with side effects for many for whom acupuncture techniques could be an alternative. Earlier studies have discussed the efficacy of acupuncture, but not its methodological aspects. Objectives To summarize the documented clinical effects of acupuncture on rated visceral pelvic endometriosis-related pain, and associated variables among individuals, within and between studied groups, and to discuss the methodological treatment aspects. Methods Published full text clinical studies, case reports, and observational studies with abstracts written in English were searched by using the keywords “Acupuncture and Endometriosis” in databases such as PubMed, Web of Science, and CINAHL. The reporting guidelines, Standards for Reporting Interventions in Clinical Trials of Acupuncture was used for the methodological report. Results Three studies were found including 99 women, 13–40 years old, with diagnosed endometriosis. The studies were different in research design, needle stimulation techniques, and evaluation instruments. Methodological similarities were seven to12 needle insertions per subject/session, and 15–25 minutes of needle retention time. The needles were placed in lower back/pelvic-abdominal area, in the shank, feet, and hands. Treatment numbers varied from nine to 16 and patients received one to two treatments per week. Similarity in reported treatment effects in the quoted studies, irrespective of research design or treatment technique, was reported decrease of rated pain intensity. Discussion Meta-analysis is the standard procedure for the evaluation of evidence of treatment effects, ie, on a group level, usually without analysis of the individual responses even with obvious spread in the

  17. Endometriosis among the Hausa/Fulani population of Nigeria.

    PubMed

    Ekwempu, C C; Harrison, K A

    1979-06-01

    In three and half years at the Ahmadu Bello University Hospital, Zaria, Nigeria, endometriosis was found in 27 Nigerians (all negroid) and one Caucasian. Age and parity distribution were similar to what has been found in patients elsewhere. In other respects, there were striking differences. The frequency (8.2 percent) is one of the highest reported in the negro. Two fifths were menopausal, majority had associated pelvic inflammatory disease, and nearly all were in women of the lowest socio-economic status. The lesions were rare in the pouch of Douglas and were totally absent from the rectovaginal septum and in the extra peritoneal space. PMID:505550

  18. Endometrial Stromal Cells and Immune Cell Populations Within Lymph Nodes in a Nonhuman Primate Model of Endometriosis

    PubMed Central

    Fazleabas, A. T.; Braundmeier, A. G.; Markham, R.; Fraser, I. S.; Berbic, M.

    2011-01-01

    Mounting evidence suggests that immunological responses may be altered in endometriosis. The baboon (Papio anubis) is generally considered the best model of endometriosis pathogenesis. The objective of the current study was to investigate for the first time immunological changes within uterine and peritoneal draining lymph nodes in a nonhuman primate baboon model of endometriosis. Paraffin-embedded femoral lymph nodes were obtained from 22 normally cycling female baboons (induced endometriosis n = 11; control n = 11). Immunohistochemical staining was performed with antibodies for endometrial stromal cells, T cells, immature and mature dendritic cells, and B cells. Lymph nodes were evaluated using an automated cellular imaging system. Endometrial stromal cells were significantly increased in lymph nodes from animals with induced endometriosis, compared to control animals (P = .033). In animals with induced endometriosis, some lymph node immune cell populations including T cells, dendritic cells and B cells were increased, suggesting an efficient early response or peritoneal drainage. PMID:21617251

  19. Targeting Src in endometriosis-associated ovarian cancer.

    PubMed

    Manek, R; Pakzamir, E; Mhawech-Fauceglia, P; Pejovic, T; Sowter, H; Gayther, S A; Lawrenson, K

    2016-01-01

    The SRC proto-oncogene is commonly overexpressed or activated during cancer development. Src family kinase inhibitors are approved for the treatment of certain leukemias, and are in clinical trials for the treatment of solid tumors. Src signaling is activated in endometriosis, a precursor of clear cell and endometrioid subtypes of epithelial ovarian cancers (OCs). We examined the expression of phosphorylated Src (Src-pY416) in 381 primary OC tissues. Thirty-six percent of OCs expressed Src-pY416. Src-pY416 expression was most common in endometriosis-associated OCs (EAOCs) (P=0.011), particularly in clear cell OCs where 58.5% of cases expressed Src-pY416. Src-pY416 expression was associated with shorter overall survival (log rank P=0.002). In vitro inhibition of Src signaling using 4-amino-5-(4-chlorophenyl)-7-(dimethylethyl)pyrazolo[3,4-d]pyrimidine (PP2) resulted in reduced anchorage-independent and -dependent growth, and in three-dimensional cell culture models PP2 disrupted aggregate formation in Src-pY416-positive but not in Src-pY416-negative cell lines. These data suggest that targeting active Src signaling could be a novel therapeutic opportunity for EAOCs, and support the further pre-clinical investigation of Src family kinase inhibitors for treating OCs expressing Src-pY416. PMID:27526105

  20. Targeting Src in endometriosis-associated ovarian cancer

    PubMed Central

    Manek, R; Pakzamir, E; Mhawech-Fauceglia, P; Pejovic, T; Sowter, H; Gayther, S A; Lawrenson, K

    2016-01-01

    The SRC proto-oncogene is commonly overexpressed or activated during cancer development. Src family kinase inhibitors are approved for the treatment of certain leukemias, and are in clinical trials for the treatment of solid tumors. Src signaling is activated in endometriosis, a precursor of clear cell and endometrioid subtypes of epithelial ovarian cancers (OCs). We examined the expression of phosphorylated Src (Src-pY416) in 381 primary OC tissues. Thirty-six percent of OCs expressed Src-pY416. Src-pY416 expression was most common in endometriosis-associated OCs (EAOCs) (P=0.011), particularly in clear cell OCs where 58.5% of cases expressed Src-pY416. Src-pY416 expression was associated with shorter overall survival (log rank P=0.002). In vitro inhibition of Src signaling using 4-amino-5-(4-chlorophenyl)-7-(dimethylethyl)pyrazolo[3,4-d]pyrimidine (PP2) resulted in reduced anchorage-independent and -dependent growth, and in three-dimensional cell culture models PP2 disrupted aggregate formation in Src-pY416-positive but not in Src-pY416-negative cell lines. These data suggest that targeting active Src signaling could be a novel therapeutic opportunity for EAOCs, and support the further pre-clinical investigation of Src family kinase inhibitors for treating OCs expressing Src-pY416. PMID:27526105

  1. Developing a Noninvasive Procedure Using Labeled Monoclonal Antibody Anti-VEGF (Bevacizumab) for Detection of Endometriosis

    PubMed Central

    Machado, Daniel Escorsim; Perini, Jamila Alessandra; Orlando, Margarida Maria Camoes; Santos-Oliveira, Ralph

    2015-01-01

    The off-label use of bevacizumab labeled with 99mTc as a new radiopharmaceutical for imaging of endometriosis is a promising noninvasive, new clinical procedure. The bevacizumab in monoclonal antibodies targeted at vascular endothelial growth factor (VEGF) is superexpressed in cases of endometriosis. In this study we evaluate the imaging of endometriosis lesion in rats (induced to endometriosis) using bevacizumab-99mTc. The results showed that bevacizumab-99mTc imaged the lesion and support his use for Nuclear Medicine applied to gynecology. Also the results appointed that this radiopharmaceutical has a hepatobiliary excretion. It is important to notice that the dose used was almost 0,01% of the usual dose for the bevacizumab. PMID:26240826

  2. Combined vesical and abdominal endometriosis following abdominal hysterotomy and tubal ligation.

    PubMed

    Dhall, K; Bhatia, K; Sharma, S K

    1980-09-01

    The article reports on the case of a 29 year old patient who developed abdominal endometriosis 4 years after having had hysterotomy and tubal ligation. About a month after the excision of the endometrial tissue she was examined for suprapubic pains, strangury, and frequency of micturition. A nodule was found in the deepest part of the abdominal wall and the patient was treated for 6 months, without success, with medroxyprogesterone acetate. A subsequent laparotomy showed bladder endometriosis, obviously still an endometrial implant at the time of hysterotomy, which was missed at the time of the first excision. Total hysterectomy was carried out and the patient recovered successfully. Bladder endometriosis is the most common site of involvement among urinary tract endometriosis. The peculiarity of the case presented here is in the total absence of hematuria, and in the fact that pains had no relation with the menstrual cycle. Hormonal therapy is often ineffective, and surgery often the only advisable form of treatment. PMID:12311304

  3. Should we diagnose and treat minimal and mild endometriosis before medically assisted reproduction?

    PubMed

    Leung, Annie S; Dahan, Michael H

    2016-04-01

    The treatment of minimal or mild endometriosis prior to assisted reproduction (ranging from intrauterine insemination to in vitro fertilization [IVF]) to improve the likelihood of success is controversial. Ovulation suppression is commonly used in endometriosis to decrease pain, however, there is little evidence to suggest improvements in fertility associated with this technique. Moreover, current evidence is sparse and does not support ovarian suppression prior to intrauterine insemination with or without ovulation induction, while there is some evidence favoring ovarian suppression with gonadotropin releasing hormone agonists prior to IVF to improve pregnancy rates. However, the majority of studies were performed in women with moderate to severe endometriosis. There is currently conflicting evidence regarding surgical ablation or removal of endometriomas prior to IVF, and its outcome on pregnancy rates. This review highlights the paucity of data in the management of endometriosis prior to assisted reproductive technologies and suggests that further studies are needed. PMID:26616457

  4. Developing a Noninvasive Procedure Using Labeled Monoclonal Antibody Anti-VEGF (Bevacizumab) for Detection of Endometriosis.

    PubMed

    Machado, Daniel Escorsim; Perini, Jamila Alessandra; Orlando, Margarida Maria Camoes; Santos-Oliveira, Ralph

    2015-01-01

    The off-label use of bevacizumab labeled with 99mTc as a new radiopharmaceutical for imaging of endometriosis is a promising noninvasive, new clinical procedure. The bevacizumab in monoclonal antibodies targeted at vascular endothelial growth factor (VEGF) is superexpressed in cases of endometriosis. In this study we evaluate the imaging of endometriosis lesion in rats (induced to endometriosis) using bevacizumab-99mTc. The results showed that bevacizumab-99mTc imaged the lesion and support his use for Nuclear Medicine applied to gynecology. Also the results appointed that this radiopharmaceutical has a hepatobiliary excretion. It is important to notice that the dose used was almost 0,01% of the usual dose for the bevacizumab. PMID:26240826

  5. Robotic-Assisted Laparoscopic Treatment of Bowel, Bladder, and Ureteral Endometriosis

    PubMed Central

    Hajhosseini, Babak; King, Louise P.

    2011-01-01

    Background: Endometriosis commonly affects the pelvic organs but can also affect organs outside the pelvis and is then termed extragenital endometriosis. Cases: Successful robotically assisted laparoscopic management of extragenital endometriosis, specifically, endometriosis of the bowel, bladder, and ureter in 5 patients. Conclusion: A substantial body of evidence supports the laparoscopic approach as the preferred method for many procedures; yet, a majority of procedures today still are performed by laparotomy. This preference for open procedures is likely due to the lack of trained endoscopic surgeons, the difficulty in obtaining proper instruments, and the long learning curve of operative laparoscopy. The recent advent of computer-enhanced technology may provide the bridge necessary for more surgeons to incorporate laparoscopic surgery in the treatment of complex cases. PMID:21985730

  6. [Psychology and sexology are essential, from diagnosis to comprehensive care of endometriosis].

    PubMed

    Leroy, A; Azaïs, H; Garabedian, C; Bregegere, S; Rubod, C; Collier, F

    2016-06-01

    Endometriosis, defined by the presence of endometrial tissue outside the uterine cavity, is a common but often under diagnosed pathology. The clinical manifestations are varied (chronic pelvic pain, urinary or gastrointestinal symptoms) and can sometimes be very frustrated, delaying the diagnosis. This delay in diagnosis can be a high source of stress responsible for an important psychological impact in these patients, having a sense of misunderstanding and neglect of the medical profession. This climate of stress and anxiety can cause alteration of behavior including sexual disorders. In addition, endometriosis can be revealed as part of an infertility evaluation, and the patient and the couple can already be affected by this situation. The clinical and psychological impact of endometriosis inevitably leads to an impairment of patient's quality of life and sexuality. The objective of this article is to show the psychological consequences of endometriosis and its impact on sexuality, in order to highlight this essential aspect for a comprehensive care of patients. PMID:27216956

  7. Organochlorine Pesticides and Risk of Endometriosis: Findings from a Population-Based Case–Control Study

    PubMed Central

    De Roos, Anneclaire J.; Thompson, Mary Lou; Sathyanarayana, Sheela; Scholes, Delia; Barr, Dana Boyd; Holt, Victoria L.

    2013-01-01

    Background: Endometriosis is considered an estrogen-dependent disease. Persistent environmental chemicals that exhibit hormonal properties, such as organochlorine pesticides (OCPs), may affect endometriosis risk. Objective: We investigated endometriosis risk in relation to environmental exposure to OCPs. Methods: We conducted the present analyses using data from the Women’s Risk of Endometriosis (WREN) study, a population-based case–control study of endometriosis conducted among 18- to 49-year-old female enrollees of a large health care system in western Washington State. OCP concentrations were measured in sera from surgically confirmed endometriosis cases (n = 248) first diagnosed between 1996 and 2001 and from population-based controls (n = 538). We estimated odds ratios (OR) and 95% CIs using unconditional logistic regression, adjusting for age, reference date year, serum lipids, education, race/ethnicity, smoking, and alcohol intake. Results: Our data suggested increased endometriosis risk associated with serum concentrations of β-hexachlorocyclohexane (HCH) (third vs. lowest quartile: OR = 1.7; 95% CI: 1.0, 2.8; highest vs. lowest quartile OR = 1.3; 95% CI: 0.8, 2.4) and mirex (highest vs. lowest category: OR = 1.5; 95% CI: 1.0, 2.2). The association between serum β-HCH concentrations and endometriosis was stronger in analyses restricting cases to those with ovarian endometriosis (third vs. lowest quartile: OR = 2.5; 95% CI: 1.5, 5.2; highest vs. lowest quartile: OR = 2.5; 95% CI: 1.1, 5.3). Conclusions: In our case–control study of women enrolled in a large health care system in the U.S. Pacific Northwest, serum concentrations of β-HCH and mirex were positively associated with endometriosis. Extensive past use of environmentally persistent OCPs in the United States or present use in other countries may affect the health of reproductive-age women. Citation: Upson K, De Roos AJ, Thompson ML, Sathyanarayana S, Scholes D, Barr DB, Holt VL. 2013

  8. Endometriosis of Extra-Abdominal Soft Tissues: A Tertiary Center Experience.

    PubMed

    Wang, Jayson; Strauss, Dirk C; Messiou, Christina; Thway, Khin

    2016-09-01

    While endometriosis, defined as the presence of endometrial tissue in extrauterine sites, is most frequently encountered within the peritoneal cavity, a small but significant proportion of cases occur at extra-abdominal soft tissue sites, particularly in relation to previous abdominal surgery. We reviewed the cases of endometriosis of soft tissue sites seen at a tertiary soft tissue center. All cases of extra-abdominal soft tissue endometriosis diagnosed at this institution over a 13-year period were reviewed, and clinical and pathologic findings were recorded. Forty-five patients had diagnoses of soft tissue endometriosis and there were 34 diagnostic biopsies and 26 surgical excision specimens. All but 1 case were abdominal wall lesions, with 1 located in the upper arm. A total of 33 patients presented with lesions in scars of previous operations (31 in Pfannenstiel incisions for Caesarean sections, presenting with a median interval of 6 years (range 1-16 years) following surgery). The lesions ranged in size from 1 to 8 cm (median 3.5 cm). One case showed decidualized stroma with trophoblast cells, while 2 had secondary adenocarcinoma arising from endometriosis. Eighteen cases were tested for β-catenin expression immunohistochemically, of which 5 showed at least focal nuclear positivity in the surrounding fibrous tissue (although not within glands or stroma). Soft tissue endometriosis is seen most commonly in surgical scars, particularly following Caesarean sections. Spontaneous endometriosis also most commonly occurs in the abdominal wall, although can occur exceptionally at unusual sites, such as extremities. Secondary changes, including carcinomas, can arise from endometriosis. The differential diagnosis of these lesions includes fibromatosis, which may be erroneously diagnosed on small, nonrepresentative core biopsy specimens. PMID:27098587

  9. Systematic enrichment analysis of microRNA expression profiling studies in endometriosis

    PubMed Central

    Wei, Shiyang; Xu, Hong; Kuang, Yan

    2015-01-01

    Objective(s): The purpose of this study was to conduct a meta-analysis on human microRNAs (miRNAs) expression data of endometriosis tissue profiles versus those of normal controls and to identify novel putative diagnostic markers. Materials and Methods: PubMed, Embase, Web of Science, Ovid Medline were used to search for endometriosis miRNA expression profiling studies of endometriosis. The miRNAs expression data were extracted, and study quality of each article was assessed. The frequently reported miRNAs with consistent regulation were screened out by a meta-profiling algorithm. The putative targets of consistently expressed miRNAs were predicted by using four target prediction tools (TargetScan, PicTar, miRanda, miRDB), and gene ontology pathway enrichment analysis (KEGG and Panther pathways) of the miRNA targets were carried out with GeneCodis web tool. Results: A total of 194 related literatures were retrieved in four databases. One hundred and thirty four differentially expressed miRNAs were found in the 12 microRNA expression profiling studies that compared endometriosis tissues with normal tissues, with 28 miRNAs reported in at least two studies, and 9882 candidate genes retrieved for 13 consistently expressed miRNAs. Kyoto encyclopedia of genes and genomes (KEGG) and Panther pathways enrichment analysis showed that endometriosis related differently expressed miRNA targets were mainly enriched in cancer, endocytosis, Wnt signalling pathway, and angiogenesis. It showed that these differently expressed miRNAs and gene are potential biomarkers of endometriosis. Conclusion: miRNAs appear to be potent regulators of gene expression in endometriosis and its associated reproductive disorders, raising the prospect of using miRNAs as biomarkers and therapeutic agent in endometriosis. PMID:26124927

  10. MicroRNAs expression profiling of eutopic proliferative endometrium in women with ovarian endometriosis

    PubMed Central

    2013-01-01

    Background The eutopic endometrium of women with endometriosis, compared with disease-free individuals, contains certain molecular alterations, including the differential expression of microRNA (miRNA). The aim of the study was to compare the expression of the most relevant miRNAs in the eutopic endometrium of women with and without ovarian endometriosis. Methods A total of 46 regularly menstruating patients, 21 patients with ovarian endometriosis and 25 controls, underwent surgery in the proliferative phase of the cycle. The eutopic endometrium was collected through aspirating biopsy prior to laparoscopy. Only patients with advanced (stage III and IV) histopathologically confirmed ovarian endometriosis were included. TaqMan MicroRNA Array Cards were applied to examine the expression of 667 human miRNAs in 10 patients with endometriosis and 10 controls. Custom-made, low-density real-time PCR arrays were used to confirm the expression of 15 selected molecules in 21 endometriosis patients and 25 disease-free individuals. Results Of 667 miRNAs, 2 were highly likely to be upregulated and 13 were downregulated in the eutopic endometrium of patients with endometriosis compared with the controls. Validation using real-time PCR showed that hsa-miR-483-5p (p = 0.012) and hsa-miR-629* (p = 0.02) are significantly downregulated in patients with endometriosis. Conclusions Changes in the expression of select miRNAs might lead to or be a consequence of an early defect in the physiological activity of the proliferative endometrium, ultimately resulting in the overgrowth of this tissue outside the uterus. PMID:23945042

  11. Patients’ report on how endometriosis affects health, work, and daily life

    PubMed Central

    Fourquet, Jessica; Gao, Xin; Zavala, Diego; Orengo, Juan C.; Abac, Sonia; Ruiz, Abigail; Laboy, Joaquín; Flores, Idhaliz

    2009-01-01

    NARRATIVE ABSTRACT The objective of this study was to assess the burden of endometriosis by obtaining Patient Reported Outcome (PRO) data describing the experience of living with this disease. Survey data from one hundred and seven women with self-reported, surgically diagnosed endometriosis showed that living with this disease may be characterized by physical limitations that disrupt health, work and daily life. PMID:19926084

  12. Increased Expression of Pattern Recognition Receptors and Nitric Oxide Synthase in Patients with Endometriosis

    PubMed Central

    Yeo, Seung Geun; Won, Yong Sung; Lee, Ho Yun; Kim, Young Il; Lee, Jin-Woo; Park, Dong Choon

    2013-01-01

    Objective: Endometriosis is characterized by repeated inflammatory changes and serious adhesions, inducing innate and adaptive immune responses within the abdominal cavity. To assess these immune responses, we evaluated the levels of expression of Toll-like receptors (TLR)-1, -2, -4, -5, and -9; nucleotide-binding oligomerization domains (NOD)-1 and -2; interleukins-1β, -6, -8, -10, and -12; interferon-γ; tumor necrosis factor-α; inducible nitric oxide synthase (iNOS) and endothelial NOS (eNOS); and immunoglobulins (Igs) in patients with endometriosis. Methods: The levels of TLRs, NODs, cytokines, and NOS mRNAs in peritoneal effusions were assessed by real time reverse transcription-polymerase chain reaction; and IgG, IgA and IgM concentrations were measured by enzyme-linked immunosorbent assays (ELISA) in 40 patients with and 40 without endometriosis. Findings from the two groups were compared. Results: We observed expression of all pattern recognition receptors (PRRs), cytokines, and NOS mRNAs and Igs in the effusion fluid of patients with and without endometriosis. The levels of TLR-2 and -9; NOD-1 and -2; iNOS and eNOS mRNAs and CA 125 were significantly higher in the endometriosis than in the non-endometriosis group (p<0.05 each). Moreover, PRR, cytokine, and NOS expression showed significant correlations (p<0.05). Conclusions: PRRs, cytokines, and NOS, which act cooperatively in the innate immune response, are closely associated with endometriosis. Increased expression of TLR-2, TLR -9, NOD-1, NOD-2, and NOS mRNA in peritoneal fluid may be associated with endometriosis. PMID:23935397

  13. The International Endometriosis Evaluation Program (IEEP Study) – A Systematic Study for Physicians, Researchers and Patients

    PubMed Central

    Burghaus, S.; Fehm, T.; Fasching, P. A.; Blum, S.; Renner, S. K.; Baier, F.; Brodkorb, T.; Fahlbusch, C.; Findeklee, S.; Häberle, L.; Heusinger, K.; Hildebrandt, T.; Lermann, J.; Strahl, O.; Tchartchian, G.; Bojahr, B.; Porn, A.; Fleisch, M.; Reicke, S.; Füger, T.; Hartung, C.-P.; Hackl, J.; Beckmann, M. W.; Renner, S. P.

    2016-01-01

    Introduction: Endometriosis is a heterogeneous disease characterized by a range of different presentations. It is usually diagnosed when patients present with pain and/or infertility, but it has also been diagnosed in asymptomatic patients. Because of the different diagnostic approaches and diverse therapies, time to diagnosis can vary considerably and the definitive diagnosis may be delayed, with some cases not being diagnosed for several years. Endometriosis patients have many unmet needs. A systematic registration and follow-up of endometriosis patients could be useful to obtain an insight into the course of the disease. The validation of biomarkers could contribute to the development of diagnostic and predictive tests which could help select patients for surgical assessment earlier and offer better predictions about patients who might benefit from medical, surgical or other interventions. The aim is also to obtain a better understanding of the etiology, pathogenesis and progression of the disease. Material and Methods: To do this, an online multicenter documentation system was introduced to facilitate the establishment of a prospective multicenter case-control study, the IEEP (International Endometriosis Evaluation Program) study. We report here on the first 696 patients with endometriosis included in the program between June 2013 and June 2015. Results: A documentation system was created, and the structure and course of the study were mapped out with regard to data collection and the collection of biomaterials. Conclusion: The documentation system permits the history and clinical data of patients with endometriosis to be recorded. The IEEP combines this information with biomaterials and uses it for scientific studies. The recorded data can also be used to evaluate clinical quality control measures such as the certification parameters used by the EEL (European Endometriosis League) to assess certified endometriosis centers. PMID:27582581

  14. Bleeding Ureter: Endometriosis Mascarading as a Ureteral Malignancy - A Case Report

    PubMed Central

    Sandeep, Puvvada; Pathade, Amey; Nagaraj, H K

    2014-01-01

    Ureteral endometriosis is a serious localization of disease burden that can lead to urinary tract obstruction, with subsequent hydroureter, hydronephrosis, and potential kidney loss. As the diagnosis is elusive, a heavy clinical suspicion is necessary. Surgical technique to treatment varies, but the goal is to salvage renal function and decrease disease burden. Here, we are presenting a rare case of bleeding ureter in a young lady who had endometriosis of the ureter. PMID:25478397

  15. Ectopic endometrium-derived leptin produces estrogen-dependent chronic pain in a rat model of endometriosis.

    PubMed

    Alvarez, P; Bogen, O; Chen, X; Giudice, L C; Levine, J D

    2014-01-31

    Endometriosis pain is a very common and extremely disabling condition whose mechanism is still poorly understood. While increased levels of leptin have been reported in patients with endometriosis, their contribution to endometriosis pain has not been explored. Using a rodent model of endometriosis we provide evidence for an estrogen-dependent contribution of leptin in endometriosis-induced pain. Rats implanted with autologous uterine tissue onto the gastrocnemius muscle developed endometriosis-like lesions and local chronic pain. Compared to eutopic uterine tissue, leptin mRNA and protein were up-regulated in the endometriosis-like lesions. Intramuscular injection of recombinant leptin in naive rats produced dose-dependent local mechanical hyperalgesia and nociceptor sensitization to mechanical stimulation. Ovariectomy attenuated the mechanical hyperalgesia induced by recombinant leptin, in rats treated with vehicle compared to those treated with 17β-estradiol replacement, at 1 and 24 h after leptin injection. Finally, intralesional injections of a pegylated leptin receptor (Ob-R) antagonist or of an inhibitor of Janus kinase2, which transduces the Ob-R signal, markedly attenuated pain in the endometriosis model. Taken together these data support the hypothesis that leptin, generated in ectopic endometrial lesions produces mechanical hyperalgesia by acting on nociceptors innervating the lesion. This sensitivity to leptin is dependent on estrogen levels. Thus, interventions targeting leptin signaling, especially in combination with interventions that lower estrogen levels, might be useful for the treatment of endometriosis pain. PMID:24239717

  16. Supporting evidences for potential biomarkers of endometriosis detected in peripheral blood☆

    PubMed Central

    Signorile, Pietro G.; Baldi, Alfonso

    2015-01-01

    Incidence of endometriosis is very high in women in the reproductive age (around 10%). To date, a reliable non-invasive diagnostic test for early diagnosis of endometriosis is not available. In this article we describe the potential value as diagnostic markers for endometriosis of two proteins (serum albumin and complement C3 precursor), previously identified as differentially expressed in women with endometriosis respect to healthy control by 2D gel analysis. A detailed description of the results obtained with this proteomic approach can be found in Signorile and Baldi [1]. ELISAs were performed on a large cohort of endometriosis (n=100) and healthy patients (n=10) to establish the differential expression of the identified proteins. ROC analyses confirmed the statistical significance of the differential expression of these proteins: serum albumin (p=0.028) ad complement C3 precursor (p=0.082). Evaluation of these two proteins, together with the already described Zn-alpha2-glycoprotein [1], could help in the early identification of endometriosis patients PMID:26759817

  17. Rectal obstruction due to endometriosis: A case report and review of the Japanese literature

    PubMed Central

    Ono, Hiromi; Honda, Shohei; Danjo, Yasushi; Nakamura, Kenji; Okabe, Mihiro; Kimura, Takashi; Kawakami, Masato; Nagashima, Kimimoto; Nishihara, Hiroshi

    2014-01-01

    INTRODUCTION Colorectal obstructive endometriosis is relatively rare in Japan and its differentiation from malignancy is often difficult. We report a case of rectal obstructive endometriosis. PRESENTATION OF CASE A 37-year-old woman was referred to our hospital with a suspected ileus. Her chief symptoms were left lower abdominal pain and vomiting. Colonoscopy showed an intraluminal mass of redness in the upper rectum. A proctectomy was performed because of the bowel obstruction. The rectum was filled with an intraluminal mass measuring 5 cm × 4 cm, and endometriosis was diagnosed pathologically. DISCUSSION A preoperative diagnosis of colorectal obstructive endometriosis is often difficult because of the lack of definite diagnostic, clinical, sonographic, or radiological findings that are characteristic of this disease. Medical treatment is not always effective for colorectal obstructive endometriosis, and surgery is often performed. CONCLUSION Colorectal obstructive endometriosis should be considered as a differential diagnosis in cases of various gastrointestinal symptoms in women who are of reproductive age. PMID:25462048

  18. Interstitial Cystitis and Endometriosis in Patients With Chronic Pelvic Pain: The “Evil Twins” Syndrome

    PubMed Central

    Chung, Rosemary P.; Gordon, David

    2005-01-01

    Objective: To determine the prevalence of interstitial cystitis and endometriosis in patients with chronic pelvic pain. Methods: A prospective analysis was conducted in 178 women with CPP who presented with bladder base/anterior vaginal wall and/or uterine tenderness, with or without irritative voiding symptoms. The Potassium Sensitivity Test was used to assess bladder epithelial dysfunction. Patients were evaluated with concurrent laparoscopy and cystoscopy with hydrodistention. Results: Laparoscopic findings among the 178 patients with chronic pelvic pain supported a diagnosis of endometriosis in 134 (75%) patients, and cystoscopy confirmed a diagnosis of interstitial cystitis in 159 (89%) patients. Both interstitial cystitis and endometriosis were diagnosed in 115 patients (65%). The Potassium Sensitivity Test was positive in 146 (82%) patients, with 140 (96%) of these patients diagnosed with interstitial cystitis and 105 (72%) with endometriosis. Conclusions: Results of this prospective study show that interstitial cystitis and endometriosis may frequently coexist in patients with chronic pelvic pain. A positive Potassium Sensitivity Test accurately predicted the presence of interstitial cystitis in 96% of these patients with chronic pelvic pain, as confirmed by cystoscopic hydrodistention. It is necessary to consider the diagnosis of endometriosis and interstitial cystitis concurrently in the evaluation of patients with chronic pelvic pain to avoid unnecessary delay in identifying either condition. PMID:15791965

  19. Association of the neutrophil-to-lymphocyte ratio and CA 125 with the endometriosis score

    PubMed Central

    Kim, Seul Ki; Park, Jung Yeon; Suh, Chang Suk; Kim, Seok Hyun

    2014-01-01

    Objective To evaluate the association between the severity of endometriosis and the preoperative neutrophil-to-lymphocyte ratio (NLR) and serum level of cancer antigen 125 (CA 125). Methods Data were obtained from the medical records of 419 patients who underwent laparoscopic conservative surgery for ovarian endometrioma between April 2005 and March 2013. Each patient's preoperative complete blood count was recorded and the endometriosis score was assessed. Results The endometriosis score was not associated with either the NLR or the serum level of CA 125. The endometriosis score was negatively related to preoperative hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration. The only positive association was between NLR and the patients' age. NLR and preoperative serum anti-Müllerian hormone level were found to be negatively related. Conclusion The severity of endometriosis was not associated with the serum level of CA 125 or the NLR. The presence of a negative correlation between the severity of endometriosis and red blood cell dynamics needs further investigation. PMID:25599037

  20. Estradiol promotes cells invasion by activating β-catenin signaling pathway in endometriosis

    PubMed Central

    Xiong, Wenqian; Zhang, Ling; Yu, Lan; Xie, Wei; Man, Yicun; Xiong, Yao; Liu, Hengwei; Liu, Yi

    2015-01-01

    Endometriosis is an estrogen-dependent disease that involves the adhesion, invasion, and angiogenesis of endometrial tissues outside of the uterine cavity. We hypothesized that a link exists between estrogen and beta-catenin (β-catenin) signaling in the pathogenesis of endometriosis. Human endometrial stromal cells (HESCs) were separated from eutopic endometrial tissues that were obtained from patients with endometriosis. β-catenin expression and cells invasiveness ability were up-regulated by 17β-estradiol (E2) in an estrogen receptor (ESR)-dependent manner, whereas β-catenin siRNA abrogated this phenomenon. Moreover, co-immunoprecipitation and dual immunofluorescence studies confirmed ESR1, β-catenin, and lymphoid enhancer factor 1/T cell factor 3 co-localization in the nucleus in HESCs after E2 treatment. To determine the role of β-catenin signaling in the implantation of ectopic endometrium, we xenotransplanted eutopic endometrium from endometriosis patients into ovariectomized severe combined immunodeficiency mice. The implantation of the endometrium was suppressed by β-catenin siRNA. Collectively, studies regarding β-catenin signaling are critical for improving our understanding of the pathogenesis of estrogen-induced endometriosis, which can translate into the development of treatments and therapeutic strategies for endometriosis. PMID:26432349

  1. Altered expression of progesterone receptor isoforms A and B in human eutopic endometrium in endometriosis patients.

    PubMed

    Wölfler, Monika Martina; Küppers, Mareike; Rath, Werner; Buck, Volker Uwe; Meinhold-Heerlein, Ivo; Classen-Linke, Irmgard

    2016-07-01

    Recent data implicate an altered expression of progesterone receptor isoform A (PR-A) and B (PR-B) in the endometrium of endometriosis patients. This prospective exploratory study aimed to precisely determine the PR-A and PR-B expression using immunohistochemical techniques in eutopic endometrium of women with endometriosis compared with disease-free women throughout the menstrual cycle. All symptomatic patients underwent laparoscopy for the diagnosis of endometriosis and histological confirmation of the disease (EO) whereas controls were proven disease-free (CO). In CO samples (n=10) an increased expression of PR-A and PR-B during the proliferative to early secretory phase and a decreased expression of both receptor isoforms during the mid to late secretory phase was ascertained in accordance with previous studies. In patients with endometriosis (n=16) no cycle dependent pattern of PR-A and PR-B expression was identified in contrast to patients without endometriosis. Moreover, in EO samples a huge variety of inter- and intra-individual differences in PR-A and PR-B expression were detected. These data provide further evidence that dysregulation of the PR-A and PR-B expression might contribute to the pathophysiology of endometriosis. PMID:27050108

  2. Beyond Endometriosis Genome-Wide Association Study: From Genomics to Phenomics to the Patient.

    PubMed

    Zondervan, Krina T; Rahmioglu, Nilufer; Morris, Andrew P; Nyholt, Dale R; Montgomery, Grant W; Becker, Christian M; Missmer, Stacey A

    2016-07-01

    Endometriosis is a heritable, complex chronic inflammatory disease, for which much of the causal pathogenic mechanism remains unknown. Genome-wide association studies (GWAS) to date have identified 12 single nucleotide polymorphisms at 10 independent genetic loci associated with endometriosis. Most of these were more strongly associated with revised American Fertility Society stage III/IV, rather than stage I/II. The loci are almost all located in intergenic regions that are known to play a role in the regulation of expression of target genes yet to be identified. To identify the target genes and pathways perturbed by the implicated variants, studies are required involving functional genomic annotation of the surrounding chromosomal regions, in terms of transcription factor binding, epigenetic modification (e.g., DNA methylation and histone modification) sites, as well as their correlation with RNA transcription. These studies need to be conducted in tissue types relevant to endometriosis-in particular, endometrium. In addition, to allow biologically and clinically relevant interpretation of molecular profiling data, they need to be combined and correlated with detailed, systematically collected phenotypic information (surgical and clinical). The WERF Endometriosis Phenome and Biobanking Harmonisation Project is a global standardization initiative that has produced consensus data and sample collection protocols for endometriosis research. These now pave the way for collaborative studies integrating phenomic with genomic data, to identify informative subtypes of endometriosis that will enhance understanding of the pathogenic mechanisms of the disease and discovery of novel, targeted treatments. PMID:27513026

  3. Various anatomic locations of surgically proven endometriosis: A single-center experience

    PubMed Central

    Lee, Hyun Ju; Park, Ye Mi; Kim, Yong Beom; Suh, Chang Suk

    2015-01-01

    Objective To report the various anatomic locations of surgically and pathologically proven endometriosis. Methods Pathologic reports (n=1,376) of women who underwent surgeries at a single center between April 2005 and March 2013 were retrieved from the electronic medical record system of the hospital. Pathologic reports were included after performing a search by using the key-words "endometrial cyst," "endometriotic cyst," "endometriosis," or "endometrioma." Only reports dealing with female patients were selected, and the pathologic reports of 1,350 women (1,374 surgery cases) were included in the analysis. Results The predominant location of endometriosis was the ovaries (96.4%), followed by the soft tissue (2.8%), gastrointestinal tract (0.3%) and urinary tract (0.2%). Laparoscopic surgery was the major surgical technique used for the pelvic endometriosis (89.2%). Adrenal gland endometriosis was found in a 55-year-old woman. Conclusion We established the various anatomic locations of surgically and pathologically proven endometriosis in Korean women. PMID:25629019

  4. Decreased Cytotoxicity of Peripheral and Peritoneal Natural Killer Cell in Endometriosis

    PubMed Central

    Jeung, InCheul; Cheon, Keunyoung; Kim, Mee-Ran

    2016-01-01

    Endometriosis causes significant chronic pelvic pain, dysmenorrhea, and infertility and affects 10% of all women. In endometriosis, ectopic endometrium surviving after retrograde menstruation exhibits an abnormal immune response characterized by increased levels of activated macrophages and inflammatory cytokines. Particularly, dysfunctional natural killer (NK) cells play an important role in the pathogenesis of the disease by either facilitating or inhibiting the survival, implantation, and proliferation of endometrial cells. NK cells in the peritoneum and peritoneal fluid exhibit reduced levels of cytotoxicity in women with endometriosis. Several cytokines and inhibitory factors in the serum and peritoneal fluid also dysregulate NK cell cytotoxicity. Additionally, increased numbers of immature peripheral NK cells and induction of NK cell apoptosis are evident in the peritoneal fluid of women with endometriosis. The high rate of endometriosis recurrence after pharmaceutical or surgical treatment, which is associated with dysfunctional NK cells, indicates that new immunomodulatory management strategies are required. A good understanding of immune dysfunction would enable improvement of current treatments for endometriosis. PMID:27294113

  5. Prevention of the recurrence of symptom and lesions after conservative surgery for endometriosis.

    PubMed

    Koga, Kaori; Takamura, Masashi; Fujii, Tomoyuki; Osuga, Yutaka

    2015-10-01

    Although surgical excision of endometriosis both improves pain and enhances fertility, recurrence can further exacerbate pain and reduce fertility, which in turn impacts the quality of life and increases personal as well as social costs. Therefore, it is crucial to prevent the recurrence of symptoms and lesions after conservative surgery. This article reviews evidence regarding the prevention of postoperative recurrence of endometriosis reported since the 1990s. Over the past 5 years, many new studies have been conducted and have demonstrated that long-term postoperative medication markedly reduces the recurrence. Most of these studies used oral contraceptives (OC), with either the cyclic or continuous regimen, while some used oral or intrauterine progestin. Continuous OC is more efficacious than cyclic OC, especially for dysmenorrhea. The levonorgestrel-releasing intrauterine system is also shown to prevent recurrence of dysmenorrhea and possibly endometriosis lesions. Dienogest, a new progestin, is shown to reduce the recurrence of endometrioma. Similar to the case of ovarian endometriosis, long-term postoperative medication after conservative surgery for deep infiltrating or extragenital endometriosis seems important, although data are limited. Regardless of the lesion and the medication type, patients who discontinued medication experienced a higher incidence of recurrence, indicating that the protective effect of these medications seems to vanish rapidly after the discontinuation. On the basis of these facts, together with the pathogenesis of recurrence (retrograde menstruation and ovulation), regular and prolonged medication until the patient wishes to conceive is highly recommended to prevent the postoperative recurrence of endometriosis. PMID:26354093

  6. Reduced connexin 43 in eutopic endometrium and cultured endometrial stromal cells from subjects with endometriosis

    PubMed Central

    Yu, Jie; Boicea, Anisoara; Barrett, Kara L.; James, Christopher O.; Bagchi, Indrani C.; Bagchi, Milan K.; Nezhat, Ceana; Sidell, Neil; Taylor, Robert N.

    2014-01-01

    Accumulating evidence indicates that reduced fecundity associated with endometriosis reflects a failure of embryonic receptivity. Microdomains composed of endometrial gap junctions, which facilitate cell–cell communication, may be implicated. Pharmacological or genetic inhibition of connexin (Cx) 43 block human endometrial cell differentiation in vitro and conditional uterine deletion of Cx43 alleles cause implantation failure in mice. The aim of this study was to determine whether women with endometriosis have reduced eutopic endometrial Cx43. Cx26 acted as a control. Endometrial biopsies were collected from age, race and cycle phase-matched women without (15 controls) or with histologically confirmed endometriosis (15 cases). Immunohistochemistry confirmed a predominant localization of Cx43 in the endometrial stroma, whereas Cx26 was confined to the epithelium. Cx43 immunostaining was reduced in eutopic biopsies of endometriosis subjects and western blotting of tissue lysates confirmed lower Cx43 levels in endometriosis cases, with Cx43/β-actin ratios =3.4 ± 1.5 in control and =1.2 ± 0.3 in endometriosis biopsies (P < 0.01). When endometrial stromal cells (ESC) were isolated from endometriosis cases, Cx43 levels and scrape loading-dye transfer were reduced by ∼45% compared with ESC from controls. In vitro decidualization of ESC derived from endometriosis versus control subjects resulted in lesser epithelioid transformation and a significantly reduced up-regulation of Cx43 protein (1.2 ± 0.2- versus 1.7 ± 0.4-fold, P < 0.01). No changes in Cx26 were observed. While basal steady-state levels of Cx43 mRNA did not differ with respect to controls, ESC from endometriosis cases failed to manifest a response to hormone treatment in vitro. In summary, eutopic endometrial Cx43 concentrations in endometriosis cases were <50% those of controls in vivo and in vitro, functional gap junctions were reduced and hormone-induced Cx43 mRNA levels were blunted. PMID:24270393

  7. Surgery for endometriosis-associated infertility: do we exaggerate the magnitude of effect?

    PubMed Central

    Rizk, B.; Turki, R.; Lotfy, H.; Ranganathan, S.; Zahed, H.; Freeman, A.R.; Shilbayeh, Z.; Sassy, M.; Shalaby, M.; Malik, R.

    2015-01-01

    Objective: Surgery remains the mainstay in the diagnosis and management of endometriosis. The number of surgeries performed for endometriosis worldwide is ever increasing, however do we have evidence for improvement of infertility after the surgery and do we exaggerate the magnitude of effect of surgery when we counsel our patients? The management of patients who failed the surgery could be by repeat surgery or assisted reproduction. What evidence do we have for patients who fail assisted reproduction and what is their best chance for achieving pregnancy? Material and methods: In this study we reviewed the evidence-based practice pertaining to the outcome of surgery assisted infertility associated with endometriosis. Manuscripts published in PubMed and Science Direct as well as the bibliography cited in these articles were reviewed. Patients with peritoneal endometriosis with mild and severe disease were addressed separately. Patients who failed the primary surgery and managed by repeat or assisted reproduction technology were also evaluated. Patients who failed assisted reproduction and managed by surgery were also studied to determine of the best course of action. Results: In patients with minimal and mild pelvic endometriosis, excision or ablation of the peritoneal endometriosis increases the pregnancy rate. In women with severe endometriosis, controlled trials suggested an improvement of pregnancy rate. In women with ovarian endometrioma 4 cm or larger ovarian cystectomy increases the pregnancy rate, decreases the recurrence rate, but is associated with decrease in ovarian reserve. In patients who have failed the primary surgery, assisted reproduction appears to be significantly more effective than repeat surgery. In patients who failed assisted reproduction, the management remains to be extremely controversial. Surgery in expert hands might result in significant improvement in pregnancy rate. Conclusion: In women with minimal and mild endometriosis, surgical

  8. Thoracic Endometriosis-A Rare Cause of Haemoptysis

    PubMed Central

    Alwadhi, Seema; Chaudhary, Bhupendra; Gehlot, Kirti

    2016-01-01

    Thoracic endometriosis is a rare condition and occurs in females of reproductive age due to the presence of active endometrial tissue in tracheobronchial tree, lung parenchyma and lung pleura. A typical history of haemoptysis during menstrual periods and strong suspicion of the disease entity is important for the diagnosis and management of the case. Diagnosis of the disease is usually delayed. Serial CT thorax during menstrual period and in non-menstrual period supports the diagnosis. We present here a case of catamenial haemoptysis. The diagnosis was missed initially but later a detailed clinical history revealed the same. Serial computed tomography of thorax taken during menstrual and after menstrual period supported the diagnosis. Though bronchoscopy was able to reveal hyperemic tissue in the tracheobronchial tree, bronchial washing was inconclusive. The patient was treated successfully with danazol. PMID:27190915

  9. [Essential data set's archetypes for nursing care of endometriosis patients].

    PubMed

    Spigolon, Dandara Novakowski; Moro, Claudia Maria Cabral

    2012-12-01

    This study aimed to develop an Essential Data Set for Nursing Care of Patients with Endometriosis (CDEEPE), represented by archetypes. An exploratory applied research with specialists' participation that was carried out at Heath Informatics Laboratory of PUCPR, between February and November of 2010. It was divided in two stages: CDEEPE construction and evaluation including Nursing Process phases and Basic Human Needs, and archetypes development based on this data set. CDEEPE was evaluated by doctors and nurses with 95.9% of consensus and containing 51 data items. The archetype "Perception of Organs and Senses" was created to represents this data set. This study allowed identifying important information for nursing practices contributing to computerization and application of nursing process during care. The CDEEPE was the basis for archetype creation, that will make possible structured, organized, efficient, interoperable, and semantics records. PMID:23596913

  10. Genome-wide enrichment analysis between endometriosis and obesity-related traits reveals novel susceptibility loci

    PubMed Central

    Rahmioglu, Nilufer; Macgregor, Stuart; Drong, Alexander W.; Hedman, Åsa K.; Harris, Holly R.; Randall, Joshua C.; Prokopenko, Inga; Nyholt, Dale R.; Morris, Andrew P.; Montgomery, Grant W.; Missmer, Stacey A.; Lindgren, Cecilia M.; Zondervan, Krina T.

