**7. Acknowledgement**

We thank Dr. Gustavo Leirós for providing technical assistance in designing figures.

#### **8. References**

124 Endometriosis - Basic Concepts and Current Research Trends

decreased in the peritoneal fluid of mice treated with letrozole but not with anastrozole

Much research has been done evaluating the effects of inhibiting COXs activity regarding the development of endometriosis with *in vivo* and *in vitro* approaches. Celecoxib has been shown to have anti-proliferative and pro-apoptotic effects over endometrial epithelial cells in culture obtained from biopsies of women with and without endometriosis; it was also effective in diminishing COX-2 expression, reducing the synthesis of VEGF and PGE2 (Olivares et al., 2008). Similar results had previously been achieved in various cancer models (Basu et al., 2005; Chun & Surh, 2004). Given that the endometrial cells at the ectopic site have a very similar behaviour to neoplasic cells; it is not surprising that treatments aim at

There is one very complete work from Efstathiou and coworkers where they compared seven different selective (rofecoxib and celecoxib) and non-selective (aspirin, ibuprofen, indomethacin, naproxen and sulindac) NSAIDs on the establishment and development of endometriosis in a mouse model (Efstathiou et al., 2005). In this work, celecoxib given orally twice daily and indomethacin administered subcutaneously daily for four weeks, were both effective in significantly diminishing the percentage of established lesions compared to the control group. All the NSAIDs evaluated in the same study, except for aspirin, significantly inhibited the growth of the established lesions compared to the control group (Efstathiou et al., 2005). A study in a rat model of endometriosis, evaluated the effect of parecoxib, another selective COX-2 inhibitor, and showed not only a significant reduction in lesion size, but also, a significant inhibition on the expression of VEGF, its receptor Flk-1 and COX-2 compared to the untreated group with endometriosis (Machado et al., 2010). Machado and coworkers also observed a significant reduction of the levels of PGE2 in endometriotic homogeneized tissue treated with parecoxib compared to the untreated group (Machado et

More recently a new approach targeting more than one molecule to prevent the development of the disease has gained importance. Promising results were achieved firstly in cancer models, which targeted COX-2 and PPARγ. This combinational therapy resulted in the inhibition of cell proliferation and apoptosis enhancement *in vitro* and increased overall survival rate *in vivo* (Mustafa & Kruger, 2008; Sun et al., 2009). When celecoxib was combined with rosiglitazone, a PPARγ agonist, for the treatment of surgically induced endometriosis in a mouse model, a reduced number of established lesions was observed as well as the volume of established ones; also induction of apoptosis and reduction of the cell

Reducing PGE2 concentration in the peritoneal environment would not only be relieving the pain caused by the disease but would also be affecting its development. This is one of the main goals of endometriosis treatments; now it is time to decide whether the drugs used to

In conclusion, PGs play a substantial role in the physiological and pathological processes in the reproductive system. PGs are known to be involved in the initiation of the phsysiological implantation and decidualization. Also, COX-2 and PGE2 were seen to be

proliferation rate and vascularization was achieved (Olivares et al., 2011).

achieve these results are the appropriate ones to manage with this disease.

(Bilotas et al., 2010).

the same targets.

al., 2010).

**6. Conclusion** 


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series prostaglandin receptor signalling are enhanced in heavy menstruation.


**8** 

*India* 

 **Genetic Polymorphisms and Molecular** 

Endometriosis occupies a unique position in medicine. The natural history of the disease is uncertain, its precise etiology is unknown, the clinical presentation is inconsistent, diagnosis is difficult and can be confirmed only by invasive procedures, and the treatment is poorly

It is one of the commonest benign gynaecological conditions affecting 15 – 25% of women in the reproductive age group. Yet, it displays features similar to malignancy, ranging from neo-vascularisation to local invasion and aggressive spread to distant organs (metastasis). The most widely accepted theory to explain endometriosis is that viable endometrial cells reach the peritoneal cavity through retrograde menstruation along the fallopian tubes. Some of the cells then adhere to the peritoneal surface and proliferate in response to the ovarian hormones. However, it is well established that menstrual debris is present in the peritoneal cavity of 90% of menstruating women, suggesting that endometrial cells from only 'some women' are capable of establishing ectopic endometrial implants. Why does this happen in only 'some (10-15%) women'? There are several possible explanations for disease susceptibility, including differences in genetic predisposition (Bischoff FZ et al, 2000), increased exposure to menstrual debris, abnormal eutopic endometrium, altered peritoneal environment, reduced immune-surveillance (Sinaii N et al, 2002), and increased angiogenic

Endometriosis, the name by itself implies an endometrial pathology but this concept has long been disputed by Thomas and Prentice in 1992. The acceptance of an endometrial origin poses the question of whether endometrium that is able to proliferate and implant at ectopic sites is in some way abnormal. The commonest site for endometriosis is the pelvis. Endometrium reaches the pelvis most commonly by retrograde menstruation which is now accepted to be an almost ubiquitous event. Endometriosis is more common in women whose normal menstrual egress is occluded by genital tract anomalies, women with an early menarche, short menstrual cycles and prolonged menses. All these factors suggest that peritoneal soiling is important but if retrograde menstruation is ubiquitous then why do not all women have endometriosis? The truth is that the presence of ectopic endometrium within the peritoneal cavity is probably universal but the association of ectopic

**1. Introduction** 

standardized.

capacity (Absenger Y et al, 2004).

**Pathogenesis of Endometriosis** 

Vijayalakshmi Kodati and Q. Hasan

*Vasavi Medical & Research Centre,* 

