WES E-Newsletter, Summer 2003

 

Introduction

Endometriosis affects more than five million women in the US and Canada; many million more worldwide. Yet it remains a condition where the diagnosis is often long-delayed. Studies indicate that it takes an average of 9.28 years for endometriosis to be diagnosed in the US; 6.8 years in the UK; and 4.4 years in Australia. Although the delay is due in part to the length of time women take to seek medical help, in the US of the 4000 women questioned 61% claimed they were told that there was nothing wrong with them when they first consulted a doctor. Almost half had to see a doctor five times or more before they were diagnosed or were referred to a doctor who correctly diagnosed the condition.

These studies were performed under the auspices of US, UK and Australian endometriosis support associations, which may introduce a sampling bias. However, it is obvious that speeding referral and diagnosis is of the utmost importance, especially given the link between endometriosis and infertility.

One way of accomplishing this is by increasing the awareness of endometriosis among general practitioners and gynecologists. Here WES members can assist by bringing WES to the attention of their colleagues and by encouraging them to join on line at www.endometriosis.ca. Published every three months the WES e-newsletter gives members a survey of the latest endometriosis literature, with comments on selected articles by WES Board members. It also gives information about new developments, meetings, members' movements and, recently, it has introduced a Discussion Link where members can ask questions, discuss new developments, air concerns or simply keep in touch.

Members are encouraged to make the WES e-newsletter work for them by sending in any information they would like disseminated to the general membership. This can be items of news, questions, comments, information about upcoming meetings (taking into account that the WES newsletter is published quarterly), or announcements of career moves, new grants for any aspect of endometriosis research etc. The address to which this should be sent is given at the end of the newsletter.

Literature Review

In the last quarter only seven new articles on endometriosis were published in core clinical journals. They are:

  1. Vercellini P, Chapron C, De Giorgi O, Consonni D, Frontino G, Crosignani PG
    Coagulation or excision of ovarian endometriomas?
    Am J Obstet Gynecol 2003 Mar 188(3) 606-10. Review

  2. Matalliotakis IM, Mahutte NG, Goumenou AG, Arici A
    Twenty-year history of endometriosis-associated pelvic pain: too much surgery or not enough?
    Amer J Obstet Gynecol 2003 Apr 188(4) 1103-4.

  3. Hara T, Araki H, Kusaka M, Harada M, Cho N, Suzuki N, Furuya S, Fujino M
    Suppression of a pituitary-ovarian axis by chronic oral administration of a novel nonpeptide gonadotropin-releasing hormone antagonist, TAK-013, in cynomolgus monkeys.
    J Clin Endocrinol Metab 2003 Apr 88(4) 1697-704.

  4. Howard FM
    Chronic pelvic pain.
    Obstet Gynecol 2003 Mar 101(3) 594-611, Review.

  5. Quinn, M
    The endometrial-myometrial interface.
    Am J Obstet Gynecol 2003 Mar 188(3) 857; author reply 857-8. No abstract
    available.

  6. Sakamoto Y, Harada T, Horie, Iba Y, Taniguchi F, Yoshida S, Iwabe, T
    Tumor necrosis factor-alpha-induced interleukin-8 (IL-*) expression in endometriotic stromal cells, probably through nuclear factor-kappa B activiation: gonadotropin- releasing hormone agonist treatment reduced IL-8 expression.
    J Clin Endocrinol Metab 2003 Feb 88(2) 730-5.

  7. Aboulghar MA, Mansour, RT, Serour GI, Al-Inany HG, Aboulghar MM
    The outcome of in vitro fertilization in advanced endometriosis with previous surgery: a case-controlled study.
    Am J Obstet Gynecol 2003 Feb 188(2) 371-5.

Comments

  1. Dr Vercellini’s review is a high quality review of relatively poor quality studies. Confounding by indication may impact on the results considerably, since poor and hasty surgeons will prefer not to perform a cyst-wall removal but a rapid (and often incomplete) coagulation of the inner lining of the cyst. This will bias the outcome in favour of more recurrences in the laser/coagulation group. We have to be aware, however, that complete removal of the cyst may on the other hand endanger the total amount of oocytes left behind. What we really need is a large prospective comparative, randomized study with adequate blinding and allocation concealment investigating both issues, recurrence rate and remaining follicle count following either of the two procedures.

  1. In this review Dr Howard repeats that history and physical examination
    are crucial in evaluating a woman with chronic pelvic pain and must address all of the possible systems potentially involved in chronic pelvic pain, not just the reproductive system.

    This article is a good review about chronic pelvic pain and discusses different approaches to diagnosis and therapy.