    2015-01-01

    Endometriosis is a chronic inflammatory condition in women that results in pelvic pain and subfertility, and has been associated with decreased body mass index (BMI). Genetic variants contributing to the heritable component have started to emerge from genome-wide association studies (GWAS), although the majority remain unknown. Unexpectedly, we observed an intergenic locus on 7p15.2 that was genome-wide significantly associated with both endometriosis and fat distribution (waist-to-hip ratio adjusted for BMI; WHRadjBMI) in an independent meta-GWAS of European ancestry individuals. This led us to investigate the potential overlap in genetic variants underlying the aetiology of endometriosis, WHRadjBMI and BMI using GWAS data. Our analyses demonstrated significant enrichment of common variants between fat distribution and endometriosis (P = 3.7 × 10−3), which was stronger when we restricted the investigation to more severe (Stage B) cases (P = 4.5 × 10−4). However, no genetic enrichment was observed between endometriosis and BMI (P = 0.79). In addition to 7p15.2, we identify four more variants with statistically significant evidence of involvement in both endometriosis and WHRadjBMI (in/near KIFAP3, CAB39L, WNT4, GRB14); two of these, KIFAP3 and CAB39L, are novel associations for both traits. KIFAP3, WNT4 and 7p15.2 are associated with the WNT signalling pathway; formal pathway analysis confirmed a statistically significant (P = 6.41 × 10−4) overrepresentation of shared associations in developmental processes/WNT signalling between the two traits. Our results demonstrate an example of potential biological pleiotropy that was hitherto unknown, and represent an opportunity for functional follow-up of loci and further cross-phenotype comparisons to assess how fat distribution and endometriosis pathogenesis research fields can inform each other. PMID:25296917

  11. Surgical History and the Risk of Endometriosis: A Hospital-Based Case-Control Study.

    PubMed

    Liu, Xishi; Long, Qiqi; Guo, Sun-Wei

    2016-09-01

    Women tend to receive more surgical procedures than men. Our mouse study shows that surgical stress promotes the development of endometriosis. This study was undertaken to test the hypothesis that surgery increases the risk of endometriosis. We recruited 208 patients with ovarian endometrioma and 212 age-matched patients with ovarian teratoma and retrieved information on the history of any surgical procedures after menarche, grouped by laparotomy, laparoscopy, gynecologically related procedures, cesarean section, and surgeries performed on torso and extremities was recorded. We then evaluated the association, if any, between endometriosis and history of surgical procedures. Cases and controls were comparable with respect to age, marital status, education level, and occupation. Eleven (5.3%) cases had laparotomy before the index surgery while 4 (1.9%) controls did. Sixty-six (31.7%) cases had Cesarean section while 53 (25.0%) controls did. Multivariate analysis identified age, at the index surgery laparotomy, and cesarean section as 3 factors positively associated with the risk of endometriosis while parity was found to be negatively associated with the risk. Laparotomy was associated with increased risk of endometriosis (odds ratio [OR] = 3.64, 95% confidence interval [CI] = 1.08-12.31), while cesarean section was associated with 2-fold increase in risk (OR = 2.16, 95% CI = 1.31-3.55). Both laparotomy and cesarean section may increase the risk of endometriosis probably by activation of adrenergic signaling, thus facilitating angiogenesis and accelerating the growth of endometriotic lesions that are already in existence. This finding may have important ramifications for the perioperative management of patients with increased risk or recurrence risk of endometriosis. PMID:26919976

  12. Dienogest reduces HSD17β1 expression and activity in endometriosis.

    PubMed

    Mori, Taisuke; Ito, Fumitake; Matsushima, Hiroshi; Takaoka, Osamu; Koshiba, Akemi; Tanaka, Yukiko; Kusuki, Izumi; Kitawaki, Jo

    2015-05-01

    Endometriosis is an estrogen-dependent disease. Abnormally biosynthesized estrogens in endometriotic tissues induce the growth of the lesion and worsen endometriosis-associated pelvic pain. Dienogest (DNG), a selective progesterone receptor agonist, is widely used to treat endometriosis and efficiently relieves the symptoms. However, its pharmacological action remains unknown. In this study, we elucidated the effect of DNG on enzymes involved in local estrogen metabolism in endometriosis. Surgically obtained specimens of 23 ovarian endometriomas (OE) and their homologous endometrium (EE), ten OE treated with DNG (OE w/D), and 19 normal endometria without endometriosis (NE) were analyzed. Spheroid cultures of stromal cells (SCs) were treated with DNG and progesterone. The expression of aromatase, 17β-hydroxysteroid dehydrogenase 1 (HSD17β1), HSD17β2, HSD17β7, HSD17β12, steroid sulfatase (STS), and estrogen sulfotransferase (EST) was evaluated by real-time quantitative PCR. The activity and protein level of HSD17β1 were measured with an enzyme assay using radiolabeled estrogens and immunohistochemistry respectively. OESCs showed increased expression of aromatase, HSD17β1, STS, and EST, along with decreased HSD17β2 expression, when compared with stromal cells from normal endometria without endometriosis (NESCs) (P<0.01) or stromal cells from homologous endometrium (EESCs) (P<0.01). In OESCs, DNG inhibited HSD17β1 expression and enzyme activity at 10(-7) M (P<0.01). Results of immunohistochemical analysis displayed reduced HSD17β1 staining intensity in OE w/D (P<0.05). In conclusion, DNG exerts comprehensive inhibition of abnormal estrogen production through inhibition of aromatase and HSD17β1, contributing to a therapeutic effect of DNG on endometriosis. PMID:25767055

  13. Role of Nociceptor Estrogen Receptor GPR30 in a Rat Model of Endometriosis Pain

    PubMed Central

    Alvarez, Pedro; Bogen, Oliver; Levine, Jon D.

    2014-01-01

    Endometriosis, the most common cause of chronic pelvic pain, is an estrogen-dependent disease in which classic estrogen receptors (ERα, ERβ) play an important role. While recent evidence suggests that the novel G protein-coupled estrogen receptor (GPR30) also plays a key role in the progression of endometriosis, whether it is also involved in endometriosis pain is still unknown. Here we tested the hypothesis that GPR30 expressed by nociceptors contributes to endometriosis pain. Intramuscular injection of the GPR30 agonists raloxifene or 17β-estradiol produced a fast-onset, persistent, mechanical hyperalgesia at the site of the injection. Intrathecal antisense (AS) oligodeoxynucleotides (ODN), but not mismatch (MM) ODN, targeting mRNA for GPR30 markedly inhibited its protein expression in nociceptors and attenuated the mechanical hyperalgesia induced by local raloxifene or 17β-estradiol. Pre-treatment with the GPR30 antagonist G-36 also inhibited the hyperalgesia induced by raloxifene or 17β-estradiol, in naïve control rats. Surgical implant of autologous uterine tissue onto the gastrocnemius muscle, which induces endometriosis-like lesions, produced local mechanical hyperalgesia. Intrathecal AS, but not MM, ODN targeting GPR30 mRNA reversibly inhibited the mechanical hyperalgesia at the site of endometriotic lesions. Finally, intralesional injection of the GPR30 antagonist G-36 also inhibited the mechanical hyperalgesia at the site of ectopic uterine tissue. We conclude that local GPR30 agonists produce persistent mechanical hyperalgesia in naïve female rats, whereas local GPR30 antagonists inhibit mechanical hyperalgesia in a model of endometriosis pain. Thus, GPR30 expressed by nociceptors innervating ectopic uterine lesions might play a major role in endometriosis pain. PMID:25280432

  14. 1H NMR- based metabolomics approaches as non- invasive tools for diagnosis of endometriosis

    PubMed Central

    Ghazi, Negar; Arjmand, Mohammad; Akbari, Ziba; Mellati, Ali Owsat; Saheb-Kashaf, Hamid; Zamani, Zahra

    2016-01-01

    Background: So far, non-invasive diagnostic approaches such as ultrasound, magnetic resonance imaging, or blood tests do not have sufficient diagnostic power for endometriosis disease. Lack of a non-invasive diagnostic test contributes to the long delay between onset of symptoms and diagnosis of endometriosis. Objective: The present study focuses on the identification of predictive biomarkers in serum by pattern recognition techniques and uses partial least square discriminant analysis, multi-layer feed forward artificial neural networks (ANNs) and quadratic discriminant analysis (QDA) modeling tools for the early diagnosis of endometriosis in a minimally invasive manner by 1H- NMR based metabolomics. Materials and Methods: This prospective cohort study was done in Pasteur Institute, Iran in June 2013. Serum samples of 31 infertile women with endometriosis (stage II and III) who confirmed by diagnostic laparoscopy and 15 normal women were collected and analyzed by nuclear magnetic resonance spectroscopy. The model was built by using partial least square discriminant analysis, QDA, and ANNs to determine classifier metabolites for early prediction risk of disease. Results: The levels of 2- methoxyestron, 2-methoxy estradiol, dehydroepiandrostion androstendione, aldosterone, and deoxy corticosterone were enhanced significantly in infertile group. While cholesterol and primary bile acids levels were decreased. QDA model showed significant difference between two study groups. Positive and negative predict value levels obtained about 71% and 78%, respectively. ANNs provided also criteria for detection of endometriosis. Conclusion: The QDA and ANNs modeling can be used as computational tools in noninvasive diagnose of endometriosis. However, the model designed by QDA methods is more efficient compared to ANNs in diagnosis of endometriosis patients. PMID:27141542

  15. Alteration in the intrafollicular thiol-redox system in infertile women with endometriosis.

    PubMed

    Choi, Young Sik; Cho, SiHyun; Seo, Seok Kyo; Park, Joo Hyun; Kim, Seok Hyun; Lee, Byung Seok

    2015-02-01

    The aim of this study was to compare intrafollicular biomarkers of thiol-redox system and chronic inflammation in infertile patients with and without endometriosis, and examine correlations between biomarkers and IVF outcomes. The study included 65 patients receiving IVF: 31 patients with endometriosis vs 34 patients without endometriosis. Follicular fluid (FF) was obtained from a single-dominant follicle during oocyte retrieval and stored at -70 °C. Malondialdehyde, superoxide dismutase, glutathione (GSH), glutathione peroxidase 3 (GPX3), thioredoxin (TRX), TRX-binding protein 2 (TBP2), and peroxiredoxin-4 levels were measured in the FF samples by ELISAs as biomarkers of oxidative stress. The inflammatory cytokines interleukin 1 beta (IL1β), IL6, IL8, and tumor-necrosis factor alpha (TNFα) were also measured by ELISAs. GSH levels were significantly lower in the endometriosis group compared with the controls. TBP2 levels were significantly higher in the endometriosis group. IL6, IL8, and TNFα levels were significantly higher in the endometriosis group. The levels of all of the inflammatory cytokines positively correlated with the levels of TRX. GSH levels positively correlated with the number of high-quality embryos. GPX3 and TRX levels negatively correlated with the percentage of mature oocytes. TNFα levels negatively correlated with the cumulative embryo score per embryo. Logistic regression analysis revealed that the number of high-quality embryos was an independent factor predicting clinical pregnancy. In conclusion, there may be an imbalance in the thiol-redox system and increased levels of inflammatory cytokines in the intrafollicular microenvironment of infertile patients with endometriosis, which may affect the qualities of the oocyte and embryo. PMID:25376627

  16. Surgical treatment of deep infiltrating rectal endometriosis: in favor of less aggressive surgery.

    PubMed

    Darwish, Basma; Roman, Horace

    2016-08-01

    Deep infiltrating endometriosis of the rectum is a severe disease concerning young women of reproductive age. Because it is a benign condition, aggressive surgical treatment and subsequent complications are not always accepted by young patients. Two surgical approaches exist: the radical approach, employing colorectal resection; and the conservative approach, based on rectal shaving or full-thickness disc excision. At present, the majority of patients with rectal endometriosis worldwide are managed by the radical approach. Conversely, as high as 66% of patients with colorectal endometriosis can be managed by either rectal shaving or full-thickness disc excision. Most arguments that used to support the large use of the radical approach may now be disputed. The presumed higher risk of recurrence related to conservative surgery can be balanced by a supposed higher risk of postoperative bowel dysfunction related to the radical approach. Bowel occult microscopic endometriosis renders debatable the hypothesis that more aggressive surgery can definitively cure endometriosis. Although most surgeons consider that radical surgery is unavoidable in patients with rectal nodules responsible for digestive stenosis, conservative surgery can be successfully performed in a majority of cases. In multifocal bowel endometriosis, multiple conservative procedures may be proposed, provided that the nodules are separated by segments of healthy bowel of longer than 5 cm. Attempting conservation of a maximum length of rectum may reduce the risk of postoperative anterior rectal resection syndrome and subsequent debilitating bowel dysfunction and impaired quality of life. Promotion of less aggressive surgery with an aim to better spare organ function has become a general tendency in both oncologic and benign pathologies; thus the management of deep colorectal endometriosis should logically be concerned, too. PMID:26851598

  17. Endometriosis Might Be Inversely Associated with Developing Chronic Kidney Disease: A Population-Based Cohort Study in Taiwan.

    PubMed

    Huang, Ben-Shian; Chang, Wen-Hsun; Wang, Kuan-Chin; Huang, Nicole; Guo, Chao-Yu; Chou, Yiing-Jen; Huang, Hsin-Yi; Chen, Tzeng-Ji; Lee, Wen-Ling; Wang, Peng-Hui

    2016-01-01

    This study was conducted to determine the risk of chronic kidney disease (CKD) among women with endometriosis in Taiwan. We conducted a retrospective cohort study using the National Health Insurance Research Database of Taiwan. A total of 27,973 women with a diagnosis of endometriosis and 27,973 multivariable-matched controls (1:1) from 2000 to 2010 were selected. Cox regression and computed hazard ratios (HR) with 95% confidence intervals (95% CI) were used to determine the risk of CKD among women with endometriosis. The incidence rates (IR, per 10,000 person-years) of CKD among women with and without endometriosis were 4.64 and 7.01, respectively, with a significantly decreased risk of CKD (crude HR 0.65, 95% CI 0.53-0.81; adjusted HR 0.69, 95% CI 0.56-0.86) among women with endometriosis. The IR of CKD progressively increased with age, but the trend of lower CKD risk among women with endometriosis was consistent. However, the lower risk of CKD in women with endometriosis was no longer statistically significant after adjusting for menopausal status (adjusted HR 0.85, 95% CI 0.65-1.10). The results suggest that endometriosis is inversely associated with CKD, but this effect was mediated by menopause. The possible mechanism of this association is worthy of further evaluation. PMID:27399682

  18. Endometriosis Might Be Inversely Associated with Developing Chronic Kidney Disease: A Population-Based Cohort Study in Taiwan

    PubMed Central

    Huang, Ben-Shian; Chang, Wen-Hsun; Wang, Kuan-Chin; Huang, Nicole; Guo, Chao-Yu; Chou, Yiing-Jen; Huang, Hsin-Yi; Chen, Tzeng-Ji; Lee, Wen-Ling; Wang, Peng-Hui

    2016-01-01

    This study was conducted to determine the risk of chronic kidney disease (CKD) among women with endometriosis in Taiwan. We conducted a retrospective cohort study using the National Health Insurance Research Database of Taiwan. A total of 27,973 women with a diagnosis of endometriosis and 27,973 multivariable-matched controls (1:1) from 2000 to 2010 were selected. Cox regression and computed hazard ratios (HR) with 95% confidence intervals (95% CI) were used to determine the risk of CKD among women with endometriosis. The incidence rates (IR, per 10,000 person-years) of CKD among women with and without endometriosis were 4.64 and 7.01, respectively, with a significantly decreased risk of CKD (crude HR 0.65, 95% CI 0.53–0.81; adjusted HR 0.69, 95% CI 0.56–0.86) among women with endometriosis. The IR of CKD progressively increased with age, but the trend of lower CKD risk among women with endometriosis was consistent. However, the lower risk of CKD in women with endometriosis was no longer statistically significant after adjusting for menopausal status (adjusted HR 0.85, 95% CI 0.65–1.10). The results suggest that endometriosis is inversely associated with CKD, but this effect was mediated by menopause. The possible mechanism of this association is worthy of further evaluation. PMID:27399682

  19. Limited value of pro-inflammatory oxylipins and cytokines as circulating biomarkers in endometriosis - a targeted 'omics study.

    PubMed

    Lee, Yie Hou; Cui, Liang; Fang, Jinling; Chern, Bernard Su Min; Tan, Heng Hao; Chan, Jerry K Y

    2016-01-01

    Endometriosis is a common, complex gynecologic disorder characterized by the presence of endometrial-like tissues at extrauterine sites. Elevation in protein and lipid mediators of inflammation including oxylipins and cytokines within the peritoneum characterize the inflamed pelvic region and may contribute to the survival and growth of displaced endometrial tissues. The presence of a clinically silent but molecularly detectable systemic inflammation in endometriosis has been proposed. Thus, we examined serum oxylipin and immunomodulatory protein levels in 103 women undergoing laparoscopy to evaluate systematically any involvement in systemic pathophysiological inflammation in endometriosis. Oxylipin levels were similar between women with and without endometriosis. Stratification by menstrual phase or severity did not offer any difference. Women with ovarian endometriosis had significantly lower 12-HETE relative to peritoneal endometriosis (-50.7%). Serum oxylipin levels were not associated with pre-operative pain symptoms. Changes to immunomodulatory proteins were minimal, with IL-12(p70), IL-13 and VEGF significantly lower in mild endometriotic women compared to non-endometriotic women (-39%, -54% and -76% respectively). Verification using C-reactive protein as a non-specific marker of inflammation further showed similar levels between groups. The implications of our work suggest pro-inflammatory mediators in the classes studied may have potentially limited value as circulating biomarkers for endometriosis, suggesting of potentially tenuous systemic inflammation in endometriosis. PMID:27193963

  20. Effects of prostaglandin E2 and vascular endothelial growth factor on sperm might lead to endometriosis-associated infertility.

    PubMed

    Lee, Te-Ching; Ho, Han-Chen

    2011-01-01

    Significantly higher levels of prostaglandin E2 and vascular endothelial growth factor were associated with the severity of endometriosis. In this study, pathologic concentrations of prostaglandin E2 and vascular endothelial growth factor found in endometriotic women significantly inhibited sperm motility, acrosome reaction, and sperm-oocyte interaction, which might result in endometriosis-associated subfertility/infertility. PMID:20864099

  1. Pain scoring in endometriosis: entry criteria and outcome measures for clinical trials. Report from the Art and Science of Endometriosis meeting.

    PubMed

    Vincent, Katy; Kennedy, Stephen; Stratton, Pamela

    2010-01-01

    Standardized entry criteria and outcome measures for clinical trials in endometriosis-related pain would facilitate the comparison of trial results and the production of systematic reviews, improving evidence-based practice in this area. This report summarizes the recommendations from an international meeting for these criteria. PMID:18990378

  2. The Risk of Epithelial Ovarian Cancer of Women With Endometriosis May be Varied Greatly if Diagnostic Criteria Are Different

    PubMed Central

    Lee, Wen-Ling; Chang, Wen-Hsun; Wang, Kuan-Chin; Guo, Chao-Yu; Chou, Yiing-Jeng; Huang, Nicole; Huang, Hsin-Yi; Yen, Ming-Shyen; Wang, Peng-Hui

    2015-01-01

    Abstract This article aims to test the hypothesis that the risk of epithelial ovarian cancer (EOC) in women with endometriosis might be changed by enrolling different population. A nationwide 14-year historic cohort study using the National Health Insurance Research Database (NHIRD) of Taiwan and the Registry for Catastrophic Illness Patients was conducted. A total of 239,385 women aged between 20 and 51 years, with at least 1 gynecologic visit after 2000, were analyzed. Cases included women with a diagnosed endometriosis, which was established along a spectrum from at least 1 medical record of endometriosis (recalled endometriosis) to tissue-proved ovarian endometriosis (n = X). Controls included women without any diagnosis of endometriosis (n = 239,385 – X). We used Cox regression, and computed hazard ratios (HRs) with 95% confidence intervals (95% CI) to determine the risk of EOC in patients. The EOC incidence rates (IRs, per 10,000 person-years) of women with endometriosis ranged from 1.90 in women with recalled endometriosis to 18.70 in women with tissue-proved ovarian endometrioma, compared with those women without any diagnosis of endometriosis (0.77–0.89), contributing to crude HRs ranging from 2.59 (95% CI, 2.09–3.21; P < 0.001) to 24.04 (95% CI, 17.48–33.05; P < 0.001). After adjustment for pelvic inflammatory disease, infertility, Charlson co-morbidity index, and age, adjusted HRs were ranged from the lowest of 1.90 (95% CI, 1.51–2.37; P < 0.001) in recalled endometriosis to the highest of 18.57 (95% CI, 13.37–25.79; P < 0.001) in tissue-proved ovarian endometrioma, which was inversely related to the prevalence rate of endometriosis (from the highest of 30.80% in recalled endometriosis to the lowest of 1.54% in tissue-proved ovarian endometrioma). The risk of EOC in women with endometriosis varied greatly by different criteria used. Women with endometriosis might have a more apparently higher risk than those reported

  3. Endometriosis Is Associated With a Shift in MU Opioid and NMDA Receptor Expression in the Brain Periaqueductal Gray.

    PubMed

    Torres-Reverón, Annelyn; Palermo, Karylane; Hernández-López, Anixa; Hernández, Siomara; Cruz, Myrella L; Thompson, Kenira J; Flores, Idhaliz; Appleyard, Caroline B

    2016-09-01

    Studies have examined how endometriosis interacts with the nervous system, but little attention has been paid to opioidergic systems, which are relevant to pain signaling. We used the autotransplantation rat model of endometriosis and allowed to progress for 60 days. The brain was collected and examined for changes in endogenous opioid peptides, mu opioid receptors (MORs), and the N-methyl-d-aspartate subunit receptor (NR1) in the periaqueductal gray (PAG), since both of these receptors can regulate PAG activity. No changes in endogenous opioid peptides in met- and leu-enkephalin or β-endorphin levels were observed within the PAG. However, MOR immunoreactivity was significantly decreased in the ventral PAG in the endometriosis group. Endometriosis reduced by 20% the number of neuronal profiles expressing MOR and reduced by 40% the NR1 profiles. Our results suggest that endometriosis is associated with subtle variations in opioidergic and glutamatergic activity within the PAG, which may have implications for pain processing. PMID:27089914

  4. Common variants upstream of KDR encoding VEGFR2 and in TTC39B associate with endometriosis.

    PubMed

    Steinthorsdottir, Valgerdur; Thorleifsson, Gudmar; Aradottir, Kristrun; Feenstra, Bjarke; Sigurdsson, Asgeir; Stefansdottir, Lilja; Kristinsdottir, Anna M; Zink, Florian; Halldorsson, Gisli H; Munk Nielsen, Nete; Geller, Frank; Melbye, Mads; Gudbjartsson, Daniel F; Geirsson, Reynir T; Thorsteinsdottir, Unnur; Stefansson, Kari

    2016-01-01

    We conducted a genome-wide association scan (GWAS) of endometriosis using 25.5 million sequence variants detected through whole-genome sequencing (WGS) of 8,453 Icelanders and imputed into 1,840 cases and 129,016 control women, followed by testing of associated variants in Danish samples. Here we report the discovery of a new endometriosis susceptibility locus on 4q12 (rs17773813[G], OR=1.28; P=3.8 × 10(-11)), upstream of KDR encoding vascular endothelial growth factor receptor 2 (VEGFR2). The variant correlates with disease severity (P=0.0046) when moderate/severe endometriosis cases are tested against minimal/mild cases. We further report association of rs519664[T] in TTC39B on 9p22 with endometriosis (P=4.8 × 10(-10); OR=1.29). The involvement of KDR in endometriosis risk highlights the importance of the VEGF pathway in the pathogenesis of the disease. PMID:27453397

  5. [Hypothetical link between endometriosis and xenobiotics-associated genetically modified food].

    PubMed

    Aris, A; Paris, K

    2010-12-01

    Endometriosis is an oestrogen-dependent inflammatory disease affecting 10 % of reproductive-aged women. Often accompanied by chronic pelvic pain and infertility, endometriosis rigorously interferes with women's quality of life. Although the pathophysiology of endometriosis remains unclear, a growing body of evidence points to the implication of environmental toxicants. Over the last decade, an increase in the incidence of endometriosis has been reported and coincides with the introduction of genetically modified foods in our diet. Even though assessments of genetically modified food risk have not indicated any hazard on human health, xenobiotics-associated genetically modified food, such as pesticides residues and xenoproteins, could be harmful in the long-term. The "low-dose hypothesis", accumulation and biotransformation of pesticides-associated genetically modified food and the multiplied toxicity of pesticides-formulation adjuvants support this hypothesis. This review summarizes toxic effects (in vitro and on animal models) of some xenobiotics-associated genetically modified food, such as glyphosate and Cry1Ab protein, and extrapolates on their potential role in the pathophysiology of endometriosis. Their roles as immune toxicants, pro-oxidants, endocrine disruptors and epigenetic modulators are discussed. PMID:21111655

  6. Incidence and Estimated Prevalence of Endometriosis and Adenomyosis in Northeast Italy: A Data Linkage Study.

    PubMed

    Morassutto, Caterina; Monasta, Lorenzo; Ricci, Giuseppe; Barbone, Fabio; Ronfani, Luca

    2016-01-01

    Despite being quite frequent and having serious implications in terms of symptomatology and fertility, data on incidence and prevalence of endometriosis and adenomyosis following gold standard definitions are dramatically lacking. The average time from onset of symptoms to diagnosis in industrialized countries still ranges from five to ten years. Using the regional centralized data linkage system, we calculated incidence and prevalence of endometriosis and adenomyosis in the female population of Friuli Venezia Giulia region, Italy, for the years 2011-2013. Cases were defined as new diagnoses from hospital discharge records, following procedures allowing direct visualization for endometriosis and hysterectomy for adenomyosis, with or without histological confirmation. Diagnoses were considered "new" after verifying women had not been diagnosed in the previous ten years. Incidence of endometriosis and adenomyosis in women aged 15-50 years is 0.14%. Prevalence, estimated from incidence, is 2.00%. Adenomyosis, representing 28% of all diagnoses, becomes increasingly prevalent after the age of 50 years. Our results shows how the study of both endometriosis and adenomyosis should not be limited to women of premenopausal age. Further efforts are needed to sensitize women and health professional, and to find new data linkage possibilities to identify undiagnosed cases. PMID:27101396

  7. Profiling of Selected MicroRNAs in Proliferative Eutopic Endometrium of Women with Ovarian Endometriosis

    PubMed Central

    Laudanski, P.; Charkiewicz, R.; Tolwinska, A.; Szamatowicz, J.; Charkiewicz, A.; Niklinski, J.

    2015-01-01

    It has been well documented that aberrant expression of selected microRNAs (miRNAs) might contribute to the pathogenesis of disease. The aim of the present study is to compare miRNA expression by the most comprehensive locked-nucleic acid (LNA) miRNA microarray in eutopic endometrium of patients with endometriosis and control. In the study we recruited 21 patients with endometriosis and 25 were disease-free women. The miRNA expression profiles were determined using the LNA miRNA microarray and validated for selected molecules by real-time PCR. We identified 1198 human miRNAs significantly differentially altered in endometriosis versus control samples using false discovery rate of <5%. However only 136 miRNAs showed differential regulation by fold change of at least 1.3. By the use of selected statistical analysis we obtained 45 potential pathways that might play a role in the pathogenesis of endometriosis. We also found that natural killer cell mediated cytotoxicity pathway was found to be inhibited which is consistent with previous studies. There are several pathways that may be potentially dysregulated, due to abnormal miRNA expression, in eutopic endometrium of patients with endometriosis and in this way contribute to its pathogenesis. PMID:26366419

  8. Pro-inflammatory cytokines for evaluation of inflammatory status in endometriosis

    PubMed Central

    Malutan, Andrei M.; Costin, Nicolae; Ciortea, Razvan; Bucuri, Carmen; Rada, Maria P.; Mihu, Dan

    2015-01-01

    The aim of the study The aim of the study was to investigate the serum pro-inflammatory cytokine profile in patients with diagnosed endometriosis. Material and methods The study included 160 women, who were divided in two study groups (Group I – endometriosis; Group 2 – healthy). We evaluated the serum levels of interleukin (IL)-1β, IL-5, IL-6, IL-7, and IL-12, and of tumour necrosis factor α (TNF-α) with the use of Human Multiplex Cytokine Panels. Results The serum level of IL-1β, IL-6, and TNF-α is significantly higher in women with endometriosis compared to women free of disease, from the control group (mean 10.777, 183.027, and 131.326, respectively, compared to 3.039, 70.043, and 75.285, respectively; p = 0.002, p < 0.001, and p = 0.015, respectively). No significant differences in the serum levels of IL-5 and IL-12 were observed between the studied groups, and IL-7 had a very low detection rate. Conclusions Women with endometriosis have elevated levels of key pro-inflammatory cytokines, i.e. IL-1β, IL-6, and TNF-α. At the same time, IL-1β and IL-6 could be used as predictors for endometriosis. PMID:26155190

  9. Endometriosis: Survey of Current Diagnostic and Therapeutic Options and Latest Research Work

    PubMed Central

    Juhasz-Böss, I.; Laschke, M. W.; Müller, F.; Rosenbaum, P.; Baum, S.; Solomayer, E. F.; Ulrich, U.

    2014-01-01

    Endometriosis is one of the most frequent benign diseases in women of child-bearing age. The main symptoms are chronic upper abdominal pain and infertility. However, the aetiology and pathogenesis of endometriosis are as yet insufficiently clarified. Thus, therapy is mainly symptomatic with laparoscopic surgery being the gold standard. The aim of drug therapy is to achieve a hypo-oestrogenic condition. In cases of severe endometriosis and a desire to have children there is often an indication for assisted reproduction. The present article illustrates almost all current aspects on the diagnosis of and therapy of endometriosis. From the clinical viewpoint, emphasis is placed on the rare cases of deeply infiltrating endometriosis that are, however, accompanied with a high morbidity. Current therapeutic options in cases of infertility are also presented in more detail. Furthermore, special attention is paid to the latest research results from both clinical and basic research fields in order to demonstrate our current knowledge on the pathogenesis and, where possible, potentially related therapeutic options. PMID:25221341

  10. Patients’ and physicians’ descriptions of occurrence and diagnosis of endometriosis: a qualitative study from Iran

    PubMed Central

    2014-01-01

    Background The prevalence of endometriosis is considerable but its diagnosis is a dilemma. The aim of this study was to explore the perception and experiences of endometriosis patients and physicians about occurrence and diagnosis of endometriosis. Methods A qualitative research using content analysis was used to obtain data from purposely selected endometriosis patients (12 participants) and gynecologists (6 participants) from January to September 2013 in Tehran. Data were coded and analyzed using a thematic approach. Results Seven themes emerged: 1) pain localization, 2) Severity of pain and struggle for pain relief, 3) Feeling inability to play the role of femininity, 4) Reducing physical health, 5) Disruption of social life, 6) Looking for a reliable diagnostic indicator, 7) Uncertainty of physical examination. The results highlighted that patients with the disease can experience different feelings that interfere with their wellbeing and their lives, and sometimes could be disabling. Conclusion Patients and physicians are looking for a certain, noninvasive and inexpensive diagnostic method. This study helps to promote clinical diagnostic view and knowledge development about description of endometriosis diagnosis to decrease diagnostic delay and mismanagement. PMID:25174639

  11. Development of pro-apoptotic peptides as potential therapy for peritoneal endometriosis

    PubMed Central

    Sugihara, K.; Kobayashi, Y.; Suzuki, A.; Tamura, N.; Motamedchaboki, K.; Huang, C.-T.; Akama, T.O.; Pecotte, J.; Frost, P.; Bauer, C.; Jimenez, J.B.; Nakayama, J.; Aoki, D.; Fukuda, M.N.

    2014-01-01

    Endometriosis is a common gynaecological disease associated with pelvic pain and infertility. Current treatments include oral contraceptives combined with nonsteroidal anti-inflammatory drugs or surgery to remove lesions, all of which provide a temporary but not complete cure. Here we identify an endometriosis-targeting peptide that is internalized by cells, designated z13, using phage display. As most endometriosis occurs on organ surfaces facing the peritoneum, we subtracted a phage display library with female mouse peritoneum tissue and selected phage clones by binding to human endometrial epithelial cells. Proteomics analysis revealed the z13 receptor as the cyclic nucleotide-gated channel β3, a sorting pathway protein. We then linked z13 with an apoptosis-inducing peptide and with an endosome-escaping peptide. When these peptides were co-administered into the peritoneum of baboons with endometriosis, cells in lesions selectively underwent apoptosis with no effect on neighbouring organs. Thus, this study presents a strategy that could be useful to treat peritoneal endometriosis in humans. PMID:25047118

  12. Putting the pieces together: endometriosis blogs, cognitive authority, and collaborative information behavior*

    PubMed Central

    Neal, Diane M; McKenzie, Pamela J

    2011-01-01

    Objective: A discourse analysis was conducted of peer-written blogs about the chronic illness endometriosis to understand how bloggers present information sources and make cases for and against the authority of those sources. Methods: Eleven blogs that were authored by endometriosis patients and focused exclusively or primarily on the authors' experiences with endometriosis were selected. After selecting segments in which the bloggers invoked forms of knowledge and sources of evidence, the text was discursively analyzed to reveal how bloggers establish and dispute the authority of the sources they invoke. Results: When discussing and refuting authority, the bloggers invoked many sources of evidence, including experiential, peer-provided, biomedical, and intuitive ones. Additionally, they made and disputed claims of cognitive authority via two interpretive repertoires: a concern about the role and interests of the pharmaceutical industry and an understanding of endometriosis as extremely idiosyncratic. Affective authority of information sources was also identified, which presented as social context, situational similarity, or aesthetic or spiritual factors. Conclusions: Endometriosis patients may find informational value in blogs, especially for affective support and epistemic experience. Traditional notions of authority might need to be revised for the online environment. Guidelines for evaluating the authority of consumer health information, informed by established readers' advisory practices, are suggested. PMID:21464850

  13. Traditional Chinese medical herbs staged therapy in infertile women with endometriosis: a clinical study

    PubMed Central

    Ding, Zhaorong; Lian, Fang

    2015-01-01

    Background: Endometriosis is a common gynecological disease defined as the presence of endometrioid tissue (glands and stroma) outside the uterus. About 30 to 40% patients with endometriosis are infertile. In traditional Chinese medical system, endometriosis associated infertility is mostly caused by kidney deficiency and blood stasis. The herb of reinforcing kidney and removing blood stasis is designed to treat the disease. Material and methods: All the 80 up-to-standard patients were divided into two different groups exactly according to the random principle. They were treated with hormone and traditional Chinese medical herb separately. After half year’s therapy, all the patients received one year’s follow-up. Their transvaginal ultrasonographic changes, serum hormone levels and pregnancy rate were recorded to analysis the effect. Results: No significant difference happened in two groups’ demographic and clinical characteristics (P > 0.05). After the treatment, the effect on serum hormone levels and specific markers are significant (P < 0.05). The transvaginal ultrasonographic changes were positive, too. The text on hepatic and renal function confirmed to the safety of the herb. Compared to hormone therapy, the traditional Chinese medical herb is safe and effective for endometriosis patients with infertility. Conclusion: Compared with hormone therapy, traditional Chinese medical herb’s two-staged therapy is effective and safe for endometriosis patients with infertility. PMID:26550373

  14. Common variants upstream of KDR encoding VEGFR2 and in TTC39B associate with endometriosis

    PubMed Central

    Steinthorsdottir, Valgerdur; Thorleifsson, Gudmar; Aradottir, Kristrun; Feenstra, Bjarke; Sigurdsson, Asgeir; Stefansdottir, Lilja; Kristinsdottir, Anna M.; Zink, Florian; Halldorsson, Gisli H.; Munk Nielsen, Nete; Geller, Frank; Melbye, Mads; Gudbjartsson, Daniel F.; Geirsson, Reynir T.; Thorsteinsdottir, Unnur; Stefansson, Kari

    2016-01-01

    We conducted a genome-wide association scan (GWAS) of endometriosis using 25.5 million sequence variants detected through whole-genome sequencing (WGS) of 8,453 Icelanders and imputed into 1,840 cases and 129,016 control women, followed by testing of associated variants in Danish samples. Here we report the discovery of a new endometriosis susceptibility locus on 4q12 (rs17773813[G], OR=1.28; P=3.8 × 10−11), upstream of KDR encoding vascular endothelial growth factor receptor 2 (VEGFR2). The variant correlates with disease severity (P=0.0046) when moderate/severe endometriosis cases are tested against minimal/mild cases. We further report association of rs519664[T] in TTC39B on 9p22 with endometriosis (P=4.8 × 10−10; OR=1.29). The involvement of KDR in endometriosis risk highlights the importance of the VEGF pathway in the pathogenesis of the disease. PMID:27453397

  15. Incidence and Estimated Prevalence of Endometriosis and Adenomyosis in Northeast Italy: A Data Linkage Study

    PubMed Central

    Ricci, Giuseppe; Barbone, Fabio; Ronfani, Luca

    2016-01-01

    Despite being quite frequent and having serious implications in terms of symptomatology and fertility, data on incidence and prevalence of endometriosis and adenomyosis following gold standard definitions are dramatically lacking. The average time from onset of symptoms to diagnosis in industrialized countries still ranges from five to ten years. Using the regional centralized data linkage system, we calculated incidence and prevalence of endometriosis and adenomyosis in the female population of Friuli Venezia Giulia region, Italy, for the years 2011–2013. Cases were defined as new diagnoses from hospital discharge records, following procedures allowing direct visualization for endometriosis and hysterectomy for adenomyosis, with or without histological confirmation. Diagnoses were considered “new” after verifying women had not been diagnosed in the previous ten years. Incidence of endometriosis and adenomyosis in women aged 15–50 years is 0.14%. Prevalence, estimated from incidence, is 2.00%. Adenomyosis, representing 28% of all diagnoses, becomes increasingly prevalent after the age of 50 years. Our results shows how the study of both endometriosis and adenomyosis should not be limited to women of premenopausal age. Further efforts are needed to sensitize women and health professional, and to find new data linkage possibilities to identify undiagnosed cases. PMID:27101396

  16. The gut microbiota: a puppet master in the pathogenesis of endometriosis?

    PubMed

    Laschke, Matthias W; Menger, Michael D

    2016-07-01

    Endometriosis is a frequent gynecologic disease with a complex, multifactorial cause. It is characterized by the cyclic estrogen-driven proliferation and bleeding of endometriotic lesions (ie, ectopic endometrial glands and stroma) outside the uterus. These lesions induce a chronic activation of the innate immune system within the peritoneal cavity that is associated with the release of various inflammatory cytokines and angiogenic growth factors into the peritoneal fluid. This stimulates angiogenesis and the further spread of the lesions and triggers the typical pain that is symptomatic of the disease. Moreover, circulating stem and progenitor cells are recruited into the ectopic endometrial tissue and contribute to its growth and vascularization. In recent years, an increasing number of studies have indicated that the gut microbiota is not only essential for a physiologic gastrointestinal function but acts as a central regulator of a variety of inflammatory and proliferative conditions. Besides, the gut flora affects estrogen metabolism and stem-cell homeostasis. Based on these findings, we hypothesize that the gut microbiota may be involved crucially in the onset and progression of endometriosis. In the future, this novel view of the pathogenesis of endometriosis may be verified by analysis of the development of endometriotic lesions in animal models with a defined composition of the gut microbiota and by investigation of the microbiota of patients with endometriosis with modern next-generation sequencing tools. This could open the door for completely new preventive, diagnostic, and therapeutic approaches for endometriosis. PMID:26901277

  17. Association study of Glutathione S-Transferase polymorphisms and risk of endometriosis in an Iranian population

    PubMed Central

    Hassani, Mina; Saliminejad, Kioomars; Heidarizadeh, Masood; Kamali, Koorosh; Memariani, Toktam; Khorram Khorshid, Hamid Reza

    2016-01-01

    Background: Endometriosis influenced by both genetic and environmental factors. Associations of glutathione S-transferases (GSTs) genes polymorphisms in endometriosis have been investigated by various researchers; however, the results are not consistent. Objective: We examined the associations of GSTM1 and GSTT1 null genotypes and GSTP1 313 A/G polymorphisms with endometriosis in an Iranian population. Materials and Methods: In this case-control study, 151 women with diagnosis of endometriosis and 156 normal healthy women as control group were included. The genotyping was determined using multiplex PCR and PCR- RFLP methods. Results: The GSTM1 null genotype was significantly higher (p=0.027) in the cases (7.3%) than the control group (1.3%). There was no significant difference between the frequency of GSTT1 genotypes between the cases and controls. The GSTP1 313 AG genotype was significantly lower (p=0.048) in the case (33.1%) than the control group (44.4%). Conclusion: Our results showed that GSTM1 and GSTP1 polymorphisms may be associated with susceptibility of endometriosis in Iranian women. PMID:27351025

  18. Fertility and clinical outcome after bowel resection in infertile women with endometriosis.

    PubMed

    Stepniewska, Anna; Pomini, Paola; Scioscia, Marco; Mereu, Liliana; Ruffo, Giacomo; Minelli, Luca

    2010-05-01

    Bowel resection for endometriosis improves pain symptoms and quality of life in symptomatic women. However, little is known about fertility after surgery, particularly after such treatment in women suffering from infertility. The aim of the present study was to evaluate post-operative fertility and long-term clinical outcome after laparoscopic colorectal resection for endometriosis in infertile women. This study reports clinical outcomes in 62 infertile women who underwent laparoscopic excision of endometriosis with segmental bowel resection performed for severe intestinal symptoms. Among women younger than 30 years trying to conceive spontaneously, the cumulative pregnancy rate was 58% and the cumulative pregnancy rate was 45% in those aged 30-34 years. The total pain recurrence was 9.7% (six cases) and endometriosis recurrence was diagnosed by ultrasound in 14.5% (nine cases) during the follow-up period. Four of these patients needed further surgery because of severe symptoms. The surgical treatment of bowel endometriosis seems to improve pain symptoms and patients' satisfaction rates, and it could also be indicated in infertile women. PMID:20359953

  19. Stress Management Affects Outcomes in the Pathophysiology of an Endometriosis Model

    PubMed Central

    Cruz, Myrella L.; Hernández, Siomara; Thompson, Kenira J.; Bayona, Manuel; Flores, Idhaliz

    2014-01-01

    We have previously shown detrimental effects of stress in an animal model of endometriosis. We now investigated whether the ability to control stress can affect disease parameters. Endometriosis was surgically induced in female Sprague-Dawley rats before exposing animals to a controllable (submerged platform) or uncontrollable (no platform) swim stress protocol. Corticosterone levels and fecal pellet numbers were measured as an indicator of stress. Uncontrollable stress increased the number and size of the endometriotic cysts. Rats receiving uncontrollable stress had higher anxiety than those exposed to controllable stress or no stress and higher corticosterone levels. Uncontrollable stressed rats had more colonic damage and uterine cell infiltration compared to no stress, while controllable stress rats showed less of an effect. Uncontrollable stress also increased both colonic and uterine motility. In summary, the level of stress controllability appears to modulate the behavior and pathophysiology of endometriosis and offers evidence for evaluating therapeutic interventions. PMID:25015902

  20. CYFRA 21-1 in urine: a diagnostic marker for endometriosis?

    PubMed

    Gjavotchanoff, Risto

    2015-01-01

    Diagnostic workup of endometriosis usually involves laparoscopic inspection and histological examination of biopsies. Unequivocal laboratory parameters for this ailment have not been available in routine diagnostic evaluations thus far. In this study, we examined urine concentrations of cytokeratin 19 (CYFRA 21-1), a structural protein specific for epithelia. We performed immunoassays for CYFRA 21-1 in urine samples from women afflicted with endometriosis throughout their menstrual cycle. We observed a significant increase in CYFRA 21-1 concentrations, corrected by creatinine levels, in the late follicular phase as compared with the level in healthy controls. We conclude that cyclically increased CYFRA 21-1 concentrations in urine could serve as a valuable noninvasive diagnostic parameter in the workup of clinically manifesting endometriosis. PMID:25709504

  1. Metabolomics Reveals Altered Lipid Metabolism in a Mouse Model of Endometriosis.

    PubMed

    Dutta, Mainak; Anitha, Mallappa; Smith, Philip B; Chiaro, Christopher R; Maan, Meenu; Chaudhury, Koel; Patterson, Andrew D

    2016-08-01

    Endometriosis is a common chronic estrogen-dependent gynecological disease affecting 10% of women in their reproductive age. It is characterized by proliferation of functional endometrial glands and stroma outside the uterine cavity. In the present study, we used mass spectrometry-based lipidomics to investigate the alterations in serum lipid profiles of mice induced with endometriosis. We identified several dysregulated lipids such as phosphatidylcholines, sphingomyelins, phosphatidylethanolamines, and triglycerides and show that triglycerides may be due to a general inflammatory condition in the peritoneum. We also show that in addition to phosphatidylcholine alteration, there is also an effect in the ratio of phosphatidylcholine/phosphatidylethanolamine in serum of mice induced with the disease and that this change may be due to increased expression of the phosphatidylethanolamine N-methyltransferase gene. The study provides new insight into the etiology of endometriosis. PMID:27246581

  2. Relevance of Imaging Examinations in the Surgical Planning of Patients with Bowel Endometriosis

    PubMed Central

    Trippia, Carlos H.; Zomer, Monica T.; Terazaki, Carlos R.T.; Martin, Rafael L.S.; Ribeiro, Reitan; Kondo, William

    2016-01-01

    Endometriosis is a benign gynecologic disease characterized by the presence of endometrial tissue outside the uterine cavity. The complexity of the disease results from its multiple clinical presentations, the multifocal pattern of distribution of the lesions, the presence of extra pelvic sites of the disease (mainly affecting the urinary and the intestinal tracts), and the difficulty in the preoperative diagnosis (by means of imaging studies) and in the surgical treatment. The preoperative mapping of the lesions, either by ultrasound or by magnetic resonance imaging, allows for an adequate surgical planning and a better preoperative patient counseling, especially in those women with deep infiltrating endometriosis affecting the bowel. Also, the choice of the surgical team that is going to perform the procedure may be based on the preoperative workup. In this paper, we highlight the important findings that should be described in the imaging examination reports for the preoperative workup of patients with deep infiltrating endometriosis of the intestine. PMID:26917983

  3. Relevance of Imaging Examinations in the Surgical Planning of Patients with Bowel Endometriosis.

    PubMed

    Trippia, Carlos H; Zomer, Monica T; Terazaki, Carlos R T; Martin, Rafael L S; Ribeiro, Reitan; Kondo, William

    2016-01-01

    Endometriosis is a benign gynecologic disease characterized by the presence of endometrial tissue outside the uterine cavity. The complexity of the disease results from its multiple clinical presentations, the multifocal pattern of distribution of the lesions, the presence of extra pelvic sites of the disease (mainly affecting the urinary and the intestinal tracts), and the difficulty in the preoperative diagnosis (by means of imaging studies) and in the surgical treatment. The preoperative mapping of the lesions, either by ultrasound or by magnetic resonance imaging, allows for an adequate surgical planning and a better preoperative patient counseling, especially in those women with deep infiltrating endometriosis affecting the bowel. Also, the choice of the surgical team that is going to perform the procedure may be based on the preoperative workup. In this paper, we highlight the important findings that should be described in the imaging examination reports for the preoperative workup of patients with deep infiltrating endometriosis of the intestine. PMID:26917983

  4. The Role of Stem Cells in the Etiology and Pathophysiology of Endometriosis.

    PubMed

    Hufnagel, Demetra; Li, Fei; Cosar, Emine; Krikun, Graciela; Taylor, Hugh S

    2015-09-01

    Human endometrium is a dynamic organ that normally undergoes repetitive cyclic regeneration. To enable this rapid regeneration, it is not surprising that the endometrium contains a reservoir of progenitor stem cells. However, this pool of cells that allows the growth of the endometrium also allows for unrestrained growth that can reach beyond the endometrium. In this review, we will address the role of stem cells in endometriosis. Recent characterization of stem cell populations within human endometrium has opened the possibility of understanding their physiologic as well as their pathologic roles. While stem cells are critical to the cyclic regeneration of a healthy endometrium, we have shown that both endometrium-derived and bone marrow-derived stem cells can migrate to ectopic sites and contribute to the development of endometriosis. Furthermore, endometriosis interferes with the normal stem cell trafficking to the uterus that is necessary for endometrial growth and repair. Altered stem cell mobility and engraftment characterize this disease. PMID:26375413

  5. Long-lasting analgesic effect of transcranial direct current stimulation in treatment of chronic endometriosis pain.

    PubMed

    Rostami, Reza; Badran, Bashar W; Kazemi, Reza; Habibnezhad, Mohammad; George, Mark S

    2015-12-01

    Approximately 10-20% of women of reproductive age suffer from endometriosis, with 70-90% of these women reporting chronic pain symptoms that persist during their menstrual cycle. We are presenting a case in which a novel form of noninvasive brain stimulation called transcranial direct current stimulation was used as an intervention in a 32-year-old woman with persistent, chronic pain symptoms caused by endometriosis for 20 years. Ten daily, 20-min sessions of 2-mA anodal transcranial direct current stimulation were applied over the left primary motor cortex. Acutely, visual analog scale pain symptoms were reduced by 60%. There were also significant decreases in modules of the Endometriosis Health Profile. At the 4-month follow-up, the patient still expressed an overall decrease in pain symptoms of 30%. PMID:26419900

  6. [Change in phospholipid content in platelets, immunocompetent cells and myometrial tissue in patients with internal endometriosis].

