Non-Steroidal Targets in the Diagnosis and Treatment of Endometriosis

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Abstract:

Endometriosis, a chronic gynecologic disease frequently resulting in chronic pelvic pain, severe dysmenorrhoea, and subfertility, is defined as the presence of endometrial tissue at extrauterine locations, most commonly on the peritoneum and ovaries. Conclusive diagnosis requires laparoscopic surgery followed by histological confirmation. The treatment options -at present- are limited to hormonal therapies and/or surgical ablation of the lesions, and are characterized by high recurrence rates, significant side-effects and limited duration of administration.

The pathogenesis of endometriosis is still unclear and numerous immunological and inflammatory factors have been suggested to be involved in the development of the disease, including interleukin (IL)-1, IL-2, IL-6, IL-8, IL-12, tumour necrosis factor -alpha (TNF-α), regulated on activation, normal T-Cell expressed and secreted (RANTES) and its receptor cognate chemokine receptor 1 (CCR1), peroxisome proliferator activated receptors (PPARs), matrix metalloproteinases (MMPs) and cyclooxygenase (COX). Another crucial mechanism in endometriosis is the vascularisation of the endometriotic lesions, with a key role for vascular endothelial growth factor (VEGF). Recently, protease activated receptors (PARs), mitogen-activated protein kinases (MAPKs) and tyrosine kinases have also been associated with the pathophysiology of endometriosis.

The aim of this article is to discuss molecules that have recently been found to have connections with the pathogenesis of endometriosis, as potential targets to develop new methods for noninvasive diagnosis and for novel medical management of this disease. This review also critically addresses how these molecules can be tested in basic, preclinical and clinical research, the status of this research and the importance of potential side effects.

Keywords: COX-2 inhibitors; Endometriosis; TNF-alpha inhibitors; anti-angiogenic therapies; diagnosis; non-steroidal targets; steroid hormone; treatment

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986708784049595

Affiliations: Director Leuven University Fertility Center, Department of Obstetrics & Gynaecology, University Hospital Gasthuisberg,Herestraat 49, B-3000 Leuven, Belgium.

Publication date: April 1, 2008

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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