  1. Sakamoto et al. Comment 1. A powerful group of respected Japanese investigators reports upon the cytokine molecular biology of ovarian endometriomata. The story so far is that women with endometroisis show increased amounts of the cytokines interleukin -6, interleukin -8 and the deliciously named tumour necrosis factor, presumably within their ovarian endometromata as well as their peritoneal fluid. Tumour necrosis factor grows endometriosis by stimulating interleukin-8, which is mitrogenic. This happens by activation of the transcription factor, nuclear factor -kB. GNRII-agonists blunt this activation. If these cytokines could be shown to be specific for endometriosis, the authors discuss their potential for new endometriosis medicines.

  1. Sakamota et al. Comment 2: Modulation of cytokine production by ovarian hormones, notably estradiol, in endometriosis is now well documented. The study of Sakamoto et al adds interesting new evidence by demonstrating that gonadotropin-releasing hormone agonist (GnRha) treatment of endometriosis patients reduces endometriotic cell responsiveness to tumor necrosis factor alpha (TNF a) and attenuates interleukin-8 (IL 8) expression. Interestingly, this study further showed that one of the mechanisms of GnRha effect is that involving the transcription factor nuclear factor-kappa B (NF-kappa B), whose activation in response to TNFa was reduced following GnRHa treatment.
    This is interesting, especially in view of the angiogenic and proliferative effects of these cytokines and their relevance to endometriosis pathophysioloy.
    The corresponding author for this study is Y Sakamoto, Department of Obstetrics and Gynecology, Tottori University School of Medicine, Yonago 683-8504, Japan.

    E-mail sakayasu@grape.med.tottori-u.ac.jp
    Key points reported in this study include:
    GnRHa treatment of endometriosis patients attenuates the expression of IL-8 by reducing TNFalpha-induced NF-kappa B activation in endometriotic stromal cells.

  1. In Dr Aboulghar’s case-controlled study the researchers demonstrated that the outcome of IVF in stage IV endometriosis with previous surgery was significantly lower compared with an age-matched group of tubal factor infertility.

    It is important to note that the cycle cancellation occurred in 29.7% of patients with previous surgical treatment for endometriosis, thus proving the poor response to gonadotrophin and the risk of “excessive surgery”.
    Of course in some condition adhesions can completely encapsulate the ovary with fibriotic tissue and provoke the poor response. Nevertheless, in the majority of cases, the poor response is due to the ovary surgery itself. It is mandatory to recommend gynecologists take precautions during laparoscopic ovarian surgery for endometrioma in order not to remove normal residual ovarian tissue.

NIH Grant News

Dr Robert Schenken, Professor and Chair of Obstetrics and Gynecology, University of Texas, San Antonio, and his co-investigator Dr Craig Witz, Associate Professor of Obstetrics and Gynecology and Chief of the Division of Reproductive Endocrinology and Infertility, have been awarded a $894,000 grant by the National Institutes of Health. The grant is to fund research to pinpoint the exact cause of endometriosis. Dr Schenken and Dr Witz are examining factors that lead to initiation of the earliest endometriosis lesions.
Specifically they are investigating CD44, which is a protein that is expressed on many different cell types, including endometrial cells. If the researchers can determine the specific factors involved in CD44, it may be possible to develop new medical approaches to prevent endometrial cells from attaching. The study began in April 2003 and will last for four years. Drs. Schenken and Witz have also produced an award-winning video on the topic.

THE OXEGENE STUDY is based at the University of Oxford and is part of the International Endogene Study, a world-wide collaboration which aims to find genes responsible for causing endometriosis. The study was established in 2001 and is expected to take at least five years. It has recruited over 1,300 families in which at least two sisters are affected with endometriosis. The Australian Gene CRC study is being led by Professor Nick Martin and Dr Susan Treloar at the Queensland Institute of Medical Research. The UK study is being led by Dr Stephen Kennedy, Professor David Barlow and Dr Helen Mardon from the Nuffield Department of Obstetrics and Gynecology at the University of Oxford. The two research institutes' commercial partners are Oxagen Ltd and Cerylid Biosciences Ltd.

The Endometriosis Association Open Research Fund announces that it is now accepting proposals for grants. The Fund was instituted to support new investigators and develop new ideas. Five to ten grants of $25,000-$50,000 are available. Areas of particular interest to the association are:

  • teen and adolescent endometriosis
  • interrelationships of endometriosis with other diseases
  • effects of exposure to hormonally active compounds

Guidelines can be obtained from The Endometriosis Association, 8585 North 76th Place, Milwaukee, WI 53223, USA. Fax (414) 355-6065. Also check the association’s web site at: www.endometriosisassn.org/news.

What’s Next

In the Fall issue of the WES newsletter (on line in September) Dr Rodolphe Maheux will review the MetrioTest, a minimally invasive procedure designed to diagnose endometriosis without laparoscopy. It was developed by Procrea Biosciences, Mount Royal, Quebec, Canada.

Spring issue of the WES e-newsletter was prepared by Gillian Hobbs in conjunction with Familles PCO

Past Society Newsletters

Spring 2003
 Fall/Winter 2002
 April 2001
 September 2000
 Fall 1999
 
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