    PubMed

    Damirov, M M; Kulakov, V I; Sliusra', N N; Bakuleva, L P; Kargapolov, A V

    1994-01-01

    A method of flow horizontal chromatography has been developed permitting investigation of blood and tissue cellular phospholipids ruling out lipid peroxidation effects on cellular membranes. Phospholipid levels of blood and myometrial tissue cells were measured by this method in 67 patients with histologically verified internal endometriosis. Phospholipid and phosphatidyl inosite levels in platelets and immunocompetent cells of these patients reliably differed from those in healthy women. Phosphatidyl inosite levels of heterotopic endometrial tissue was increased by 1.4 times vs. the norm on an average. In parallel with this, a reliable change of phosphatidyl cholines and inosites levels in endometriosis foci were detected as against their levels in intact tissue. The authors suggest a method for the diagnosis of internal endometriosis by phosphatidyl inosite levels in blood lymphocytes. PMID:8209956

  7. Obstetric Scar Endometriosis: Retrospective Study on 19 Cases and Review of the Literature.

    PubMed

    Kaplanoglu, Mustafa; Kaplanoğlu, Dilek Kaya; Dincer Ata, Ceren; Buyukkurt, Selim

    2014-01-01

    Endometriosis is defined as the presence of functioning endometrial tissue outside the uterine cavity. This disease is one of the most common gynecologic disorders in reproductive age women. It generally occurs in pelvic cavity. But extrapelvic location has been defined (such as extremities, central nervous system, lungs, pleurae, liver, umbilicus, pericardium, urinary tract, intestines, and surgical scar tissue). Scar endometriosis is a rare disease and defined as presence of endometriotic lesions on the abdominal (such as cesarean section and hysterectomy) or vaginal (episiotomy) excision line. It is difficult to diagnose due to the extreme variability in presentation. The symptoms are nonspecific, typically involving pain, swelling at the incision site at the time of menstruation. Excision and histopathologic examination are necessary for diagnosis. We present a case series of obstetric scar endometriosis and review of the literature. PMID:27379258

  8. Promotion of angiogenesis and proliferation cytokines patterns in peritoneal fluid from women with endometriosis.

    PubMed

    Rakhila, Halima; Al-Akoum, Mahera; Bergeron, Marie-Eve; Leboeuf, Mathieu; Lemyre, Madeleine; Akoum, Ali; Pouliot, Marc

    2016-08-01

    Studies have long sought specific cytokines that could characterize endometriosis. Either due to variations between study designs regarding the assessment criteria for the cytokine or to low power resulting from small sample size, no factor proved to be sufficiently specific to endometriosis. In other clinical fields, a combination of several markers proved to be more powerful than a single-molecule approach. As well, in the context of endometriosis, simultaneous assessment of several cytokines present in the peritoneal fluid might help in unveiling patho-physiological processes, thus contributing to a better understanding of the condition. Therefore, the objective of this study was to investigate peritoneal fluid cytokines-derived of endometriotic women. For this retrospective case-control study, peritoneal fluid samples were obtained at laparoscopy and assessed by multiplex. Our data showed distinct patterns of peritoneal fluid cytokine concentrations in endometriotic women most notably a marked increase in EGF, FGF-2, IL-1α, MIP-1β, TGFα, PDGF-AA, PDGF-BB, MCP-3, sCD40L, Gro Pan, IL-17α, MDC and Rantes. The overall effect of fertility status revealed a significant difference for only one cytokine, namely MDC. Furthermore, FLT-3L and IP-10 levels were decreased in endometriosis patients, the former in both menstrual cycle phases and the latter in the secretory phase. A significant inverse Pearson correlation (p<0.05) was noted between pro-angiogenic cytokines EGF and FGF and the anti-angiogenic cytokine IP-10 in endometriosis patients at stages III-IV and in the secretory phase. These changes may exacerbate the local peritoneal angiogenic and proliferative reaction observed in women with endometriosis, and contributes to its pathophysiology. PMID:27128987

  9. Serum anti-inflammatory cytokines for the evaluation of inflammatory status in endometriosis

    PubMed Central

    Măluţan, Andrei Mihai; Drugan, Tudor; Ciortea, Răzvan; Mocan-Hognogi, Radu Florin; Bucuri, Carmen; Rada, Maria Patricia; Mihu, Dan

    2015-01-01

    Background: Endometriosis is a frequent gynecologic disease with a severe impact on the quality of life in the affected women; its pathogenesis is yet to be fully understood, with an altered immunity as a possible key factor. The present study aimed to investigate the serum anti-inflammatory cytokine profile in the patients with endometriosis compared with the healthy controls. Materials and Methods: One hundred and sixty women were included, divided into two study groups (Group I — endometriosis; Group 2 — healthy women). We evaluated the serum levels of interleukin-1 receptor antagonist (IL-1Ra), IL-2, IL-2R, IL-4, IL-10, IL-13, and IL-15 with the use of Human multiplex cytokine panels. Statistical analyses (normality distribution analysis, independent t-test, Mann–Whitney U-test) were performed using IBM SPSS software (version 22.0) and GraphPad Prism (version 5.00); receiver operating characteristic curve were used to demonstrate the diagnostic performance of the studied markers. Results: The mean serum level of IL-1Ra, IL-4, and IL-10 were significantly higher in women with endometriosis compared to women free of disease from the control group (30.155, 138.459, and 1.489, respectively, compared to 14.109, 84.710, and 0.688, respectively; P < 0.001, P < 0.001, and P = 0.002, respectively.). No significant differences in the mean serum levels of IL-2, IL-13, and IL-15 were observed between the studied groups and IL-2R had a very low detection rate. Conclusion: Endometriosis is associated with elevated levels of anti-inflammatory cytokines, IL-1Ra, IL-4, and IL-10, markers that have a potential role as a prognostic factor for endometriosis. PMID:26622256

  10. Comparison study on effectiveness of pentoxifyllin with LD to prevent recurrent endometriosis

    PubMed Central

    Ghahiri, Ataollah; Najafian, Aida; Ghasemi, Mojdeh; Najafian, Alireza

    2012-01-01

    Background: About 75% of the symptomatic patients who involved with endometriosis have pelvic pain and dysmenorrhea. Pentoxifyllin is one of the drugs that according to its mechanism could be effective for pain relief of endometriosis which has been used for endometriosis treatment recently. Objective: We conducted a comparative study for detecting the effect of pentoxifylin (as an immonomodelator) in preventing recurrence endometriotic pain with pentoxifylin plus a combined contraceptive pill with low dose estrogen (LD) and also the LD pill alone. Materials and Methods: This was a comparative clinical trial on 83 patients with the chief complaint (CC) of pain (dysmenorrheal /or pelvic pain) and with the end diagnosis of endometriosis, in an operative laparoscopy. Patients, dividing to 3 groups, were treated with pentoxifylin, pentoxifylin+LD and LD alone for 10 months. The severity of pain (dismenorhea and/or pelvic pain) was detected by visual analogue scale (VAS) before and after the treatment. The severity of endometriosis in the patients was: I in class I and II in class II and III in class III. The groups were matched for the pain. The number of the patients in group 1, 2 and 3 were 28, 28 and 27 respectively. Results: The pain was reduced in the groups of pentoxifylin+LD (p<0.001) and LD alone (p=0.00). The pain relief was not significant in the group of pentoxifylin alone (p=0.136). After treatment, the severity of pain was not significantly different between the LD group and the LD+penthoxyfillin group, but there was difference between these two groups and the group of penthoxyfillin alone. Conclusion: This study showed that penthoxyfillin actually could not have any effect on the pain relief of endometriosis. It also made it clear that penthoxyfillin could not increase the efficacy of LD when used with this medication. PMID:25242996

  11. Reducing low-value care in endometriosis between limited evidence and unresolved issues: a proposal.

    PubMed

    Vercellini, Paolo; Giudice, Linda C; Evers, Johannes L H; Abrao, Mauricio S

    2015-09-01

    Quantification of benefits and harms of medical interventions should be based on high-quality evidence, which is not always the case in the endometriosis field. In many clinical circumstances, healthcare decisions in women with endometriosis are taken based on suboptimal evidence or on evidence of coexistence of benefits and harms that must be balanced. In these conditions, it is important to avoid or reduce the use of low-value care, i.e. interventions with defined harms and uncertain benefits, or whose effectiveness is comparable with less expensive alternatives. In particular, we suggest that: (i) non-surgical diagnosis based on symptoms, physical findings and transvaginal ultrasonography is possible in most women with symptomatic endometriosis. Thus, except in doubtful cases, laparoscopy should be intended for surgical treatment, not for diagnostic purposes: early diagnosis and diagnostic laparoscopy are not synonymous; (ii) future trials on new drugs for endometriosis should address those outcomes that are most important to patients, should be designed as superiority trials and should include a progestin or an estrogen-progestin as a comparator. Moreover, limitation of repetitive surgery for recurrent endometriosis is among the objectives of long-term medical treatment; (iii) indications for surgery should be the result of a balance between demonstrated benefits in terms of fertility enhancement and pain relief, specific risks associated with excision of different types of endometriotic lesions, cost-effectiveness and patient preference after detailed information; (iv) physicians, health professionals and policy makers should discriminate between screening for and diagnosis of endometriosis. Limited peritoneal foci, which are frequently observed also in asymptomatic women, regress or remain stable in about two thirds of cases. Therefore, the theoretical premises for a screening campaign are currently unclear; (v) physicians should develop the ability to

  12. Endometrial BCL6 Overexpression in Eutopic Endometrium of Women With Endometriosis.

    PubMed

    Evans-Hoeker, Emily; Lessey, Bruce A; Jeong, Jae Wook; Savaris, Ricardo F; Palomino, Wilder A; Yuan, Lingwen; Schammel, David P; Young, Steven L

    2016-09-01

    The objective of this study was to examine B-cell CLL/lymphoma 6 (BCL6) expression in human eutopic endometrium across the menstrual cycle in women with and without endometriosis and to establish a cutoff for future studies. This design was a series of case-control studies in tertiary University teaching hospitals. We examined BCL6 expression by messenger RNA and immunohistochemically in prospectively collected samples in both the proliferative (P) and the secretory phases. BCL6 is minimally increased in the mid-secretory phase of the menstrual cycle compared to the P phase in normal patients. BCL6 protein expression was significantly higher in the secretory phase of patients with endometriosis (n = 29) versus fertile controls without endometriosis at laparoscopy (n = 20; P < .0001). Normal fertile controls (n = 28) recruited for endometrial biopsy also had low levels of secretory phase BCL6 expression compared to women with unexplained infertility (UI; n = 119). A receiving-operator characteristic analysis of these data revealed an area under the curve of 94% (95% confidence interval 85%-100%; P < .0001) with an HSCORE cutoff of 1.4 to differentiate cases with and without endometriosis. Using this cutoff value, BCL6 was positive in 88% of cases with UI. Laparoscopic examination of a subset of 65 patients confirmed abnormalities in 98% of cases; 61 (93.8%) were found to have endometriosis, 3 (4.6%) with hydrosalpinx, and 1 (1.5%) with a normal pelvis. These data suggest that BCL6 is a promising candidate as a single diagnostic biomarker for detection of endometriosis in women with otherwise UI and may be associated with endometrial dysfunction, including progesterone resistance. PMID:27222232

  13. Periclitoral endometriosis: the dilemma of a chronic disease invading a rare location.

    PubMed

    Grimstad, Frances W; Carey, Erin

    2015-01-01

    Endometriosis affects 6% to 10% of women of reproductive age; extrapelvic endometriosis is considered a rare event with perineal endometriosis being even rarer still (only a few cases of spontaneous episodes described, the majority being from episiotomy scars). We present a unique case of periclitoral endometriosis, which to the best of our knowledge is the first in the literature. It is a 29-year-old nulligravida female with a painful fluctuant right periclitoral mass that had been growing with no response to antibiotic therapy. At the initial removal, pathology reported the lesion as endometriosis. The patient was placed on oral contraceptives, and she was noted to have monthly swelling and shrinking of the site with her menstrual cycles. When she went off hormonal contraception, she represented with the growing lesion 3.5 weeks after her last menses; she underwent re-excision. Because of the extension of the lesion medially and its adherence to the clitoral body, the decision was made to evacuate only as much of the capsule that could be safely identified to minimize the risk of damaging the clitoris. Complete excision in this case was difficult without sacrificing a portion of the clitoris and potentially resulting in decreased sexual function and persistent clitoral pain. In a patient in whom complete excision is not possible, there is potential for mass recurrence in the setting of residual tissue. Reviewing the literature suggests that there are risks with both recurrence and clitoral excision. We found that in-depth patient counseling, hormonal suppression, and close follow-up are necessary when dealing with periclitoral endometriosis postexcision. PMID:25680686

  14. Safety and tolerability of dienogest in endometriosis: pooled analysis from the European clinical study program

    PubMed Central

    Strowitzki, Thomas; Faustmann, Thomas; Gerlinger, Christoph; Schumacher, Ulrike; Ahlers, Christiane; Seitz, Christian

    2015-01-01

    Background In four randomized, controlled, European trials, dienogest 2 mg once daily demonstrated significant efficacy for lesion reduction and reduction in pain intensity in endometriosis. We describe a pooled analysis of the safety and tolerability data from these trials to confirm and further characterize the safety profile of dienogest in the treatment of endometriosis. Methods All 332 women treated with dienogest 2 mg who participated in the four clinical trials were included in the pooled analyses for safety assessments, including adverse events, laboratory tests, vital signs, body weight, and bleeding patterns. Safety variables were analyzed using descriptive statistics. Results Pooled analyses of this large patient population confirmed that dienogest 2 mg is well tolerated, with a favorable safety profile extending over a period up to 65 weeks in women with endometriosis. The most common adverse drug reactions were headache, breast discomfort, depressed mood, and acne, each occurring in <10% of women. All these adverse events were generally of mild-to-moderate intensity and associated with low discontinuation rates. The bleeding pattern associated with dienogest 2 mg was well tolerated, and only two women (0.6%) reported bleeding events as the primary reason for premature discontinuation. Laboratory and vital sign assessments indicated no safety concerns for dienogest. Estradiol levels were maintained within the low-physiological range, in support of previous evidence indicating that dienogest 2 mg demonstrates therapeutic efficacy without inducing estradiol deficiency. Conclusion In this pooled analysis of 332 women with endometriosis, dienogest was well tolerated with a favorable safety profile extending over a period of up to 65 weeks. There is a paucity of randomized trial evidence to support the use of many treatments in endometriosis. These pooled analyses from four clinical trials of dienogest 2 mg represent a contribution to evidence-based medicine

  15. Radical Surgery for Endometriosis: Analysis of Quality of Life and Surgical Procedure

    PubMed Central

    De la Hera-Lazaro, Cristina M.; Muñoz-González, Jose L.; Perez, Reyes Oliver; Vellido-Cotelo, Rocío; Díez-Álvarez, Alvaro; Muñoz-Hernando, Leticia; Alvarez-Conejo, Carmen; Jiménez-López, Jesús S.

    2016-01-01

    OBJECTIVE The main aim of this study is to determine the improvement in quality of life in patients who have undergone radical surgery because of severe endometriosis. PATIENTS AND METHODS This nonrandomized interventional study (quasi experimental) was carried out between January 2009 and September 2014. A total of 46 patients with diagnosis of severe endometriosis were included. Radical surgery, including hysterectomy, was performed. Acting as their own control group, the patients were asked to fill in a validated questionnaire of quality of life [Endometriosis Health Profile-5 (EHP-5)] and a visual analog scale of pain at the moment of the preoperative visit (one month prior to surgery) and six months after the surgery. RESULTS Radical surgery for endometriosis was performed in 46 patients at our center over the period of six years. Among the patients, 73.9% of them had undergone previous surgery for endometriosis. In 82.6% of cases, a complete laparoscopic resection was carried out. Gastrointestinal tract resection was performed in 21.7%, and urinary tract resection was necessary in 8.7%. The mean age of the patients was 38.6 years. The rate of complications was 30.4%. Six months after the surgery, all items of the EHP-5 questionnaire had a lower score, which means an improvement in all aspects of quality of life related to endometriosis. The difference obtained between the scores before and after the surgery was statistically significant. The mean visual analog scale score before the surgery was 8.5, whereas it decreased to 1.4 after the surgery (P < 0.001). CONCLUSION Performing a radical surgery is a difficult decision to make; however, it can provide optimal results in terms of improvement of quality of life and, therefore, should be considered when conservative therapy fails. PMID:26966396

  16. Bladder Endometriosis and Endocervicosis: Presentation of 2 Cases with Endoscopic Management and Review of Literature

    PubMed Central

    Fuentes Pastor, Javier; Ballestero Diego, Roberto; Correas Gómez, Miguel Ángel; Torres Díez, Eduardo; Fernández Flórez, Alejandro; Ballesteros Olmos, Gerardo; Gutierrez Baños, Jose Luis

    2014-01-01

    Urinary tract endometriosis and endocervicosis are an uncommon pathologic finding, with a common embryological origin. We present 2 cases of female patients with bladder mass. The first one was a finding of a nodular formation in the bladder during study of a nonviable foetus and the second was an incidental finding of a neoformation in the fundus of the bladder during the realization of an ultrasound. In both cases, we performed a surgical management with transurethral resection. Histopathological examination revealed a bladder endometrioma in the first case and endocervicosis with associated endometriosis in the second. PMID:25184072

  17. Endometriosis, Ovarian Reserve and Live Birth Rate Following In Vitro Fertilization/Intracytoplasmic Sperm Injection.

    PubMed

    Coelho Neto, Marcela Alencar; Martins, Wellington de Paula; Luz, Caroline Mantovani da; Jianini, Bruna Talita Gazeto Melo; Ferriani, Rui Alberto; Navarro, Paula Andrea

    2016-05-01

    Purpose To evaluate whether women with endometriosis have different ovarian reserves and reproductive outcomes when compared with women without this diagnosis undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI), and to compare the reproductive outcomes between women with and without the diagnosis considering the ovarian reserve assessed by antral follicle count (AFC). Methods This retrospective cohort study evaluated all women who underwent IVF/ICSI in a university hospital in Brazil between January 2011 and December 2012. All patients were followed up until a negative pregnancy test or until the end of the pregnancy. The primary outcomes assessed were number of retrieved oocytes and live birth. Women were divided into two groups according to the diagnosis of endometriosis, and each group was divided again into a group that had AFC ≤ 6 (poor ovarian reserve) and another that had AFC ≥ 7 (normal ovarian reserve). Continuous variables with normal distribution were compared using unpaired t-test, and those without normal distribution, using Mann-Whitney test. Binary data were compared using either Fisher's exact test or Chi-square (χ(2)) test. The significance level was set as p < 0.05. Results 787 women underwent IVF/ICSI (241 of which had endometriosis). Although the mean age has been similar between women with and without the diagnosis of endometriosis (33.8 ± 4 versus 33.7 ± 4.4 years, respectively), poor ovarian reserves were much more common in women with endometriosis (39.8 versus 22.7%). The chance of achieving live birth was similar between women with the diagnosis of endometriosis and those without it (19.1 versus 22.5%), and also when considering only women with a poor ovarian reserve (9.4 versus 8.9%) and only those with a normal ovarian reserve (25.5 versus 26.5%). Conclusions Women diagnosed with endometriosis are more likely to have a poor ovarian reserve; however, their chance of conceiving by

  18. Persistent Mullerian Duct Syndrome with Ovarian Endometriosis-A Rare Case Report

    PubMed Central

    Hippargi, Surekha B.; Mestri, Namrata B.; Mehrotra, Nikhil M.

    2016-01-01

    Persistent Mullerian Duct Syndrome (PMDS) is a rare form of internal male pseudohermaphroditism, characterised by presence of Mullerian duct derivatives in a genotypic and phenotypic male. It is caused by absence of anti- Mullerian hormone or defective functioning of its receptors. We report a case of 19-year-old cryptorchid male with history of orchideopexy who was clinically and radiologically diagnosed as left sided chylocele. A definitive diagnosis of PMDS with ovarian endometriosis was made on histopathological examination which is important for genetic counselling and to reduce complications like infertility and neoplastic transformation. We report this case of PMDS with ovary showing evidence of endometriosis for its rarity. PMID:27042476

  19. Risk factors associated with endometriosis: importance of study population for characterizing disease in the ENDO Study

    PubMed Central

    Peterson, C. Matthew; Johnstone, Erica B.; Hammoud, Ahmad O.; Stanford, Joseph B.; Varner, Michael W.; Kennedy, Anne; Chen, Zhen; Sun, Liping; Fujimoto, Victor Y.; Hediger, Mary L.; Buck Louis, Germaine M.

    2014-01-01

    OBJECTIVE We sought to identify risk factors for endometriosis and their consistency across study populations in the Endometriosis: Natural History, Diagnosis, and Outcomes (ENDO) Study. STUDY DESIGN In this prospective matched, exposure cohort design, 495 women aged 18–44 years undergoing pelvic surgery (exposed to surgery, operative cohort) were compared to an age- and residence-matched population cohort of 131 women (unexposed to surgery, populationcohort). Endometriosis was diagnosed visually at laparoscopy/laparotomy or by pelvic magnetic resonance imaging in the operative and population cohorts, respectively. Logistic regression estimated the adjusted odds ratios (AORs) and 95% confidence intervals (CIs) for each cohort. RESULTS The incidence of visualized endometriosis was 40% in the operative cohort (11.8% stage 3–4 by revised criteria from the American Society for Reproductive Medicine), and 11% stage 3–4 in the population cohort by magnetic resonance imaging. An infertility history increased the odds of an endometriosis diagnosis in both the operative (AOR, 2.43; 95% CI, 1.57–3.76) and population (AOR, 7.91; 95% CI, 1.69–37.2) cohorts. In the operative cohort only, dysmenorrhea (AOR, 2.46; 95% CI, 1.28–4.72) and pelvic pain (AOR, 3.67; 95% CI, 2.44–5.50) increased the odds of diagnosis, while gravidity (AOR, 0.49; 95% CI, 0.32–0.75), parity (AOR, 0.42; 95% CI, 0.28–0.64), and body mass index (AOR, 0.95; 95% CI, 0.93–0.98) decreased the odds of diagnosis. In all sensitivity analyses for different diagnostic subgroups, infertility history remained a strong risk factor. CONCLUSION An infertility history was a consistent risk factor for endometriosis in both the operative and population cohorts of the ENDO Study. Additionally, identified risk factors for endometriosis vary based upon cohort selection and diagnostic accuracy. Finally, endometriosis in the population may be more common than recognized. PMID:23454253

  20. Expect the unexpected: Endometriosis mimicking a rectal carcinoma in a post-menopausal lady

    PubMed Central

    Jakhmola, C. K.; Kumar, Ameet; Sunita, B. S.

    2016-01-01

    Altered bowels habits along with rectal mass in an elderly would point toward a rectal cancer. We report an unusual case of a post-menopausal lady who presented with these complaints. We had difficulties in establishing a pre-operative diagnosis. With a tentative diagnosis of a rectal cancer/gastrointestinal stromal tumor, she underwent a laparoscopic anterior resection. On histopathology, this turned out to be endometriosis. Bowel endometriosis is an uncommon occurrence. That it occurred in a post-menopausal lady was a very unusual finding. We discuss the case, its management, and the relevant literature. PMID:27073315

  1. Minimising menopausal side effects whilst treating endometriosis and fibroids.

    PubMed

    Simpson, Paul D; McLaren, James S; Rymer, Janice; Morris, Edward P

    2015-03-01

    Medical management of endometriosis and fibroids involves manipulation of the hypothalamic-pituitary-gonadal axis to alter the balance of sex hormones thereby inhibiting disease progression and ameliorate symptoms. Unfortunately, resultant menopausal symptoms sometimes limit the tolerability and duration of such treatment. The use of gonadotrophin-releasing hormone agonists to treat these diseases can result in short-term hypoestrogenic and vasomotor side effects as well as long-term impacts on bone health and cardiovascular risk. The routine use of add-back hormone replacement has reduced these risks and increased patient compliance, making this group of drugs more useful as a medium-term treatment option. The estrogen threshold hypothesis highlights the concept of a 'therapeutic window' in which bone loss is minimal but the primary disease is not aggravated. It explains why add-back therapy is appropriate for such patients and helps to explain the basis behind new developments in the treatment of hormonally responsive gynaecological conditions such as gonadotrophin-releasing hormone antagonists and progesterone receptor modulators. PMID:25802141

  2. Identification of Biomarkers for Endometriosis Using Clinical Proteomics

    PubMed Central

    Zhao, Yang; Liu, Ya-Nan; Li, Yi; Tian, Li; Ye, Xue; Cui, Heng; Chang, Xiao-Hong

    2015-01-01

    Background: We investigated possible biomarkers for endometriosis (EM) using the ClinProt technique and proteomics methods. Methods: We enrolled 50 patients with EM, 34 with benign ovarian neoplasms and 40 healthy volunteers in this study. Serum proteomic spectra were generated by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MS) combined with weak cationic exchange (WCX) magnetic beads. Possible biomarkers were analyzed by a random and repeat pattern model-validation method that we designed, and ClinProtools software, results were refined using online liquid chromatography-tandem MS. Results: We found a cluster of 5 peptides (4210, 5264, 2660, 5635, and 5904 Da), using 3 peptides (4210, 5904, 2660 Da) to discriminate EM patients from healthy volunteers, with 96.67% sensitivity and 100% specificity. We selected 4210 and 5904 m/z, which differed most between patients with EM and controls, and identified them as fragments of ATP1B4, and the fibrinogen alpha (FGA) isoform 1/2 of the FGA chain precursor, respectively. Conclusions: ClinProt can identify EM biomarkers, which – most notably – distinguish even early-stage or minimal disease. We found 5 stable peaks at 4210, 5264, 2660, 5635, and 5904 Da as potential EM biomarkers, the strongest of which were associated with ATP1B4 (4210 Da) and FGA (5904 Da); this indicates that ATP1B4 and FGA are associated with EM pathogenesis. PMID:25673457

  3. Elevated levels of whole blood nickel in a group of Sri Lankan women with endometriosis: a case control study

    PubMed Central

    2013-01-01

    Background Endometriosis is characterized by the persistence of endometrial tissue in ectopic sites outside the uterine cavity. Presence of nickel, cadmium and lead in ectopic endometrial tissue has been reported previously. While any association between blood levels of nickel and endometriosis is yet to be described in literature, conflicting reports are available with regards to cadmium and lead levels in blood and urine. Findings In fifty patients with endometriosis and fifty age-matched controls confirmed by laparoscopy or laparotomy, whole blood samples were collected and digested using supra pure 65% HNO3. Whole blood levels of nickel and lead were measured using Total Reflection X-ray Fluorescence (TXRF) while cadmium levels were evaluated using graphite furnace atomic absorption spectroscopy (GFASS). Women with endometriosis had significantly higher (P=0.016) geometric mean (95% CI) whole blood nickel levels [2.6(1.9-3.3) μg/L] as compared to women without endometriosis [0.8 (0.7-0.9) μg/L]. Whole blood levels of cadmium and lead were similar between the two groups. Conclusions Although women with endometriosis in this study population had higher levels of nickel in whole blood compared to controls, whether nickel could be considered as an aetiological factor in endometriosis remains inconclusive in view of the smaller sample that was evaluated. PMID:23317102

  4. The association between interleukin-4 -590C/T genetic polymorphism, IL-4 serum level, and advanced endometriosis

    PubMed Central

    Malutan, Andrei M.; Drugan, Tudor; Ciortea, Razvan; Mihu, Dan

    2016-01-01

    Aim of the study Aim of the study was to investigate interleukin (IL)-4 serum levels in patients with advanced endometriosis and whether IL-4 promoter region (-590C/T) genetic polymorphism is involved in genetic susceptibility to endometriosis. Material and methods IL-4 serum levels and IL-4 -590C/T genetic polymorphism were determined for 80 patients with advanced endometriosis and 85 healthy fertile women using a multiplex cytokine kit, with a Luminex 200 system; high molecular weight genomic DNA was extracted from peripheral blood leukocytes, and further analyzed by PCR amplification and restriction fragment length polymorphism (PCR-PFLP). The relationship between IL-4 serum levels, genotypes and haplotypes and the presence of endometriosis was explored. Results Interleukin 4 serum levels were significantly higher in the endometriosis group compared to controls (138,459 compared to 84,710, p < 0.001). No significant difference was observed in IL-4 serum levels between genotypes. There were no differences in IL-4 -590C/T genotypes and allele frequencies between control women and patients with endometriosis (χ2 = 0.496, and χ2 = 0.928, OR = 1.3636, CI: 0.725-2.564). Conclusions The results suggest that in patients with advanced stages of endometriosis there is a higher serum level of IL-4, and that this value, or the presence of the disease, is not influenced by the presence of IL-4 -590C/T genetic polymorphism. PMID:27536203

  5. Whole-exome sequencing of endometriosis identifies frequent alterations in genes involved in cell adhesion and chromatin-remodeling complexes.

    PubMed

    Li, Xiaolei; Zhang, Yan; Zhao, Luyang; Wang, Lingxiong; Wu, Zhiqiang; Mei, Qian; Nie, Jing; Li, Xiang; Li, Yali; Fu, Xiaobing; Wang, Xiaoning; Meng, Yuanguang; Han, Weidong

    2014-11-15

    Endometriosis is a complex and enigmatic disease that arises from the interplay among multiple genetic and environmental factors. The defining feature of endometriosis is the deposition and growth of endometrial tissues at sites outside of the uterine cavity. Studies to date have established that endometriosis is heritable but have not addressed the causal genetic variants for this disease. Here, we conducted whole-exome sequencing to comprehensively search for somatic mutations in both eutopic and ectopic endometrium from 16 endometriosis patients and five normal control patients using laser capture microdissection. We compared the mutational landscape of ectopic endometrium with the corresponding eutopic sample from endometriosis patients compared with endometrium from normal women and identified previously unreported mutated genes and pathway alternations. Statistical analysis of exome data identified that most genes were specifically mutated in both eutopic and ectopic endometrium cells. In particular, genes that are involved in biological adhesion, cell-cell junctions, and chromatin-remodeling complex(es) were identified, which partially supports the retrograde menstruation theory that proposes that endometrial cells are refluxed through the fallopian tubes during menstruation and implanted onto the peritoneum or pelvic organs. Conspicuously, when we compared exomic mutation data for paired eutopic and ectopic endometrium, we identified a mutational signature in both endometrial types for which no overlap in somatic single nucleotide variants were observed. These mutations occurred in a mutually exclusive manner, likely because of the discrepancy in endometriosis pathology and physiology, as eutopic endometrium rapidly regrows, and ectopic endometrial growth is inert. Our findings provide, to our knowledge, an unbiased view of the landscape of genetic alterations in endometriosis and vital information for indicating that genetic alterations in cytoskeletal and

  6. The involvement of T lymphocytes in the pathogenesis of endometriotic tissues overgrowth in women with endometriosis.

    PubMed Central

    Szyllo, Krzysztof; Tchorzewski, Henryk; Banasik, Malgorzata; Glowacka, Ewa; Lewkowicz, Przemyslaw; Kamer-Bartosinska, Anna

    2003-01-01

    BACKGROUND: Endometriosis, uncontrolled proliferation of ectopic and eutopic endometriotic tissues, is common in women at reproductive age, and may affect fertility. The role of macrophages in the pathogenesis is well proved, but engagement of T cells in the pathogenesis of endometriosis is a matter of controversy. AIMS: T-cell involvement in the pathogenesis of endometriosis was the objective of our study performed on women aged 24-46 years with diagnosed endometriosis. All the patients that were studied underwent diagnostic laparoscopy. METHODS: We evaluated the distribution of T-lymphocyte subpopulations in peripheral blood (PB), peritoneal fluid (PF) and in endometriotic tissues (ET), as well as cytokines [interleukin (IL)-2, IL-4, IL-10, IL-12, interferon (IFN)-gamma] production by peripheral blood lymphocytes. IFN-gamma, tumor necrosis factor (TNF)-alpha, IL-4 and IL-6 were investigated for their intracellular presence. The experiments were carried out before and after 6 months treatment with the GnRH-Analogous Goserelin (Zeneca Pharmaceuticals). The number of performed investigations is presented. Statistical analysis was performed using Statistica/Win 5.0 software and Student's t-test, the paired Student t-test and Fisher's exact test when appropriate. RESULTS: We have compared the lymphocyte subset re-distribution with regard to the American Fertility Society (AFS) stages and scores, but no differences were observed. The significant increase in CD4:CD8 ratio, the decrease in the number of natural killer (NK) cells in PB and the decrease in CD4:CD8 ratio in PF and ET of women with endometriosis was noted. The diminished IFN-gamma secretion by phytohemagglutinim (PHA)-stimulated lymphocytes in vitro derived from women with endometriosis and increased IL-4 production may be responsible for defective immunosurveillance against overgrowth of endometriotic tissues. The diminished NK cells number in PB of women with endometriosis argues for such a hypothesis. The

  7. B lymphocyte stimulator -817C>T promoter polymorphism and the predisposition for the development of deep infiltrating endometriosis.

    PubMed

    de Graaff, Aisha A; Dunselman, Gerard A J; Delvoux, Bert; van Kaam, Kim J; Smits, Luc J M; Romano, Andrea

    2010-08-01

    The prevalence of the BLyS -817C>T polymorphic variant among women with either deep infiltrating endometriosis or adenomyosis compared with a group of gynecologic patients without symptomatic endometriosis and a group of healthy women was assessed in this study. Patients with deep infiltrating endometriosis had less often a BLyS -817C/T genotype as compared with the reference group, with an odds ratio of 0.50 (95% confidence interval 0.27-0.93 versus the C/C genotype). PMID:20004378

  8. What is the societal burden of endometriosis-associated symptoms? a prospective Belgian study.

    PubMed

    Klein, Sarah; D'Hooghe, Thomas; Meuleman, Christel; Dirksen, Carmen; Dunselman, Gerard; Simoens, Steven

    2014-01-01

    Endometriosis is a complex disease that affects a large number of women of reproductive age and imposes a significant burden on patients and society. The aim of this study was to evaluate diagnosis, comorbidities, healthcare resource use, treatment patterns, costs and quality of life of women with endometriosis seen in a Belgian tertiary care centre. A total of 134 patients were included in a prospective questionnaire-based cost-of-illness study. Patients were diagnosed after a median delay of 2 years after onset of symptoms. Almost all patients reported having at least one comorbidity. Total annual costs per patient were €9872 (95% confidence interval €7930–11,870), with costs of productivity loss representing 75% of total costs. Hospitalizations, surgeries, infertility treatments, pain and anxiety increased total costs significantly (P 0.001). Patients generated an average of 0.82 QaLY over a 1-year time horizon. This study showed that direct and indirect costs attributable to endometriosis-associated symptoms are substantial. Earlier diagnosis and cost-effective treatment of endometriosis may decrease productivity loss, quality of life impairment and healthcare consumption and consequently reduce total costs to patients and society. PMID:24268732

  9. Rectal mucosal endometriosis primarily misinterpreted as adenocarcinoma: a case report and review of literature

    PubMed Central

    Chen, Hui; Luo, Qiuping; Liu, Shaoyan; Xiong, Hanzhen; Jiang, Qingping

    2015-01-01

    Endometriosis involving intestinal mucosa is relatively uncommon. It poses a diagnostic challenge for clinicians and pathologists. We herein report a case of colonoscopic specimen revealing rectal mucosal endometriosis. A 39-year-old woman complained of red rectal bleeding and intermittent abdominal pain. Colonoscopic examination showed a rectal mass with ulceration and circum wall involvement. Biopsy was processed in the suspicious of carcinoma. Morphologically, irregular glands replaced residual colorectal ones, displayed mucin depletion, nuclear stratification and subtile subnuclear vacuoles. The stroma was full of spindle cells with abundant pink cytoplasm and unclear boundary. Due to subjectively interpreting as dysplastic glands in desmoplastic setting, primary rectal adenocarcinoma was firstly raised. Immunohistochemically, CK7, ER and CD10 identified the essence of ectopic endometrium. CK20 and CDX2 highlighted residual glands. In case of misdiagnosis, any pathologists should be aware of intestinal endometriosis for each female’s colorectal biopsy, especially for that morphology not typical for primary adenocarcinoma or endometriosis. Reading slides carefully combined with a panel of immunomarkers would solve the pitfall. PMID:26191316

  10. Polymorphic variants in vitamin D signaling pathway genes and the risk of endometriosis-associated infertility.

    PubMed

    Szczepańska, Malgorzata; Mostowska, Adrianna; Wirstlein, Przemyslaw; Skrzypczak, Jana; Misztal, Matthew; Jagodziński, Paweł P

    2015-11-01

    It has recently been reported that vitamin D blood plasma levels are associated with reduced risk of endometriosis. The present study aimed to investigate whether the vitamin D binding protein (GC), vitamin D receptor (VDR), and retinoid X receptor (RXR) gene variants may be genetic risk factors for endometriosis‑associated infertility. The subjects consisted of 154 women with endometriosis‑associated infertility and 347 controls. Using polymerase chain reaction restriction fragment length polymorphism and high resolution melt techniques, the GC rs1155563, rs2298849 and rs7041; RXRA rs10881578, rs10776909 and rs749759; VDR BsmI rs1544410; and FokI rs2228570 single nucleotide polymorphisms (SNPs) were investigated in the patients with endometriosis and the healthy controls. The results indicated that no significant differences were observed between the genotype and allele frequencies of all experimental SNPs in the vitamin D signaling pathway genes in women with endometriosis-associated infertility and controls. However, a significant association was present between the A‑T haplotype, consisting of VDR rs1544410 and rs222857 minor alleles, and endometriosis-associated infertility [OR=1.659 (1.122‑2.453), P=0.011]. The results of the present study suggested that VDR gene variants act as genetic risk factors for endometriosis‑associated infertility. PMID:26398313

  11. Glucoregulatory Function in Adult Rhesus Macaques (Macaca mulatta) Undergoing Treatment with Medroxyprogesterone Acetate for Endometriosis

    PubMed Central

    Cruzen, Christina L; Baum, Scott T; Colman, Ricki J

    2011-01-01

    Endometriosis affects a large percentage of the rhesus macaques (Macaca mulatta) at our institution. When the disease is diagnosed in macaques on long-term research protocols, the treatment of choice in our facility is monthly administration of medroxyprogesterone acetate (MPA) to decrease estrogen release and subsequently diminish clinical signs associated with the disease. Because hormonal fluctuations associated with the normal menstrual cycle are known to affect parameters of glucoregulatory function in rhesus macaques, we evaluated the effect of MPA treatment on glucoregulatory function cross-sectionally in 6 animals and longitudinally in 4 animals with endometriosis. Our hypothesis was that monthly administration of MPA for the treatment of endometriosis would negatively affect glucoregulatory function in rhesus macaques. We found that adult female rhesus macaques on MPA therapy for 1.4 to 36.1 mo had lower insulin sensitivity than did age- and weight-matched healthy control animals. In addition, glucoregulatory function was reduced after MPA treatment as compared with pretreatment levels in a group of 4 macaques. These data suggest that glucoregulatory function should be considered when endometriosis treatment is planned for rhesus macaques. PMID:22330788

  12. Macrophages: are they involved in endometriosis, abortion and preeclampsia and how?

    PubMed

    Hutter, Stefan; Heublein, Sabine; Knabl, Julia; Andergassen, Ulrich; Vrekoussis, Thomas; Makrigiannakis, Antonis; Friese, Klaus; Mayr, Doris; Jeschke, Udo

    2013-01-01

    Macrophages hold a key role in both regulating and executing the body's own immune response under various conditions. Hence, although endometriosis, preeclampsia and abortions are clinically different, all three are regarded to involve highly complex immunological processes. The aim of our current work was to evaluate the role of macrophages within these gynaecological disorders. Macrophages have been shown to invade endometriosis lesions and to mediate propagation of endometriotic cyst growth. However this is the first time that significant GPER up-regulation in macrophages is demonstrated. This highlights a potential alternative way through which estrogen may modulate immune response of macrophages in endometriosis. In addition, during spontaneous miscarriages the macrophage population increases significantly. This deregulation may possibly support an inflammatory scheme further triggering abortive procedures. Macrophage-mediated apoptosis of extravillous trophoblasts (EVT) has been associated with preeclampsia. Larger numbers of apoptotic EVT were detected in preeclamptic placentas compared with normal. In preeclamptic placentas, decidual macrophages were found to be Fas ligand (FasL)-positive. Our results highlight a new aspect of macrophage biology in endometriosis and pregnancy physiology and patho-physiology. Further studies with larger samples are needed to verify the current results and evaluate their clinical impact. Our data strongly indicate that macrophages hold key roles in various gynaecological disorders and might be crucial to further elucidate their patho-physiology. PMID:23657062

  13. Oxidative Stress and Antioxidant Defense in Endometriosis and Its Malignant Transformation

    PubMed Central

    Iwabuchi, Takuya; Yoshimoto, Chiharu; Shigetomi, Hiroshi; Kobayashi, Hiroshi

    2015-01-01

    The aim of this study was to investigate the role of redox status in endometriosis and its malignant transformation. A search was conducted between 1990 and 2014 through the English language literature (online MEDLINE PubMed database) using the keywords endometriosis combined with malignant transformation, oxidative stress, and antioxidant defense. In benign endometriosis, autoxidation and Fenton reaction of hemoglobin from the ferrous Fe2+ (oxyhemoglobin) state to the ferric Fe3+ (methemoglobin) state lead to production of excess reactive oxygen species (ROS) such as O2− and ∙OH. Hemoglobin, heme, and iron derivatives in endometriotic cysts cause distortion in the homeostatic redox balance. Excess oxidative stress could trigger DNA damage and cell death. In contrast, endometriosis-associated ovarian cancer (EAOC) might be associated with an effective antioxidant defense, including heme oxygenases, cytochrome P450 family, and glutathione transferase family. The pattern of redox balance supports that enhanced antioxidants may be involved in the pathogenesis of malignant transformation. In conclusion, oxidant/antioxidant balance function is a double-edged sword, promoting cell death or carcinogenesis. Upregulation of antioxidant functions in endometriotic cyst may result in restoration of cell survival and subsequent malignant transformation. PMID:26185594

  14. Advantages of the robotic approach to deep infiltrating rectal endometriosis: because less is more.

    PubMed

    Araujo, Sergio Eduardo Alonso; Seid, Victor Edmond; Marques, Renato Moretti; Gomes, Mariano Tamura Vieira

    2016-06-01

    For symptomatic deep infiltrating endometriosis, surgery is often required to achieve symptom relief and restore fertility. A minimally invasive approach using laparoscopy is considered the gold standard. However, specific limitations of the laparoscopic approach deep in the pelvis keep challenging even surgeons with a solid experience with minimally invasive techniques. Robotic surgery has the potential to compensate for technical drawbacks inherent in conventional laparoscopic surgery, such as limited degree of freedom, two-dimensional vision, and the fulcrum effect. In the present report, we aim at demonstrating the central role of robotic surgery for deep infiltrating endometriosis, with special emphasis in the ability to practice organ (rectal) preservation. A 45-year-old white female with a 4-month history of chronic pelvic pain, dyschezia, and dysmenorrhea, refractory to hormonal therapy was referred to our unit. MRI findings were diagnostic of deep infiltrating endometriosis (retrocervical and rectovaginal) extending to the anterior rectal serosal layer (partial-thickness rectal invasion). Using a fully robotic approach, appropriate dissection of the rectovaginal septum and of the extraperitoneal rectum followed by complete excision of the endometriotic rectal nodule with organ (rectal) preservation was undertaken. It is our belief that using a robotic approach, the potential to boost rectal preservation might be established. Moreover, it is possible that in many cases, a robotic operation may allow the surgeon to perform the intervention with greater accuracy and comfort. As a result, more patients with deep infiltrating endometriosis may benefit from rectal sparing procedures. PMID:27072152

  15. National German Guideline (S2k): Guideline for the Diagnosis and Treatment of Endometriosis*

    PubMed Central

    Ulrich, U.; Buchweitz, O.; Greb, R.; Keckstein, J.; von Leffern, I.; Oppelt, P.; Renner, S. P.; Sillem, M.; Stummvoll, W.; De Wilde, R.-L.; Schweppe, K.-W.

    2014-01-01

    In this guideline, recommendations and standards for optimum diagnosis and treatment of endometriosis are presented. They are based on the analysis of the available scientific evidence as published in prospective randomized and retrospective studies as well as in systematic reviews. The guideline working group consisted of experts from Austria, Germany, Switzerland, and the Czech Republic. PMID:26157194

  16. Aberrant levels of Wnt/β-catenin pathway components in a rat model of endometriosis.

    PubMed

    de Mattos, Rômulo Medina; Pereira, Paula Rodrigues; Barros, Eliane Gouvêa de Oliveira; da Silva, Julianna Henriques; Palmero, Celia Yelimar; da Costa, Nathália Meireles; Pinto, Luis Felipe Ribeiro; Gimba, Etel Rodrigues Pereira; Hecht, Fabio; Ferreira, Luciana Bueno; Machado, Daniel Escorsim; de Oliveira, Felipe Leite; Nasciutti, Luiz Eurico

    2016-08-01

    Endometriosis is a benign gynecological disease affecting approximately 10-15% of women of reproductive age and 25-50% of all infertile women. It is characterized by the presence of glands and/or endometrial stroma outside the uterine cavity. Angiogenesis is a crucial process for the development and maintenance of endometriotic lesions. The Wnt/β-catenin pathway is a major promoter of angiogenesis in both physiological and pathological conditions. In the present study, we evaluated the expression of molecules related to the Wnt/β-catenin pathway in a rat model of peritoneal endometriosis. mRNA analyses showed significantly increased expression of Wnt4 and Wnt7b and decreased expression of Gsk3beta and E-cadherin in endometriotic lesions. However, there were no differences in β-catenin and Fzd2 mRNA expression. In addition, we observed a significant increase of nuclear β-catenin in endometriotic lesions, a hallmark of Wnt/ β-catenin pathway activation. Stromal β-catenin staining was found in 45.4% of endometrial tissues and 77.8% of endometriotic lesions. β-catenin nuclear localization was found in 18.2% of the endometrial tissues and 33.3% of endometriotic lesions. Finally, the expression of galectin-3, a regulator of this pathway, was increased in endometriosis. In summary, this pattern of Wnt/β-catenin components expression suggests an increased activity of this pathway in endometriosis. PMID:26853489

  17. Continuous Amenorrhea May Be Insufficient to Stop the Progression of Colorectal Endometriosis.

    PubMed

    Millochau, Jenny-Claude; Abo, Carole; Darwish, Basma; Huet, Emmanuel; Dietrich, Gauthier; Roman, Horace

    2016-01-01

    We present the case of a patient in whom consecutive imaging assessment and surgery demonstrated the obvious progression of colorectal endometriosis under continuous medical therapy. A 26-year-old nullipara presented with secondary dysmenorrhea, deep dyspareunia, diarrhea, and constipation during menstruation. Magnetic resonance imaging (MRI) assessment revealed 2 right ovarian endometriomas, but no deep endometriosis lesion. Intraoperatively, we found a 2-cm length of thickened and congestive area of sigmoid colon, along with small superficial lesions arising in the small bowel and appendix. We performed ablation of ovarian endometriomas and appendectomy, and decided to not resect the bowel. Postoperative computed tomography-based virtual colonoscopy (CTC) revealed a slight abnormality of the sigmoid colon. Endorectal ultrasound identified a normal rectum and sigmoid colon. Despite long-term continuous medical treatment, the patient presented 4 years later with impaired digestion consisting in constipation alternating with diarrhea, bloating, dyschesia, and pelvic pain. MRI and CTC revealed an abnormal sigmoid colon from 42 to 50 cm above the anus, with digestive tract diameter reduced from 10 mm down to the virtual lumen, along with an overall rigid appearance. Laparoscopy revealed the extent of endometriosis lesions in the sigmoid colon and multiple implantations in the small bowel. We performed sigmoid and small bowel resection. This case demonstrates the obvious progression of deep rectal endometriosis despite 4 years of continuous hormonal therapy. PMID:27130533

  18. Endometriosis, in vitro fertilisation and the risk of gynaecological malignancies, including ovarian and breast cancer.

    PubMed

    Vlahos, Nikos F; Economopoulos, Konstantinos P; Fotiou, Stylianos

    2010-02-01

    There is evidence that endometriosis as well as drugs used in the process of in vitro fertilisation appear to associate with increased risk for gynaecological cancer. In this review, we attempt to describe this relationship according to the most recent epidemiologic data and to present the possible mechanisms on the molecular level that could potentially explain this correlation. There are data to support that ovarian endometriosis could have the potential for malignant transformation. Epidemiologic and genetic studies support this notion. It seems that endometriosis is associated with specific types of ovarian cancer (endometrioid and clear cell). There is no clear association between endometriosis and breast or endometrial cancer. More studies are needed to establish the risk factors that may lead to malignant transformation of this condition and to identify predisposed individuals who may require closer surveillance. Currently, there is no proven relationship between any type of gynaecological cancer and drugs used for infertility treatment. In principle, infertile women have increased risk for gynaecologic malignancies. Nulligravidas who received treatment are at increased risk for malignancy compared with women who had conceived after treatment. There is limited evidence that clomiphene citrate use for more than six cycles or 900mg or treatment of women over the age of 40 could increase their risk for ovarian and breast cancer. More studies with the appropriate statistical power and follow-up time are required to evaluate accurately the long-term effects of these drugs and procedures. PMID:19733123

  19. Pregnancy Rate after Controlled Ovarian Hyperstimulation and Intrauterine Insemination for the Treatment of Endometriosis following Surgery

    PubMed Central

    Keresztúri, Attila; Kozinszky, Zoltan; Daru, József; Pásztor, Norbert; Sikovanyecz, János; Zádori, János; Márton, Virág; Koloszár, Sándor; Szöllősi, János; Németh, Gábor

    2015-01-01

    Objective. To compare pregnancy rate after controlled ovarian hyperstimulation and intrauterine insemination (COH-IUI) with no treatment in patients with endometriosis-associated infertility treated with laparoscopy. Design. A clinical cohort study. Setting. University-level tertiary care center. Patients. 238 women with various stages of endometriosis after laparoscopic treatment. Interventions. Either COH-IUI or follow-up for 12 months. Main Outcome Measures. The primary outcome measures were clinical pregnancy and live birth rate. Predictive factors evaluated were female age, maternal BMI, and duration of infertility. Results. The pregnancy rate attained after the integrated laparoscopy–COH-IUI approach was 53.4%, while it was significantly lower (38.5%) in the control group. Similarly, a significant difference was observed in live births (48.3% versus 34.2%). Patients with severe endometriosis were less likely to achieve pregnancy (38%) and live birth (35%) than their counterparts with milder forms (57% and 53%). Conclusions. In patients with endometriosis-based infertility, surgery followed by COH-IUI is more effective than surgery alone. PMID:26247014

  20. [A case of intestinal occlusion caused by endometriosis of the cecum].

    PubMed

    Veneziano, M; Zaraca, F; Framarino, M; Di Paola, M; Giobbe, M; Montemurro, L; Fabiani, C; Filippoussis, P; Mancicni, B; Marzetti, L; Carboni, M

    1999-01-01

    The purpose of this study is to heighten awareness of intestinal endometriosis, a disease that may mimic other abdominal pathologies (bowel carcinoma, intestinal inflammatory disease, diverticulitis), sometimes found in the emergency setting. The Authors report a case of acute bowel obstruction due to coecal endometriosis with appendix mucocele, peritoneal pseudomyxoma and ovarian endometrioma. The patient was operated on in the emergency setting, a right colectomy was performed and she then received pharmacological suppressive treatment with Gn-RH analogues and danatrol. We remark that preoperative diagnosis is very difficult in those cases that do not have a past history of pelvic endometriosis. An accurate anamnesis regarding the chronology of pain onset (typically only during the menstruation at first), but especially intraoperative histopathologic examination are useful for diagnosis. An increased awareness of intestinal endometriosis in reproductive age women with acute bowel obstruction, associated with an accurate anamnesis of menstrual history may allow pre- or intraoperative diagnosis, which is the clue to a less aggressive operation. Postoperative follow up and hormonal therapy are mandatory. PMID:10793771

  1. Systematic approach to sonographic evaluation of the pelvis in women with suspected endometriosis, including terms, definitions and measurements: a consensus opinion from the International Deep Endometriosis Analysis (IDEA) group.

    PubMed

    Guerriero, S; Condous, G; van den Bosch, T; Valentin, L; Leone, F P G; Van Schoubroeck, D; Exacoustos, C; Installé, A J F; Martins, W P; Abrao, M S; Hudelist, G; Bazot, M; Alcazar, J L; Gonçalves, M O; Pascual, M A; Ajossa, S; Savelli, L; Dunham, R; Reid, S; Menakaya, U; Bourne, T; Ferrero, S; Leon, M; Bignardi, T; Holland, T; Jurkovic, D; Benacerraf, B; Osuga, Y; Somigliana, E; Timmerman, D

    2016-09-01

    The IDEA (International Deep Endometriosis Analysis group) statement is a consensus opinion on terms, definitions and measurements that may be used to describe the sonographic features of the different phenotypes of endometriosis. Currently, it is difficult to compare results between published studies because authors use different terms when describing the same structures and anatomical locations. We hope that the terms and definitions suggested herein will be adopted in centers around the world. This would result in consistent use of nomenclature when describing the ultrasound location and extent of endometriosis. We believe that the standardization of terminology will allow meaningful comparisons between future studies in women with an ultrasound diagnosis of endometriosis and should facilitate multicenter research. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. PMID:27349699

  2. Comparison of ovarian cancer markers in endometriosis favours HE4 over CA125.

    PubMed

    Mckinnon, Brett; Mueller, Michael D; Nirgianakis, Konstantinos; Bersinger, Nick A

    2015-10-01

    Endometriosis is a gynaecological condition with an associated chronic inflammatory response. The ectopic growth of 'lesions', consisting of endometrial cells outside the uterine cavity, stimulates an inflammatory response initiating the activation of macrophages, and resulting in increased cytokine and growth factor concentrations in the peritoneal fluid (PF). Endometriosis‑associated inflammation is chronic and long lasting. In patients with endometriosis, the risk of developing ovarian cancer within 10 years, particularly of the endometrioid or clear cell subtype, is increased 2.5‑4 times. Endometriosis creates a peritoneal environment that exposes the affected endometriotic and the normal ovarian surface epithelial cells to agents that have been suggested to be involved in the pathogenesis of cancer. Concentrations of several cytokines and growth factors were increased in the PF of patients with endometriosis. The ovarian cancer marker, CA125, was one such growth factor; however, this remains to be confirmed. Human epididymis protein 4 (HE4) was detected at high concentrations in patients with ovarian cancer and was identified as the best biomarker for the detection of ovarian cancer. The present study determined the levels of HE4 and CA125 in the peritoneal fluid of 258 patients with and 100 control individuals without endometriosis attending the Department of Obstetrics and Gynaecology, University of Berne (Berne, Switzerland) between 2007 and 2014. The cases were subdivided into groups without hormonal treatment (n=107), or treated with combined oral contraceptives (n=45), continuous gestagens (n=56) or GnRH agonists (n=50). Both of these markers were significantly increased in the non‑treated endometriosis samples compared with the control group. Hormone treatment with either of the three agents mentioned resulted in the concentration of CA125 returning to the control levels and the concentration of HE4 decreasing to below the control levels. CA125

  3. Neural involvement in endometriosis: Review of anatomic distribution and mechanisms.

    PubMed

    Siquara De Sousa, Ana C; Capek, Stepan; Amrami, Kimberly K; Spinner, Robert J

    2015-11-01

    Endometriosis (EM) is an infrequent cause of peripheral neuropathy, most commonly sciatic. Perineural spread has recently been introduced as an alternate explanation for cases of lumbosacral or sciatic nerve EM. We performed a literature review to collect all reported cases of peripheral and central nervous system EM in search of anatomic patterns of involvement; potentially to support the perineural spread theory. If available, intraneural invasion and presence of peritoneal EM were recorded. The search revealed 83 articles describing 365 cases of somatic peripheral nervous EM and 13 cases of central nervous EM. The most frequently involved site was the sacral plexus (57%, n = 211), followed by the sciatic nerve (39%, n = 140). Other nerves were reported in significantly smaller numbers. Ninety seven percent (97%, n = 355) of peripheral nerve cases presented with pain, 20% (n = 72) reported weakness and 31% (n = 114), numbness. Thirty four percent (34%, n = 38) had solely intraneural EM of which 89% (n = 33) had no peritoneal EM (percentage based on available information). In the central nervous system, the conus medullaris and/or cauda equina constituted the majority of cases with 54% (n = 7). Apart from perineural spread, other discussed mechanisms include retrograde menstruation with peritoneal seeding, hematogenous and lymphogenous spread, stem cell implantation either hematogenously or via retrograde menstruation with subsequent EM differentiation, and coelomic or Müllerian duct metaplasia. We believe this literature review supports perineural spread as an alternate mechanism for EM of nerve, particularly the subgroup with intraneural EM and without peritoneal disease. PMID:26296428

  4. 17β-estradiol and lipopolysaccharide additively promote pelvic inflammation and growth of endometriosis.

    PubMed

    Khan, Khaleque Newaz; Kitajima, Michio; Inoue, Tsuneo; Fujishita, Akira; Nakashima, Masahiro; Masuzaki, Hideaki

    2015-05-01

    Endometriosis is a multifactorial disease mostly affecting women of reproductive age. An additive effect between inflammation and stress reaction on the growth of endometriosis has been demonstrated. Here we investigated the combined effect between 17β-estradiol (E2) and lipopolysaccharide (LPS) on pelvic inflammation and growth of endometriotic cells. Peritoneal fluid was collected from 46 women with endometriosis and 30 control women during laparoscopy. Peritoneal macrophages (Mφ) and stromal cells from eutopic/ectopic endometrial stromal cells (ESCs) were isolated from 10 women each with and without endometriosis in primary culture. Changes in cytokine secretion (interleukin 6 [IL-6] and tumor necrosis factor α [TNF-α]) by Mφ and proliferation of ESCs in response to single and combined treatment with E2 and LPS were measured by enzyme-linked immunosorbent assay and by bromodeoxyuridine incorporation assay, respectively. A significantly increased secretion of IL-6 and TNF-α in Mφ culture media was found in response to E2 (10(-8) mol/L) compared to nontreated Mφ. This effect of E2 was abrogated after pretreatment of cells with ICI 182720 (10(-6) mol/L; an estrogen receptor [ER] antagonist). Combined treatment with E2 and LPS (10 ng/mL) additively promoted IL-6 and TNF-α secretion by peritoneal Mφ and growth of eutopic/ectopic ESCs. The additive effects of E2 + LPS on cytokine secretion and growth of ESCs were effectively suppressed after combined blocking of ER and Toll-like receptor 4. An additive effect was observed between E2 and LPS on promoting proinflammatory response in pelvis and growth of endometriosis. PMID:25355803

  5. Molecular Evidence for Differences in Endometrium in Severe Versus Mild Endometriosis

    PubMed Central

    Aghajanova, Lusine; Giudice, Linda C.

    2011-01-01

    Women with stage III/IV versus stage I/II endometriosis have lower implantation and pregnancy rates in natural and assisted reproduction cycles. To elucidate potential molecular mechanisms underlying these clinical observations, herein we investigated the transcriptome of eutopic endometrium across the menstrual cycle in the setting of severe versus mild endometriosis. Proliferative (PE), early secretory (ESE), and mid-secretory (MSE) endometrial tissues were obtained from 63 participants with endometriosis (19 mild and 44 severe). Purified RNA was subjected to microarray analysis using the Gene 1.0 ST Affymetrix platform. Data were analyzed with GeneSpring and Ingenuity Pathway Analysis and subsequently validated. Comparison of differentially regulated genes, analyzed by cycle phase, revealed dysregulation of progesterone and/or cyclic adenosine monophosphate (cAMP)-regulated genes and genes related to thyroid hormone action and metabolism. Also, members of the epidermal growth factor receptor (EGFR) signaling pathway were observed, with the greatest upregulation of EGFR in severe versus mild disease during the early secretory phase. The extracellular matrix proteoglycan versican (VCAN), which regulates cell proliferation and apoptosis, was the most highly expressed gene in severe versus mild disease. Upregulation of microRNA 21 (MIR21) and DICER1 transcripts suggests roles for microRNAs (miRNAs) in the pathogenesis of severe versus mild endometriosis, potentially through regulation of gene silencing and epigenetic mechanisms. These observed differences in transcriptomic signatures and signaling pathways may result in poorly programmed endometrium during the cycle, contributing to lower implantation and pregnancy rates in women with severe versus mild endometriosis. PMID:21063030

  6. CHARACTERIZATION OF UTERINE NK CELLS IN WOMEN WITH INFERTILITY OR RECURRENT PREGNANCY LOSS AND ASSOCIATED ENDOMETRIOSIS

    PubMed Central

    Giuliani, Emma; Parkin, Kirstin L.; Lessey, Bruce A.; Young, Steven L.; Fazleabas, Asgerally T.

    2014-01-01

    Problem Uterine natural killer cells (uNK) have been thought to play a key role in endometriosis and infertility. We investigated the expression of CD56, CD16 and NKp46 in endometrial tissues from 61 women with unexplained recurrent pregnancy loss (uRPL) or infertility (UI), and correlated this with the presence or absence of endometriosis. The results from the patients with sub-fertility were compared to those from 10 fertile patients. Method of study Mid-secretory phase endometrial biopsies were obtained and the endometrial expression of CD56, CD16 or NKp46 was identified by immunohistochemistry and quantified (ImageJ Software). Results The percentage of CD16+ cells was higher in women with uRPL (7.9±3.2) and UI (9.0±5.5), even when these conditions were associated with endometriosis (8.9±5.3), compared to fertile patients (5.6±2.4, p<0.05). Likewise, the ratio of NKp46+:CD56+ cells was higher in women with uRPL (0.28±0.25) and UI (0.21±0.2), even when these conditions were associated with endometriosis (0.19±0.14), compared to fertile patients (0.1±0.1, p<0.05). No differences were observed when comparing CD56. Conclusions Women, with or without endometriosis, who have larger populations of cytotoxic CD16+ uNK cells and/or higher populations of NKp46+CD56+ cells may be at greater risk for infertility disorders resulting from an inflammtory environment occuring during implantation or later during decidualization. PMID:24807109

  7. Altered levels of acylcarnitines, phosphatidylcholines, and sphingomyelins in peritoneal fluid from ovarian endometriosis patients.

    PubMed

    Vouk, Katja; Ribič-Pucelj, Martina; Adamski, Jerzy; Rižner, Tea Lanišnik

    2016-05-01

    Endometriosis is a complex, polygenic, and estrogen-dependent disease that affects 6% to 10% of women of reproductive age, and 30% to 50% of women with infertility and/or pelvic pain. Surgical diagnosis of endometriosis is still the gold standard, as there are currently no diagnostic biomarkers available. Due to the invasive diagnostics, it can take up to 11 years before affected women are diagnosed and receive the appropriate treatment. We performed a targeted metabolomics study to search for potential semi-invasive biomarkers in peritoneal fluid from endometriosis patients. Our case-control study comprised 29 ovarian endometriosis patients and 36 healthy control women. The 148 metabolites included acylcarnitines, glycerophospholipids, and sphingolipids, which were quantified by electrospray ionization tandem mass spectrometry. The strength of association between the metabolites and the metabolite ratios and disease was assessed using crude and adjusted odds ratios. The best combination of biomarkers was then selected by performing step-wise logistic regression. Our analysis reveals significantly decreased concentrations of 10 metabolites, of carnitine and acylcarnitines (C0, C8:1, C6C4:1 DC, C10:1), phosphatidylcholines (PC aa C38:3, PC aa C38:4, PC aa C40:4, PC aa C40:5), and sphingomyelins (SM C16:1, SM C18:1), and 125 significantly altered metabolite ratios in patients versus control women. The best model includes two ratios: a carnitine to a phosphatidylcholine (C0/PC ae C36:0); and between two phosphatidylcholines (PC aa C30:0/PC ae C32:2). When adjusted for age, this provides sensitivity of 82.8% and specificity of 94.4%, with AUC of 0.944. Our study supports the importance of carnitine, phosphatidylcholine, and sphingomyelin metabolites in the pathophysiology of endometriosis, and confirms the potential for the combination of individual metabolite ratios to provide biomarkers for semi-invasive diagnostics. PMID:26921767

  8. Estradiol Is a Critical Mediator of Macrophage-Nerve Cross Talk in Peritoneal Endometriosis

    PubMed Central

    Greaves, Erin; Temp, Julia; Esnal-Zufiurre, Arantza; Mechsner, Sylvia; Horne, Andrew W.; Saunders, Philippa T.K.

    2016-01-01

    Endometriosis occurs in approximately 10% of women and is associated with persistent pelvic pain. It is defined by the presence of endometrial tissue (lesions) outside the uterus, most commonly on the peritoneum. Peripheral neuroinflammation, a process characterized by the infiltration of nerve fibers and macrophages into lesions, plays a pivotal role in endometriosis-associated pain. Our objective was to determine the role of estradiol (E2) in regulating the interaction between macrophages and nerves in peritoneal endometriosis. By using human tissues and a mouse model of endometriosis, we demonstrate that macrophages in lesions recovered from women and mice are immunopositive for estrogen receptor β, with up to 20% being estrogen receptor α positive. In mice, treatment with E2 increased the number of macrophages in lesions as well as concentrations of mRNAs encoded by Csf1, Nt3, and the tyrosine kinase neurotrophin receptor, TrkB. By using in vitro models, we determined that the treatment of rat dorsal root ganglia neurons with E2 increased mRNA concentrations of the chemokine C-C motif ligand 2 that stimulated migration of colony-stimulating factor 1–differentiated macrophages. Conversely, incubation of colony-stimulating factor 1 macrophages with E2 increased concentrations of brain-derived neurotrophic factor and neurotrophin 3, which stimulated neurite outgrowth from ganglia explants. In summary, we demonstrate a key role for E2 in stimulating macrophage-nerve interactions, providing novel evidence that endometriosis is an estrogen-dependent neuroinflammatory disorder. PMID:26073038

  9. Colorectal resection in deep pelvic endometriosis: Surgical technique and post-operative complications

    PubMed Central

    Milone, Marco; Vignali, Andrea; Milone, Francesco; Pignata, Giusto; Elmore, Ugo; Musella, Mario; De Placido, Giuseppe; Mollo, Antonio; Fernandez, Loredana Maria Sosa; Coretti, Guido; Bracale, Umberto; Rosati, Riccardo

    2015-01-01

    AIM: To investigate the impact of different surgical techniques on post-operative complications after colorectal resection for endometriosis. METHODS: A multicenter case-controlled study using the prospectively collected data of 90 women (22 with and 68 without post-operative complications) who underwent laparoscopic colorectal resection for endometriosis was designed to evaluate any risk factors of post-operative complications. The prospectively collected data included: gender, age, body mass index, American Society of Anesthesiologists risk class, endometriosis localization (from anal verge), operative time, conversion, intraoperative complications, and post-operative surgical complications such as anastomotic dehiscence, bleeding, infection, and bowel dysfunction. RESULTS: A similar number of complicated cases have been registered for the different surgical techniques evaluated (laparoscopy, single access, flexure mobilization, mesenteric artery ligation, and transvaginal specimen extraction). A multivariate regression analysis showed that, after adjusting for major clinical, demographic, and surgical characteristics, complicated cases were only associated with endometriosis localization from the anal verge (OR = 0.8, 95%CI: 0.74-0.98, P = 0.03). After analyzing the association of post-operative complications and each different surgical technique, we found that only bowel dysfunction after surgery was associated with mesenteric artery ligation (11 out of 44 dysfunctions in the mesenteric artery ligation group vs 2 out of 36 cases in the no mesenteric artery ligation group; P = 0.03). CONCLUSION: Although further randomized clinical trials are needed to give a definitive conclusion, laparoscopic colorectal resection for deep infiltrating endometriosis appears to be both feasible and safe. Surgical technique cannot be considered a risk factor of post-operative complications. PMID:26715819

  10. Improving accuracy of intraoperative diagnosis of endometriosis: Role of firefly in minimal access robotic surgery

    PubMed Central

    Lue, John R.; Pyrzak, Adam; Allen, Jennifer

    2016-01-01

    Endometriosis continues to be a major primary gynecologic etiology of chronic pelvic pain. The symptom profile, which includes cyclic pelvic pain, dysmenorrhea, and dyspareunia or dyschezia, is nonspecific and does not correlate with the extent or severity of disease. Trans-vaginal or trans-rectal ultrasound, as well as magnetic resonance imaging, can help visualize endometriomas and deeply infiltrating endometriosis. Additionally, there have been no serum marker tests available so far. However, even intraoperatively, the diagnosis may be missed, leading to under diagnosis and delayed or noninitiation of treatment. There are thought to be three distinct endometriotic lesions of the pelvis that are seen laparoscopically. The first is that which is visible on the pelvic peritoneal surface or the surface of the ovary, which is commonly termed peritoneal endometriosis. Second, endometriotic lesions that occur within the ovary and form cysts that are often lined with endometrioid mucosa are termed endometriomas. Lastly, rectovaginal endometriomas are endometriotic lesions that contain a mixture of adipose and fibrous tissue located between the rectum and vagina. All of these lesions can be singular or multiple and the pelvis may contain one or all three types of lesions. The shared histologic feature with all three lesions is the presence of endometrial epithelial cells or endometrial stroma. During a diagnostic procedure, the da-Vinci robot and its firefly mode allow for three dimensional visualization and seven degrees of instrument articulation for meticulous dissection of fibrotic areas of peritoneum that may contain deep infiltrating lesions of endometriosis. This case report describes a relatively new and innovative technique for effectively diagnosing and successfully treating endometriosis when other less invasive methods have failed. PMID:27073317

  11. Cyst fluid hemoglobin species in endometriosis and its malignant transformation: The role of metallobiology

    PubMed Central

    IWABUCHI, TAKUYA; YOSHIMOTO, CHIHARU; SHIGETOMI, HIROSHI; KOBAYASHI, HIROSHI

    2016-01-01

    The aim of the present study was to assess the relative concentrations of hemoglobin (Hb) species in endometriosis as a possible indicator of malignancy. Electronic absorption spectroscopy was employed to quantify the Hb species present in the cyst fluid collected from 8 patients with endometriosis-associated ovarian cancer (EAOC), and compared with those present in the cyst fluid of 35 patients with benign endometriotic cysts. The 620/580 nm ratio in the electronic absorption spectrum, which was used as a surrogate indicator of the methemoglobin (metHb)/(oxyhemoglobin+metHb) ratio, was measured in each cyst fluid by ultraviolet/visible grating spectrophotometric microplate reader. The optimal cutoff value was defined according to the analysis of receiver operating characteristic (ROC) curve. The sensitivity and specificity of detection were calculated on the basis of the cutoff value to differentiate EAOC from endometriosis. The 620/580 nm ratio of cyst fluid in EAOC patients was much lower than that measured in women with benign cysts (0.389±0.266 vs. 0.666±0.188, P=0.021). ROC curve analysis performed using 0.35 as the optimal cutoff value indicated that the 620/580 nm ratio had a sensitivity, specificity, positive predictive value (PPV) and negative predictive value of 62.5, 100.0, 100.0 and 92.1%, respectively, in the diagnosis of EAOC. In conclusion, metHb is one of the most abundant Hb species in benign cysts, and the absorption 620/580 nm ratio of cyst fluid exhibits high specificity and PPV as a surveillance test for the early detection of malignant transformation of endometriosis. Thus, metallobiology highlights diverse features involved in Hb homeostasis and the pathogenesis of malignant transformation of endometriosis. PMID:27123121

  12. Improving accuracy of intraoperative diagnosis of endometriosis: Role of firefly in minimal access robotic surgery.

    PubMed

    Lue, John R; Pyrzak, Adam; Allen, Jennifer

    2016-01-01

    Endometriosis continues to be a major primary gynecologic etiology of chronic pelvic pain. The symptom profile, which includes cyclic pelvic pain, dysmenorrhea, and dyspareunia or dyschezia, is nonspecific and does not correlate with the extent or severity of disease. Trans-vaginal or trans-rectal ultrasound, as well as magnetic resonance imaging, can help visualize endometriomas and deeply infiltrating endometriosis. Additionally, there have been no serum marker tests available so far. However, even intraoperatively, the diagnosis may be missed, leading to under diagnosis and delayed or noninitiation of treatment. There are thought to be three distinct endometriotic lesions of the pelvis that are seen laparoscopically. The first is that which is visible on the pelvic peritoneal surface or the surface of the ovary, which is commonly termed peritoneal endometriosis. Second, endometriotic lesions that occur within the ovary and form cysts that are often lined with endometrioid mucosa are termed endometriomas. Lastly, rectovaginal endometriomas are endometriotic lesions that contain a mixture of adipose and fibrous tissue located between the rectum and vagina. All of these lesions can be singular or multiple and the pelvis may contain one or all three types of lesions. The shared histologic feature with all three lesions is the presence of endometrial epithelial cells or endometrial stroma. During a diagnostic procedure, the da-Vinci robot and its firefly mode allow for three dimensional visualization and seven degrees of instrument articulation for meticulous dissection of fibrotic areas of peritoneum that may contain deep infiltrating lesions of endometriosis. This case report describes a relatively new and innovative technique for effectively diagnosing and successfully treating endometriosis when other less invasive methods have failed. PMID:27073317

  13. Supporting and Inhibiting Factors When Coping with Endometriosis From the Patientsʼ Perspective

    PubMed Central

    Kundu, S.; Wildgrube, J.; Schippert, C.; Hillemanns, P.; Brandes, I.

    2015-01-01

    Aim: Endometriosis is a chronic gynaecological disorder with manifold symptoms and psychosocial effects on the lives of affected women. The prevalence of endometriosis is estimated to be up to ten percent of women of reproductive age. As a result of its unclear aetiology, only limited treatment options are available. The treatment and care of affected women is therefore a challenge for their doctors. There is a need for healthcare services to provide affected women with support to cope with the disorder better. The aim of the study was to identify supporting and inhibiting factors on disease management to develop new support ideas. Materials and Methods: The results are based on a content analysis evaluation of text responses from 135 women with confirmed endometriosis. Open questions about disease management were posed in a patient questionnaire. A classification system was developed according to Mayrings Qualitative Content Analysis, which allowed the main topics to be identified and summarised qualitatively using a quantitative intermediate step. Results: Social support, treatment, as well as professional and healthcare system performance were found to be particularly supportive by patients. However, when questioned about inhibiting factors, healthcare system professionals and their performance were most commonly criticised. Just over 50 % of women expressed their criticism of doctors. Quality of care and empathy towards the patients were especially criticised. There is also a need for improvement with regard to communication and general support from doctors. The results illustrate the importance of doctors for women affected by endometriosis, but make it clear that there is a great need for improvement with regard to the profession. Conclusion: The results provide the first indication of problem areas in the management of endometriosis from which approaches could be developed to improve care. However, it must be pointed out that the perspective of affected

  14. Recent advances in the understanding of endometriosis: the role of inflammatory mediators in disease pathogenesis and treatment

    PubMed Central

    Nothnick, Warren; Alali, Zahraa

    2016-01-01

    In this review, we focus on recent advancements in our understanding of the roles of inflammatory mediators in endometriosis pathophysiology and the potential for improved therapies based upon targeting these pathways. We review the association between endometriosis and inflammation and the initial promise of anti-tumor necrosis factor therapies based upon experimental evidence, and how and why these studies have not translated to the clinic. We then discuss emerging data on the role of inter-relationship among macrophage migration inhibitory factor, prostaglandin E 2, and estrogen receptor-beta, and the potential utility of targeting these factors in endometriosis treatment. In doing so, we highlight the strengths and discuss the current research on identification of novel, anti-inflammatory-based therapy and the necessity to expand experimental endpoints to include clinically relevant measures when assessing the efficacy of potential new therapies for endometriosis. PMID:26949527

  15. Performance of Circulating Placental Growth Factor as A Screening Marker for Diagnosis of Ovarian Endometriosis: A Pilot Study

    PubMed Central

    Zucchini, Cinzia; De Sanctis, Paola; Facchini, Chiara; Di Donato, Nadine; Montanari, Giulia; Bertoldo, Valentina; Farina, Antonio; Curti, Alessandra; Seracchioli, Renato

    2016-01-01

    Background The aim of this study is to compare the circulating placental growth factor (PlGF) concentration in women with and without endometrioma to verify the performance of this marker to diagnose the disease. Materials and Methods In this case-control study, thirteen women with histological diagnosis of ovarian endometriosis were compared with women without endometriosis disease. PlGF plasma levels of endometriotic patients and controls were investigated using a fluorescence immunoassay technique. Results PlGF showed a direct correlation with body mass index (BMI) only in the control group (P=0.013). After adjustment for BMI values, PlGF median value in endometriosis group (14.7 pg/mL) resulted higher than in control group (13.8 pg/ mL, P=0.004). Conclusion PlGF is a promising peripheral blood marker that can discriminate between patients with and without ovarian endometriosis. PMID:26985335

  16. I never know from one day to another how I will feel: pain and uncertainty in women with endometriosis.

    PubMed

    Denny, Elaine

    2009-07-01

    Endometriosis is a chronic condition of women in which endometrial tissue is present outside of the uterus. It is characterized by pelvic pain. The aim of this prospective study was to explore women's experience of living with endometriosis. A sample of 30 women was recruited from a dedicated endometriosis clinic. Semistructured interviews were conducted upon recruitment and after one year, these data being supplemented by diary keeping by a volunteer sample. As a storytelling approach was utilized for data collection, narrative analysis was considered most appropriate. The findings are presented using the concept of uncertainty, which has been found in previous research to be a feature of long-term illness. Uncertainty exists around diagnosis, the course of the disease, and the future. It is argued that the way in which the pain of endometriosis is interpreted and managed by women and health professionals is integral to this uncertainty. PMID:19470614

  17. Adhesions and endometriosis: challenges in subfertility management : (An expert opinion of the ANGEL-The ANti-Adhesions in Gynaecology Expert PaneL-group).

    PubMed

    De Wilde, R L; Alvarez, J; Brölmann, H; Campo, R; Cheong, Y; Lundorff, P; Pawelczyk, L; Roman, H; di Spiezio Sardo, A; Wallwiener, M

    2016-08-01

    There is molecular evidence that endometriosis has a negative impact on the ovaries, although the exact pathophysiology concerning endometriosis-associated subfertility is not known. The negative impact on the tubo-ovarian unit can be directly by distorting the anatomy, indirectly by invoking inflammation or by oxidative damage with poorer-quality oocytes. Endometriosis even seems to have a negative effect on pregnancy outcome after in vitro fertilization. PMID:26894304

  18. The role of NADPH-derived reactive oxygen species production in the pathogenesis of endometriosis: a novel mechanistic approach.

    PubMed

    Nassif, J; Abbasi, S A; Nassar, A; Abu-Musa, A; Eid, A A

    2016-01-01

    Endometriosis is defined as endometriotic tissue growing outside the uterine cavity. It is a common gynecological disorder in women of reproductive age and is associated with chronic pelvic pain and infertility. Despite several studies and theories to explain its cause, the exact pathogenesis of endometriosis remains unclear. Retrograde menstruation is the most plausible theory, however, it is not exclusive. The disparity between the actual prevalence of retrograde menstruation and the prevalence of endometriosis suggests that other factors may determine the susceptibility to endometriosis development. Oxidative stress has been associated with endometriosis. This study aimed to explore the role of NADPH oxidase family in the production of reactive oxygen species (ROS) and to determine whether ROS induce the proliferation of endometriotic implants via mammalian target of rapamycin (mTOR) signaling. Anonymous endometriotic tissue samples were collected from women undergoing laparoscopy for endometriosis. The samples were stained with dihydroethidium and fluorescent images of the slides were taken to detect ROS production. After extraction of RNA from the samples and c-DNA generation, quantitative real-time PCR, protein extraction and Western blot were performed to study gene and protein expression of NADPH oxidase 1 (NOX 1), mTOR and fibronectin. The results showed an increase in ROS levels and NOX 1 gene and protein expression in the endometriotic tissues compared to the normal surrounding tissue control. Also, mTOR and fibronectin, gene expression was found to be increased. Up regulation of NOX at gene and protein level leads to increased production of ROS in the endometriotic tissue, which in turn causes proliferation of the ectopic tissue via alteration of the mTOR signaling pathway. Increased fibronectin gene expression points towards tissue injury in endometriosis as compared to the normal surrounding tissue. This manuscript adds a new insight into the

  19. Activated Hippo/Yes-Associated Protein Pathway Promotes Cell Proliferation and Anti-apoptosis in Endometrial Stromal Cells of Endometriosis

    PubMed Central

    Song, Yong; Fu, Jing; Zhou, Min; Xiao, Li; Feng, Xue; Chen, Hengxi

    2016-01-01

    Context: The imbalance in cell proliferation and apoptosis is considered an important role in the pathogenesis of endometriosis, but the exact mechanisms remains unclear. A newly established signaling pathway–Hippo/Yes-associated protein (YAP) pathway plays a critical role in the proliferation and apoptosis processes. However, studies focusing on Hippo/YAP pathway and endometriosis are lacking. Objective: The objective was to explore the function of the Hippo/YAP pathway in endometriosis. Setting and Design: The expression of YAP was first investigated in endometrium of women with or without endometriosis. The role of YAP in cell proliferation and apoptosis is identified by transfection of endometrial stromal cells (ESCs) in vitro, subsequent Verteporfin treatments in eutopic ESCs in vitro, and endometriosis animal model of nude mice in vivo. Results: Our results revealed that increased expression of YAP and decreased expression of p-YAP in ectopic and eutopic endometrium compared with normal endometrium. YAP knockdown in eutopic ESCs decreased cell proliferation and enhanced cell apoptosis companied with decreased expression of TEAD1, CTGF, and B-cell lymphoma/leukemia (BCL)-2; whereas overexpression of YAP resulted in increased proliferation and decreased apoptosis of normal ESCs with increased expression of TEAD1, CTGF, and BCL-2. By chromatin immunoprecipitation qPCR CTGF and BCL-2 were identified as directly downstream target genes of YAP-TEAD1 active complex. Eutopic ESCs treated with Verteporfin revealed decreased proliferation and enhanced apoptosis whereas in endometriosis animal models of nude mice treated with Verteporfin, the size of endometriotic lesions was significantly reduced. Conclusions: Our study suggests that the Hippo/YAP-signaling pathway plays a critical role in the pathogenesis of endometriosis and should present a novel therapeutic method against endometriosis. PMID:26977530

  20. Anastomotic Leakage in a Patient with Acute Intestinal Obstruction Secondary to Appendiceal and Ileal Endometriosis: A Case Report

    PubMed Central

    Yabanoglu, Hakan; Hasbay, Bermal

    2016-01-01

    Endometriosis is a commonly encountered problem in women of reproductive age. It usually causes chronic abdominal pain. However, it rarely causes complications such as intestinal obstruction. The most commonly performed procedure for these patients is bowel resection and anastomosis. Unless it is complicated with anastomotic leakage. We present a 39-year-old woman presented with intestinal obstruction due to appendiceal and ileal endometriosis complicated with anastomotic leakage after surgery. PMID:27190890

  1. Nickel Allergy Is a Risk Factor for Endometriosis: An 11-Year Population-Based Nested Case-Control Study

    PubMed Central

    Yuk, Jin-Sung; Shin, Jong Seung; Shin, Ji-Yeon; Oh, Eunsuk; Kim, Hyunmee; Park, Won I.

    2015-01-01

    Background A cross-sectional study has reported that nickel allergy is associated with endometriosis. However, causal studies of this association are limited. Objective The objective of this study was to compare the prevalence of nickel allergy in women with and without endometriosis. Methods We used a National Health Insurance Service (NHIS) sample cohort dataset that included approximately 1 million individuals from South Korea; the data were obtained between January 01, 2002, and December 31, 2013. We selected the endometriosis group according to diagnosis code (N80.X), surgery codes, and drug codes during the years 2009~2013. The controls were randomly matched to the endometriosis patients at a ratio of 4:1 by age and socioeconomic status. Patients with nickel allergy were defined in the cohort dataset as those with a simultaneous diagnosis code (L23.0) and patch test code during 2002~2008. Results In total, 4,985 women were selected from the NHIS cohort database and divided into an endometriosis group (997 women) and a control group (3,988 women). The number of patients with nickel allergy in the endometriosis group was eight (0.8%), and that in the control group was thirteen (0.3%). After adjustment for age and socioeconomic status, the rate of nickel allergy in was higher in the endometriosis group than in the control group [odds ratio: 2.474; 95% confidence interval: 1.023~5.988; p = 0.044]. Conclusions We found that nickel allergy is a risk factor for endometriosis. PMID:26439741

  2. ABO and Rhesus Blood Groups and Risk of Endometriosis in a French Caucasian Population of 633 Patients Living in the Same Geographic Area

    PubMed Central

    Chartier, Mélanie; Souza, Carlos; Santulli, Pietro; Lafay-Pillet, Marie-Christine; de Ziegler, Dominique; Chapron, Charles

    2014-01-01

    Objectives. The identification of epidemiological factors increasing the risk of endometriosis could shorten the time to diagnosis. Specific blood groups may be more common in patients with endometriosis. Study Design. We designed a cross-sectional study of 633 Caucasian women living in the same geographic area. Study group included 311 patients with histologically proven endometriosis. Control group included 322 patients without endometriosis as checked during surgery. Frequencies of ABO and Rhesus groups in the study and control groups were compared using univariate and multivariate analyses. Results. We observed a higher proportion of Rh-negative women in the study group, as compared to healthy controls. Multivariate analysis showed that Rh-negative women are twice as likely to develop endometriosis (aOR = 1.90; 95% CI: 1.20–2.90). There was no significant difference in ABO group distribution between patients and controls. There was no difference when taking into account either the clinical forms (superficial endometriosis, endometrioma, and deep infiltration endometriosis) or the rAFS stages. Conclusion. Rh-negative women are twice as likely to develop endometriosis. Chromosome 1p, which contains the genes coding for the Rhesus, could also harbor endometriosis susceptibility genes. PMID:25243164

  3. Comparing protective effect of grape seed extract versus atorvastatin on endometriosis in rat model: Evidence for immunohistochemical and biochemical alterations

    PubMed Central

    Kakaiy, Arash; Ayen, Esmail; Sadrkhanlou, Rajabali; Sarrafzadeh Rezaei, Farshid

    2015-01-01

    Thirty six Wistar albino rats with implant induced endometriosis were randomly divided into six groups of six animals each. The rats in the first group received nothing and were euthanized at day 21. In the second group, rats received nothing and were euthanized at day 36. The third group received atorvastatin (ATV; 5 mg kg-1 per day, orally) until 21 days from induction of endometriosis, and the fourth group received ATV from the 15th day after induction of endometriosis for 21 days. The fifth group received grape seed extract (GET; 450 mg kg-1 per day, orally) until 21 days from induction of endometriosis. In the sixth group, GET was administered from the 15th day after induction of endometriosis for 21 days. The estrogen receptor positive cells (ER+) distribution and angiogenesis were assessed using immunohistochemical and immunoflourescent analyzes, respectively. The active cells with intracytoplasmic carbohydrate content were analyzed. Erα mRNA expression was assessed using semiquantitative real time-PCR and the tissue levels of malondialdehyde (MDA), glutathione peroxidase (GSH-px) and superoxide dismutase (SOD) were evaluated. The GET and ATV-treated animals showed significant reduction in endometriosis-increased ER+ cells distribution as well as significant decrease in Erα mRNA levels (p < 0.05(. Our data suggests that GET exerts a potent inhibitory effect on development of endometriotic implants similar to ATV. PMID:26261704

  4. Reduction of blood nitric oxide levels is associated with clinical improvement of the chronic pelvic pain related to endometriosis

    PubMed Central

    Rocha, M.G.; Gomes, V.A.; Tanus-Santos, J.E.; Rosa-e-Silva, J.C.; Candido-dos-Reis, F.J.; Nogueira, A.A.; Poli-Neto, O.B.

    2015-01-01

    The objective of this prospective study was to determine the plasma levels of nitric oxide (NO) in women with chronic pelvic pain secondary to endometriosis (n=24) and abdominal myofascial pain syndrome (n=16). NO levels were measured in plasma collected before and 1 month after treatment. Pretreatment NO levels (μM) were lower in healthy volunteers (47.0±12.7) than in women with myofascial pain (64.2±5.0, P=0.01) or endometriosis (99.5±12.9, P<0.0001). After treatment, plasma NO levels were reduced only in the endometriosis group (99.5±12.9 vs 61.6±5.9, P=0.002). A correlation between reduction of pain intensity and reduction of NO level was observed in the endometriosis group [correlation = 0.67 (95%CI = 0.35 to 0.85), P<0.0001]. Reduction of NO levels was associated with an increase of pain threshold in this group [correlation = -0.53 (-0.78 to -0.14), P<0.0001]. NO levels appeared elevated in women with chronic pelvic pain diagnosed as secondary to endometriosis, and were directly associated with reduction in pain intensity and increase in pain threshold after treatment. Further studies are needed to investigate the role of NO in the pathophysiology of pain in women with endometriosis and its eventual association with central sensitization. PMID:25714893

  5. Asymmetric dimethylarginine (ADMA), nitric oxide metabolite, and estradiol levels in serum and peritoneal fluid in women with endometriosis

    PubMed Central

    Kianpour, Maryam; Nematbakhsh, Mehdi; Ahmadi, Sayad Mehdi

    2015-01-01

    Background: Increase in nitric oxide (NO) concentration accompanied by alteration in peritoneal immune defense reactions is involved in the pathogenesis of endometriosis. Asymmetric dimethylarginine is an endogenous competitive inhibitor of NO synthase. This study was designed to compare NO metabolite (nitrite), asymmetric dimethylarginine, and estradiol concentrations in serum and peritoneal fluid (PF) of patients with and without endometriosis. Materials and Methods: Subjects were assigned to two groups based on their laparoscopic results. The groups consisted of women with and without endometriosis (90 and 89 participants, respectively). The serum and peritoneal levels of nitrite (stable NO metabolite), asymmetric dimethylarginine, and estradiol were measured using enzyme-linked immunosorbent assay (ELISA) kits. These parameters were analyzed and compared between the groups statistically using SPSS software version 16. Results: Both nitrite and asymmetric dimethylarginine levels were significantly higher in the serum of the participants from both groups than those in the PF group (P < 0.05). However, no significant difference in the asymmetric dimethylarginine level was detected between the two groups. In addition, the PF level of nitrite increased significantly in patients with endometriosis when compared with non-endometriosis subjects (P < 0.05). The PF levels of estradiol in both groups were significantly higher than the serum levels of estradiol (P < 0.05). Conclusions: The NO metabolite level of PF implies the possible role of NO in the pathogenesis of endometriosis. PMID:26257805

  6. Integrated Bioinformatics, Environmental Epidemiologic and Genomic Approaches to Identify Environmental and Molecular Links between Endometriosis and Breast Cancer

    PubMed Central

    Roy, Deodutta; Morgan, Marisa; Yoo, Changwon; Deoraj, Alok; Roy, Sandhya; Yadav, Vijay Kumar; Garoub, Mohannad; Assaggaf, Hamza; Doke, Mayur

    2015-01-01

    We present a combined environmental epidemiologic, genomic, and bioinformatics approach to identify: exposure of environmental chemicals with estrogenic activity; epidemiologic association between endocrine disrupting chemical (EDC) and health effects, such as, breast cancer or endometriosis; and gene-EDC interactions and disease associations. Human exposure measurement and modeling confirmed estrogenic activity of three selected class of environmental chemicals, polychlorinated biphenyls (PCBs), bisphenols (BPs), and phthalates. Meta-analysis showed that PCBs exposure, not Bisphenol A (BPA) and phthalates, increased the summary odds ratio for breast cancer and endometriosis. Bioinformatics analysis of gene-EDC interactions and disease associations identified several hundred genes that were altered by exposure to PCBs, phthalate or BPA. EDCs-modified genes in breast neoplasms and endometriosis are part of steroid hormone signaling and inflammation pathways. All three EDCs–PCB 153, phthalates, and BPA influenced five common genes—CYP19A1, EGFR, ESR2, FOS, and IGF1—in breast cancer as well as in endometriosis. These genes are environmentally and estrogen responsive, altered in human breast and uterine tumors and endometriosis lesions, and part of Mitogen Activated Protein Kinase (MAPK) signaling pathways in cancer. Our findings suggest that breast cancer and endometriosis share some common environmental and molecular risk factors. PMID:26512648

  7. The Serum Levels of the Soluble Factors sCD40L and CXCL1 Are Not Indicative of Endometriosis

    PubMed Central

    Pateisky, Petra; Pils, Dietmar; Kuessel, Lorenz; Szabo, Ladislaus; Walch, Katharina; Obwegeser, Reinhard; Wenzl, René; Yotova, Iveta

    2016-01-01

    Endometriosis is a benign but troublesome gynecological condition, characterized by endometrial-like tissue outside the uterine cavity. Lately, the discovery and validation of noninvasive diagnostic biomarkers for endometriosis is one of the main priorities in the field. As the disease elicits a chronic inflammatory reaction, we focused our interest on two factors well known to be involved in inflammation and neoplastic processes, namely, soluble CD40 Ligand and CXCL1, and asked whether differences in the serum levels of sCD40L and CXCL1 in endometriosis patients versus controls can serve as noninvasive disease markers. A total of n = 60 women were included in the study, 31 endometriosis patients and 29 controls, and the serum levels of sCD40L and CXCL1 were measured by enzyme-linked immunosorbent assay. Overall, there were no statistically significant differences in the levels of expression of both sCD40L and CXCL1 between patients and controls. This study adds useful clinical data showing that the serum levels of the soluble factors sCD40L and CXCL1 are not associated with endometriosis and are not suitable as biomarkers for disease diagnosis. However, we found a trend toward lower levels of sCD40L in the deep infiltrating endometriosis subgroup making it a potentially interesting target worth further investigation. PMID:27190986

  8. Increased oxidation-related glutathionylation and carbonic anhydrase activity in endometriosis.

    PubMed

    Andrisani, Alessandra; Donà, Gabriella; Brunati, Anna Maria; Clari, Giulio; Armanini, Decio; Ragazzi, Eugenio; Ambrosini, Guido; Bordin, Luciana

    2014-06-01

    This study examined the possible involvement of carbonic anhydrase activation in response to an endometriosis-related increase in oxidative stress. Peripheral blood samples obtained from 27 healthy controls and 30 endometriosis patients, classified as having endometriosis by histological examination of surgical specimens, were analysed by multiple immunoassay and carbonic anhydrase activity assay. Red blood cells (RBC) were analysed for glutathionylated protein (GSSP) content in the membrane, total glutathione (GSH) in the cytosol and carbonic anhydrase concentration and activity. In association with a membrane increase of GSSP and a cytosolic decrease of GSH content in endometriosis patients, carbonic anhydrase significantly increased (P < 0.0001) both monomerization and activity compared with controls. This oxidation-induced activation of carbonic anhydrase was positively and significantly correlated with the GSH content of RBC (r = 0.9735, P < 0.001) and with the amount of the 30-kDa monomer of carbonic anhydrase (r = 0.9750, P < 0.001). Because carbonic anhydrase activation is implied in many physiological and biochemical processes linked to pathologies such as glaucoma, hypertension, obesity and infections, carbonic anhydrase activity should be closely monitored in endometriosis. These data open promising working perspectives for diagnosis and treatment of endometriosis and hopefully of other oxidative stress-related diseases. Endometriosis is a chronic disease associated with infertility and local inflammatory response, which is thought to spread rapidly throughout the body as a systemic subclinical inflammation. One of the causes in the pathogenesis/evolution of endometriosis is oxidative stress, which occurs when reactive oxygen species are produced faster than the endogenous antioxidant defence systems can neutralize them. Once produced, reactive oxygen species can alter the morphological and functional properties of endothelial cells, including

  9. Genome-wide expressions in autologous eutopic and ectopic endometrium of fertile women with endometriosis

    PubMed Central

    2012-01-01

    Background In order to obtain a lead of the pathophysiology of endometriosis, genome-wide expressional analyses of eutopic and ectopic endometrium have earlier been reported, however, the effects of stages of severity and phases of menstrual cycle on expressional profiles have not been examined. The effect of genetic heterogeneity and fertility history on transcriptional activity was also not considered. In the present study, a genome-wide expression analysis of autologous, paired eutopic and ectopic endometrial samples obtained from fertile women (n = 18) suffering from moderate (stage 3; n = 8) or severe (stage 4; n = 10) ovarian endometriosis during proliferative (n = 13) and secretory (n = 5) phases of menstrual cycle was performed. Methods Individual pure RNA samples were subjected to Agilent’s Whole Human Genome 44K microarray experiments. Microarray data were validated (P < 0.01) by estimating transcript copy numbers by performing real time RT-PCR of seven (7) arbitrarily selected genes in all samples. The data obtained were subjected to differential expression (DE) and differential co-expression (DC) analyses followed by networks and enrichment analysis, and gene set enrichment analysis (GSEA). The reproducibility of prediction based on GSEA implementation of DC results was assessed by examining the relative expressions of twenty eight (28) selected genes in RNA samples obtained from fresh pool of eutopic and ectopic samples from confirmed ovarian endometriosis patients with stages 3 and 4 (n = 4/each) during proliferative and secretory (n = 4/each) phases. Results Higher clustering effect of pairing (cluster distance, cd = 0.1) in samples from same individuals on expressional arrays among eutopic and ectopic samples was observed as compared to that of clinical stages of severity (cd = 0.5) and phases of menstrual cycle (cd = 0.6). Post hoc analysis revealed anomaly in the expressional profiles of several genes

  10. Risk and prognosis of ovarian cancer in women with endometriosis: a meta-analysis

    PubMed Central

    Kim, H S; Kim, T H; Chung, H H; Song, Y S

    2014-01-01

    Background: The risk and prognosis of ovarian cancer have not been well established in women with endometriosis. Thus, we investigated the impact of endometriosis on the risk and prognosis for ovarian cancer, and evaluated clinicopathologic characteristics of endometriosis-associated ovarian cancer (EAOC) in comparison with non-EAOC. Methods: After we searched an electronic search to identify relevant studies published online between January 1990 and December 2012, we found 20 case–control and 15 cohort studies including 444 255 patients from 1 625 potentially relevant studies. In the meta-analysis, ovarian cancer risk by endometriosis and clinicopathologic characteristics were evaluated using risk ratio (RR) or standard incidence ratio (SIR), and prognosis was investigated using hazard ratio (HR) with 95% confidence interval (CI). Heterogeneity was evaluated using Higgins I2 to select fixed-effect (I2 ⩽50%) or random effects models (I2>50%), and found no publication bias using funnel plots with Egger's test (P>0.05). Furthermore, we performed subgroup analyses based on study design, assessment of endometriosis, histology, disease status, quality of study and adjustment for potential confounding factors to minimise bias. Results: Endometriosis increased ovarian cancer risk in case–control or two-arm cohort studies (RR, 1.265; 95% CI, 1.214–1.318) and single-arm cohort studies (SIR, 1.797; 95% CI, 1.276–2.531), which were similar in subgroup analyses. Although progression-free survival was not different between EAOC and non-EAOC (HR, 1.023; 95% CI, 0.712–1.470), EAOC was associated with better overall survival than non-EAOC in crude analyses (HR, 0.778; 95% CI, 0.655–0.925). However, progression-free survival and overall survival were not different between the two groups in subgroup analyses. Stage I–II disease, grade 1 disease and nulliparity were more common in EAOC (RRs, 1.959, 1.319 and 1.327; 95% CIs, 1.367–2.807, 1.149–1.514 and 1.245

  11. Intranasal treatment with luteinising hormone releasing hormone agonist in women with endometriosis.

    PubMed Central

    Shaw, R W; Fraser, H M; Boyle, H

    1983-01-01

    An agonist analogue of luteinising hormone releasing hormone (buserelin) was successfully used to treat women with endometriosis. A dose of 200 micrograms administered intranasally thrice daily was found to be effective in five patients, in whom the endometriotic lesions resolved after six months' treatment. Failure occurred in a sixth patient, who received only 400 micrograms once daily. Anovulation was induced in all subjects together with suppression of menstruation after the first month of treatment. Symptoms of abdominal pain, dysmenorrhoea, and dyspareunia were relieved during treatment, and one previously infertile patient conceived within two months of stopping treatment. No side effects were reported with this dosage, and the results suggest a new form of treatment for patients with endometriosis. PMID:6416542

  12. Eutopic endometrium in women with endometriosis: ground zero for the study of implantation defects.

    PubMed

    Lessey, Bruce A; Lebovic, Dan I; Taylor, Robert N

    2013-03-01

    The endometrium is ground zero when it comes to understanding how implantation occurs and how it might also fail, resulting in infertility or pregnancy loss. Many of the causes of diminished uterine receptivity are acquired during a woman's lifetime. Endometriosis, a major inflammatory disease affecting women, is also a leading cause of infertility and miscarriage. Once established, the inflammatory changes can, in some women, lead to progesterone resistance and downstream changes in endometrial gene expression. Much is now known about how inflammation translates to progesterone resistance and infertility, but much remains to be learned. In this review we provide an overview for understanding how the endometrium becomes dysfunctional, what biomarkers may hold promise for the diagnosis of endometriosis, and how progesterone resistance leads to infertility. Understanding the pathophysiology of this disease will likely lead to better treatment options. PMID:23446858

  13. Characteristics of Multipotent Mesenchymal Stromal Cells Isolated from Human Endometrium and Endometriosis Lesions.

    PubMed

    Savilova, A M; Yushina, M N; Rudimova, Yu V; Khabas, G N; Chuprynin, V D; Sukhikh, G T

    2016-08-01

    Cell cultures isolated from endometriosis lesions by enzymatic dissociation consisted of fibroblast-like cells expressing CD90, CD73, and CD105; cell viability in these cultures was >90%, but this parameter decreased by passage 3. Zero passage cultures contained 10-25% epithelial cells expressing cytokeratin-7, but by passage 2, the cultures became more homogeneous and epithelial cells disappeared. The proportion of proliferating cells and population doubling level increased from passage 1 to passage 3. The cultures from the endometrium were induced to adipogenic and osteogenic differentiation in vitro. The cultures derived from ectopic endometrium have properties of multipotent mesenchymal stromal cells that exhibited in vitro similarities and differences from cell cultures from eutopic endometrium, which allows using this cell model for the search and testing of new drugs and technologies aimed at suppression of the growth and spread of endometriosis lesions. PMID:27590769

  14. Laser vaporization in treatment of superficial endometriosis of the uterine cervix

    NASA Astrophysics Data System (ADS)

    Wozniak, Jakub; Wilczak, Maciej; Opala, Tomasz; Pisarska-Krawczyk, Magdalena; Cwojdzinski, Marek; Pisarski, Tadeusz

    1996-03-01

    The study shows the treatment of superficial endometriosis of the uterine cervix in 79 patients. After first vaporization 74 patients were cured successfully. In two cases the laser procedure should be repeated and in 3 women the operation should be performed for the third time. All patients are still under control in our department and there is no recurrence observed. Carbon- dioxide laser vaporization under colposcopic control is an efficient method of treatment of superficial endometriosis of the uterine cervix that requires no anaesthesia. The healing process after laser procedures is fast and without complications. The number of recurrences is low. Use of carbon-dioxide laser under colposcopic control because of precise destruction of lesions, fast healing and a low number of recurrences seems to be the method of choice.

  15. Ovarian endometriosis-associated stromal cells reveal persistently high affinity for iron

    PubMed Central

    Mori, Masahiko; Ito, Fumiya; Shi, Lei; Wang, Yue; Ishida, Chiharu; Hattori, Yuka; Niwa, Masato; Hirayama, Tasuku; Nagasawa, Hideko; Iwase, Akira; Kikkawa, Fumitaka; Toyokuni, Shinya

    2015-01-01

    Ovarian endometriosis is a recognized risk for infertility and epithelial ovarian cancer, presumably due to iron overload resulting from repeated hemorrhage. To find a clue for early detection and prevention of ovarian endometriosis-associated cancer, it is mandatory to evaluate catalytic (labile) ferrous iron (catalytic Fe(II)) and to study iron manipulation in ovarian endometriotic lesions. By the use of tissues from women of ovarian endometriosis as well as endometrial tissue from women with and without endometriosis, we for the first time performed histological analysis and cellular detection of catalytic Fe(II) with a specific fluorescent probe (HMRhoNox-M), and further evaluated iron transport proteins in the human specimens and in co-culture experiments using immortalized human eutopic/ectopic endometrial stromal cells (ESCs) in the presence or absence of epithelial cells (EpCs). The amounts of catalytic Fe(II) were higher in ectopic endometrial stromal cells (ecESCs) than in normal eutopic endometrial stromal cells (n-euESCs) both in the tissues and in the corresponding immortalized ESCs. ecESCs exhibited higher transferrin receptor 1 expression both in vivo and in vitro and lower ferroportin expression in vivo than n-euESCs, leading to sustained iron uptake. In co-culture experiments of ESCs with iron-loaded EpCs, ecESCs received catalytic ferrous iron from EpCs, but n-euESCs did not. These data suggest that ecESC play a protective role for cancer-target epithelial cells by collecting excess iron, and that these characteristics are retained in the immortalized ecESCs. PMID:26498255

  16. Evaluation of antimullerian hormone levels before and after laparoscopic management of endometriosis

    PubMed Central

    Mostaejeran, Fatemeh; Hamoush, Zeinab; Rouholamin, Safoura

    2015-01-01

    Background: Serum antimullerian hormone (AMH) proposed to be a reliable marker of ovarian reserve; the aim of this study was to evaluate the influence and value of laparoscopic management in endometriosis as measured by serum AMH levels. Materials and Methods: In this cross-sectional study, 33 infertile patients who referred to fertility - Infertility Center of Isfahan - with different stages of endometriosis managed by diagnostic operative laparoscopy and serum AMH levels were measured pre and one month postoperative laparoscopy. Main outcome measures were serum AMH levels in correlation with the type of infertility, stage of endometriosis, and type of surgery in infertile patients. Results: 33 infertile patients enrolled in the study with mean age 28.9 ± 5 years, and thus did not show a significant difference. Mean serum AMH levels was 4.23 ± 3.75 ng/ml and 2.2 ± 2.47 ng/ml, respectively, in primary and secondary infertility groups before and one month after laparoscopy, which shows a significant difference (P < 0.001). Median AMH level changes in Cauterization (0.67 ± 0.76 ng/ml), endometrioma excision 2 ± 0.6 ng/ml, both 2.18 ± 0.81 ng/ml and shows no significant differences. Mean serum AMH levels were definitely decreased in minimal/mild and severe stage endometriosis before and 1 month after laparoscopy, (1.84 ± 2.06 ng/ml and 2.18 ± 3.45 ng/ml), respectively. Also serum AMH according to ovarian appearance and evolvement showed no significant differences after laparoscopy: (5.5 ± 1.4 ng/ml and 2.76 ± 0.96 ng/ml) and (3.37 ± 2.2 ng/ml and 1.84 ± 1.5 ng/ml). Conclusion: Serum AMH levels clearly decreased 1 month after operative laparoscopy. PMID:26605221

  17. Endometriosis Is Characterized by a Distinct Pattern of Histone 3 and Histone 4 Lysine Modifications

    PubMed Central

    Monteiro, Janice B.; Colón-Díaz, Maricarmen; García, Miosotis; Gutierrez, Sylvia; Colón, Mariano; Seto, Edward; Laboy, Joaquín

    2014-01-01

    Background: The histone modification patterns in endometriosis have not been fully characterized. This gap in knowledge results in a poor understanding of the epigenetic mechanisms (and potential therapeutic targets) at play. We aimed to (1) assess global acetylation status of histone 3 (H3) and histone 4 (H4), (2) measure levels of H3 and H4 lysine (K) acetylation and methylation, and (3) to identify histone acetylation patterns in promoter regions of candidate genes in tissues from patients and controls. Methods: Global and K-specific acetylation/methylation levels of histones were measured in 24 lesions, 15 endometrium from patients, and 26 endometrium from controls. Chromatin immunoprecipitation (ChIP)–polymerase chain reaction was used to determine the histone acetylation status of the promoter regions of candidate genes in tissues. Results: The lesions were globally hypoacetylated at H3 (but not H4) compared to eutopic endometrium from controls. Lesions had significantly lower levels of H3K9ac and H4K16ac compared to eutopic endometrium from patients and controls. Tissues from patients were hypermethylated at H3K4, H3K9, and H3K27 compared to endometrium from controls. The ChIP analysis showed hypoacetylation of H3/H4 within promoter regions of candidate genes known to be downregulated in endometriosis (e.g., HOXA10, ESR1, CDH1, and p21WAF1/Cip1) in lesions versus control endometrium. The stereoidogenic factor 1 (SF1) promoter region was enriched for acetylated H3 and H4 in lesions versus control tissues, correlating with its reported high expression in lesions. Conclusions: This study describes the histone code of lesions and endometrium from patients with endometriosis and provides support for a possible role of histone modification in modulation of gene expression in endometriosis. PMID:23899551

  18. Somatic Copy Number Alterations Associated with Japanese or Endometriosis in Ovarian Clear Cell Adenocarcinoma

    PubMed Central

    Okamoto, Aikou; Sehouli, Jalid; Yanaihara, Nozomu; Hirata, Yukihiro; Braicu, Ioana; Kim, Byoung-Gie; Takakura, Satoshi; Saito, Misato; Yanagida, Satoshi; Takenaka, Masataka; Yamaguchi, Noriko; Morikawa, Asuka; Tanabe, Hiroshi; Yamada, Kyosuke; Yoshihara, Kosuke; Enomoto, Takayuki; Itamochi, Hiroaki; Kigawa, Junzo; Matsumura, Noriomi; Konishi, Ikuo; Aida, Satoshi; Aoki, Yuko; Ishii, Nobuya; Ochiai, Kazunori; Akiyama, Tetsu; Urashima, Mitsuyoshi

    2015-01-01

    When compared with other epithelial ovarian cancers, the clinical characteristics of ovarian clear cell adenocarcinoma (CCC) include 1) a higher incidence among Japanese, 2) an association with endometriosis, 3) poor prognosis in advanced stages, and 4) a higher incidence of thrombosis as a complication. We used high resolution comparative genomic hybridization (CGH) to identify somatic copy number alterations (SCNAs) associated with each of these clinical characteristics of CCC. The Human Genome CGH 244A Oligo Microarray was used to examine 144 samples obtained from 120 Japanese, 15 Korean, and nine German patients with CCC. The entire 8q chromosome (minimum corrected p-value: q = 0.0001) and chromosome 20q13.2 including the ZNF217 locus (q = 0.0078) were amplified significantly more in Japanese than in Korean or German samples. This copy number amplification of the ZNF217 gene was confirmed by quantitative real-time polymerase chain reaction (Q-PCR). ZNF217 RNA levels were also higher in Japanese tumor samples than in non-Japanese samples (P = 0.027). Moreover, endometriosis was associated with amplification of EGFR gene (q = 0.047), which was again confirmed by Q-PCR and correlated with EGFR RNA expression. However, no SCNAs were significantly associated with prognosis or thrombosis. These results indicated that there may be an association between CCC and ZNF217 amplification among Japanese patients as well as between endometriosis and EGFR gene amplifications. PMID:25658832

  19. [Endometriosis genitalis--clinical classification on the background of uncertain etiology and therapeutic anarchy].

    PubMed

    Nalbanski, A

    2008-01-01

    Clinical confusion and inappropriate management continues to surround endometriosis. It is poorly recognized that the disorder can exist in two different morphological forms that have different symptoms, signs and prognosis. Earlier classification systems have been useful for research but are of limited value in aiding day-to-day management. In the clinic, two discrete phenotypes can be defined by the presence or absence of palpable nodules in the deep pelvis. Patients with such nodules with or without associated ovarian endometrioma usually have severe symptoms with significant risks of bowel and urinary tract involvement. The predominant histological feature of these lesions is extensive fibromuscular hyperplasia (adenomyoma). These patients will often need extensive surgical intervention. Patients without such palpable lesions usually have the classic superficial subperitoneal lesions with endometrial-like glands and stroma on histological examination. This group often has less severe symptoms and has little risk of developing serious associated problems. These lesions may be helped by medications and/or simple ablative surgery. It is suggested that these collections of symptoms and signs or syndromes be named after the pioneers who first described the lesions. Cullen's syndrome can be used to describe those patients with severe symptoms of endometriosis associated with palpable pelvic nodules. Sampson's syndrome can describe those with similar symptoms associated with a structurally normal pelvis. This paper seeks to present evidence to suggest the reality of this 'two forms of endometriosis' concept, and the possibility of developing a simple clinically useful method of differentiating them. PMID:18756833

  20. Abdominal Wall Endometriosis Excision with Mesh Closure - Report of Two Cases.

    PubMed

    Vaz-de-Macedo, Carolina; Gomes-da-Costa, Ana; Mendes, Sofia; Barata, Sónia; Alho, Conceição; Jorge, Carlos Calhaz; Osório, Filipa

    2016-04-01

    Abdominal wall endometriosis (AWE) is a rare condition included in the differential diagnosis of an abdominal wall mass and/or pelvic pain in women of reproductive age. It usually occurs after pelvic surgery, most commonly caesarean section. Given the variable clinical presentation, diagnosis can be challenging if a high index of suspicion for AWE does not exist. Consequently, the correct diagnosis is often missed in the preoperative assessment. The presence of endometriosis in other locations can aid in the diagnosis, but other endometriotic lesions do not always exist. Image studies, particularly ultrasound and magnetic resonance imaging, can also be of help in the differential diagnosis. Even though new management techniques such as ultrasound-guided percutaneous cryoablation seem to be promising, surgical excision is still the mainstay of treatment. When the aponeurosis is involved, lesion excision might need to be followed by wall closure with the use of a mesh to lessen tissue tension. We present two typical cases of AWE after caesarean section, one of them recurrent, in patients with concurrent endometriosis of other locations. Total lesion excision followed by polypropylene mesh closure has been performed, with very good post-operative outcomes. We aim to raise awareness towards this diagnosis and to highlight the importance of complete lesion excision and adequate closure of the abdominal wall. PMID:27042795

  1. Endometriosis-Related Hemoperitoneum in Pregnancy: A Diagnosis to Keep in Mind

    PubMed Central

    Cozzolino, Mauro; Corioni, Serena; Maggio, Luana; Sorbi, Flavia; Guaschino, Secondo; Fambrini, Massimiliano

    2015-01-01

    Background Endometriosis is an important gynecologic clinical entity, pathologically defined by the ectopic presence of endometrium and frequently associated with pelvic pain, that affects approximately 10% of females of reproductive age. A rare but severe complication of endometriosis during pregnancy is spontaneous hemoperitoneum in pregnancy (SHiP), severe intraabdominal bleeding that can be life threatening. Case Report We present the case of a patient with SHiP at 29 weeks of pregnancy. A supraumbilical midline laparotomy was performed, and pelvic exploration revealed a lacerated and bleeding right ovary. Right annessiectomy was performed, and a cesarean section was performed because hemostasis was not achievable. A healthy baby was born, and hemostasis was finally achieved. Conclusion We believe that in gravid females with a history of endometriosis, severe abdominal pain, and a reduction of hemoglobin, physicians should always suspect SHiP. Because SHiP is a life-threatening condition for both the mother and the baby, a prompt diagnosis must lead to prompt treatment. PMID:26413000

  2. [Genetic aspects of endometriosis: features of the distribution of polymorphic gene frequencies].

    PubMed

    Spitsyn, V A; Andreeva, E N; Adamian, L V; Agapova, R K; Sandoval', Kh R

    1996-12-01

    In a group of patients with endometriosis and in a control group of healthy women, the polymorphism of the following systems were studied: ABO and RH blood-group systems; serum proteins haptoglobin (HP), transferrin (TF), vitamin D-transporting protein (GC), protease inhibitor (PI), and the third component of the complement (C3); serum enzymes-amylase of the loci 1 and 2 (AMY1 and AMY2), pseudocholinesterase (E2), and alkaline phosphatase (PP); erythrocytic enzymes-acid phosphatase (ACP1), phosphoglucomutase (PGM1), superoxide dismutase (SOD-A), esterase D (ESD), and glyoxalase (GLO1). Statistically significant differences between the groups compared were established for five genetic systems: ABO, E2, C3, TF, and PGM1. Among patient with endometriosis, the rare alleles of the locus ESD-ESD5 and ESD7-were found, along with ESD 5-5 homozygotes. Several genetic loci can be involved in the pathogenesis of endometriosis; their products can be specifically realized due to peculiarities of biochemical reactions in the organisms of people predisposed to this pathology. PMID:9102363

  3. Recto-sigmoid endoscopic-ultrasonography in the staging of deep infiltrating endometriosis

    PubMed Central

    Roseau, Gilles

    2014-01-01

    Recto-sigmoid endoscopic ultrasonography (RS-EUS) has first been used in the staging of pelvic deep infiltrating endometriosis in the early 1990's. Since then, although publications have been sparse, RS-EUS is routinely used for this indication in few centers. In this paper, we focus on technical aspects and operating method of rectal and sigmoid endo-sonography, and describe the most characteristic echographic presentations of endometriosis of the lower digestive tract. Through a literature review, results obtained with different types of endo-rectal probes, either flexible endoscopic, or blind rigid, are presented and compared with those of other close imaging techniques: magnetic resonance imaging and the more recent trans-vaginal sonography. As well as these two latter techniques, RS-EUS appears as an interesting method in the staging of pelvic deep infiltrating endometriosis particularly to evaluate rectal and sigmoid infiltrations. However, more prospective studies are required, to correctly define respective indications for each exam, in the light of recent advancements in treating this frequent disease. PMID:25400866

  4. Epigenetic Modulation of Collagen 1A1: Therapeutic Implications in Fibrosis and Endometriosis.

    PubMed

    Zheng, Ye; Khan, Zaraq; Zanfagnin, Valentina; Correa, Luiz F; Delaney, Abigail A; Daftary, Gaurang S

    2016-04-01

    Progressive fibrosis is recalcitrant to conventional therapy and commonly complicates chronic diseases and surgical healing. We evaluate here a novel mechanism that regulates scar-tissue collagen (COL1A1/Col1a1) expression and characterizes its translational relevance as a targeted therapy for fibrosis in an endometriosis disease model. Endometriosis is caused by displacement and implantation of uterine endometrium onto abdominal organs and spreads with progressive scarring. Transcription factor KLF11 is specifically diminished in endometriosis lesions. Loss of KLF11-mediated repression of COL1A1/Col1a1 expression resulted in increased fibrosis. To determine the biological significance of COL1A1/Col1a1 expression on fibrosis, we modulated its expression. In human endometrial-stromal fibroblasts, KLF11 recruited SIN3A/HDAC (histone deacetylase), resulting in COL1A1-promoter deacetylation and repression. This role of KLF11 was pharmacologically replicated by a histone acetyl transferase inhibitor (garcinol). In contrast, opposite effects were obtained with a HDAC inhibitor (suberoyl anilide hydroxamic acid), confirming regulatory specificity for these reciprocally active epigenetic mechanisms. Fibrosis was concordantly reversed in Klf11(-/-)animals by histone acetyl transferase inhibitor and in wild-type animals by HDAC inhibitor treatments. Aberrant lesional COL1A1 regulation is significant because fibrosis depended on lesion rather than host genotype. This is the first report demonstrating feasibility for targeted pharmacological reversal of fibrosis, an intractable phenotype of diverse chronic diseases. PMID:26935598

  5. EFFECT OF PELVIC ENDOMETRIOSIS, ENDOMETRIOMAS AND RECURRENT ENDOMETRIOMAS ON IVF-ET/ICSI OUTCOMES

    PubMed Central

    Xing, Weijie; Lin, Haiyan; Wu, Zexuan; Li, Yu; Zhang, Qingxue

    2016-01-01

    Introduction: Endometriosis, the most common gynecological disorder, is a challenging disease observed in 20% - 40% of subfertile women. Material and Methods: 380 women were divided into four groups. Group A consisted of 176 women with pelvic endometriosis. Group B consisted of 125 women who had previously undergone a laparoscopic endometrioma cystectomy. Group C consisted of 38 women with recurrent endometriomas without aspiration before IVF-ET/ICSI. Group D consisted of 41 women with recurrent endometriomas undergone aspiration before IVF-ET/ICSI. Results: Baseline FSH level (8.61 ± 3.42 mIU/mL) and total dose of Gn (2337.15 ± 853.00 IU) in Group A were the lowest (p < 0.05). The number of retrieved oocytes in Group B (7.98 ± 5.05) was significantly fewer than those in Group A and D (p < 0.05). The numbers of MII oocytes in Groups A, C and D were significantly larger than that in Group B. The number of retrieved oocytes, high-quality embryos, implantation and pregnancy rates were similar in Groups C and D. Conclusions: Pelvic endometriosis had a less adverse effect on ovarian reserve than endometrioma. No advantage was found in transvaginal aspiration for recurrent endometriomas before IVF-ET/ICSI. PMID:27147911

  6. Utero-tubal sperm transport and its impairment in endometriosis and adenomyosis.

    PubMed

    Kissler, Stefan; Zangos, Stephan; Wiegratz, Inka; Kohl, Joachim; Rody, Achim; Gaetje, Regine; Doebert, Natascha; Wildt, Ludwig; Kunz, Georg; Leyendecker, Gerhard; Kaufmann, Manfred

    2007-04-01

    The uterus is composed of different smooth muscle layers that serve various functions. First, menstrual debris is expulsed at the time of the menses. Second, sperm is transported in the preovulatory phase to maximize fertility, and third, the human embryo is placed in an adequate setting during implantation. Endometriosis is a gynecologic disorder leading to severe pain symptoms such as severe pain during menstruation (dysmenorrhea), chronic pelvic pain, pain during sexual intercourse (dyspareunia), and abnormal uterine bleeding. Besides, endometriosis is often associated with female infertility and exhibits a massive impairment in the physiology of uterine contractility that can be documented by the in vivo examination method of hysterosalpingoscintigraphy (HSSG). In addition, endometriosis is associated in 80-90% of subjects with adenomyosis and our data clearly indicate that sperm transport is disturbed by hyperperistalsis when at least one focus of adenomyosis can be detected via magnetic resonance imaging (MRI) and turns into dysperistalsis (a complete failure in sperm transport capacity) when diffuse adenomyosis affecting all myometrial uterine muscle layers is detected. Hence, dysperistalsis is significantly associated with reduced spontaneous pregnancy rates. We therefore recommend MRI and HSSG in every sterility workup. PMID:17344532

  7. Multi-disciplinary centres/networks of excellence for endometriosis management and research: a proposal.

    PubMed

    D'Hooghe, T; Hummelshoj, L

    2006-11-01

    Centres/networks of excellence are the only way forward to ensure that women with endometriosis receive consistent, evidence-based care, ensuring excellence, continuity of care, multi-disciplinarity, research, training and cost-effectiveness. Clinical excellence should be achieved by proper training, adherence to evidence-based guidelines, quality management and continuous measurement of patient outcome as a central focus. To ensure continuity of care, the first step is to assign to each patient a central gynaecologist who must have continuously updated knowledge regarding all diagnostic and management options for endometriosis and who must set priorities and realistic expectations together with the woman using a long-term multi-disciplinary treatment plan. Scientific research within and scientific collaboration between centres/networks of excellence will create the critical mass of patients and tissue samples that is needed to make progress. Centres/networks of excellence should be accredited as training centres by professional bodies. They should aim at improving the cost-effectiveness of the management of endometriosis by a reduction in the time to diagnosis, a reduction in the time before individualized specialist care is invoked, a reduction of expensive hit-and-miss treatments and a reduction in expensive fertility treatments, if the disease is under control before fertility is impaired. PMID:16982655

  8. Accurate Diagnosis of Sigmoid Colon Endometriosis by Immunohistochemistry and Transmission Electron Microscopy - A Case Report.

    PubMed

    Constantin, V; Carăp, A; Bobic, S; Pâun, I; Brâtilâ, E; Socea, B; Moroşanu, A-M; Mirancea, N

    2015-01-01

    Endometriosis is described as the presence of functioning endometrial tissue at sites outside the uterus. Up to 15% ofwomen in their reproductive period are affected by this condition. Endometriosis is mostly foundon the uterosacral ligaments, inside the rectovaginalseptum or vagina, in the rectosigmoid area, ovarianfossa, pelvic peritoneum, ureters, and bladder, causinga distortion of the pelvic anatomy. Colonic involvement is rare but is usually found at the level of the rectum or the sigmoid colon. Acute presentation with intestinal obstruction or perforation is rare. While malignant transformation of endometrial lesions is rare, findings of dysplasia on pathology sections can give rise to questions of management. Immunohistochemistry and electron microscopy can help decision making. We present the case of a 38 year old woman with intestinal obstruction caused by sigmoid colon endometriosis with moderate dysplasia in which transmission electron microscopy was used for postoperative diagnosis. Detailed analysis of these cases, while logistically difficult, can prove useful in understanding the etiology and pathophysiology of the disease. PMID:26531796

  9. Genome-wide association meta-analysis identifies new endometriosis risk loci

    PubMed Central

    Nyholt, Dale R.; Low, Siew-Kee; Anderson, Carl A.; Painter, Jodie N.; Uno, Satoko; Morris, Andrew P.; MacGregor, Stuart; Gordon, Scott D.; Henders, Anjali K.; Martin, Nicholas G.; Attia, John; Holliday, Elizabeth G.; McEvoy, Mark; Scott, Rodney J.; Kennedy, Stephen H.; Treloar, Susan A.; Missmer, Stacey A.; Adachi, Sosuke; Tanaka, Kenichi; Nakamura, Yusuke; Zondervan, Krina T.; Zembutsu, Hitoshi; Montgomery, Grant W.

    2012-01-01

    We conducted a genome-wide association (GWA) meta-analysis of 4,604 endometriosis cases and 9,393 controls of Japanese1 and European2 ancestry. We show that rs12700667 on chromosome 7p15.2, previously found in Europeans, replicates in Japanese (P = 3.6 × 10−3), and confirm association of rs7521902 on 1p36.12 near WNT4. In addition, we establish association of rs13394619 in GREB1 on 2p25.1 and identify a novel locus on 12q22 near VEZT (rs10859871). Excluding European cases with minimal or unknown severity, we identified additional novel loci on 2p14 (rs4141819), 6p22.3 (rs7739264) and 9p21.3 (rs1537377). All seven SNP effects were replicated in an independent cohort and produced P < 5 × 10−8 in a combined analysis. Finally, we found a significant overlap in polygenic risk for endometriosis between the European and Japanese GWA cohorts (P = 8.8 × 10−11), indicating that many weakly associated SNPs represent true endometriosis risk loci and risk prediction and future targeted disease therapy may be transferred across these populations. PMID:23104006

  10. Endometriosis-Related Infertility: The Role of the Assisted Reproductive Technologies

    PubMed Central

    Surrey, Eric S.

    2015-01-01

    The assisted reproductive technologies, particularly in vitro fertilization (IVF), represent the most efficient and successful means of overcoming infertility associated with endometriosis. Although older studies suggest that IVF outcomes are compromised in endometriosis patients, more contemporary reports show no differences compared to controls. The exception may be evidence of poorer outcomes and diminished ovarian response in women with advanced disease, particularly those with significant ovarian involvement or prior ovarian surgery. Prolonged pre-IVF cycle suppressive medical therapy, particularly gonadotropin releasing hormone agonists, appears to improve success rates in a subset of endometriosis patients. However, as of yet, there is no diagnostic marker to specifically identify those who would most benefit from this approach. Pre-IVF cycle surgical resection of nonovarian disease has not been consistently shown to improve outcomes with the possible exception of resection of deeply invasive disease, although the data is limited. Precycle resection of ovarian endometriomas does not have benefit and should only be performed for gynecologic indications. Indeed, there is a large body of evidence to suggest that this procedure may have a deleterious impact on ovarian reserve and response. A dearth of appropriately designed trials makes development of definitive treatment paradigms challenging. PMID:26240824

  11. Estrogen Receptor (ER) β Regulates ERα Expression in Stromal Cells Derived from Ovarian Endometriosis

    PubMed Central

    Trukhacheva, Elena; Lin, Zhihong; Reierstad, Scott; Cheng, You-Hong; Milad, Magdy; Bulun, Serdar E.

    2009-01-01

    Context: Estradiol and its nuclear receptors, estrogen receptor (ER) α and ERβ, play critical roles in endometrium and endometriosis. Levels of ERβ, due to pathological hypomethylation of its promoter, are significantly higher in endometriotic vs. endometrial tissue and stromal cells, whereas ERα levels are lower in endometriosis. Estradiol regulates ERα gene expression via its alternatively used promoters A, B, and C. Objective: The aim of the study was to determine whether high levels of ERβ in endometriotic stromal cells from ovarian endometriomas regulate ERα gene expression. Results: ERβ knockdown significantly increased ERα mRNA and protein levels in endometriotic stromal cells. Conversely, ERβ overexpression in endometrial stromal cells decreased ERα mRNA and protein levels. ERβ knockdown significantly decreased proliferation of endometriotic stromal cells. Chromatin immunoprecipitation assays demonstrated that estradiol enhanced ERβ binding to nonclassical activator protein 1 and specificity protein 1 motifs in the ERα gene promoters A and C and a classic estrogen response element in promoter B in endometriotic stromal cells. Conclusions: High levels of ERβ suppress ERα expression and response to estradiol in endometrial and endometriotic stromal cells via binding to classic and nonclassic DNA motifs in alternatively used ERα promoters. ERβ also regulates cell cycle progression and might contribute to proliferation of endometriotic stromal cells. We speculate that a significantly increased ratio of ERβ:ERα in endometriotic tissues may also suppress progesterone receptor expression and contribute to progesterone resistance. Thus, ERβ may serve as a significant therapeutic target for endometriosis. PMID:19001520

  12. Limited value of pro-inflammatory oxylipins and cytokines as circulating biomarkers in endometriosis – a targeted ‘omics study

    PubMed Central

    Lee, Yie Hou; Cui, Liang; Fang, Jinling; Chern, Bernard Su Min; Tan, Heng Hao; Chan, Jerry K. Y.

    2016-01-01

    Endometriosis is a common, complex gynecologic disorder characterized by the presence of endometrial-like tissues at extrauterine sites. Elevation in protein and lipid mediators of inflammation including oxylipins and cytokines within the peritoneum characterize the inflamed pelvic region and may contribute to the survival and growth of displaced endometrial tissues. The presence of a clinically silent but molecularly detectable systemic inflammation in endometriosis has been proposed. Thus, we examined serum oxylipin and immunomodulatory protein levels in 103 women undergoing laparoscopy to evaluate systematically any involvement in systemic pathophysiological inflammation in endometriosis. Oxylipin levels were similar between women with and without endometriosis. Stratification by menstrual phase or severity did not offer any difference. Women with ovarian endometriosis had significantly lower 12-HETE relative to peritoneal endometriosis (−50.7%). Serum oxylipin levels were not associated with pre-operative pain symptoms. Changes to immunomodulatory proteins were minimal, with IL-12(p70), IL-13 and VEGF significantly lower in mild endometriotic women compared to non-endometriotic women (−39%, −54% and −76% respectively). Verification using C-reactive protein as a non-specific marker of inflammation further showed similar levels between groups. The implications of our work suggest pro-inflammatory mediators in the classes studied may have potentially limited value as circulating biomarkers for endometriosis, suggesting of potentially tenuous systemic inflammation in endometriosis. PMID:27193963

  13. The Risk of Epithelial Ovarian Cancer of Women With Endometriosis May be Varied Greatly if Diagnostic Criteria Are Different: A Nationwide Population-Based Cohort Study.

    PubMed

    Lee, Wen-Ling; Chang, Wen-Hsun; Wang, Kuan-Chin; Guo, Chao-Yu; Chou, Yiing-Jeng; Huang, Nicole; Huang, Hsin-Yi; Yen, Ming-Shyen; Wang, Peng-Hui

    2015-09-01

    This article aims to test the hypothesis that the risk of epithelial ovarian cancer (EOC) in women with endometriosis might be changed by enrolling different population. A nationwide 14-year historic cohort study using the National Health Insurance Research Database (NHIRD) of Taiwan and the Registry for Catastrophic Illness Patients was conducted. A total of 239,385 women aged between 20 and 51 years, with at least 1 gynecologic visit after 2000, were analyzed. Cases included women with a diagnosed endometriosis, which was established along a spectrum from at least 1 medical record of endometriosis (recalled endometriosis) to tissue-proved ovarian endometriosis (n = X). Controls included women without any diagnosis of endometriosis (n = 239,385 - X). We used Cox regression, and computed hazard ratios (HRs) with 95% confidence intervals (95% CI) to determine the risk of EOC in patients. The EOC incidence rates (IRs, per 10,000 person-years) of women with endometriosis ranged from 1.90 in women with recalled endometriosis to 18.70 in women with tissue-proved ovarian endometrioma, compared with those women without any diagnosis of endometriosis (0.77-0.89), contributing to crude HRs ranging from 2.59 (95% CI, 2.09-3.21; P < 0.001) to 24.04 (95% CI, 17.48-33.05; P < 0.001). After adjustment for pelvic inflammatory disease, infertility, Charlson co-morbidity index, and age, adjusted HRs were ranged from the lowest of 1.90 (95% CI, 1.51-2.37; P < 0.001) in recalled endometriosis to the highest of 18.57 (95% CI, 13.37-25.79; P < 0.001) in tissue-proved ovarian endometrioma, which was inversely related to the prevalence rate of endometriosis (from the highest of 30.80% in recalled endometriosis to the lowest of 1.54% in tissue-proved ovarian endometrioma). The risk of EOC in women with endometriosis varied greatly by different criteria used. Women with endometriosis might have a more apparently higher risk than those reported by systematic review and meta-analysis. PMID

  14. Low Birth Weight Is Strongly Associated with the Risk of Deep Infiltrating Endometriosis: Results of a 743 Case-Control Study

    PubMed Central

    Borghese, Bruno; Sibiude, Jeanne; Santulli, Pietro; Lafay Pillet, Marie-Christine; Marcellin, Louis; Brosens, Ivo; Chapron, Charles

    2015-01-01

    The influence of intrauterine environment on the risk of endometriosis is still controversial. Whether birth weight modifies the risk of endometriosis in adulthood remains an open question. For this purpose, we designed a case-control study involving 743 women operated on for benign gynecological indications from January 2004 to December 2011. Study group included 368 patients with histologically proven endometriosis: 54 superficial endometriosis (SUP), 79 endometriomas (OMA) and 235 deep infiltrating endometriosis (DIE). Control group included 375 patients without endometriosis as surgically checked. Mean birth weights were compared between patients and controls, according to endometriosis groups and rAFS stages. Mean birth weight was significantly lower for patients with endometriosis as compared to controls (3,119g ± 614 and 3,251g ± 557 respectively; p = 0.002). When compared to controls, patients with DIE had the lowest birth weight with a highly significant difference (3,103g ± 620, p = 0.002). In univariate analysis, patients with low birth weight (LBW), defined as a BW < 2,500g, had a higher risk of endometriosis, especially DIE, as compared to the reference group (OR = 1.5, 95%CI: 1.0-2.3 and OR = 1.7, 95%CI: 1.0-2.7, respectively). Multivariate analysis, adjusted on ethnicity and smoking status, showed the persistence of a significant association between endometriosis and LBW with a slight increase in the magnitude of the association (aOR = 1.7, 95%CI: 1.0-2.6 for endometriosis, aOR = 1.8; 95%CI: 1.1-2.9 for DIE). In conclusion, LBW is independently associated with the risk of endometriosis in our population. Among patients with LBW, the risk is almost two-times higher to develop DIE. This association could reflect common signaling pathways between endometriosis and fetal growth regulation. There is also the possibility of a role played by placental insufficiency on the development of the neonate’s pelvis and the occurrence of neonatal uterine

  15. 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography-Positive Lymph Node Endometriosis Masquerading as Lymph Node Metastasis of a Malignant Tumor

    PubMed Central

    Mori, Taisuke; Matsushima, Hiroshi; Sawada, Morio

    2014-01-01

    Endometriosis is defined as the presence of endometrium-like tissues at extrauterine sites, most commonly in the abdominal cavity. Lymph node endometriosis is a rare but clinically important type of endometriosis that can mimic lymph node metastasis of a malignant tumor. 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) is a useful tool for diagnosing malignant tumors, although it occasionally shows false positive results in tissues with high metabolic activity caused by severe inflammation. In the present report, we describe a case of lymph node endometriosis that mimicked lymph node metastasis of a malignant tumor and showed a positive result on 18F-FDG PET/CT. The findings of the present case suggest that lymph node endometriosis could present as swollen lymph nodes with 18F-FDG PET/CT-positive results and provide important information for determining an appropriate treatment strategy. PMID:25180115

  16. Full-Thickness Excision versus Shaving by Laparoscopy for Intestinal Deep Infiltrating Endometriosis: Rationale and Potential Treatment Options

    PubMed Central

    Trovato, Maria Antonietta; Palmara, Vittorio Italo; Rapisarda, Agnese Maria Chiara; Sturlese, Emanuele; De Dominici, Rosanna; Alecci, Stefano; D'Amico, Paolo; Triolo, Onofrio

    2016-01-01

    Endometriosis is defined as the presence of endometrial mucosa (glands and stroma) abnormally implanted in locations other than the uterine cavity. Deep infiltrating endometriosis (DIE) is considered the most aggressive presentation of the disease, penetrating more than 5 mm in affected tissues, and it is reported in approximately 20% of all women with endometriosis. DIE can cause a complete distortion of the pelvic anatomy and it mainly involves uterosacral ligaments, bladder, rectovaginal septum, rectum, and rectosigmoid colon. This review describes the state of the art in laparoscopic approach for DIE with a special interest in intestinal involvement, according to recent literature findings. Our attention has been focused particularly on full-thickness excision versus shaving technique in deep endometriosis intestinal involvement. Particularly, the aim of this paper is clarifying from the clinical and methodological points of view the best surgical treatment of deep intestinal endometriosis, since there is no standard of care in the literature and in different surgical settings. Indeed, this review tries to suggest when it is advisable to manage the full-thickness excision or the shaving technique, also analyzing perioperative management, main complications, and surgical outcomes. PMID:27579309

  17. Full-Thickness Excision versus Shaving by Laparoscopy for Intestinal Deep Infiltrating Endometriosis: Rationale and Potential Treatment Options.

    PubMed

    Laganà, Antonio Simone; Vitale, Salvatore Giovanni; Trovato, Maria Antonietta; Palmara, Vittorio Italo; Rapisarda, Agnese Maria Chiara; Granese, Roberta; Sturlese, Emanuele; De Dominici, Rosanna; Alecci, Stefano; Padula, Francesco; Chiofalo, Benito; Grasso, Roberta; Cignini, Pietro; D'Amico, Paolo; Triolo, Onofrio

    2016-01-01

    Endometriosis is defined as the presence of endometrial mucosa (glands and stroma) abnormally implanted in locations other than the uterine cavity. Deep infiltrating endometriosis (DIE) is considered the most aggressive presentation of the disease, penetrating more than 5 mm in affected tissues, and it is reported in approximately 20% of all women with endometriosis. DIE can cause a complete distortion of the pelvic anatomy and it mainly involves uterosacral ligaments, bladder, rectovaginal septum, rectum, and rectosigmoid colon. This review describes the state of the art in laparoscopic approach for DIE with a special interest in intestinal involvement, according to recent literature findings. Our attention has been focused particularly on full-thickness excision versus shaving technique in deep endometriosis intestinal involvement. Particularly, the aim of this paper is clarifying from the clinical and methodological points of view the best surgical treatment of deep intestinal endometriosis, since there is no standard of care in the literature and in different surgical settings. Indeed, this review tries to suggest when it is advisable to manage the full-thickness excision or the shaving technique, also analyzing perioperative management, main complications, and surgical outcomes. PMID:27579309

  18. Molecular and preclinical basis to inhibit PGE2 receptors EP2 and EP4 as a novel nonsteroidal therapy for endometriosis

    PubMed Central

    Arosh, Joe A.; Lee, JeHoon; Balasubbramanian, Dakshnapriya; Stanley, Jone A.; Long, Charles R.; Meagher, Mary W.; Osteen, Kevin G.; Bruner-Tran, Kaylon L.; Burghardt, Robert C.; Starzinski-Powitz, Anna; Banu, Sakhila K.

    2015-01-01

    Endometriosis is a debilitating, estrogen-dependent, progesterone-resistant, inflammatory gynecological disease of reproductive age women. Two major clinical symptoms of endometriosis are chronic intolerable pelvic pain and subfertility or infertility, which profoundly affect the quality of life in women. Current hormonal therapies to induce a hypoestrogenic state are unsuccessful because of undesirable side effects, reproductive health concerns, and failure to prevent recurrence of disease. There is a fundamental need to identify nonestrogen or nonsteroidal targets for the treatment of endometriosis. Peritoneal fluid concentrations of prostaglandin E2 (PGE2) are higher in women with endometriosis, and this increased PGE2 plays important role in survival and growth of endometriosis lesions. The objective of the present study was to determine the effects of pharmacological inhibition of PGE2 receptors, EP2 and EP4, on molecular and cellular aspects of the pathogenesis of endometriosis and associated clinical symptoms. Using human fluorescent endometriotic cell lines and chimeric mouse model as preclinical testing platform, our results, to our knowledge for the first time, indicate that selective inhibition of EP2/EP4: (i) decreases growth and survival of endometriosis lesions; (ii) decreases angiogenesis and innervation of endometriosis lesions; (iii) suppresses proinflammatory state of dorsal root ganglia neurons to decrease pelvic pain; (iv) decreases proinflammatory, estrogen-dominant, and progesterone-resistant molecular environment of the endometrium and endometriosis lesions; and (v) restores endometrial functional receptivity through multiple mechanisms. Our novel findings provide a molecular and preclinical basis to formulate long-term nonestrogen or nonsteroidal therapy for endometriosis. PMID:26199416

  19. Prototype of Multiplex Bead Assay for Quantification of Three Serum Biomarkers for In Vitro Diagnosis of Endometriosis.

    PubMed

    Signorile, Pietro Giulio; Baldi, Alfonso

    2016-12-01

    Endometriosis is a very common disease, affecting 10% of women in the reproductive age. To date, a significant delay between onset of the symptoms and definitive diagnosis is caused by the lack of a reliable non-invasive diagnostic test. Recently, the potential value as diagnostic markers for endometriosis of three proteins (Zn-alpha2-glycoprotein, serum albumin, and complement C3 precursor), has been showed. In this article, we have defined the experimental conditions for the development of a multiplex bead array assay for rapid and simultaneous quantification of these three biomarkers in the serum of patients with endometriosis. Finally, pivotal experiments on a small cohort of patients have confirmed the diagnostic value of this assay. J. Cell. Physiol. 231: 2622-2627, 2016. © 2016 Wiley Periodicals, Inc. PMID:27137486

  20. Expression profiling of endometrium from women with endometriosis reveals candidate genes for disease-based implantation failure and infertility.

    PubMed

    Kao, L C; Germeyer, A; Tulac, S; Lobo, S; Yang, J P; Taylor, R N; Osteen, K; Lessey, B A; Giudice, L C

    2003-07-01

    Endometriosis is clinically associated with pelvic pain and infertility, with implantation failure strongly suggested as an underlying cause for the observed infertility. Eutopic endometrium of women with endometriosis provides a unique experimental paradigm for investigation into molecular mechanisms of reproductive dysfunction and an opportunity to identify specific markers for this disease. We applied paralleled gene expression profiling using high-density oligonucleotide microarrays to investigate differentially regulated genes in endometrium from women with vs. without endometriosis. Fifteen endometrial biopsy samples (obtained during the window of implantation from eight subjects with and seven subjects without endometriosis) were processed for expression profiling on Affymetrix Hu95A microarrays. Data analysis was conducted with GeneChip Analysis Suite, version 4.01, and GeneSpring version 4.0.4. Nonparametric testing was applied, using a P value of 0.05, to assess statistical significance. Of the 12,686 genes analyzed, 91 genes were significantly increased more than 2-fold in their expression, and 115 genes were decreased more than 2-fold. Unsupervised clustering demonstrated down-regulation of several known cell adhesion molecules, endometrial epithelial secreted proteins, and proteins not previously known to be involved in the pathogenesis of endometriosis, as well as up-regulated genes. Selected dysregulated genes were randomly chosen and validated with RT-PCR and/or Northern/dot-blot analyses, and confirmed up-regulation of collagen alpha2 type I, 2.6-fold; bile salt export pump, 2.0-fold; and down-regulation of N-acetylglucosamine-6-O-sulfotransferase (important in synthesis of L-selectin ligands), 1.7-fold; glycodelin, 51.5-fold; integrin alpha2, 1.8-fold; and B61 (Ephrin A1), 4.5-fold. Two-way overlapping layer analysis used to compare endometrial genes in the window of implantation from women with and without endometriosis further identified three

  1. Fine needle aspiration cytology: a tool to diagnose cervical and vaginal endometriosis in low-income places.

    PubMed

    Oliveira-Filho, Manoel; Rao, Vietla S; Eleutério, José; Medeiros, Francisco C

    2013-01-01

    Regarded as infrequent, vaginal and cervical endometriosis is probably more common than is generally realized. The apparent rarity of the lesion may be ascribed to the limited awareness of its clinical appearance, combined with technical difficulty in obtaining suitable biopsy material for confirmation. Thus, clinical recognition and tissue confirmation become essential. This paper focuses on vaginal and cervical endometriosis, documenting the clinical, macroscopic, cytological and colposcopic findings in 4 cases seen at a single physical vaginal examination. Diagnosis in these patients was facilitated and improved by fine needle aspiration cytology and confirmed by histology. This technique, which is not used for the diagnosis of endometriosis, could be an option in low-income areas. PMID:23406608

  2. A prospective study of insulin-like growth factor 1, its binding protein 3, and risk of endometriosis.

    PubMed

    Mu, Fan; Hankinson, Susan E; Schernhammer, Eva; Pollak, Michael N; Missmer, Stacey A

    2015-07-15

    Several retrospective case-control studies suggested that insulin-like growth factor 1 (IGF-1) or insulin-like growth factor binding protein 3 (IGFBP-3) was associated with endometriosis. However, results are inconsistent and no prospective study exists. We prospectively evaluated associations between plasma levels of IGF-1 and IGFBP-3 and laparoscopically confirmed endometriosis in a case-control study nested within the Nurses' Health Study II. Between blood collections in 1996-1999 and 2007, we ascertained 310 premenopausal women with incident endometriosis and 615 matched controls. We estimated incidence rate ratios and 95% confidence intervals using multivariable conditional logistic regression. We observed no statistically significant associations between endometriosis and IGF-1 (incidence rate ratio (IRR) = 0.88, 95% confidence interval (CI): 0.61, 1.27; Ptrend = 0.48), IGFBP-3 (IRR = 1.12, 95% CI: 0.80, 1.57; Ptrend = 0.51), and the IGF-1:IGFBP-3 molar ratio (IRR = 0.94, 95% CI: 0.66, 1.34; Ptrend = 0.64), comparing the top with the bottom tertile. IGF-1, IGFBP-3, and the molar ratio appeared to be positively associated with endometriosis risk among women aged <40 years at blood draw (IGF-1: IRR = 1.60, 95% CI: 0.86, 2.98; IGFBP-3: IRR = 1.85, 95% CI: 1.08, 3.16; IGF-1:IGFBP-3: IRR = 1.57, 95% CI: 0.85, 2.88) but not among women aged ≥40 years at blood draw (all Pheterogeneity ≤ 0.05). Overall, these data suggest that, if IGF-1 or IGFBP-3 plays a role in the etiology of endometriosis, it is minimal and perhaps only among younger women. PMID:26121987

  3. A Prospective Study of Insulin-Like Growth Factor 1, Its Binding Protein 3, and Risk of Endometriosis

    PubMed Central

    Mu, Fan; Hankinson, Susan E.; Schernhammer, Eva; Pollak, Michael N.; Missmer, Stacey A.

    2015-01-01

    Several retrospective case-control studies suggested that insulin-like growth factor 1 (IGF-1) or insulin-like growth factor binding protein 3 (IGFBP-3) was associated with endometriosis. However, results are inconsistent and no prospective study exists. We prospectively evaluated associations between plasma levels of IGF-1 and IGFBP-3 and laparoscopically confirmed endometriosis in a case-control study nested within the Nurses' Health Study II. Between blood collections in 1996–1999 and 2007, we ascertained 310 premenopausal women with incident endometriosis and 615 matched controls. We estimated incidence rate ratios and 95% confidence intervals using multivariable conditional logistic regression. We observed no statistically significant associations between endometriosis and IGF-1 (incidence rate ratio (IRR) = 0.88, 95% confidence interval (CI): 0.61, 1.27; Ptrend = 0.48), IGFBP-3 (IRR = 1.12, 95% CI: 0.80, 1.57; Ptrend = 0.51), and the IGF-1:IGFBP-3 molar ratio (IRR = 0.94, 95% CI: 0.66, 1.34; Ptrend = 0.64), comparing the top with the bottom tertile. IGF-1, IGFBP-3, and the molar ratio appeared to be positively associated with endometriosis risk among women aged <40 years at blood draw (IGF-1: IRR = 1.60, 95% CI: 0.86, 2.98; IGFBP-3: IRR = 1.85, 95% CI: 1.08, 3.16; IGF-1:IGFBP-3: IRR = 1.57, 95% CI: 0.85, 2.88) but not among women aged ≥40 years at blood draw (all Pheterogeneity ≤ 0.05). Overall, these data suggest that, if IGF-1 or IGFBP-3 plays a role in the etiology of endometriosis, it is minimal and perhaps only among younger women. PMID:26121987

  4. Spontaneous Healing of a Rectovaginal Fistula Developing after Laparoscopic Segmental Bowel Resection for Intestinal Deep Infiltrating Endometriosis

    PubMed Central

    Trippia, Carlos Henrique; Zomer, Monica Tessmann

    2013-01-01

    The surgical treatment of intestinal deep infiltrating endometriosis has an associated risk of major complications such as dehiscence of the intestinal anastomosis, pelvic abscess, and rectovaginal fistula. The management of postoperative rectovaginal fistula frequently requires a reoperation and the construction of a stoma for temporary fecal diversion. In this paper we describe a 27-year-old woman undergoing laparoscopic treatment of deep infiltrating endometriosis (extramucosal cystectomy, resection of the uterosacral ligaments, resection of the posterior vaginal fornix, and segmental bowel resection) complicated by a rectovaginal fistula, which healed spontaneously with nonsurgical conservative treatment. PMID:23710392

  5. Diagnosis and laparoscopic management of a rare endometriosis-related peritoneal mass with rapid growth in early pregnancy.

    PubMed

    Di Donato, Nadine; Facchini, Chiara; Leggieri, Concetta; Caprara, Giacomo; Seracchioli, Renato

    2015-08-01

    Herein is described the diagnosis, clinical management and laparoscopic removal of a rapid growing retro-uterine mass in a pregnant woman. After laparoscopic removal of the pelvic mass, diagnosis of peritoneal endometriotic cyst was made on histology. The patient was asymptomatic and no history of endometriosis was reported. The laparoscopic management of the peritoneal mass was safe and effective and to our knowledge this is the first case report describing a decidualized endometriotic lesion in the absence of a pre-pregnancy endometriosis diagnosis. PMID:25976375

  6. Structural and molecular features of the endomyometrium in endometriosis and adenomyosis.

    PubMed

    Benagiano, Giuseppe; Brosens, Ivo; Habiba, Marwan

    2014-01-01

    BACKGROUND Adenomyosis and endometriosis were initially described as 'adenomyoma'. When the retrograde menstruation theory became widely accepted to explain the pathogenesis of endometriosis, since it does not explain adenomyosis, the two conditions came to be seen as distinct entities. However, emerging evidence suggests that both diseases may be linked to changes in the inner portion of the myometrium. In addition, similar anomalies were found in the eutopic endometrium of the two conditions and the debate has re-opened. A common origin for both adenomyosis and endometriosis would have relevance not only for understanding uterine function and pathophysiology, but also for clinical management and treatment. METHODS The Scopus and Medline databases were searched for all original articles published in English up to the end of 2012. Search terms included 'adenomyosis'; 'endometriosis'; 'endometrium'; 'eutopic endometrium'; 'inner myometrium'; 'junctional zone'. Special attention was paid to articles comparing features of eutopic endometrium in the two conditions. RESULTS A number of similarities exist between adenomyosis and endometriosis and, by using magnetic resonance and laparoscopy, it was found that, at least in some subgroups, the two conditions often coexist. In both situations the inner myometrium (or junctional zone) is altered, although alterations are much more marked in adenomyosis where a thickness >12 mm is today considered sufficient for diagnosis. Research has shown differences between the eutopic endometrium of women with both diseases when compared with controls. There is an immune dysfunction and there are alterations of adhesion molecules, cell proliferation and apoptosis. An increase in cytokines and inflammatory mediators has also been observed. Finally, the presence of oxidative stress and anomalies in free-radical metabolism may alter uterine receptivity. When the two conditions were compared, dissimilarities were also observed in the extent

  7. Multiple Beneficial Roles of Repressor of Estrogen Receptor Activity (REA) in Suppressing the Progression of Endometriosis.

    PubMed

    Zhao, Yuechao; Chen, Yiru; Kuang, Ye; Bagchi, Milan K; Taylor, Robert N; Katzenellenbogen, John A; Katzenellenbogen, Benita S

    2016-02-01

    Endometriosis is an estrogen-dependent, inflammation-driven gynecologic disorder in which endometrial tissue creates inflammatory lesions at extrauterine sites, leading to pelvic pain and impaired fertility. Although dysregulated estrogen receptor (ER) signaling has been implicated, understanding of this disease is incomplete and current therapies are of limited benefit. Using an immunocompetent syngeneic murine model, we used combinations of donor uterine tissue and/or recipient host mice with partial genetic deletion of the ER coregulator, repressor of ER activity (REA) (also known as prohibitin 2), to investigate roles of REA in the contributions of donor uterine tissue and host cell influences on endometriosis establishment and progression. Ectopic lesions derived from donor tissue with half the wild-type gene dosage of REA (REA(+/-)) grown in REA(+/-) hosts displayed enhanced proliferation, vascularization, and markedly increased neuron innervation and inflammatory responses, including elevated cytokine production, nuclear factor kappa B activation, cyclooxygenase-2 expression, and immune cell infiltration. Although lesion progression was greatest when REA was reduced in both donor tissue and host animals, other donor/host combinations indicated that distinct stimulatory inputs were derived from ectopic tissue (proliferative signals) and host cells (inflammatory signals). Importantly, depletion of REA in primary human endometriotic stromal cells led to elevated proliferation and expression of cell cycle regulators. Notably, REA was significantly lower in human endometriotic tissue versus normal human endometrium. Thus, REA modulates cross talk among multiple cell types in the uterine tissue and host background, serving as a brake on the estradiol-ER axis and restraining multiple aspects that contribute to the pathologic progression of endometriosis. PMID:26653759

  8. MiR-202 promotes endometriosis by regulating SOX6 expression

    PubMed Central

    Zhang, Dongli; Li, Yanyun; Tian, Jun; Zhang, Hongxia; Wang, Shelian

    2015-01-01

    Objectives: This study is to investigate the role and mechanism of microRNA-202 (miR-202) in endometriosis. Methods: Forty-five cases of ectopic endometrial tissues, 25 cases of eutopic endometrial tissues and 26 cases of normal endometrial tissues were collected. MiR-202 expression was detected by quantitative RT-PCR. The protein expressions of SOX6 (sex determining region Y-box 6) and its downstream proteins (p21, cyclin D1 and pRb (retinoblastoma protein)) were detected by immunochemistry and western blot. MTT and transwell assays were used to examine cell proliferation and cell migration. The dual luciferase assay was applied to validate whether miR-202 can directly target SOX6 gene. Results: MiR-202 was highly expressed in eutopic and ectopic endometrial tissues than normal endometrial tissues (P < 0.05), and the expression was higher in tissues with III/IV stages than I/II stages (P < 0.05). The expression of SOX6 protein was lower in ectopic endometrial tissues than in normal endometrial tissues. In ectopic endometrial tissues, the expression of p21 was decreased while cyclin D1 and pRb was up-regulated than in normal endometrial tissues (P < 0.05). In cultured endometrial cells, miR-202 down-regulation induced up-regulation of SOX6 and p21 whereas down-regulation of cyclin D1 and pRb. MiR-202 promoted the proliferation and metastasis of endometrial cells. And, miR-202 could complementary bind to SOX6 3’UTR to regulate the expression of SOX6. Conclusion: MiR-202 was up-regulated in the endometriosis. Through targeting SOX6 and its downstream proteins (p21, cyclin D1 and pRb), miR-202 can promote the progression of endometriosis. PMID:26770366

  9. Quasi-resonance enhancement of laser-induced-fluorescence diagnosis of endometriosis

    NASA Astrophysics Data System (ADS)

    Hill, Ralph H., Jr.; Vancaillie, Thierry G.

    1990-05-01

    Endometriosis, a common disease in women in the reproductive age group, is defined pathologically by the presence of endometrial tissue (inner lining of the uterus) outside the uterus. The displaced tissue is histologically identical to endometrium. In addition to being a highly prevalent disease, this disease is associated with many distressing and debilitating symptoms. Motivated by the need to improve diagnosis by endoscopic imaging instrumentation, we have previously used several drugs to cause selective laser-induced fluorescence of active surgically induced endometriosis in the rabbit model in vivo using ultraviolet-wavelength (351.1 and 363.8 nm) excitation from an argon-ion laser. In the present study we have investigated methods of enhancing differentiation between normal and abnormal tissue by using other excitation wavelengths. In addition to an enhanced capability for detecting abnormal tissue, there are several other advantages associated with using visible-wavelength excitation, such as deeper penetration into the tissue, as well as increased equipment performance, reliability, versatility, and availability. The disadvantage is that because only wavelengths longer than the excitation wavelength can be used for detection, some of the spectral information is lost. Because human endomeiriosis samples were somewhat limited in quantity, as well as specimen size, we used normal ovarian tissue for the laser-induced-fluorescence differentiation-enhancement studies. Positive enhancement of the laser-induced- fluorescence differentiation was found in human ovarian tissue in vitro utilizing 514.5-nm excitation from an argonion laser. Additionally, preliminary verification of this concept was accomplished in active surgically induced endometriosis in the rabbit model in vivo with visible argon-ion laser excitation of two tetracycline-based drugs. Future experiments with other drug treatments and excitation/detection parameters are planned.

  10. The immunoprofile of interstitial Cajal cells within adenomyosis/endometriosis lesions.

    PubMed

    Drăghici, Isabela Magdalena; Drăghici, Liviu; Cojocaru, Manole; Gorgan, Carmen Loredana; Vrabie, Camelia Doina

    2015-01-01

    Adenomyosis and endometriosis are lesions which have aroused the interest for the investigation of antibodies specific to the structures from the composition, but also for the cause behind the appearance of these lesions in completely different structures. The impact they have on fertility is not known entirely, for they are difficult to diagnose. Endometriosis causes infertility and it is a hard to treat lesion. The research performed in the last years has been focused on the so-called linkage analysis, or reverse genetics. It refers to identifying the genes which are prone to developing this affection. We investigated clinically 40 female inpatients (n=40) who had underwent genital surgery and received a variegate diagnosis in the "Sf. Ioan" Emergency Hospital, Bucharest, Romania, between January-September 2014 and also their histopathology and immunohistochemistry. We proceeded with the histopathology examination in order to establish a diagnosis in respect to the admission diagnosis and then, using the ABC (Avidin-Biotin complex) method, we analyzed the immunohistochemistry of the following markers: S100 protein (for detection of ganglia and nerve cells), CD117÷c-kit (selective detection of interstitial Cajal cells - ICC), desmin and vimentin (intermediary filaments for detecting ICC-like cells, which cohabit with uterine myocytes and are not contractile cells) and CD10 (a sensitive and useful immunomarker in the diagnosis of endometrial stroma and, in some cases, of neoplasia). Our study, regarding the immunoprofile of some markers of adenomyosis÷endometriosis lesions, supports the hypothesis that the interstitial Cajal cells are non-reactive, they are not in relationship with investigated lesions, but CD10 is a very useful marker to highlight the endometrial stroma in query cases. PMID:25826497

  11. System of multifunctional laser polarimetry of phase and amplitude anisotropy in the diagnosis of endometriosis

    NASA Astrophysics Data System (ADS)

    Ushenko, Yu. O.; Dubolazov, O. V.; Olar, O. V.

    2015-11-01

    The theoretical background of azimuthally stable method Jones matrix mapping of histological sections of biopsy of uterine neck on the basis of spatial-frequency selection of the mechanisms of linear and circular birefringence is presented. The comparative results of measuring the coordinate distributions of complex degree of mutual anisotropy formed by polycristalline networks of blood plasma layers of donors (group 1) and patients with endometriosis (group 2). The values and ranges of change of the statistical (moments of the 1st - 4th order) parameters of complex degree of mutual anisotropy coordinate distributions are studied. The objective criteria of diagnostics of the pathology and differentiation of its severity degree are determined.

  12. Multifunctional polarization tomography of optical anisotropy of biological layers in diagnosis of endometriosis

    NASA Astrophysics Data System (ADS)

    Ushenko, O. G.; Koval, L. D.; Dubolazov, O. V.; Ushenko, Yu. O.; Savich, V. O.; Sidor, M. I.; Marchuk, Yu. F.

    2015-09-01

    The theoretical background of azimuthally stable method Jones matrix mapping of histological sections of biopsy of uterine neck on the basis of spatial-frequency selection of the mechanisms of linear and circular birefringence is presented. The comparative results of measuring the coordinate distributions of complex degree of mutual anisotropy formed by polycristalline networks of blood plasma layers of donors (group 1) and patients with endometriosis (group 2). The values and ranges of change of the statistical (moments of the 1st - 4th order) parameters of complex degree of mutual anisotropy coordinate distributions are studied. The objective criteria of diagnostics of the pathology and differentiation of its severity degree are determined.

  13. Nonoperative management of an anastomotic leak following rectosigmoid resection and anastomosis for Stage IV endometriosis

    PubMed Central

    DeStephano, Christopher C.; Paz-Fumagalli, Ricardo; Pettit, Paul D.

    2016-01-01

    Anastomotic leakage is a dreaded complication of gastrointestinal surgery. The complication is difficult to manage and is associated with prolonged hospitalizations and increased morbidity and mortality. We present the nonsurgical management and the use of a fibrin sealant for an anastomotic leak that followed rectosigmoid resection and anastomosis for Stage IV endometriosis. This approach requires a clinically stable patient who is willing to follow-up over a prolonged period of time until the leak is completely sealed. Tissue sealants can be considered when an air leak or fistulous tract persists despite drainage and antibiotics. PMID:27147717

  14. Women with endometriosis improved their peripheral antioxidant markers after the application of a high antioxidant diet

    PubMed Central

    Mier-Cabrera, Jennifer; Aburto-Soto, Tania; Burrola-Méndez, Soraya; Jiménez-Zamudio, Luis; Tolentino, Mari C; Casanueva, Esther; Hernández-Guerrero, César

    2009-01-01

    Background Oxidative stress has been identified in the peritoneal fluid and peripheral blood of women with endometriosis. However, there is little information on the antioxidant intake for this group of women. The objectives of this work were 1) to compare the antioxidant intake among women with and without endometriosis and 2) to design and apply a high antioxidant diet to evaluate its capacity to reduce oxidative stress markers and improve antioxidant markers in the peripheral blood of women with endometriosis. Methods Women with (WEN, n = 83) and without endometriosis (WWE, n = 80) were interviewed using a Food Frequency Questionnaire to compare their antioxidant intake (of vitamins and minerals). Then, the WEN participated in the application of a control (n = 35) and high antioxidant diet (n = 37) for four months. The high antioxidant diet (HAD) guaranteed the intake of 150% of the suggested daily intake of vitamin A (1050 μg retinol equivalents), 660% of the recommended daily intake (RDI) of vitamin C (500 mg) and 133% of the RDI of vitamin E (20 mg). Oxidative stress and antioxidant markers (vitamins and antioxidant enzymatic activity) were determined in plasma every month. Results Comparison of antioxidant intake between WWE and WEN showed a lower intake of vitamins A, C, E, zinc, and copper by WEN (p < 0.05, Mann Whitney Rank test). The selenium intake was not statistically different between groups. During the study, the comparison of the 24-hour recalls between groups showed a higher intake of the three vitamins in the HAD group. An increase in the vitamin concentrations (serum retinol, alpha-tocopherol, leukocyte and plasma ascorbate) and antioxidant enzyme activity (superoxide dismutase and glutathione peroxidase) as well as a decrease in oxidative stress markers (malondialdehyde and lipid hydroperoxides) were observed in the HAD group after two months of intervention. These phenomena were not observed in the control group. Conclusion WEN had a lower

  15. Endometriosis as a detrimental condition for granulosa cell steroidogenesis and development: From molecular alterations to clinical impact.

    PubMed

    Sanchez, Ana Maria; Somigliana, Edgardo; Vercellini, Paolo; Pagliardini, Luca; Candiani, Massimo; Vigano, Paola

    2016-01-01

    Endometriosis is an estrogen-dependent chronic inflammatory condition that affects women in their reproductive period. Alterations in ovarian follicle morphology and function have been documented in affected women. The local intrafollicular environment has been as well examined by various groups. In the present review, we aimed to summarize the molecular evidence supporting the idea that endometriosis can negatively influence growth, steroidogenesis and the function of the granulosa cells (GCs). Reduced P450 aromatase expression, increased intracellular ROS generation and altered WNT signaling characterize the GCs of women with endometriosis. Clear evidence for an increased level of GC apoptosis has been provided in association with the downregulation of pro-survival factors. Other potentially negative effects include decreased progesterone production, locally decreased AMH production and lower inflammatory cytokine expression, although these have been only partially clarified. The possibility that endometriosis per se may influence IVF clinical results as a consequence of the detrimental impact on the local intrafollicular environment is also discussed. PMID:26407755

  16. Abnormal Expression of Prostaglandins E2 and F2α Receptors and Transporters in Patients with Endometriosis

    PubMed Central

    Rakhila, Halima; Bourcier, Nathalie; Akoum, Ali; Pouliot, Marc

    2015-01-01

    Objective. To investigate the level of expression of prostaglandin receptivity and uptake factors in eutopic and ectopic endometrium of women with endometriosis. Design. Prospective study. Setting. Human reproduction research laboratory. Patients. Seventy-eight patients with endometriosis and thirty healthy control subjects. Intervention(s). Endometrial and endometriotic tissue samples were obtained during laparoscopic surgery. Main Outcome Measure(s). Real-time polymerase chain reaction assay of mRNA encoding prostaglandin E2 receptors (EP1, EP2, EP3, and EP4), prostaglandin F2α receptor (FP), prostaglandin transporter (PGT), and multidrug resistance-associated protein 4 (MRP4); immunohistochemical localization of expressed proteins. Results. Marked increases in receptors EP3, EP4, and FP and transporters PGT and MRP4 in ectopic endometrial tissue were noted, without noticeable change associated with disease stage. An increase in EP3 expression and decreases in FP and PGT were observed in the eutopic endometrium of endometriosis patients in conjunction with the phases of the menstrual cycle. Conclusion(s). This study is the first to demonstrate a possible relationship between endometriosis and enhanced prostaglandin activity. In view of the wide range of prostaglandin functions, increasing cell receptivity and facilitating uptake in endometrial tissue could contribute to the initial steps of overgrowth and have an important role to play in the pathogenesis and symptoms of this disease. PMID:26240828

  17. Endometrial CXCL13 Expression Is Cycle Regulated in Humans and Aberrantly Expressed in Humans and Rhesus Macaques With Endometriosis

    PubMed Central

    Franasiak, Jason M.; Burns, Katherine A.; Slayden, Ov; Yuan, Lingwen; Fritz, Marc A.; Korach, Kenneth S.; Lessey, Bruce A.

    2014-01-01

    C-X-C ligand 13 (CXCL13), a regulator of mucosal immunity, is secreted by human endometrial epithelium and may be involved in embryo implantation. However, cyclic expression of human endometrial CXCL13 in health and disease is not well studied. This study examines cycle stage-specific endometrial CXCL13 expression in normal humans when compared to those with biopsy-confirmed, stage 1 to 4 endometriosis using real-time reverse transcriptase, real-time polymerase chain reaction and immunohistochemistry. Eutopic endometrial CXCL13 expression was also compared between normal, control Rhesus macaques, and macaques with advanced endometriosis. In healthy women, CXLC13 messenger RNA expression was minimal in the proliferative phase and maximal in the secretory phase. However, in the presence of endometriosis, proliferative-phase endometrial expression markedly increased in both humans and rhesus subjects (P < .05). The cross-species and cross-stage concordance suggests a pathophysiologic role for CXCL13 in endometriosis and its use as a biomarker for disease. PMID:25031316

  18. Hyaluronic acid-modified magnetic iron oxide nanoparticles for MR imaging of surgically induced endometriosis model in rats.

    PubMed

    Zhang, He; Li, Jingchao; Sun, Wenjie; Hu, Yong; Zhang, Guofu; Shen, Mingwu; Shi, Xiangyang

    2014-01-01

    Endometriosis is defined as the presence of endometrial tissue outside the uterine, which may affect nearly 60% of women in reproductive age. Deep infiltrating endometriosis (DIE) defined as an endometriotic lesion penetrating into the retroperitoneal space or the wall of the pelvic organs to a depth of at least 5 mm represents the most diagnostic challenge. Herein, we reported the use of hyaluronic acid (HA)-modified magnetic iron oxide nanoparticles (HA-Fe3O4 NPs) for magnetic resonance (MR) imaging of endometriotic lesions in the rodent model. Sixteen endometriotic lesions were surgically induced in eight rats by autologous transplantation. Four weeks after lesion induction, three rats were scanned via MR imaging after tail vein injection of the HA-Fe3O4 NPs. Accordingly, the remaining five mice were sacrificed in the corresponding time points. The ectopic uterine tissues (EUTs) were confirmed by histological analysis. Quantification of Fe in the EUT was also performed by inductively coupled plasma-optical emission spectroscopy. Our results showed that by using the HA-Fe3O4 NPs, the EUTs were able to be visualized via T2-weighted MR imaging at 2 hours post injection, corroborating the Prussian blue staining results. The developed HA-Fe3O4 NPs could be used as negative contrast agents for sensitively detecting endometriosis in a mouse model and may be applied for future hyperthermia treatment of endometriosis. PMID:24722347

  19. Idiopathic brachial plexus neuritis after laparoscopic treatment of endometriosis: a complication that may mimic position-related brachial plexus injury.

    PubMed

    Minas, Vasileios; Aust, Thomas

    2013-01-01

    We report the case of a 37-year-old woman who developed idiopathic brachial plexus neuritis, also referred to as Parsonage-Turner syndrome, after laparoscopic excision of endometriosis. The differential diagnosis between this non-position-related neuritis and brachial plexus injury is discussed. The aim of this report was to raise awareness on this distressing postoperative complication. PMID:24183278

  20. A tissue specific magnetic resonance contrast agent, Gd-AMH, for diagnosis of stromal endometriosis lesions: a phase I study.

    PubMed

    Signorile, Pietro G; Baldi, Alfonso

    2015-06-01

    The anti-mullerian hormone (AMH) is a homodimeric glycoprotein member of the transforming growth factor β (TGF-β) superfamily, is secreted by Sertoli cells in the embryonic testes and is responsible of the regression of the mullerian duct. The physiological functions of this protein remain largely unknown, and its expression in human tissues has yet to be completely determined. Firstly, we analyzed AMH expression in human tissues by immunohistochemistry. AMH was distributed in many organs, although with different tissue and cell localization and various expression levels; we also demonstrated strong AMH expression in endometriosis tissues. Secondly, we demonstrated the ability of an anti-AMH antibody, labeled with gadiolinium, to be directly detected by magnetic resonance in small endometriosis lesions (5 mm in diameter) in vivo in a mouse model. In conclusion, our data suggest that based on its expression pattern, AMH may serve to maintain physiological cellular homeostasis in different human tissues and organs. Moreover, it is strongly expressed in endometriosis lesions as a selective tissue specific contrast agent for in vivo detection of stromal endometriosis lesions. The potential significance of these findings could be further validated in a clinical setting. PMID:25370738

  1. A population-based case–control study of urinary bisphenol A concentrations and risk of endometriosis

    PubMed Central

    Upson, Kristen; Sathyanarayana, Sheela; De Roos, Anneclaire J.; Koch, Holger M.; Scholes, Delia; Holt, Victoria L.

    2014-01-01

    STUDY QUESTION Is bisphenol A (BPA) exposure associated with the risk of endometriosis, an estrogen-driven disease of women of reproductive age? SUMMARY ANSWER Our study suggests that increased urinary BPA is associated with an increased risk of non-ovarian pelvic endometriosis, but not ovarian endometriosis. WHAT IS KNOWN ALREADY BPA, a high-volume chemical used in the polymer industry, has been the focus of public and scientific concern given its demonstrated estrogenic effects in vivo and in vitro and widespread human exposure. Prior studies of BPA and endometriosis have yielded inconsistent results and were limited by the participant sampling framework, small sample size or use of serum (which has very low/transient concentrations) instead of urine to measure BPA concentrations. STUDY DESIGN, SIZE, DURATION We used data from the Women's Risk of Endometriosis study, a population-based case–control study of endometriosis, conducted among female enrollees of a large healthcare system in the US Pacific Northwest. Cases were women with incident, surgically confirmed endometriosis diagnosed between 1996 and 2001 and controls were women randomly selected from the defined population that gave rise to the cases, without a current or prior diagnosis of endometriosis. PARTICIPANTS/MATERIALS, SETTINGS, METHODS Total urinary BPA concentrations were measured in 143 cases and 287 population-based controls using single, spot urine samples collected after disease diagnosis in cases. Total urinary BPA concentration (free and conjugated species) was quantified using a high-performance liquid chromatography-mass spectrometry method. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression, adjusting for urinary creatinine concentrations, age and reference year. We also evaluated the association by disease subtypes, ovarian and non-ovarian pelvic endometriosis, that may be etiologically distinct. MAIN RESULTS AND THE ROLE OF CHANCE

  2. Treatment of Endometriosis with the GnRHa Deslorelin and Add-Back Estradiol and Supplementary Testosterone

    PubMed Central

    Agarwal, Sanjay K.; Daniels, AnnaMarie; Drosman, Steven R.; Udoff, Laurence; Foster, Warren G.; Pike, Malcolm C.; Spicer, Darcy V.; Daniels, John R.

    2015-01-01

    Background. This randomized, multicenter, open-label clinical trial was intended to generate pilot data on the efficacy and safety of the gonadotropin-releasing hormone agonist (GnRHa) deslorelin (D) with low-dose estradiol ± testosterone (E2  ± T) add-back for endometriosis-related pelvic pain. Methods. Women with pelvic pain and laparoscopically confirmed endometriosis were treated with a six-month course of daily intranasal D with concurrent administration of either transdermal E2, intranasal E2, or intranasal E2  + T. Efficacy data included evaluation of dyspareunia, dysmenorrhea, pelvic pain, tenderness, and induration. Cognition and quality of life were also assessed. Safety parameters included assessment of endometrial hyperplasia, bone mineral density (BMD), and hot flashes. Results. Endometriosis symptoms and signs scores decreased in all treatment arms from a baseline average of 7.4 to 2.5 after 3 months of treatment and 3.4 after 6 months. BMD changes and incidence of hot flashes were minimal, and no endometrial hyperplasia was observed. Patient-reported outcomes showed significant improvement across multiple domains. Conclusions. Daily intranasal D with low dose E2  ± T add-back resulted in significant reduction in severity of endometriosis symptoms and signs with few safety signals and minimal hypoestrogenic symptoms that would be expected with the use of a GnRHa alone. PMID:26881208

  3. Gamete intra-fallopian transfer or intrauterine insemination after controlled ovarian hyperstimulation for treatment of infertility due to endometriosis.

    PubMed

    Lodhi, S; Abdel Fattah, A; Abozaid, T; Murphy, J; Formantini, E; Sasy, M; Barber, K; Abuzeid, M

    2004-09-01

    We compared the effectiveness of gamete intra-Fallopian transfer (GIFT) and intrauterine insemination (IUI) after controlled ovarian hyperstimulation (COH) in the treatment of infertility due to endometriosis. This was a retrospective study carried out at a tertiary teaching medical center. A total of 127 consecutive patients with endometriosis were treated with GIFT or IUI after COH between June 1990 and December 1998. Patients were divided into two groups. Group 1 (n = 97) included patients with stages 1 and 2 endometriosis, and group 2 (n = 30) included patients with stages 3 and 4 endometriosis. Laparoscopic conservative surgery for endometriosis was performed prior to IUI for patients in both group 1 and group 2. In group 1, 55 patients underwent 95 cycles of IUI after COH and 42 patients underwent 57 cycles of GIFT. In group 2, 14 patients underwent 16 cycles of IUI after COH, while 16 patients underwent 22 cycles of GIFT. The stimulation protocol for both GIFT and IUI was mid-luteal pituitary down-regulation with a gonadotropin releasing hormone agonist (GnRH-a) followed by gonadotropins. In group 1, the pregnancy rates (GIFT = 50.9%, IUI = 29.4%) and the delivery rates (GIFT = 28.1%, IUI = 14.7%) per cycle were significantly higher in GIFT compared to IUI (p = 0.009 and p = 0.05, respectively). There was no significant differences in the pregnancy rate (GIFT 69%, IUI 50.9%, respectively) or the delivery rate (GIFT 38.1%, IUI 25.5%) per patient. In group 2, there was no significant difference in the pregnancy rate (GIFT 54.5%, IUI 31.3%) or the delivery rate (GIFT 40.9%, IUI 12.5%) per cycle, but the difference in the pregnancy rate (GIFT 75%, IUI 35.7%) and the delivery rate (GIFT 56.3%, IUI 14.3%) per patient was significantly higher in GIFT compared to IUI (p = 0.04 and p = 0.02, respectively). We conclude that, when the same stimulation protocol is used in the early stages of endometriosis, a few cycles of IUI can achieve similar results to GIFT, and

  4. Pharmaceutical treatments to prevent recurrence of endometriosis following surgery: a model-based economic evaluation

    PubMed Central

    Sanghera, Sabina; Barton, Pelham; Bhattacharya, Siladitya; Horne, Andrew W; Roberts, Tracy Elizabeth

    2016-01-01

    Objective Conduct an economic evaluation based on best currently available evidence comparing alternative treatments levonorgestrel-releasing intrauterine system, depot-medroxyprogesterone acetate, combined oral contraceptive pill (COCP) and ‘no treatment’ to prevent recurrence of endometriosis after conservative surgery in primary care, and to inform the design of a planned trial-based economic evaluation. Methods We developed a state transition (Markov) model with a 36-month follow-up. The model structure was informed by a pragmatic review and clinical experts. The economic evaluation adopted a UK National Health Service perspective and was based on an outcome of incremental cost per quality-adjusted life year (QALY). As available data were limited, intentionally wide distributions were assigned around model inputs, and the average costs and outcome of the probabilistic sensitivity analyses were reported. Results On average, all strategies were more expensive and generated fewer QALYs compared to no treatment. However, uncertainty attributing to the transition probabilities affected the results. Inputs relating to effectiveness, changes in treatment and the time at which the change is made were the main causes of uncertainty, illustrating areas where robust and specific data collection is required. Conclusions There is currently no evidence to support any treatment being recommended to prevent the recurrence of endometriosis following conservative surgery. The study highlights the importance of developing decision models at the outset of a trial to identify data requirements to conduct a robust post-trial analysis. PMID:27084280

  5. Intramuscular abdominal wall endometriosis treated by ultrasound-guided ethanol injection.

    PubMed

    Bozkurt, Murat; Çil, A Said; Bozkurt, Duygu Kara

    2014-12-01

    Abdominal wall endometriosis (AWE) is a rare condition that usually develops in a surgical scar resulting from a Caesarean section. While commonly seen in the cutaneous and subcutaneous fat tissue at the Caesarean scar level, its intramuscular localization is quite rare. Its treatment options consist of the excision of the lesion and/or hormonal therapies, although wide surgical excision is the treatment of choice in the literature. Wide surgical excision may create a defect in the abdominal wall and may increase the risk of hernia formation and mesh complications. This case report describes the clinical and radiological findings and treatment modalities of endometriosis that have appeared in the rectus abdominis muscle of a 25-year-old patient at the Caesarean scar level. Sclerotherapy may be used for endometrioma. We present a new and alternative treatment method using ultrasound-guided intralesional ethanol injection for AWE. Compared with the complications of surgical excision, the complications of sclerotherapy by ethanol are at a more acceptable level. Sclerotherapy by ethanol injection may be an alternative treatment to surgery for AWE. PMID:24667221

  6. Intramuscular Abdominal Wall Endometriosis Treated by Ultrasound-Guided Ethanol Injection

    PubMed Central

    Bozkurt, Murat; Çil, A. Said; Bozkurt, Duygu Kara

    2014-01-01

    Abdominal wall endometriosis (AWE) is a rare condition that usually develops in a surgical scar resulting from a Caesarean section. While commonly seen in the cutaneous and subcutaneous fat tissue at the Caesarean scar level, its intramuscular localization is quite rare. Its treatment options consist of the excision of the lesion and/or hormonal therapies, although wide surgical excision is the treatment of choice in the literature. Wide surgical excision may create a defect in the abdominal wall and may increase the risk of hernia formation and mesh complications. This case report describes the clinical and radiological findings and treatment modalities of endometriosis that have appeared in the rectus abdominis muscle of a 25-year-old patient at the Caesarean scar level. Sclerotherapy may be used for endometrioma. We present a new and alternative treatment method using ultrasound-guided intralesional ethanol injection for AWE. Compared with the complications of surgical excision, the complications of sclerotherapy by ethanol are at a more acceptable level. Sclerotherapy by ethanol injection may be an alternative treatment to surgery for AWE. PMID:24667221

  7. A Novel Noninvasive Model of Endometriosis for Monitoring the Efficacy of Antiangiogenic Therapy

    PubMed Central

    Becker, Christian M.; Wright, Renee D.; Satchi-Fainaro, Ronit; Funakoshi, Tae; Folkman, Judah; Kung, Andrew L.; D’Amato, Robert J.

    2006-01-01

    Endometriosis, the presence of ectopic endometrial tissue, is a common disease associated with high morbidity and socioeconomic problems. Angiogenesis, the formation of new blood vessels, plays an important role in the formation and growth of endometriotic lesions. We have created a novel, noninvasive model to monitor the growth of these lesions and the associated angiogenesis in vivo. First, we generated luciferase-expressing transgenic mice by inserting the human ubiquitin C promoter coupled to the firefly luciferase reporter. Injection of luciferin in these mice causes full-body bioluminescence, which can be detected using a low-light CCD camera. Endometrial tissue from these transgenic mice was surgically implanted into nonluminescent recipients. Bioluminescence of lesions was noninvasively imaged after intravenous or intraperitoneal injection of luciferin. Transabdominal luminescence compared well with the location of the transgenic endometriotic lesions, and lesion size correlated with the intensity of luminescence. Systemic treatment with the angiogenesis inhibitors caplostatin and endostatin peptide mP-1 delayed and suppressed the onset and intensity of the luminescent signal. Caplostatin suppressed the growth of endometriotic lesions by 59% compared with controls. This novel, noninvasive model of endometriosis provides a means to study early angiogenesis in vivo and to monitor endometriotic growth and the efficacy of systemic antiangiogenic therapy. PMID:16723720

  8. Molecular Network Analysis of Endometriosis Reveals a Novel Role for c-Jun Regulated Macrophage Activation

    PubMed Central

    Beste, Michael T.; Pfäffle-Doyle, Nicole; Prentice, Emily A.; Morris, Stephanie N.; Lauffenburger, Douglas A.; Isaacson, Keith B.; Griffith, Linda G.

    2014-01-01

    Clinical management of endometriosis is limited by the complex relationship between symptom severity, heterogeneous surgical presentations, and variability in clinical outcomes. As a complement to visual classification schemes, molecular profiles of disease activity may improve risk stratification to better inform treatment decisions and identify novel approaches to targeted treatment. Here, we employ a network analysis of information flow within and between inflammatory cells to discern consensus behaviors characterizing patient sub-populations. Unsupervised multivariate analysis of cytokine profiles quantified by multiplex immunoassays identified a subset of patients with a shared “consensus signature” of thirteen elevated cytokines that was associated with common clinical features, but was not observed among patient subpopulations defined by morphologic presentation alone. Enrichment analysis of consensus markers reinforced the primacy of peritoneal macrophage infiltration and activation, which was demonstrably elevated in ex vivo cultures. Although familiar targets of the NFκB family emerged among over-represented transcriptional binding sites for consensus markers, our analysis provides evidence for a previously unrecognized contribution from c-Jun, c-Fos, and AP-1 effectors of mitogen associated kinase signaling. Their crucial involvement in propagation of macrophage-driven inflammatory networks was confirmed via targeted inhibition of upstream kinases. Collectively, these analyses provide in vivo validation of a clinically relevant inflammatory network that may serve as an objective measure for guiding treatment decisions for endometriosis management, and in the future may provide a mechanistic endpoint for assessing efficacy of novel agents aimed at curtailing inflammatory mechanisms that drive disease progression. PMID:24500404

  9. Correlation Between the Clinical Parameters and Tissue Phenotype in Patients Affected by Deep-Infiltrating Endometriosis.

    PubMed

    Vinci, Giovanna; Arkwright, Sylviane; Audebourg, Anne; Radenen, Brigitte; Chapron, Charles; Borghese, Bruno; Dousset, Bertrand; Mehats, Celine; Vaiman, Daniel; Vacher-Lavenu, Marie-Cécile; Gogusev, Jean

    2016-09-01

    The current study aimed to identify and validate an applicable immunohistochemistry panel including Ki-67, c-MYC, estrogen receptor-α (ER-α), and progesterone receptor isoforms A/B (PR-A/B) in correlation with clinicopathological parameters in patients affected by deep infiltrating endometriosis. Tissue microarrays were prepared from a cohort of 113 patients. Phenotypic profile of the panel molecules was evaluated in glands and stroma in parallel with microvessels and stroma density measurements. Principal component analysis was performed on 8 immunohistochemical variables, 2 histological variables, and 8 subgroups of clinical parameters. The immunohistochemical profiling showed consistent Ki-67 immunostaining in 17.9% of the samples and c-MYC in 83.1%, while intense ER-α immunoreactivity was detected in 84% of the samples and PR-A/B isoforms in 24.1% of them. The combination of clinical parameters and tissue phenotype allowed a stratification of endometriosis-affected patients. Such novel phenotypical and clinical correlation could be helpful in the future studies for a better stratification of the disease aiming at a personalized patient care. PMID:26994067

  10. Photodynamic therapy (PDT) of endometrium primary cultures serving as an in-vitro model for endometriosis

    NASA Astrophysics Data System (ADS)

    Herter, Wiebke; Viereck, Volker; Keckstein, J.; Steiner, Rudolf W.; Rueck, Angelika C.

    1994-05-01

    As a new treatment model for endometriosis, photodynamic therapy (PDT) was applied to endometrium cultures. Endometriosis is a benign disease. Therefore primary cultures were used instead of cell lines. Endometrium is composed of epithelial and stromal cells which can also be found in primary culture. While stromal cells take a polygonal shape in culture, epithelial cells form cell colonies. PSIII (Photasan III), which is similar to hematorporphyrin derivate (HpD), meso-tetra (4-sulfonatophenyl) porphyrin (TPPS4), which posses a high fluorescence quantum yield and may be useful in fluorescence diagnosis of subtle endometriotic spots, and methylene blue (MB), a vital dye with phototoxic properties, were used as photosensitizers. Different sensitizer concentrations and incubation times were applied. The highest phototoxicity was observed for PSIII; TPPS4 and MB were less phototoxic. We compared our results with the sensitivity of cell lines described in the literature. The necessary irradiation to destroy stromal cells was relatively high but still in the same dimension as for cell lines. However they were even more sensitive than epithelial cells. This was true for all sensitizers used.

  11. Photodynamic treatment (PDT) of endometrium primary cultures serving as an in-vitro-model for endometriosis

    NASA Astrophysics Data System (ADS)

    Werter, Wiebke; Viereck, Volker; Keckstein, J.; Steiner, Rudolf W.; Rueck, Angelika C.

    1994-05-01

    As a new treatment model for endometriosis, photodynamic therapy (PDT) was applied to endometrium cultures. Endometriosis is a benign disease. Therefore primary cultures were used instead of cell lines. Endometrium is composed of epithelial and stromal cells which can also be found in primary culture. While stromal cells take a polygonal shape in culture, epithelial cells form cell colonies. PSIII (Photasan III), which is similar to hematorporphyrin derivate (HpD), meso-tetra (4-sulfonatophenyl) porphyrin (TPPS4), which posses a high fluorescence quantum yield and may be useful in fluorescence diagnosis of subtle endometriotic spots, and methylene blue (MB), a vital dye with phototoxic properties, were used as photosensitizers. Different sensitizer concentrations and incubation times were applied. The highest phototoxicity was observed for PSIII; TPPS4 and MB were less phototoxic. We compared our results with the sensitivity of cell lines described in the literature. The necessary irradiation to destroy stromal cells was relatively high but still in the same dimension as for cell lines. However they were even more sensitive than epithelial cells. This was true for all sensitizers used.

  12. Evaluation of biodegradable microspheres containing nomegestrol acetate in a rat model of endometriosis.

    PubMed

    Zhang, Jianfeng; Zhu, Yan; Zhou, Xianying; Hao, Shufang; Xie, Shuwu; Zhou, Jieyun; Guo, Xiangjie; Li, Zhao; Huang, Yunsheng; Chen, Qinghua

    2014-12-18

    We assessed the efficacy of biodegradable microspheres (MSs) containing nomegestrol acetate (NOMAC) for treatment of endometriosis in a rat model and investigated its preliminary mechanism of action. Sprague-Dawley rats with surgically implanted endometrial autografts were divided randomly into four groups of thirteen rats each, and subcutaneously injected twice (10d apart) with either empty MSs or MSs containing nomegestrol acetate (NOMAC-MS; 27-800mg per kg of rat body weight). Twenty-one days after the first injection, blood and endometriotic tissues were collected and assayed for changes in endometriotic tissue, serum hormone, liver function parameters, and apoptotic protein. No remarkable irritation was observed at the site of injection. NOMAC-MS treatment significantly reduced the volume of the endometrial autografts, decreased serum levels of estradiol, progesterone, triiodothyronine, and alanine aminotransferase, and decreased levels of estrogen receptor alpha protein. Furthermore, NOMAC-MS at the highest dose significantly reduced serum aspartate aminotransferase and endometrial antibody, reduced the Bcl-2/Bax protein ratio, and increased caspase-3 and caspase-9 proteins. There was no pronounced difference observed in alkaline phosphatase, carbohydrate antigen 125, progesterone receptor, or vascular endometrial growth factor receptor 2 (VEGFR2) in any of the tested groups relative to the control. NOMAC-MS significantly changed the expression of apoptotic protein only at the highest dose. Our findings warrant the further investigation of sustained application of steroid hormone via microspheres for the treatment of endometriosis. PMID:25201168

  13. Demographic and Clinical Features of Endometrial Polyps in Patients with Endometriosis

    PubMed Central

    Wang, Ningning; Zhang, Yufeng; Liu, Bin

    2016-01-01

    Aims. To compare the clinical features of endometrial polyps (EPs) between patients with endometriosis (EM) (EM group) and without EM (non-EM group). Methods and Results. Seventy-six cases in the EM group and 133 cases in the non-EM group underwent laparotomy or hysteroscopy and laparoscopy; later, it was confirmed that the results by pathology from July 2002 to April 2008 in the Department of Gynecology and Obstetrics at the First Affiliated Hospital of Sun Yat-sen University. The recurrence of EPs was followed up after the surgery until 2013. The following parameters were assessed: age, gravidity, parity, infertility, and menstrual cycle changes, as well as polyps diameters, locations, number, association with the revised American Fertility Society (r-AFS) classification, and their recurrence. On review, 76 EPs cases of EM group histologically resembled EPs but the majority of EPs with EM occurred in primary infertility cases and in fewer pregnancy rate women who had stable and smaller EPs without association with the AFS stage. The recurrence rate of EPs in EM group was higher than that in non-EM group. Conclusion. It is important to identify whether infertile patients with EM are also having EPs. Removing any coexisting EPs via hysteroscopy would be clinically helpful in treating endometriosis-related infertility in these patients. PMID:27243030

  14. Altered Retinoid Uptake and Action Contributes to Cell Survival in Endometriosis

    PubMed Central

    Pavone, Mary Ellen; Reierstad, Scott; Sun, Hui; Milad, Magdy; Bulun, Serdar E.; Cheng, You-Hong

    2010-01-01

    Context: Retinoic acid (RA) controls multiple biological processes via exerting opposing effects on cell survival. Retinol uptake into cells is controlled by stimulated by RA 6 (STRA6). RA is then produced from retinol in the cytosol. Partitioning of RA between the nuclear receptors RA receptor α and peroxisome-proliferator-activated receptor β/δ is regulated by cytosol-to-nuclear shuttling proteins cellular RA binding protein 2 (CRABP2) and fatty acid binding protein 5 (FABP5), which induce apoptosis or enhance survival, respectively. The roles of these mechanisms in endometrium or endometriosis remain unknown. Objective: The aim was to determine the regulation of retinoid uptake and RA action in primary stromal cells from endometrium (n = 10) or endometriosis (n = 10). Results: Progesterone receptor was necessary for high STRA6 and CRABP2 expression in endometrial stromal cells. STRA6, which was responsible for labeled retinoid uptake, was strikingly lower in endometriotic cells compared to endometrial cells. CRABP2 knockdown in endometrial cells increased survival, and FABP5 knockdown in endometriotic cells decreased survival without altering the expression of downstream nuclear retinoic acid receptor α and peroxisome-proliferator-activated receptor β/δ. Conclusions: In endometrial stromal cells, progesterone receptor up-regulates expression of STRA6 and CRABP2, which control retinol uptake and growth-suppressor actions of RA. In endometriotic stromal cells, decreased expression of these genes leads to decreased retinol uptake and dominant FABP5-mediated prosurvival activity. PMID:20702525

  15. Evaluation of mean platelet volume, neutrophil/lymphocyte ratio and platelet/lymphocyte ratio in advanced stage endometriosis with endometrioma

    PubMed Central

    Yavuzcan, Ali; Çağlar, Mete; Üstün, Yusuf; Dilbaz, Serdar; Özdemir, İsmail; Yıldız, Elif; Özkara, Atilla; Kumru, Selahattin

    2013-01-01

    Objective We compared the preoperative values of mean platelet volume (MPV) and peripheral systemic inflammatory response (SIR) markers (neutrophil/lymphocyte ratio and platelet/lymphocyte ratio) between patients with advanced-stage (stage 3/4) endometriosis having endometrioma (OMA) and patients with a non-neoplastic adnexal mass other than endometrioma (non-OMA). Material and Methods Patients who underwent operations with the pre-diagnosis of infertility or adnexal mass and who underwent laparoscopic tubal ligation were included. Results Haemoglobin levels, leucocyte count, platelet count, neutrophil count and lymphocyte count were not significantly different between patients with advanced stage endometriosis having OMA, patients with non-OMA and patients in the control group (p=0.970, p=0.902, p=0.373, p=0.501 and p=0.463, respectively). Patients with stage 3/4 endometriosis having OMA, patients with non-OMA and control patients were also not significantly different in terms of MPV (p=0.836), neutrophil/lymphocyte ratio (NLR) (p=0.555) and platelet/lymphocyte ratio (PLR) (p=0.358). Preoperative cancer antigen 125 (Ca-125) levels were significantly higher in patients with OMA (p=0.006). Mean size of the OMAs was significantly lower than non-OMAs (p=0.000). Conclusion It is very important to determine advanced stage endometriosis and OMAs during preoperative evaluation in order to inform patients and plan an appropriate surgical approach. We demonstrate that MPV, NLR and PLR values are not useful for this purpose in patients with advanced stage endometriosis that are proven to develop severe inflammation at either the cellular or molecular level. PMID:24592108

  16. A GFP endometriosis model reveals important morphological characteristics of the angiogenic process that govern benign and malignant diseases.

    PubMed

    Machado, Daniel Escorsim; Palumbo, Antônio; Santos, João Marcos; Mattos, Rômulo Medina; dos Santos, Thiago Alves; Seabra, Sergio Henrique; Boldrini, Leonardo da Cunha; Perini, Jamila Alessandra; Nasciutti, Luiz Eurico

    2014-07-01

    Endometriosis involves the growth of endometriotic tissue outside the uterine cavity, and is frequently associated with different malignancies. A well-reported alteration in the disease microenvironment is the proliferation of new blood vessels around the lesions, as part of a necessary repertory to contribute to the invasiveness and development of infiltrating endometriosis. Therefore, the establishment of a reliable experimental model is essential to elucidate the contribution of angiogenesis and to develop new therapeutic approaches to endometriosis treatment. For this purpose we transplanted endometrial fragments from green fluorescent protein (GFP)-mice (n=20) into the peritoneal cavity of wild-type mice (n=20), and then analyzed the morphological changes and the process of angiogenesis. The lesions were cystic and vascularized, and showed morphological hallmarks such as endometrial glands and stroma. An increase in endometriotic lesion vascular density was revealed by immunostaining and RNAm expression for Vegf and its receptor Flk-1, and the lesions were confirmed as a tissue-donor source by GFP fluorescent cells. The same pattern was observed through staining of activated macrophages and an increase of about 25% in the number of macrophage-positive cells was also demonstrated in endometriotic lesions by flow cytometry, which concords with previous data that correlate endometriosis, angiogenesis and inflammation. According to our understanding, this is the first demonstration that the pattern of the angiogenic process in the GFP endometriosis model is very similar to that of cancer. These observations will be useful for investigation of the process of angiogenesis involved in the attachment and invasion of endometrial cells, as well as an in vivo platform model to study the effects of antiangiogenic drugs. PMID:24385307

  17. Macrophage Migration Inhibitory Factor Is Involved in Ectopic Endometrial Tissue Growth and Peritoneal-Endometrial Tissue Interaction In Vivo: A Plausible Link to Endometriosis Development

    PubMed Central

    Rakhila, Halima; Girard, Karine; Leboeuf, Mathieu; Lemyre, Madeleine

    2014-01-01

    Pelvic inflammation is a hallmark of endometriosis pathogenesis and a major cause of the disease's symptoms. Abnormal immune and inflammatory changes may not only contribute to endometriosis-major symptoms, but also contribute to ectopic endometrial tissue growth and endometriosis development. A major pro-inflammatory factors found elevated in peritoneal fluid of women with endometriosis and to be overexpressed in peritoneal fluid macrophages and active, highly vascularized and early stage endometriotic lesions, macrophage migration inhibitory factor (MIF) appeared to induce angiogenic and inflammatory and estrogen producing phenotypes in endometriotic cells in vitro and to be a possible therapeutic target in vivo. Using a mouse model where MIF-knock out (KO) mice received intra-peritoneal injection of endometrial tissue from MIF-KO or syngeneic wild type (WT) mice and vice versa, our current study revealed that MIF genetic depletion resulted in a marked reduction ectopic endometrial tissue growth, a disrupted tissue structure and a significant down regulation of the expression of major inflammatory (cyclooxygenease-2), cell adhesion (αv and β3 integrins), survival (B-cell lymphoma-2) and angiogenic (vascular endothelial cell growth) factorsrelevant to endometriosis pathogenesis, whereas MIF add-back to MIF-KO mice significantly restored endometriosis-like lesions number and size. Interestingly, cross-experiments revealed that MIF presence in both endometrial and peritoneal host tissues is required for ectopic endometrial tissue growth and pointed to its involvement in endometrial-peritoneal interactions. This study provides compelling evidence for the role of MIF in endometriosis development and its possible interest for a targeted treatment of endometriosis. PMID:25329068

  18. Adverse pregnancy and neo-natal outcomes after assisted reproductive treatment in patients with pelvic endometriosis: a case-control study.

    PubMed

    Jacques, Marianne; Freour, Thomas; Barriere, Paul; Ploteau, Stéphane

    2016-06-01

    To assess the impact of endometriosis on obstetric outcomes and to determine whether the severity, location and surgical treatment of the disease before the pregnancy had an impact on the prevalence of these disorders, a monocentric, case-control study was performed. In total, 113 pregnancies obtained by assisted reproductive treatment among patients with endometriosis were matched with control selected among assisted reproductive treatment pregnancies due to male infertility. The main result measures were pregnancy outcome at the obstetrical and neo-natal levels. The incidence of first trimester bleeding, pre-eclampsia, premature delivery threat, pelvic pain and Caesarean section was significantly higher (P < 0.05) in women with endometriosis. Except for gestational diabetes and intrauterine growth restriction (IUGR), the severity, location of lesions and surgical treatment of endometriosis did not have an impact on either pregnancy outcome or risk of obstetric complications. The IUGR is mainly due to deep locations and the revised American Fertility Society (rAFS) stages III-IV. Newborns with a mother suffering from endometriosis are at greater risk of being premature, smaller for their gestational age and more frequently hospitalized than the control group. Deep location of endometriosis is associated with more prematurity, hospitalization and smaller birthweight than ovarian locations. PMID:27068240

  19. Evaluation of KRAS Gene Expression and LCS6 Variant in Genomic and Cell-Free DNA of Iranian Women With Endometriosis

    PubMed Central

    Farahani, Maryam Shahrabi; Moghaddam, Soheila Amini; Mahdian, Reza

    2015-01-01

    Since the activation of KRAS results in de novo endometriosis in mice, KRAS is regarded as a crucial gene in ectopic endometrial implantation. Recently, it has been reported that 31% of women with endometriosis have KRAS let-7 complementary binding site 6 single-nucleotide polymorphism (LCS6 SNP). This study addresses the correlation between KRAS LCS6 SNP and endometriosis in a case–control study. To detect probable somatic mutation in ectopic endometrial tissue, we evaluated LCS6 SNP in cell-free DNA samples. Quantitative real-time reverse transcription-polymerase chain reaction was performed to determine the expression of KRAS transcripts in eutopic endometrial tissue. Our results suggest that the variant is not associated with the development of endometriosis in Iranian women. We observed higher levels of KRAS messenger RNA (mRNA) expression in eutopic endometrium of patients with endometriosis compared to controls. Although, the KRAS LCS6 is neither constitutional nor somatic biomarker for endometriosis, increased expression ratio of KRAS mRNA indicates its role in the implantation of endometrial tissue outside the uterine cavity. PMID:25361550

  20. Involvement of vascular endothelial growth factor −460 C/T, +405 G/C and +936 C/T polymorphisms in the development of endometriosis

    PubMed Central

    SZCZEPAŃSKA, MALGORZATA; MOSTOWSKA, ADRIANNA; WIRSTLEIN, PRZEMYSLAW; SKRZYPCZAK, JANA; JAGODZIŁSKI, PAWEŁ P.

    2015-01-01

    There are inconsistent data on the contribution of vascular endothelial growth factor (VEGF) −460 C/T (rs833061), +405 G/C (rs2010963) and +936 C/T (rs3025039) single-nucleotide polymorphisms (SNPs) to endometriosis in different ethnicities. Therefore, using high-resolution melting curve analysis, the present study examined the distribution of these SNPs in females with endometriosis-related infertility and a control group. None of the three VEGF SNPs were associated with endometriosis-related infertility in the dominant and recessive models. The lowest P-values of the trend were observed for the VEGF +936 C/T (rs3025039) SNP in endometriosis-related infertility (Ptrend =0.149). Similarly, haplotype analyses of VEGF SNPs did not demonstrate any SNP combination as a risk for endometriosis-related infertility, and the lowest overall P-values, P=0.141 and Pcorr =0.395, were observed for a haplotype (TGT) of the above SNPs. Taken together, these results did not demonstrate the contribution of VEGF C/T, +405 G/C and +936 C/T SNPs to endometriosis-related infertility. PMID:26075076

  1. Evaluation of KRAS Gene Expression and LCS6 Variant in Genomic and Cell-Free DNA of Iranian Women With Endometriosis.

    PubMed

    Farahani, Maryam Shahrabi; Shahbazi, Shirin; Moghaddam, Soheila Amini; Mahdian, Reza

    2015-06-01

    Since the activation of KRAS results in de novo endometriosis in mice, KRAS is regarded as a crucial gene in ectopic endometrial implantation. Recently, it has been reported that 31% of women with endometriosis have KRAS let-7 complementary binding site 6 single-nucleotide polymorphism (LCS6 SNP). This study addresses the correlation between KRAS LCS6 SNP and endometriosis in a case-control study. To detect probable somatic mutation in ectopic endometrial tissue, we evaluated LCS6 SNP in cell-free DNA samples. Quantitative real-time reverse transcription-polymerase chain reaction was performed to determine the expression of KRAS transcripts in eutopic endometrial tissue. Our results suggest that the variant is not associated with the development of endometriosis in Iranian women. We observed higher levels of KRAS messenger RNA (mRNA) expression in eutopic endometrium of patients with endometriosis compared to controls. Although, the KRAS LCS6 is neither constitutional nor somatic biomarker for endometriosis, increased expression ratio of KRAS mRNA indicates its role in the implantation of endometrial tissue outside the uterine cavity. PMID:25361550

  2. Association between endometriosis and risk of histological subtypes of ovarian cancer: a pooled analysis of case–control studies

    PubMed Central

    Pearce, Celeste Leigh; Templeman, Claire; Rossing, Mary Anne; Lee, Alice; Near, Aimee M; Webb, Penelope M; Nagle, Christina M; Doherty, Jennifer A; Cushing-Haugen, Kara L; Wicklund, Kristine G; Chang-Claude, Jenny; Hein, Rebecca; Lurie, Galina; Wilkens, Lynne R; Carney, Michael E; Goodman, Marc T; Moysich, Kirsten; Kjaer, Susanne K; Hogdall, Estrid; Jensen, Allan; Goode, Ellen L; Fridley, Brooke L; Larson, Melissa C; Schildkraut, Joellen M; Palmieri, Rachel T; Cramer, Daniel W; Terry, Kathryn L; Vitonis, Allison F; Titus, Linda J; Ziogas, Argyrios; Brewster, Wendy; Anton-Culver, Hoda; Gentry-Maharaj, Alexandra; Ramus, Susan J; Anderson, A Rebecca; Brueggmann, Doerthe; Fasching, Peter A; Gayther, Simon A; Huntsman, David G; Menon, Usha; Ness, Roberta B; Pike, Malcolm C; Risch, Harvey; Wu, Anna H; Berchuck, Andrew

    2012-01-01

    Summary Background Endometriosis is a risk factor for epithelial ovarian cancer; however, whether this risk extends to all invasive histological subtypes or borderline tumours is not clear. We undertook an international collaborative study to assess the association between endometriosis and histological subtypes of ovarian cancer. Methods Data from 13 ovarian cancer case–control studies, which were part of the Ovarian Cancer Association Consortium, were pooled and logistic regression analyses were undertaken to assess the association between self-reported endometriosis and risk of ovarian cancer. Analyses of invasive cases were done with respect to histological subtypes, grade, and stage, and analyses of borderline tumours by histological subtype. Age, ethnic origin, study site, parity, and duration of oral contraceptive use were included in all analytical models. Findings 13 226 controls and 7911 women with invasive ovarian cancer were included in this analysis. 818 and 738, respectively, reported a history of endometriosis. 1907 women with borderline ovarian cancer were also included in the analysis, and 168 of these reported a history of endometriosis. Self-reported endometriosis was associated with a significantly increased risk of clear-cell (136 [20·2%] of 674 cases vs 818 [6·2%] of 13 226 controls, odds ratio 3·05, 95% CI 2·43–3·84, p<0·0001), low-grade serous (31 [9·2%] of 336 cases, 2·11, 1·39–3·20, p<0·0001), and endometrioid invasive ovarian cancers (169 [13·9%] of 1220 cases, 2·04, 1·67–2·48, p<0·0001). No association was noted between endometriosis and risk of mucinous (31 [6·0%] of 516 cases, 1·02, 0·69–1·50, p=0·93) or high-grade serous invasive ovarian cancer (261 [7·1%] of 3659 cases, 1·13, 0·97–1·32, p=0·13), or borderline tumours of either subtype (serous 103 [9·0%] of 1140 cases, 1·20, 0·95–1·52, p=0·12, and mucinous 65 [8·5%] of 767 cases, 1·12, 0·84–1·48, p=0·45). Interpretation

  3. Pathophysiology of Endometriosis: Role of High Mobility Group Box-1 and Toll-Like Receptor 4 Developing Inflammation in Endometrium.

    PubMed

    Yun, Bo Hyon; Chon, Seung Joo; Choi, Young Sik; Cho, SiHyun; Lee, Byung Seok; Seo, Seok Kyo

    2016-01-01

    Oxidative stress has been proposed as a potential factor associated with the establishment and progression of endometriosis. Although a few studies have shown possible mechanisms which may play roles in development, progression of endometriosis, few are known in regards of initiation of the disease, especially in the relationship with endometrium. The aim of our study was to investigate whether normal endometrium may be changed by Damage-associated molecular patterns (DAMPs), which may contribute developing pathologic endometrium to induce endometriosis. Endometrial tissues were obtained from 10 patients with fibroids undergoing hysterectomy at a university hospital. High mobility group box-1 (HMGB-1), which is a representative DAMP, has been chosen that may induce alteration in endometrium. In preceding immunohistochemistry experiments using paraffin-block sections from endometriosis (N = 33) and control (N = 27) group, retrospectively, HMGB-1 expression was shown in both epithelial and stromal cell. HMGB-1 expression was significantly increased in secretory phase of endometriosis group, comparing to the controls. To examine the alteration of endometrial stromal cell (HESC) by oxidative stress in terms of HMGB-1, cell proliferation and expression of its receptor, TLR4 was measured according to recombinant HMGB-1 use. Cell proliferation was assessed by CCK-8 assay; real-time PCR and western blotting were used to quantify Toll like receptor 4 (TLR4) mRNA and protein expression respectively. A TLR4 antagonist (LPS-RS) and an inhibitor of the NF-κB pathway (TPCA-1, an IKK-2 inhibitor) were used to confirm the relationships between HMGB-1, TLR4, and the NF-κB pathway. Passive release of HMGB-1 was significantly proportional to the increase in cell death (P<0.05). HESCs showed significant proliferation following treatment with rHMGB-1 (P<0.05), and increased TLR4 expression was observed following rHMGB-1 treatment (P<0.05) in a concentration-dependent manner

  4. Analysis of subsequent surgery rates among endometriosis patients who underwent surgery with and without concomitant leuprolide acetate therapy.

    PubMed

    Soliman, Ahmed M; Bonafede, Machaon; Farr, Amanda M; Castelli-Haley, Jane; Winkel, Craig

    2016-06-01

    Objective To compare subsequent endometriosis-related surgery following initial laparoscopy among women treated with leuprolide acetate (LA) or other endometriosis therapies versus women who received no pharmacotherapy. Research design and methods This retrospective cohort analysis utilized MarketScan Commercial claims data. Women with endometriosis aged 18-49 who underwent laparoscopy between 1 January 2005 and 31 December 2011 were identified using diagnosis and procedures codes and were categorized into four cohorts based on claims within 90 days of laparoscopy: surgery plus adherent LA, surgery plus non-adherent LA, surgery plus other therapy, and surgery alone. Patients with proportion of days covered ≥0.80 in the 6 months after laparoscopy were considered adherent to LA. Main outcome measures Subsequent endometriosis-related surgery (laparoscopy, laparotomy or other excision/ablation/fulguration of endometriosis lesions, oophorectomy, or hysterectomy) was measured in the 6 and 12 months following initial laparoscopy. Risk of subsequent surgery was compared using multivariable Cox proportional hazards modeling. Results Most women were treated with surgery only (n = 9865); fewer were treated with LA (adherent: n = 202; non-adherent: n = 490) or other therapies (n = 230). The proportion of patients with subsequent surgery ranged from 2.0% to 10.0% during the 6 month follow-up (12 month: 9.7% to 13.5%). Adherent LA use was associated with significantly lower risk of surgery compared to surgery alone (hazard ratio [HR] = 0.31, p = 0.020) while use of other therapies was associated with significantly higher risk (HR = 1.51, p = 0.045) over the 6 month follow-up. There was no significant difference between the surgery plus non-adherent LA and surgery only cohort over 6 months (p = 0.247). The association between adherent LA and subsequent surgery was not significant over the 12 month follow-up. Conclusion Therapy with LA after

  5. The Complementary and Alternative Medicine for Endometriosis: A Review of Utilization and Mechanism

    PubMed Central

    Kong, Sai; Zhang, Yue-Hui; Liu, Chen-Fang; Tsui, Ilene; Guo, Ying; Ai, Bei-Bei; Han, Feng-Juan

    2014-01-01

    Endometriosis (EM) is one of the common gynecological conditions causing menstrual and pelvic pain and affects 10%–15% of women of reproductive age. In recent years, the complementary and alternative medical (CAM) treatment for EM has become popular due to the few adverse reactions reported. The CAM therapy for EM includes several different treatments such as herbs (herbal prescription, extract, and patent), acupuncture, microwave physiotherapy, and Chinese herb medicine enema (CHM enema). These CAM therapies are effective at relieving dysmenorrhoea, shrinking adnexal masses, and promoting pregnancy, with less unpleasant side effects when compared to hormonal and surgical treatments. In this review, we focus on the status quo of CAM on EM and try to identify therapeutic efficacy and mechanisms based on some clinical and experimental studies. We hope to provide some instructive suggestions for clinical treatment and experimental research in the future. PMID:24701237

  6. Desmoid tumor of the anterior abdominal wall in female patients: comparison with endometriosis.

    PubMed

    Krentel, H; Tchartchian, G; De Wilde, R L

    2012-01-01

    In female patients presenting a tumor of the lower abdominal wall especially after cesarian section, an endometriotic tumor as well as an aggressive desmoid tumor should be considered. Symptoms in correlation with the monthly period can facilitate the presurgical differentiation between endometriosis and fibromatosis. Ultrasound reveals the typical location of both tumors and its remarkable sonographic appearance. In the clinical practice, the desmoid fibromatosis of the lower abdominal wall is a very rare disease. We present a case of a 25-year-old pregnant and discuss diagnostic and therapeutic options by a PubMed literature review. With the knowledge of the prognosis of the desmoid fibromatosis and the respective treatment options including wait and see, complete surgical resection with macroscopically free margins and adjuvant approaches is essential to avoid further interventions and progression of the locally destructive tumor. PMID:22778752

  7. Desmoid Tumor of the Anterior Abdominal Wall in Female Patients: Comparison with Endometriosis

    PubMed Central

    Krentel, H.; Tchartchian, G.; De Wilde, R. L.

    2012-01-01

    In female patients presenting a tumor of the lower abdominal wall especially after cesarian section, an endometriotic tumor as well as an aggressive desmoid tumor should be considered. Symptoms in correlation with the monthly period can facilitate the presurgical differentiation between endometriosis and fibromatosis. Ultrasound reveals the typical location of both tumors and its remarkable sonographic appearance. In the clinical practice, the desmoid fibromatosis of the lower abdominal wall is a very rare disease. We present a case of a 25-year-old pregnant and discuss diagnostic and therapeutic options by a PubMed literature review. With the knowledge of the prognosis of the desmoid fibromatosis and the respective treatment options including wait and see, complete surgical resection with macroscopically free margins and adjuvant approaches is essential to avoid further interventions and progression of the locally destructive tumor. PMID:22778752

  8. [The clinical picture, diagnosis and treatment of the corpus-isthmus location of uterine endometriosis interna].

    PubMed

    Damirov, M M; Kulakov, V I; Bakuleva, L P; Shabanov, A M; Sarkisov, S E; Sliusar', N N

    1993-01-01

    The authors analyze the results of comprehensive examinations and treatment of 79 patients with corporal isthmic adenomyosis. Comprehensive examinations making use of clinical, instrumental (hysteroscopy, hysterosalpingography, echography), biochemical (measurements of blood and myometrial phosphatidylinosites), and morphologic methods are needed for a reliable diagnosis of this condition. Blood phosphatidylinosite measurements may be used as an objective test to assess the efficacy of hormonal therapy. Trental and lipostabil forte are advisable for adenomyosis therapy. If amputation of the uterus has to be resorted to, intraoperative histologic express testing of the lower edge of the uterus for endometriosis may help choose the optimal volume of surgical intervention and prevent extirpation of the uterus that is not at all neutral for the body. PMID:8048686

  9. Immunomodulatory Role of Adipose-Derived Stem Cells on Equine Endometriosis

    PubMed Central

    Falomo, Maria Elena; Ferroni, Letizia; Tocco, Ilaria; Gardin, Chiara; Zavan, Barbara

    2015-01-01

    Endometriosis is a degenerative process due to a chronic inflammatory damage leading to extracellular matrix components deposition and glandular fibrosis. It is known that mesenchymal stem cells secrete a wide range of bioactive molecules, some of them modulating the immune inflammatory response, and others providing regeneration and remodeling of injured tissue. We have performed in vitro experiments in order to analyze the capability of allogenic equine adipose-derived stem cells (ADSCs) to infiltrate mares' endometrial tissues and to stimulate the expression of cytokines and metallopeptidases. Differences in the biologic response to the exposure to ADSCs between pathological and healthy endometrial tissue have been identified. These results could challenge researchers to progress forward with future studies for the development of a biological therapy with a possible application in translational medicine. PMID:26180781

  10. Allelic Imbalance in Regulation of ANRIL through Chromatin Interaction at 9p21 Endometriosis Risk Locus

    PubMed Central

    Nakaoka, Hirofumi; Gurumurthy, Aishwarya; Hayano, Takahide; Ahmadloo, Somayeh; Omer, Waleed H; Yoshihara, Kosuke; Yamamoto, Akihito; Kurose, Keisuke; Enomoto, Takayuki; Akira, Shigeo; Hosomichi, Kazuyoshi; Inoue, Ituro

    2016-01-01

    Genome-wide association studies (GWASs) have discovered numerous single nucleotide polymorphisms (SNPs) associated with human complex disorders. However, functional characterization of the disease-associated SNPs remains a formidable challenge. Here we explored regulatory mechanism of a SNP on chromosome 9p21 associated with endometriosis by leveraging “allele-specific” functional genomic approaches. By re-sequencing 1.29 Mb of 9p21 region and scrutinizing DNase-seq data from the ENCODE project, we prioritized rs17761446 as a candidate functional variant that was in perfect linkage disequilibrium with the original GWAS SNP (rs10965235) and located on DNase I hypersensitive site. Chromosome conformation capture followed by high-throughput sequencing revealed that the protective G allele of rs17761446 exerted stronger chromatin interaction with ANRIL promoter. We demonstrated that the protective allele exhibited preferential binding affinities to TCF7L2 and EP300 by bioinformatics and chromatin immunoprecipitation (ChIP) analyses. ChIP assays for histone H3 lysine 27 acetylation and RNA polymerase II reinforced the enhancer activity of the SNP site. The allele specific expression analysis for eutopic endometrial tissues and endometrial carcinoma cell lines showed that rs17761446 was a cis-regulatory variant where G allele was associated with increased ANRIL expression. Our work illuminates the allelic imbalances in a series of transcriptional regulation from factor binding to gene expression mediated by chromatin interaction underlie the molecular mechanism of 9p21 endometriosis risk locus. Functional genomics on common disease will unlock functional aspect of genotype-phenotype correlations in the post-GWAS stage. PMID:27055116

  11. Progesterone Action in Endometrial Cancer, Endometriosis, Uterine Fibroids, and Breast Cancer

    PubMed Central

    Kim, J. Julie; Kurita, Takeshi

    2013-01-01

    Progesterone receptor (PR) mediates the actions of the ovarian steroid progesterone, which together with estradiol regulates gonadotropin secretion, prepares the endometrium for implantation, maintains pregnancy, and differentiates breast tissue. Separation of estrogen and progesterone actions in hormone-responsive tissues remains a challenge. Pathologies of the uterus and breast, including endometrial cancer, endometriosis, uterine fibroids, and breast cancer, are highly associated with estrogen, considered to be the mitogenic factor. Emerging evidence supports distinct roles of progesterone and its influence on the pathogenesis of these diseases. Progesterone antagonizes estrogen-driven growth in the endometrium, and insufficient progesterone action strikingly increases the risk of endometrial cancer. In endometriosis, eutopic and ectopic tissues do not respond sufficiently to progesterone and are considered to be progesterone-resistant, which contributes to proliferation and survival. In uterine fibroids, progesterone promotes growth by increasing proliferation, cellular hypertrophy, and deposition of extracellular matrix. In normal mammary tissue and breast cancer, progesterone is pro-proliferative and carcinogenic. A key difference between these tissues that could explain the diverse effects of progesterone is the paracrine interactions of PR-expressing stroma and epithelium. Normal endometrium is a mucosa containing large quantities of distinct stromal cells with abundant PR, which influences epithelial cell proliferation and differentiation and protects against carcinogenic transformation. In contrast, the primary target cells of progesterone in the breast and fibroids are the mammary epithelial cells and the leiomyoma cells, which lack specifically organized stromal components with significant PR expression. This review provides a unifying perspective for the diverse effects of progesterone across human tissues and diseases. PMID:23303565

  12. Microarray analysis of microRNA deregulation and angiogenesis-related proteins in endometriosis.

    PubMed

    Yang, R Q; Teng, H; Xu, X H; Liu, S Y; Wang, Y H; Guo, F J; Liu, X J

    2016-01-01

    We examined the aberrant microRNA (miRNA) expression profile responsible for the changes in angiogenesis observed in endometriotic lesions. This study revealed characteristic miRNA expression profiles associated with endometriosis in endometrial tissue and endometriotic lesions from the same patient, and their correlation with the most important angiogenic and fibrinolytic factors. miRNA expression was quantified using a microRNA array and reverse-transcription microRNA polymerase chain reaction. Levels of vascular endothelial growth factor A (VEGFA), epidermal growth factor receptor 2 (EGFR2), phosphatase and tensin homolog (PTEN), and C-X-C chemokine receptor type 4 (CXCR4) were quantified using enzyme-linked immunosorbent assay. The endometrial tissue showed significantly lower levels of miR-200b, miR-15a-5p, miR-19b-1-5p, miR-146a-5p, and miR-200c, and higher levels of miR-16-5p, miR-106b-5p, and miR-145-5p. VEGFA was significantly upregulated, whereas EGFR2, PTEN, and CXCR4 were markedly downregulated, in the endometriotic tissues compared to that in the normal endometrial tissues. In conclusion, differences in the miRNA levels could modulate the expression of VEGFA, EGFR2, PTEN, and CXCR4, and may play an important role in the pathogenesis of endometriosis. The higher angiogenic and proteolytic activities observed in the eutopic endometrium might facilitate the implantation of endometrial cells at ectopic sites. PMID:27323121

  13. Methylation status and protein expression of RASSF1A in endometriosis

    PubMed Central

    WU, YU; ZHANG, MINGDE; ZHANG, XIAN; XU, ZHENZHOU; JIN, WEIGUO

    2016-01-01

    Ras association domain family 1A (RASSF1A) gene inactivation by promoter hypermethylation is a common event in the development of a variety of types of human cancer. Accumulated evidence has demonstrated that DNA methylation serve a critical role in the pathogenesis of endometriosis. The aim of the present study was to analyze the methylation status and protein expression of RASSF1A in endometriosis (EMS). The ectopic and corresponding eutopic endometrium tissues were collected from 45 women with EMS (EMS group) and normal endometrium tissues from 20 women without EMS (control group). The methylation status of RASSF1A was examined by methylation specific polymerase chain reaction (MSP). Immunohistochemistry was performed to measure RASSF1A protein level in endometrium tissues. In normal endometrium samples, RASSF1A protein expression was significantly higher at the secretory phase than the proliferative phase. RASSF1A protein expression in the ectopic endometrium tissues and eutopic endometrium tissues were significantly reduced than in normal endometrium (P<0.05). The frequency of aberrant methylation of RASSF1A was 55.56% in ectopic endometrium and 33.33% in paired eutopic endometrium, whereas such methylation was not detected in normal endometrium. Moreover, RASSF1A promoter hypermethylation was frequently associated with reduced expression of RASSF1A, and was common in advanced stage in ectopic endometrium of EMS. Epigenetic inactivation of RASSF1A through aberrant promoter methylation may be important in the formation and progression of EMS, and assessment of RASSF1A methylation status in eutopic endometrium may be a potentially useful biomarker to enhance the early detection of EMS. PMID:27313749

  14. A Novel Angiogenesis Inhibitor Bevacizumab Induces Apoptosis in the Rat Endometriosis Model

    PubMed Central

    Soysal, D; Kızıldağ, S; Saatlı, B; Posacı, C; Soysal, S; Koyuncuoğlu, M; Doğan, ÖE

    2014-01-01

    Our aim was to investigate the effects of anti-vascular endothelial growth factor (anti-VEGF) antibody Bevacizumab on endometrial explants and on apoptotic gene expression levels in the rat endometriosis model. Endometriotic implants were surgically formed, and rats treated with (i) 1 mg/kg single subcutaneous injection of depot leuprolide acetate; (ii) 2.5 mg/kg of single intaperitoneal injection of bevacizumab; (iii) intraperitoneal injection of saline. Histopathologic scores and adhesion scores of endometriotic foci and levels of Bcl-2-associated X protein (Bax), Cytochrome c (Cyt-c), B-cell lymphoma/leukemia 2 (Bcl-2) and B-cell lymphoma-extra large (Bcl-xl) mRNA gene expressions of endometriotic foci. Bevacizumab treatment decreased the endometriotic explant size compared with control. Bevacizumab-treated rats had lower total adhesion scores when compared with the control group. Semi-quantitative evaluation of the persistence of endometrial epithelial cells in the explants showed a lower score in gonadotropin-releasing hormone (GnRH) agonist-treated rats compared with control rats. In Bevacizumab increased expression of Bax 3.1-fold, Cyt-c 1.3-fold and decreased expression of Bcl-2 0.4-fold, Bcl-xl 0.8-fold compared with the control group. The GnRH agonist increased expression of Bax 3.0 fold, Cyt-c 1.3 fold and decreased expression of Bcl-2 0.4-fold, Bcl-xl 0.8-fold, compared with the control group. This study suggests that a novel angiogenesis inhibitor, anti-VEGF antibody bevacizumab is as effective as GnRH agonist in the regression of the endometriotic lesions in rat endometriosis model. One possible mechanism of this effect is the induction of apoptosis. PMID:25937801

  15. Allelic Imbalance in Regulation of ANRIL through Chromatin Interaction at 9p21 Endometriosis Risk Locus.

    PubMed

    Nakaoka, Hirofumi; Gurumurthy, Aishwarya; Hayano, Takahide; Ahmadloo, Somayeh; Omer, Waleed H; Yoshihara, Kosuke; Yamamoto, Akihito; Kurose, Keisuke; Enomoto, Takayuki; Akira, Shigeo; Hosomichi, Kazuyoshi; Inoue, Ituro

    2016-04-01

    Genome-wide association studies (GWASs) have discovered numerous single nucleotide polymorphisms (SNPs) associated with human complex disorders. However, functional characterization of the disease-associated SNPs remains a formidable challenge. Here we explored regulatory mechanism of a SNP on chromosome 9p21 associated with endometriosis by leveraging "allele-specific" functional genomic approaches. By re-sequencing 1.29 Mb of 9p21 region and scrutinizing DNase-seq data from the ENCODE project, we prioritized rs17761446 as a candidate functional variant that was in perfect linkage disequilibrium with the original GWAS SNP (rs10965235) and located on DNase I hypersensitive site. Chromosome conformation capture followed by high-throughput sequencing revealed that the protective G allele of rs17761446 exerted stronger chromatin interaction with ANRIL promoter. We demonstrated that the protective allele exhibited preferential binding affinities to TCF7L2 and EP300 by bioinformatics and chromatin immunoprecipitation (ChIP) analyses. ChIP assays for histone H3 lysine 27 acetylation and RNA polymerase II reinforced the enhancer activity of the SNP site. The allele specific expression analysis for eutopic endometrial tissues and endometrial carcinoma cell lines showed that rs17761446 was a cis-regulatory variant where G allele was associated with increased ANRIL expression. Our work illuminates the allelic imbalances in a series of transcriptional regulation from factor binding to gene expression mediated by chromatin interaction underlie the molecular mechanism of 9p21 endometriosis risk locus. Functional genomics on common disease will unlock functional aspect of genotype-phenotype correlations in the post-GWAS stage. PMID:27055116

  16. Perioperative Outcomes of Robotic Assisted Laparoscopic Surgery Versus Conventional Laparoscopy Surgery for Advanced-Stage Endometriosis

    PubMed Central

    Sirota, Ido

    2014-01-01

    Background and Objectives: To determine perioperative outcome differences in patients undergoing robotic-assisted laparoscopic surgery (RALS) versus conventional laparoscopic surgery (CLS) for advanced-stage endometriosis. Methods: This retrospective cohort study at a minimally invasive gynecologic surgery center at 2 academically affiliated, urban, nonprofit hospitals included all patients treated by either robotic-assisted or conventional laparoscopic surgery for stage III or IV endometriosis (American Society for Reproductive Medicine criteria) between July 2009 and October 2012 by 1 surgeon experienced in both techniques. The main outcome measures were extent of surgery, estimated blood loss, operating room time, intraoperative and postoperative complications, and length of stay, with medians for continuous measures and distributions for categorical measures, stratified by body mass index values. Robotically assisted laparoscopy and conventional laparoscopy were then compared by use of the Wilcoxon rank sum, χ2, or Fisher exact test, as appropriate. Results: Among 86 conventional laparoscopic and 32 robotically assisted cases, the latter had a higher body mass index (27.36 kg/m2 [range, 23.90–34.09 kg/m2] versus 24.53 kg/m2 [range, 22.27–26.96 kg/m2]; P < .0079) and operating room time (250.50 minutes [range, 176–328.50 minutes] versus 173.50 minutes [range, 123–237 minutes]; P < .0005) than did conventional laparoscopy patients. After body mass index stratification, obese patients varied in operating room time (282.5 minutes [range, 224–342 minutes] for robotic-assisted laparoscopy versus 174 minutes [range, 130–270 minutes] for conventional laparoscopy; P < .05). No other significant differences were noted between the robotic-assisted and conventional laparoscopy groups. Conclusion: Despite a higher operating room time, robotic-assisted laparoscopy appears to be a safe minimally invasive approach for patients, with all other perioperative

  17. Primary Vaginal Adenosarcoma With Sarcomatous Overgrowth Arising in Recurrent Endometriosis: Feasibility of Laparoscopic Treatment and Review of the Literature.

    PubMed

    Pontrelli, Giovanni; Cozzolino, Mauro; Stepniewska, Anna; Bruni, Francesco; Pesci, Anna; Ceccaroni, Marcello

    2016-01-01

    We report a case of a primary vaginal adenosarcoma with sarcomatous overgrowth in a postmenopausal 58-year-old woman with recurrent endometriosis. In the past 5 years she underwent several biopsies of a polypoid lesion on the vaginal cuff, and the last histologic examination of the biopsy showed an adenosarcoma with "sarcomatous overgrowth" in a background of endometriosis. There was no evidence of distant metastatic disease on the diagnostic workup, and we performed a laparoscopy to remove the pelvic mass. We reviewed the literature on the electronic databases Medline, Embase, and Science Direct on articles published in English from 1990 to 2015. We identified 5 articles in which the surgical treatment was performed via a laparotomic approach. The present case is the first in the literature to report feasibility of laparoscopic treatment for this kind of pathology with a detailed description of the surgical technique. PMID:27041653

  18. Association between glutathione S-transferase M1/T1 gene polymorphisms and susceptibility to endometriosis: A systematic review and meta-analysis

    PubMed Central

    XIN, XIAOYAN; JIN, ZHISHAN; GU, HUAJIAN; LI, YUANYUE; WU, TINGTING; HUA, TENG; WANG, HONGBO

    2016-01-01

    Endometriosis is a polygenic/multifactorial disease caused by interactions between multiple genes and the environment. Findings from studies evaluating the association between the glutathione S-transferase (GST) M1/T1 null genotype and susceptibility to endometriosis are inconsistent. This meta-analysis updated and reevaluated the possible associations between GSTM1, GSTT1 and combined GSTM1/GSTT1 (null genotype versus wild-type) gene polymorphisms and susceptibility to endometriosis. The PubMed, Embase and Chinese BioMedical Literature databases and Google Scholar were searched for case-control genetic association studies on GSTM1/GSTT1 (null genotype versus wild-type) gene polymorphisms and endometriosis in comparison with non-endometriosis or healthy controls. Fixed-effect and random-effect meta-analytical techniques were conducted for the outcome measure and subgroup analyses. The meta-analysis demonstrated significant associations between the GSTM1 [odds ratio (OR)=1.56; 95% confidence interval (CI): 1.25–1.95; P<0.0001), GSTT1 (OR=1.31; 95% CI: 1.02–1.68; P=0.037) and GSTM1/GSTT1 (OR=1.68; 95% CI: 1.29–2.17; P<0.0001) null genotypes and increased risk for endometriosis. The results suggest that the GSTM1, GSTT1, and combined GSTM1/GSTT1 null genotypes increase susceptibility to endometriosis. Additional well-designed studies and precise analyses are warranted to confirm these findings. PMID:27168783

  19. Effects of steroid hormone on estrogen sulfotransferase and on steroid sulfatase expression in endometriosis tissue and stromal cells.

    PubMed

    Piccinato, Carla A; Neme, Rosa M; Torres, Natália; Sanches, Lívia Renta; Derogis, Priscilla Bento Mattos Cruz; Brudniewski, Heloísa F; Rosa e Silva, Júlio C; Ferriani, Rui A

    2016-04-01

    Endometriosis is an estrogen-dependent disease that afflicts about 10% of women in their reproductive age, causing severe pain and infertility. The potential roles of female steroid hormones in modulating key estrogen-metabolizing enzymes, steroid sulfatase (STS) and estrogen sulfotransferase (SULT1E1), were investigated. The expression of STS and SULT1E1 mRNA in biopsy samples (n=78) of superficial and deep endometriotic lesions, eutopic endometrium of women with endometriosis and endometrium from control patients were compared according to the menstrual cycle phase. Increased STS gene expression was detected in superficial and deep-infiltrating lesions and a reduced SULT1E1 expression was also observed in the eutopic endometrium relative to the superficial lesions. Additionally, a significantly positive correlation was detected between STS and SULT1E1 mRNA expression levels in biopsy specimens collected from the endometriosis patients, and not in control individuals. The actions of female steroid hormones on SULT1E1 and STS expression were evidenced in endometriosis, revealed by increased expression levels in the luteal phase of the cycle. There was an increased STS expression in primary eutopic and ectopic endometrial stromal cells treated with estradiol and progesterone (representative of the luteal phase, n=3). Although an increased STS mRNA expression was observed in hormone-induced endometrial stromal cells in vitro, no difference could be detected between the hormone treatment groups in estradiol formation from estradiol sulfate measured by LC-MS-MS. Interestingly, a greater expression of STS was observed in stromal cells from eutopic endometrium with an agreement in estradiol formation originated from estradiol sulfate. The differential regulation of STS and SULT1E1 could provide insights for novel studies of the therapeutic use of STS inhibitors. PMID:26723541

  20. Quality of life associated to chronic pelvic pain is independent of endometriosis diagnosis-a cross-sectional survey

    PubMed Central

    2011-01-01

    Background Pain is strongly related to poor quality of life. We performed a cross-sectional study in a universitary hospital to investigate quality of life in women suffering from chronic pelvic pain (CPP) due to endometriosis and others conditions. Methods Fifty-seven patients aged between 25 and 48 years-old submitted to laparoscopy because of CPP were evaluated for quality of life and depressive symptoms. Quality of life was accessed by a quality of life instrument [World Health Organization Quality of Life Assessment-Bref (WHOQOL-bref)]. Causes of pelvic pain were determined and severity of CPP was measured with a visual analogue scale. According to the intensity of pelvic pain score, patients were classified in two groups (group Low CPP < 25th percentile visual analogue scale and group High CPP > 25th percentile). Four dimensions on quality of life were measured (physical, psychological, social and environmental). We stratified the analysis of quality of life according CPP causes (presence or not of endometriosis in laparoscopy). Results Patients with higher pain scores presented lower quality of life status in psychological and environmental dimensions. We found a negative correlation between pain scores and psychological dimension of quality of life (r = -0.310, P = .02). Quality of life scores were similar between groups with and without endometriosis (physical 54.2 ± 12.8 and 51.1 ± 13.8, P = 0.504; psychological 56.2 ± 14.4 and 62.8 ± 12.4, P = 0.182; social 55.6 ± 18.2 and 62.1 ± 19.1, P = 0.325; environmental 59.2 ± 11.7 61.2 ± 10.8, P = 0.608; respectively) Conclusions Higher pain scores are correlated to lower quality of life; however the fact of having endometriosis in addition to CPP does not have an additional impact upon the quality of life. PMID:21663624

  1. A comparison between serum levels of interleukin-6 and CA125 in patients with endometriosis and normal women

    PubMed Central

    Kashanian, Maryam; Sariri, Elaheh; Vahdat, Mansoureh; Ahmari, Maryam; Moradi, Yousef; Sheikhansari, Narges

    2015-01-01

    Background: The purpose of the present study was to compare the serum levels of IL6 and CA125 in women with and without endometriosis. They were also compared in mild, moderate and severe cases. Methods: In this case-control study, CA125 and IL6 levels in 76 women with laparoscopic proven endometriosis were compared with 76 women without evidence of endometriosis. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values were then calculated for each test. Results: Both groups did not show significant difference in their age, BMI, ESR and gravidity. Mean serum levels of IL-6 and CA125 were significantly higher in the case group (30.4±6.43 vs 13.9±3.17 Pg/ml and 62.6±10.69 vs 16.6±1.79 IU/ml respectively). Considering a cutoff point of 30 Pg/ml for IL-6, sensitivity, specifically, PPV and NPV value of 21.1%, 66.6%, 86.8% and 23.37% were obtained, respectively. Considering a cutoff point of 35 IU/ml for CA125, sensitivity, specifically, PPV and NPV were 44.76%, 94.73%, 89.47% and 63.15%, respectively. Area under the ROC curve was 0.69 for CA125 and 0.54 for IL6, which showed a low value for these tests. Conclusion: Although CA125 and IL-6 were higher than normal controls in endometriosis, area under the ROC curve, did not show significant any diagnostic value for these tests. PMID:26793671

  2. Galectin-1 overexpression in endometriosis and its regulation by neuropeptides (CRH, UCN) indicating its important role in reproduction and inflammation.

    PubMed

    Vergetaki, Aikaterini; Jeschke, Udo; Vrekoussis, Thomas; Taliouri, Eirini; Sabatini, Luca; Papakonstanti, Evangelia A; Makrigiannakis, Antonis

    2014-01-01

    Endometriosis is an inflammatory disease of women of reproductive age featured by the presence of ectopic endometrium and is strongly related to infertility. Galectins, carbonhydrate-binding proteins, have been found to have pro- or anti-inflammatory roles in the reproductive tract and in pathological conditions concerning infertility. Galectin-1, which is expressed at endometrium and decidua, plays a major role in implantation and trophoblast invasion. Also, the neuropeptides, corticotropin releasing hormone (CRH) and urocortin (UCN) and their receptors are expressed in eutopic and ectopic endometrium showing a differential expression pattern in endometriotic women compared to healthy ones. The aim of this study was to examine the galectin-1 expression in endometriotic lesions and compare its expression in eutopic endometrium of endometriotic and healthy women. Furthermore, we examined the effect of CRH and UCN in galectin-1 expression in Ishikawa cell line and macrophages and investigated the implication of CRHR1 in these responses. Eutopic and ectopic endometrium specimens, Ishikawa cell line and mice macrophages were used. Immunohistochemistry and western blot analysis were performed in order to identify galectin-1 expression in ectopic and eutopic endometrium of women with and without endometriosis and the regulatory effect of CRH and UCN on galectin-1 expression. This study presents for the first time that galectin-1 is overexpressed in endometriotic lesions compared to eutopic endometrium of endometriotic women and is more abundantly expressed in eutopic endometrium of disease women compared to healthy ones. Furthermore, it is shown that CRH and UCN upregulate galectin-1 expression in Ishikawa cell line and macrophages and this effect is mediated through CRHR1. These results suggest that galectin-1 might play an important role in endometriosis pathology and infertility profile of women suffering from endometriosis by being at the same time regulated by CRH

  3. Galectin-1 Overexpression in Endometriosis and Its Regulation by Neuropeptides (CRH, UCN) Indicating Its Important Role in Reproduction and Inflammation

    PubMed Central

    Vergetaki, Aikaterini; Jeschke, Udo; Vrekoussis, Thomas; Taliouri, Eirini; Sabatini, Luca; Papakonstanti, Evangelia A.; Makrigiannakis, Antonis

    2014-01-01

    Endometriosis is an inflammatory disease of women of reproductive age featured by the presence of ectopic endometrium and is strongly related to infertility. Galectins, carbonhydrate-binding proteins, have been found to have pro- or anti-inflammatory roles in the reproductive tract and in pathological conditions concerning infertility. Galectin-1, which is expressed at endometrium and decidua, plays a major role in implantation and trophoblast invasion. Also, the neuropeptides, corticotropin releasing hormone (CRH) and urocortin (UCN) and their receptors are expressed in eutopic and ectopic endometrium showing a differential expression pattern in endometriotic women compared to healthy ones. The aim of this study was to examine the galectin-1 expression in endometriotic lesions and compare its expression in eutopic endometrium of endometriotic and healthy women. Furthermore, we examined the effect of CRH and UCN in galectin-1 expression in Ishikawa cell line and macrophages and investigated the implication of CRHR1 in these responses. Eutopic and ectopic endometrium specimens, Ishikawa cell line and mice macrophages were used. Immunohistochemistry and western blot analysis were performed in order to identify galectin-1 expression in ectopic and eutopic endometrium of women with and without endometriosis and the regulatory effect of CRH and UCN on galectin-1 expression. This study presents for the first time that galectin-1 is overexpressed in endometriotic lesions compared to eutopic endometrium of endometriotic women and is more abundantly expressed in eutopic endometrium of disease women compared to healthy ones. Furthermore, it is shown that CRH and UCN upregulate galectin-1 expression in Ishikawa cell line and macrophages and this effect is mediated through CRHR1. These results suggest that galectin-1 might play an important role in endometriosis pathology and infertility profile of women suffering from endometriosis by being at the same time regulated by CRH

  4. Elagolix, an Oral GnRH Antagonist, Versus Subcutaneous Depot Medroxyprogesterone Acetate for the Treatment of Endometriosis

    PubMed Central

    Dmowski, W. Paul; O’Brien, Chris; Jiang, Ping; Burke, Joshua; Jimenez, Roland; Garner, Elizabeth; Chwalisz, Kristof

    2014-01-01

    This randomized double-blind study, with 24-week treatment and 24-week posttreatment periods, evaluated the effects of elagolix (150 mg every day, 75 mg twice a day) versus subcutaneous depot medroxyprogesterone acetate (DMPA-SC) on bone mineral density (BMD), in women with endometriosis-associated pain (n = 252). All treatments induced minimal mean changes from baseline in BMD at week 24 (elagolix 150 mg: −0.11%/−0.47%, elagolix 75 mg: −1.29%/−1.2%, and DMPA-SC: 0.99%/−1.29% in the spine and total hip, respectively), with similar or less changes at week 48 (posttreatment). Elagolix was associated with improvements in endometriosis-associated pain, assessed with composite pelvic signs and symptoms score (CPSSS) and visual analogue scale, including statistical noninferiority to DMPA-SC in dysmenorrhea and nonmenstrual pelvic pain components of the CPSSS. The most common adverse events (AEs) in elagolix groups were headache, nausea, and nasopharyngitis, whereas the most common AEs in the DMPA-SC group were headache, nausea, upper respiratory tract infection, and mood swings. This study showed that similar to DMPA-SC, elagolix treatment had minimal impact on BMD over a 24-week period and demonstrated similar efficacy on endometriosis-associated pain. PMID:25249568

  5. Combining oral contraceptives with a natural nuclear factor-kappa B inhibitor for the treatment of endometriosis-related pain.

    PubMed

    Maia, Hugo; Haddad, Clarice; Casoy, Julio

    2013-01-01

    Endometriosis is a chronic disease in which a persistent state of heightened inflammation is maintained by nuclear factor-kappa B (NF-κB) activation. The progestins present in oral contraceptives are potent inhibitors of NF-κB translocation to cell nuclei, while Pycnogenol® (Pinus pinaster) acts by blocking post-translational events. In this study, the effects of Pycnogenol on pain scores were investigated in patients with endometriosis using oral contraceptives containing either gestodene or drospirenone in extended regimens. Pain scores were determined using a visual analog scale before and after 3 months of treatment. Oral contraceptives, used alone (groups 1 and 3) or in association with Pycnogenol (groups 2 and 4), resulted in significant decreases in pain scores after 3 months of treatment; however, this reduction was significantly greater in the groups using oral contraceptives + Pycnogenol (groups 2 and 4) compared with those using oral contraceptives alone (groups 1 and 3). In the groups using oral contraceptives alone, 50% of patients became pain-free by the end of the third month of treatment. These results suggest that Pycnogenol increases the efficacy of oral contraceptives for the treatment of endometriosis-related pain. PMID:24379702

  6. Platelets drive smooth muscle metaplasia and fibrogenesis in endometriosis through epithelial-mesenchymal transition and fibroblast-to-myofibroblast transdifferentiation.

    PubMed

    Zhang, Qi; Duan, Jie; Liu, Xishi; Guo, Sun-Wei

    2016-06-15

    Smooth muscle metaplasia (SMM) and fibrotic tissues are frequently seen in endometriotic lesions, yet the mechanisms underlying their formation are poorly understood. In this study, we investigated the roles of activated platelets in driving epithelial-mesenchymal transition (EMT) and fibroblast-to-myofibroblast transdifferentiation (FMT) in endometriosis. Through in vitro experimentations, we found that activated platelets, through the release of TGF-β1 and the induction of TGF-β/Smad signaling pathway, promoted EMT and FMT in endometriosis, resulting in increased cell contractility, collagen production, and ultimately to fibrosis. TGF-β blockade reversed these processes. Prolonged exposure of endometriotic stromal cells to activated platelets induced increased expression of α-SMA as well as markers of differentiated smooth muscle cells. Consequently, endometriotic lesions and their microenvironment contain all the necessary molecular machinery to promote SMM and fibrogenesis. Our results suggest that endometriotic lesions are wounds that undergo repeated injury and healing, highlighting the importance of platelets in the development of endometriosis. PMID:26992563

  7. A Prospective Randomized Experimental Study to Investigate the Eradication Rate of Endometriosis after Surgical Resection versus Aerosol Plasma Coagulation in a Rat Model

    PubMed Central

    Rothmund, Ralf; Scharpf, Marcus; Tsaousidis, Christos; Planck, Constanze; Enderle, Markus Dominik; Neugebauer, Alexander; Kroeker, Kristin; Nuessle, Daniela; Fend, Falko; Brucker, Sara; Kraemer, Bernhard

    2016-01-01

    Purpose To investigate the eradication rate of endometriosis after surgical resection (SR) vs. thermal ablation with aerosol plasma coagulation (AePC) in a rat model. Methods In this prospective, randomized, controlled, single-blinded animal study endometriosis was induced on the abdominal wall of 34 female Wistar rats. After 14 days endometriosis was either removed by SR or ablated by AePC. 14 days later the rats were euthanized to evaluate the eradication rate histopathologically. Intervention times were recorded. Results Eradication rate of endometriosis after 14 days did not significantly differ between AePC and SR (p=0.22). Intervention time per endometrial lesion was 22.1 s for AePC and 51.8 s for SR (p<0.0001). Conclusions This study compares the eradication rate of the new aerosol plasma coagulation device versus standard surgical resection of endometriosis in a rat model. Despite being a thermal method, AePC showed equality towards SR regarding eradication rate but with significantly shorter intervention time. PMID:26941579

  8. Identification of Susceptibility Genes for Peritoneal, Ovarian, and Deep Infiltrating Endometriosis Using a Pooled Sample-Based Genome-Wide Association Study

    PubMed Central

    Borghese, Bruno; Tost, Jörg; de Surville, Magalie; Busato, Florence; Letourneur, Frank; Mondon, Françoise; Vaiman, Daniel; Chapron, Charles

    2015-01-01

    Characterizing genetic contributions to endometriosis might help to shorten the time to diagnosis, especially in the most severe forms, but represents a challenge. Previous genome-wide association studies (GWAS) made no distinction between peritoneal endometriosis (SUP), endometrioma (OMA), and deep infiltrating endometriosis (DIE). We therefore conducted a pooled sample-based GWAS and distinguished histologically confirmed endometriosis subtypes. We performed an initial discovery step on 10-individual pools (two pools per condition). After quality control filtering, a Monte-Carlo simulation was used to rank the significant SNPs according to the ratio of allele frequencies and the coefficient of variation. Then, a replication step of individual genotyping was conducted in an independent cohort of 259 cases and 288 controls. Our approach was very stringent but probably missed a lot of information due to the Monte-Carlo simulation, which likely explained why we did not replicate results from “classic” GWAS. Four variants (rs227849, rs4703908, rs2479037, and rs966674) were significantly associated with an increased risk of OMA. Rs4703908, located close to ZNF366, provided a higher risk of OMA (OR = 2.22; 95% CI: 1.26–3.92) and DIE, especially with bowel involvement (OR = 2.09; 95% CI: 1.12–3.91). ZNF366, involved in estrogen metabolism and progression of breast cancer, is a new biologically plausible candidate for endometriosis. PMID:25722978

  9. Effect of vascular endothelial growth factor and interleukin-1beta on apoptosis in endometrial cell cultures from patients with endometriosis and controls.

    PubMed

    Bilotas, Mariela; Meresman, Gabriela; Buquet, Ricardo; Sueldo, Carlos; Barañao, Rosa Inés

    2010-03-01

    The aim of this study was to evaluate the effect of vascular endothelial growth factor (VEGF) and interleukin-1beta (IL-1beta) on apoptosis induced by leuprolide acetate (LA) in endometrial epithelial cell cultures from patients with endometriosis. Primary endometrial epithelial cell cultures were obtained from uterine endometrial biopsies of patients with endometriosis and control women. Endometrial epithelial cells were incubated with LA; a combination of LA and VEGF; a combination of LA and IL-1beta; or in basal conditions. LA was added 3h prior to addition of VEGF and IL-1beta. After stimulation, the percentage of apoptotic cells was evaluated by the acridine orange-ethidium bromide technique and Bax expression was assessed by western blot. Treatment with LA enhanced the percentage of apoptotic cells in endometrial epithelial cells from subjects with endometriosis and control subjects. Addition of either VEGF or IL-1beta after exposure to LA restored the percentage of apoptotic cells to basal levels. Moreover, treatment with LA increased Bax expression in endometrial epithelial cells from patients with endometriosis. This effect was reverted by the addition of either VEGF or IL-1beta. Our results show that VEGF and IL-1beta reduce apoptosis and decrease Bax expression in endometrial epithelial cells from patients with endometriosis. This study suggests that VEGF and IL-1beta may protect endometriotic cells from undergoing apoptosis in addition to exerting their pro-angiogenic role. PMID:20137818

  10. The Treatment of Mild Endometriosis With Laser Laparoscopy: a Two-step Treatment Analysis of Patients Whose Primary Therapy Was Successful

    PubMed Central

    Habli, Mounira; Alizade, Azer; Borromeo, Rita

    2006-01-01

    Objectives: The most advantageous treatment for pelvic endometriosis that is not extensive has long been the subject of debate. In recent years, the ability to detect atypical presentations has allowed the gynecological surgeon to treat this entity more readily. The treatment in the past has been concerned with the singular treatment being applied at the time, not on the prior treatment effects on current therapy. The purpose of the current study was to see whether previous successful treatment modalities affected the success of subsequent laparoscopic laser fulguration treatment of endometriosis. Methods: Patients who were previously treated for their endometriosis (minimal and mild) and had success in achieving pregnancy were treated for their disease after failing to become pregnant after delivery. They were treated with laparoscopic laser fulguration of the disease and the results were examined by chi-square (χ2) analysis. Results: There appears to be no difference in current pregnancy rates in patients who were successfully treated in the original treatment for endometriosis, no matter which of the therapies had been used. Conclusion: If endometriosis is diagnosed at the time of laparoscopy and is easily amenable to treatment, it should be treated at the time of surgery regardless of prior treatment and results. PMID:16709353

  11. The combination of letrozole and melatonin causes regression in size not histopathological scores on endometriosis in an experimental rat model

    PubMed Central

    Yıldırım, Gazi; Attar, Rukset; Fıçıcıoğlu, Cem; Karateke, Ateş; Özkan, Ferda; Kılıç, Ertuğrul; Yılmaz, Bayram; Yeşildağlar, Narter

    2009-01-01

    Objective To determine the effects of the combination of letrozole and melatonin on surgically induced endometriosis. Material and Methods This prospective, randomized, controlled, experimental study was carried out at Yeditepe University Experimental Research Center (YUDETAM). Female non-pregnant, 17 nulligravid Wistar - Hannover albino rats with surgically induced endometriosis were used in this study. Endometriosis was induced by using homologous uterine horn transplantation in the rats. Four operations were performed on each rat. The induction of endometriosis was performed in the first operation. After two weeks of estradiol treatment the second operation was performed and endometriotic lesions were evaluated. Estrogen was then discontinued and in the study groups medications were started. During two weeks the rats were given medications and the third operation was performed for the assessment of the effects of the medications on the endometriotic foci. Then all the medications were stopped and estrogen was started again. Two weeks later all the rats were euthanized and recurrence of endometriosis was evaluated. Results The sum of the lesion volumes in the control group was 93.6±31.7 mm3 at the end of the second week. After the cessation of estradiol it decreased to 85.0±23.8 mm3 (P=0.31) and increased to 119.7±29.4 mm3 at the sixth week (P=0.02). A significant reduction in histopathologic scores were seen after cessation of the estradiol (p=0.04). At the end of the sixth week, histopathological scores reached the pretreatment values. In the letrozole and melatonin group the sum of the lesion volumes decreased significantly after the treatment (82.8±21.0 mm3 and 15.7±8.0 mm3 respectively). At the end of the sixth week, the mean volume was calculated as 43.9±31.8 mm3 (p=0.002). Histopathologic scores were 2.3±0.1, 2.0±0.2 and 2.2±0.3 at the end of the second, fourth and sixth weeks, respectively, in the letrozole and melatonin group. Conclusions

  12. TGF-βI Regulates Cell Migration through Pluripotent Transcription Factor OCT4 in Endometriosis

    PubMed Central

    Au, Heng-Kien; Chang, Jui-Hung; Wu, Yu-Chih; Kuo, Yung-Che; Chen, Yu-Hsi; Lee, Wei-Chin; Chang, Te-Sheng; Lan, Pei-Chi; Kuo, Hung-Chih; Lee, Kha-Liang; Lee, Mei-Tsu; Tzeng, Chii-Ruey; Huang, Yen-Hua

    2015-01-01

    Transforming growth factor (TGF-β)/TGF-β receptor signal is known to promote cell migration. Up-regulation of TGF-β in serum/peritoneal fluid and increased levels of pluripotent transcription factor OCT4 in endometriotic tissues are frequently observed in patients with endometriosis. However, the mechanisms underlying how TGF-β/TGF-β receptor and OCT4 affect endometriotic cell migration still remain largely unknown. Therefore, endometriotic tissue with high cell migratory capacity were collected from patients with adenomyotic myometrium (n = 23) and chocolate cyst (n = 24); and endometrial tissue with low cell migratory capacity in normal endometrium or hyperplastic endometrium (n = 8) were collected as the controls. We found the mRNA levels of TGF-β receptor I (TGF-β RI) and OCT4 were significantly higher in the high-migratory ectopic endometriotic tissues than those of the low-migratory normal or hyperplastic endometrium. Positive correlations between TGF-β RI and OCT4, and either TGF-β RI or OCT4 with migration-related genes (SNAIL, SLUG and TWIST) regarding the mRNA levels were observed in human endometriotic tissues. TGF-βI dose-dependently increased the gene and protein levels of OCT4, SNAIL and N-Cadherin (N-CAD) and silencing of endogenous OCT4 significantly suppressed the TGF-βI-induced expressions of N-CAD and SNAIL in primary human endometriotic stromal cells and human endometrial carcinoma cell lines RL95-2 and HEC1A. Furthermore, TGF-βI significantly increased the migration ability of endometriotic cells and silencing of OCT4 dramatically suppressed the TGF-βI-induced cell migration activity evidenced by wound-closure assay, transwell assay, and confocal image of F-actin cellular distribution. In conclusion, the present findings demonstrate that the niche TGF-β plays a critical role in initiating expressions of pluripotent transcription factor OCT4 which may contribute to the ectopic endometrial growth by stimulating endometrial cell

  13. Therapeutic Affordances of Online Support Group Use in Women With Endometriosis

    PubMed Central

    2016-01-01

    Background The Internet has provided women living with endometriosis new opportunities to seek support online. Online support groups may provide a range of therapeutic affordances that may benefit these women. Objective To examine the presence of therapeutic affordances as perceived by women who use endometriosis online support groups. Methods Sixty-nine women (aged 19-50 years, mean 34.2 years; 65.2% (45/69) United Kingdom, 21.7% (15/69) United States) participated in a Web-based interview exploring online support group use. Participants had been using online support groups for an average of 2 years and 4 months (range = 1 month to 14 years, 9 months). Responses were analyzed using inductive thematic analysis. Results The analysis revealed 4 therapeutic affordances related to online support group use: (1) “connection,” that is, the ability to connect in order to support each other, exchange advice, and to try to overcome feelings of loneliness; (2) “exploration,” that is, the ability to look for information, learn, and bolster their knowledge; (3) “narration,” that is, the ability to share their experiences, as well as read about the experiences of others; and (4) “self-presentation,” that is, the ability to manage how they present themselves online. The associated outcomes of use were predominantly positive, such as reassurance and improved coping. However, a number of negative aspects were revealed including the following: concerns about the accuracy of information, arguments between members, overreliance on the group, becoming upset by negative experiences or good news items, and confidentiality of personal information. Conclusions Our findings support the previously proposed SCENA (Self-presentation, Connection, Exploration, Narration, and Adaptation) model and reveal a range of positive aspects that may benefit members, particularly in relation to reassurance and coping. However, negative aspects need to be addressed to maximize the potential

  14. High-Fat Diet Promotion of Endometriosis in an Immunocompetent Mouse Model is Associated With Altered Peripheral and Ectopic Lesion Redox and Inflammatory Status.

    PubMed

    Heard, Melissa E; Melnyk, Stepan B; Simmen, Frank A; Yang, Yanqing; Pabona, John Mark P; Simmen, Rosalia C M

    2016-07-01

    Endometriosis is a benign gynecological condition that causes considerable morbidity due to associated infertility, debilitating pelvic pain and inflammatory dysfunctions. Diet is a highly modifiable risk factor for many chronic diseases, but its contribution to endometriosis has not been extensively investigated, due partly to the paradoxical inverse association between obesity and disease incidence. Nevertheless, chronic exposure to dietary high-fat intake has been linked to greater systemic inflammation and oxidative stress, both features of women with endometriosis. Here, we evaluated the effects of a high-fat diet (HFD) (45% fat kcal) on endometriosis progression using an immunocompetent mouse model where ectopic lesion incidence was induced in wild-type recipients by ip administration of endometrial fragments from transcription factor Krüppel-like factor 9-null donor mice. We show that HFD significantly increased ectopic lesion numbers in recipient mice with no significant weight gain and modifications in systemic ovarian steroid hormone and insulin levels, relative to control diet-fed (17% fat kcal) mice. HFD promotion of lesion establishment was associated with reductions in stromal estrogen receptor 1 isoform and progesterone receptor expression, increased F4/80-positive macrophage infiltration, higher stromal but not glandular epithelial proliferation, and enhanced expression of proinflammatory and prooxidative stress pathway genes. Lesion-bearing HFD-fed mice also displayed higher peritoneal fluid TNFα and elevated local and systemic redox status than control diet-fed counterparts. Our results suggest that HFD intake exacerbates endometriosis outcome in the absence of ovarian dysfunction and insulin resistance in mice and warrants further consideration with respect to clinical management of endometriosis progression and recurrence in nonobese patients. PMID:27175969

  15. Peritoneal VEGF-A expression is regulated by TGF-β1 through an ID1 pathway in women with endometriosis

    PubMed Central

    Young, Vicky J.; Ahmad, Syed F.; Brown, Jeremy K.; Duncan, W. Colin; Horne, Andrew W.

    2015-01-01

    VEGF-A, an angiogenic factor, is increased in the peritoneal fluid of women with endometriosis. The cytokine TGF-β1 is thought to play a role in the establishment of endometriosis lesions. Inhibitor of DNA binding (ID) proteins are transcriptional targets of TGF-β1 and ID1 has been implicated in VEGF-A regulation during tumor angiogenesis. Herein, we determined whether peritoneal expression of VEGF-A is regulated by TGF-β1 through the ID1 pathway in women with endometriosis. VEGF-A was measured in peritoneal fluid by ELISA (n = 16). VEGF-A and ID1 expression was examined in peritoneal biopsies (n = 13), and primary peritoneal and immortalized mesothelial cells (MeT5A) by immunohistochemistry, qRT-PCR and ELISA. VEGF-A was increased in peritoneal fluid from women with endometriosis and levels correlated with TGF-β1 concentrations (P < 0.05). VEGF-A was immunolocalized to peritoneal mesothelium and TGF-β1 increased VEGFA mRNA (P < 0.05) and protein (P < 0.05) in mesothelial cells. ID1 was increased in peritoneum from women with endometriosis and TGF-β1 increased concentrations of ID1 mRNA (P < 0.05) in mesothelial cells. VEGF-A regulation through ID1 was confirmed by siRNA in MeT5A cells (P < 0.05). Our data supports role for ID1 in the pathophysiology of endometriosis, as an effector of TGFβ1 dependent upregulation of VEGF-A, and highlights a novel potential therapeutic target. PMID:26577912

  16. [The dynamics of the rapid changes in the phospholipids of the whole blood and blood cells in patients with endometriosis interna].

    PubMed

    Kulakov, V I; Sliusar', N N; Bakuleva, L P; Damirov, M M; Kargapolov, A V

    1993-01-01

    Time course of rapid changes in blood phospholipids and blood cells was studied in 44 patients with endometriosis. Rapid reversible blood phospholipid changes were observed when these patients' red cells and lymphocytes were incubated with calcium chloride. Time course of rapid changes in phosphoinosites, sphyngomyelines, phosphatidylserines, phosphlatidylethanolamines of patients' red and white blood cells, whole blood, and myometrial tissue differed significantly from that in healthy women. The authors suppose that cellular proliferation processes in endometriosis are connected with phospholipid homeostasis disorders in blood cells and tissue. PMID:8250135

  17. miRNAs Regulation and Its Role as Biomarkers in Endometriosis.

    PubMed

    Marí-Alexandre, Josep; Sánchez-Izquierdo, Dolors; Gilabert-Estellés, Juan; Barceló-Molina, Moisés; Braza-Boïls, Aitana; Sandoval, Juan

    2016-01-01

    MicroRNAs (miRNAs) are small non-coding RNAs (18-22 nt) that function as modulators of gene expression. Since their discovery in 1993 in C. elegans, our knowledge about their biogenesis, function, and mechanism of action has increased enormously, especially in recent years, with the development of deep-sequencing technologies. New biogenesis pathways and sources of miRNAs are changing our concept about these molecules. The study of the miRNA contribution to pathological states is a field of great interest in research. Different groups have reported the implication of miRNAs in pathologies such as cancer, diabetes, cardiovascular, and gynecological diseases. It is also well-known that miRNAs are present in biofluids (plasma, serum, urine, semen, and menstrual blood) and have been proposed as ideal candidates as disease biomarkers. The goal of this review is to highlight the current knowledge in the field of miRNAs with a special emphasis to their role in endometriosis and the newest investigations addressing the use of miRNAs as biomarkers for this gynecological disease. PMID:26771608

  18. Kuntai Capsule Inhibited Endometriosis via Inducing Apoptosis in a Rat Model

    PubMed Central

    Ma, Aying; Zhu, Jianping; Li, Guoting; Xie, Shuwu; Li, Zhao; Gui, Youlun

    2016-01-01

    We evaluated the effectiveness of Kuntai Capsule (KTC) for treating endometriosis using rat model and investigated its preliminary mechanism of action involved. SD rats were implanted with endometrial tissues and treated with KTC for three weeks. Then, laparotomy was performed to examine volume changes of the autografts. The serum levels of TNF-α, IL-6, COX-2, E2, and P4 were measured through ELISA. TUNEL was performed to analyze the apoptosis on ectopic endometrium. Protein levels of caspases 8, 9, and 3 and cytochrome c in the ectopic and eutopic endometrium were measured by western blotting. Results showed that KTC significantly decreased the volumes of ectopic endometrium. The level of TNF-α increased and E2 decreased in the KTC treatment groups. TUNEL and western blot assay showed that KTC could induce apoptosis of endometriotic tissues, accompanied with the increased protein expression of caspases 8 and 9, activated caspase-3, and cytochrome c in a dose-dependent manner. However, these protein expression profiles were not affected in eutopic endometrium. Our findings suggest that KTC could inhibit the growth of ectopic endometrial tissue through upregulating the level of TNF-α and its downstream signaling, including caspases and cytochrome c. PMID:27597876

  19. Views on treatment of endometriosis by using laser acupuncture and moxibustion

    NASA Astrophysics Data System (ADS)

    Ye, Hongzheng

    1993-03-01

    This article emphasizes the treatment of endometriosis by using laser acupuncture and moxibustion which belongs to Shi Zhen. The major pathophysiology is that the circulation of the Qi and blood is obstructed. The obstruction of Qi leads to a block of blood and poor circulation which causes pain. The treatment should be introduced mainly by adjusting Qi and blood. We used an He-Ne low level laser instrument. Its export function is >= 20 mw, wavelength 6328 angstroms with a single-red light. By using a double tube fiber bundle it strikes directly on Liv. 3, Ren. 6, SP. 8. Each of the three points needs to be struck for five to ten minutes once a day. One therapy phase requires seven applications continually. This treatment results in cleaning the liver, adjusting the oxygen, and disencumbering the piles and the pain. When it makes the circulation of Qi free, the blood is normally transported and the pain disappears. After one or two phases of therapy, clinical re-examination indicated the disappearance of scleromata in the uterus. Five patients treated and continually re-checked recovered. Finally, their menses turned normal and clinical symptoms vanished within six months.

  20. Photodynamic therapy of endometriosis with HpD (Photosan III) in a new in vitro model

    NASA Astrophysics Data System (ADS)

    Viereck, Volker; Werter, Wiebke; Rueck, Angelika C.; Steiner, Rudolf W.; Keckstein, J.

    1994-07-01

    As a new treatment model for endometriosis, photodynamic therapy was applied to endometriotic and endometrial cultures. It could be demonstrated that both endometrial components (epithelium and stroma) were present in the cultures, proved by immunocytology and electron microscopy. No major differences were seen between endometriotic and endometrial cells. The cultures were treated by HpD-sensitized PDT. Incubation time was 24 h and concentrations of 5 and 10 (mu) g/ml were used. Irradiation was performed by an argon-pumped dye laser at 630 nm with a power density of 80 mW/cm2. Evaluation both morphologically and by trypan blue exclusion test, was effected 24 h after irradiation. Toxicity in endometriotic and endometrial cultures was practically identical. Stroma cells were more sensitive to photodynamic treatment than epithelial cells. Complete stromal cell destruction was reached at 15 J/cm2, whereas epithelial cells showed 100 lethality at 40 J/cm2 (10(mu) g/ml HpD). These and subsequent results demonstrate that the sensitivity of stromal cells was about seven times higher than that of epithelial cells.

  1. Kuntai Capsule Inhibited Endometriosis via Inducing Apoptosis in a Rat Model.

    PubMed

    Zhong, Ruihua; Ma, Aying; Zhu, Jianping; Li, Guoting; Xie, Shuwu; Li, Zhao; Gui, Youlun; Zhu, Yan

    2016-01-01

    We evaluated the effectiveness of Kuntai Capsule (KTC) for treating endometriosis using rat model and investigated its preliminary mechanism of action involved. SD rats were implanted with endometrial tissues and treated with KTC for three weeks. Then, laparotomy was performed to examine volume changes of the autografts. The serum levels of TNF-α, IL-6, COX-2, E2, and P4 were measured through ELISA. TUNEL was performed to analyze the apoptosis on ectopic endometrium. Protein levels of caspases 8, 9, and 3 and cytochrome c in the ectopic and eutopic endometrium were measured by western blotting. Results showed that KTC significantly decreased the volumes of ectopic endometrium. The level of TNF-α increased and E2 decreased in the KTC treatment groups. TUNEL and western blot assay showed that KTC could induce apoptosis of endometriotic tissues, accompanied with the increased protein expression of caspases 8 and 9, activated caspase-3, and cytochrome c in a dose-dependent manner. However, these protein expression profiles were not affected in eutopic endometrium. Our findings suggest that KTC could inhibit the growth of ectopic endometrial tissue through upregulating the level of TNF-α and its downstream signaling, including caspases and cytochrome c. PMID:27597876

  2. The Effects and Possible Mechanisms of Puerarin to Treat Endometriosis Model Rats

    PubMed Central

    Zhao, Li; Zhang, Danying; Zhai, Dongxia; Shen, Wei; Bai, Lingling; Liu, Yiqun; Cai, Zailong; Li, Ji; Yu, Chaoqin

    2015-01-01

    Objective. To explore the effects of puerarin to treat endometriosis (EMT) model rats and the possible regulatory mechanisms. Methods. EMT model rats were surgically induced by autotransplantion of endometrial tissues. The appropriate dosage of puerarin to treat EMT model rats was determined by observing the pathologic morphology of ectopic endometrial tissues and by detecting the levels of estradiol (E2) and prostaglandin E2 (PGE2) of both serum and ectopic endometrial tissues. The related genes and proteins of ectopic endometrial tissues were analyzed by Real-time PCR and immunohistochemistry (IHC) to explore the possible mechanisms. Results. Puerarin could reduce the levels of E2 and PGE2 and prevent the growth of ectopic endometrium tissues by inhibiting the expression of aromatase cytochrome P450 (p450arom) and cyclooxygenase-2 (cox-2); puerarin could adjust the anabolism of E2 by upregulating the expression of 17β-hydroxysteroid-2 (17β-hsd-2) and downregulating the expression of 17β-hydroxysteroid-1 (17β-hsd-1) of the ectopic endometrium tissues; puerarin could increase the expression of ERβ and improve the inflammatory microenvironment of EMT model rats. Conclusions. Our data suggest that puerarin has a therapeutic effect on EMT model rats and could be a potential therapeutic agent for the treatment of EMT in clinic. PMID:25815028

  3. miRNAs Regulation and Its Role as Biomarkers in Endometriosis

    PubMed Central

    Marí-Alexandre, Josep; Sánchez-Izquierdo, Dolors; Gilabert-Estellés, Juan; Barceló-Molina, Moisés; Braza-Boïls, Aitana; Sandoval, Juan

    2016-01-01

    MicroRNAs (miRNAs) are small non-coding RNAs (18–22 nt) that function as modulators of gene expression. Since their discovery in 1993 in C. elegans, our knowledge about their biogenesis, function, and mechanism of action has increased enormously, especially in recent years, with the development of deep-sequencing technologies. New biogenesis pathways and sources of miRNAs are changing our concept about these molecules. The study of the miRNA contribution to pathological states is a field of great interest in research. Different groups have reported the implication of miRNAs in pathologies such as cancer, diabetes, cardiovascular, and gynecological diseases. It is also well-known that miRNAs are present in biofluids (plasma, serum, urine, semen, and menstrual blood) and have been proposed as ideal candidates as disease biomarkers. The goal of this review is to highlight the current knowledge in the field of miRNAs with a special emphasis to their role in endometriosis and the newest investigations addressing the use of miRNAs as biomarkers for this gynecological disease. PMID:26771608

  4. [Urinary functional disorders bound to deep endometriosis and to its treatment: review of the literature].

    PubMed

    Campin, L; Borghese, B; Marcellin, L; Santulli, P; Bourret, A; Chapron, C

    2014-06-01

    Lower urinary tract disorders in case of deep endometriosis are common (up to 50% of patients), although often masked by pelvic pain. They result from damage to the pelvic autonomic nervous system by direct infiltration of these structures by endometriotic lesions or surgical trauma (especially in resection of the uterosacral ligaments, rectum or vagina). These are mainly sensory disturbances and bladder voiding dysfunction. They impact quality of life and could be responsible for long-term complications (recurrent urinary tract infections on a persistent residual urine or pelvic floor disorders due to chronic thrusting). It is therefore important to diagnose and treat early these troubles by well-conducted interviews or standardized questionnaires. Different drug treatments have been proposed, such as cholinergics or prokinetics, but their effectiveness has not been demonstrated yet. Neuromodulation of the superior hypogastric plexus for treatment of refractory atonic bladder with persistent urinary retention after surgery seems promising but should be confirmed by further studies. To date, standard treatment of urinary retention after surgery remains self-catheterization. In terms of prevention, surgical nerve sparing techniques have been developed in order to minimize intraoperative injury of pelvic nerve plexus and reduce postoperative morbidity. PMID:24831568

  5. Tubal origin of ovarian endometriosis and clear cell and endometrioid carcinoma

    PubMed Central

    Wang, Yiying; Mang, Maggie; Wang, Yue; Wang, Lijie; Klein, Robert; Kong, Beihua; Zheng, Wenxin

    2015-01-01

    Current research has strongly proposed that contrary to prior beliefs, many ovarian epithelial cancers (OECs) do not, as their name suggests, originate in the ovaries. Recent findings regarding both high-grade and low-grade serous carcinomas has implicated the fallopian tube as a cell source for these OECs, but until now, there has been little insight into the cellular source for clear cell and endometrioid carcinomas. In this commentary review article, we aimed to discuss the new findings that support the possible contribution from the fallopian tube in clear cell and endometrioid carcinomas. Specifically, we have provided results that showcased ovarian surface epithelia (OSE) and ovarian epithelial inclusions (OEIs) as having mesothelial and tubal origins and have strongly recognized the secondary müllerian system and the ability for tubal epithelia to implant upon the ovarian surface as contributing to fallopian tube-derived OEIs (F-OEIs). We have provided initial indications of these F-OEIs and their relationship to endometriosis and then clear cell and endometrioid carcinomas and subsequently offer our new proposal of a probable tubal origin. This new proposal is a paradigm that drastically changes the understanding behind the origin of these OECs and has significant clinical implications in the near future. PMID:26045974

  6. Curbing Inflammation in Multiple Sclerosis and Endometriosis: Should Mast Cells Be Targeted?

    PubMed Central

    Hart, David A.

    2015-01-01

    Inflammatory diseases and conditions can arise due to responses to a variety of external and internal stimuli. They can occur acutely in response to some stimuli and then become chronic leading to tissue damage and loss of function. While a number of cell types can be involved, mast cells are often present and can be involved in the acute and chronic processes. Recent studies in porcine and rabbit models have supported the concept of a central role for mast cells in a “nerve-mast cell-myofibroblast axis” in some inflammatory processes leading to fibrogenic outcomes. The current review is focused on the potential of extending aspects of this paradigm into treatments for multiple sclerosis and endometriosis, diseases not usually thought of as having common features, but both are reported to have activation of mast cells involved in their respective disease processes. Based on the discussion, it is proposed that targeting mast cells in these diseases, particularly the early phases, may be a fruitful avenue to control the recurring inflammatory exacerbations of the conditions. PMID:26550518

  7. Clinical Effectiveness of Modified Laparoscopic Fimbrioplasty for the Treatment of Minimal Endometriosis and Unexplained Infertility

    PubMed Central

    Franjoine, Sarah E.; Bedaiwy, Mohamed A.; AbdelHafez, Faten F.; Geng, Cuiyu; Liu, James H.

    2015-01-01

    Objective. To study the reproductive outcomes of modified laparoscopic fimbrioplasty (MLF), a surgical technique designed to increase the working surface area of the fimbriated end of the fallopian tube. We postulated that an improvement in fimbrial function through MLF will improve reproductive outcomes. Design. Retrospective cohort study. Setting. Academic tertiary-care medical center. Patients. Women with minimal endometriosis or unexplained infertility, who underwent MLF during diagnostic laparoscopy (n = 50) or diagnostic laparoscopy alone (n = 87). Intervention. MLF involved gentle, circumferential dilatation of the fimbria and lysis of fimbrial adhesions bridging the fimbrial folds. Main Outcome Measures. The primary outcome was pregnancy rate and the secondary outcome was time to pregnancy. Results. The pregnancy rate for the MLF group was 40.0%, compared to 28.7% for the control group. The average time to pregnancy for the MLF group was 13 weeks, compared to 18 weeks for the control group. The pregnancy rate in the MLF group was significantly higher for patients ≤35 ys (51.5% versus 28.8%), but not for those >35 ys (17.6% versus 28.6%). Conclusion. MLF was associated with a significant increase in pregnancy rate for patients ≤35 ys. PMID:26064680

  8. Use of mifepristone to treat endometriosis: a review of clinical trials and trial-like studies conducted in China.

    PubMed

    Guo, Sun-Wei; Liu, Maohua; Shen, Fanghua; Liu, Xishi

    2011-01-01

    China was the first country in the world that approved mifepristone (RU-486) for abortion. A total of 6 years after the report published in the Western world indicated that mifepristone may also be effective in treating endometriosis, the first paper on the same topic was published in China in 1997. Since then, over 160 studies on this topic have been published in China. We retrieved 104 papers on clinical trials and trial-like studies conducted in China evaluating the use of mifepristone to treat endometriosis that were published in the last 11 years. We found that the quality of these studies is well below an acceptable level, making it difficult to judge whether mifepristone is truly efficacious. There are intriguing signs that these studies, as a whole, have serious anomalies. The areas that are glaringly deficient are informed consent, choice of outcome measures, the evaluation of outcome measures, data analysis and randomization. The uniformly low quality is disquieting, given the large quantity of studies, the enormous amount of resource and energy put into these studies and, above all, the weighty issue of treatment efficacy that concerns each and every patient with endometriosis. Equally disquieting are the low-quality repetition, the absence of a critical, systematic review on the subject, the lack of suggestions for multicenter clinical trials and the seemingly unnecessary duplication of clinical trials without due informed consent. In view of this, it may be time to institute changes in attitude and practice, and to change education and training programs in the methodology of clinical trials in obstetrics and gynecology research in China. PMID:21175391

  9. Compatibility of a novel thrombospondin-1 analog with fertility and pregnancy in a xenograft mouse model of endometriosis.

    PubMed

    Nakamura, Diane S; Edwards, Andrew K; Ahn, Soo Hyun; Thomas, Richard; Tayade, Chandrakant

    2015-01-01

    Endometriosis is a gynecological disease defined by the growth of endometrium outside of the uterus. Although endometriosis contributes to 50% of female infertility cases, medical treatments are incompatible with pregnancy. Angiogenesis, the growth of blood vessels from existing vasculature, plays a crucial role in endometriotic lesion growth and survival. Previously, we demonstrated the effectiveness of thrombospondin-1 analog, ABT-898 (Abbott Laboratories) to inhibit endometriotic lesion vascularization in mice. We have now evaluated the trans-generational implications of ABT-898 treatment before and during mouse pregnancy. We hypothesized that ABT-898 would target lesion vasculature without affecting pregnancy, offspring development, or ovarian and uterine vascularity in mice. Endometriosis was induced using human endometrium in β-estradiol-primed BALB/c-Rag-2-/-Il2rγ-/- mice receiving intraperitoneal injections of ABT-898 (25 mg/kg) or 5% dextrose control for 21 days. Ultrasound assessment of lesion vascularization revealed a reduction in blood flow supplying treated lesions. Excised ABT-898 treated lesions stained for CD31+ endothelial cells exhibited a decrease in microvessel density. Following confirmation of estrous cycling, mice were bred and treated with ABT-898 on gestation days 7, 9, 11, 13, 15, 17, and 19. ABT-898 did not affect estrous cycling or pregnancy parameters including litter size across generations and offspring weight gain. Quantification of angiogenic cytokine plasma levels revealed no significant differences between treatment groups. Vimentin staining of the uterus and ovary revealed no observable effects of ABT-898. Similarly, no obvious histological anomalies were observed in the kidney, liver, ovary, or uterus following ABT-898 treatment. These results suggest that ABT-898 effectively inhibit endometriotic lesion vascularization without affecting trans-generational pregnancy outcomes in mice. PMID:25811892

  10. Inhibition of Adhesion, Proliferation, and Invasion of Primary Endometriosis and Endometrial Stromal and Ovarian Carcinoma Cells by a Nonhyaluronan Adhesion Barrier Gel

    PubMed Central

    Renner, Stefan P.; Strissel, Pamela L.; Beckmann, Matthias W.; Lermann, Johannes; Hackl, Janina; Fasching, Peter A.

    2015-01-01

    Endometriosis is a chronic disease of women in the reproductive age, defined as endometrial cells growing outside of the uterine cavity and associated with relapses. Relapses are hypothesized to correlate with incomplete surgical excision or result from nonrandom implantation of new endometrial implants in adjacent peritoneum. Thus, surgical excision could lead to free endometriotic cells or tissue residues, which readhere, grow, and invade into recurrent lesions. Barrier agents are frequently used to prevent postoperative adhesions. We tested if the absorbable cell adhesion barrier gel Intercoat consisting of polyethylene oxide and sodium carboxymethyl cellulose could inhibit cellular adhesion, proliferation, and invasion of primary endometriosis and endometrial cells. Due to an association of endometriosis with ovarian carcinoma, we tested two ovarian carcinoma cell lines. Prior to cell seeding, a drop of the barrier gel was placed in cell culture wells in order to test inhibition of adherence and proliferation or coated over a polymerized collagen gel to assay for prevention of invasion. Results showed that the barrier gel significantly inhibited cell adherence, proliferation, and invasion of endometriosis and endometrial stromal cells as well as ovarian carcinoma cells in culture. Our findings could help to prevent local cell growth/invasion and possible consequent recurrences. PMID:25785270

  11. Ovarian endometrioid carcinoma and endometriosis developing in a postmenopausal breast cancer patient during tamoxifen therapy: a case report and review of the literature.

    PubMed

    Cohen, I; Altaras, M M; Lew, S; Tepper, R; Beyth, Y; Ben-Baruch, G

    1994-12-01

    We present the first case of ovarian endometrioid carcinoma and endometriosis in a postmenopausal patient who was treated with tamoxifen for breast cancer. The association with prolonged unopposed estrogen-like stimulation with tamoxifen as a possible factor in the development of ovarian endometrioid carcinoma is discussed. PMID:7835785

  12. Comparative Analysis of Differentially Expressed miRNAs and their Downstream mRNAs in Ovarian Cancer and its Associated Endometriosis

    PubMed Central

    Wu, Richard Licheng; Ali, Shadan; Bandyopadhyay, Sudeshna; Alosh, Baraa; Hayek, Kinda; Daaboul, MHD Fayez; Winer, Ira; Sarkar, Fazlul H; Ali-Fehmi, Rouba

    2015-01-01

    Objective There is an increased risk of developing ovarian cancer (OC) in patients with endometriosis. Hence, development of new biomarkers may provide a positive clinical outcome for early detection. MicroRNAs (miRNAs) are small non-coding RNAs that play an important role in biological and pathological process and are currently used as diagnostic and prognostic markers in various cancers. In the current study, we assessed the differential expression of miRNAs from 19 paired ovarian cancer and its associated endometriosis tissue samples. In addition we also analyzed the downstream targets of those miRNAs. Methods Nineteen paired cases of ovarian cancer and endometriosis foci were identified by a gynecologic pathologist and macro-dissected. The total RNAs were extracted and subjected to comprehensive miRNA profiling from the pooled samples of these two different entities using microarray analysis. Later, the abnormal expressions of few selected miRNAs were validated in individual cases by quantitative real-time PCR (qRT-PCR). Ingenuity pathway analysis revealed target mRNAs which were validated by qRT-PCR. Results The miRNA profiling identified deregulation of greater than 1156 miRNAs in OC, of which the top seven were further validated by qRT-PCR. The expression of miR-1, miR-133a, and miR-451 were reduced significantly (p<0.0001) in the OC patients compared to its associated endometriosis. In contrast, the expression of miR-141, miR-200a, miR-200c, and miR-3613 were elevated significantly (p<0.05) in most of the OC patients. Furthermore, among the downstream mRNAs of these miRNAs, the level of PTEN expression was significantly (p<0.05) reduced in OC compared to endometriosis while no significant difference was observed in NF-κB expression. Conclusion The expression of miRNAs and mRNAs in OC were significantly different compared to its concurrent endometriosis. These differential expressed miRNAs may serve as potential diagnostic and prognostic biomarkers for OC

  13. Puerarin Suppresses Invasion and Vascularization of Endometriosis Tissue Stimulated by 17β-Estradiol

    PubMed Central

    Han, Jie; Zai, Dongxia; Ji, Mei; Cheng, Wen; Xu, Ling; Yang, Luxi; He, Miaoxia; Ni, Jian; Cai, Zailong; Yu, Chaoqin

    2011-01-01

    Background Puerarin, a phytoestrogen with a weak estrogenic effect, binds to estrogen receptors, thereby competing with 17β-estradiol (E2) and producing an anti-estrogenic effect. This study was to investigate whether puerarin could suppress the invasion and vascularization of E2-stimulated endometriotic tissue. Methodology/Principal Findings The endometriotic stromal cells (ESCs) were successfully established and their invasive ability under different treatments was assessed through a Transwell Assay. Simultaneously, matrix metallopeptidase 9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) were detected by western blotting. Vascularization of endometriotic tissues was observed by chicken chorioallantoic membrane (CAM) assay. The staining of MMP-9, intercellular adhesion molecule 1 (ICAM-1), TIMP-1, and vascular endothelial growth factor (VEGF) in grafted endometriotic tissues was examined using immunohistochemistry analysis. The purity of ESCs in isolated cells was >95%, as determined by the fluoroimmunoassay of vimentin. E2 (10−8 mol/L) promoted the invasiveness of ESCs by increasing MMP-9 accumulation and decreasing TIMP-1 accumulation. Interestingly, puerarin (10−9 mol/L) significantly reversed these effects (P<0.01). The CAM assay indicated that puerarin (10−9 mol/L) also inhibited the angiopoiesis of endometriotic tissue stimulated by the E2 (10−8 mol/L) treatment (P<0.05). Accordingly, immunohistochemistry showed that the accumulation of MMP-9, ICAM-1, and VEGF was reduced whereas that of TIMP-1 increased in the combination treatment group compared with the E2 treatment group. Conclusions/Significance This study demonstrated that puerarin could suppress the tissue invasion b