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.
Cytochrome P-450 aromatase is responsible for catalysing the conversion of androstendione into estrone, so its expression in endometriotic tissue could contribute to the development of endometriosis. The aims of this study were, on the one hand, to determine the presence of aromatase in eutopic and ectopic endometrium, healthy peritoneum, myometrium and leiomyomas from patients with (n = 61) and without endometriosis (n = 12) and, on the other hand, to determine the effect of peritoneal fluid (PF), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNFalpha) on aromatase activity from endometriotic stromal cells and subcutaneous adipocytes. After immunohistochemical analysis, aromatase expression was detected in the endometriotic tissue of 61% of patients, whereas the rest of the tissues, as well as those from disease-free women, were negative. Cell cultures were made to determine aromatase activity in endometriotic stromal cells and adipocytes. The addition of PF, TNFalpha and especially IL-6 (P < 0.05) stimulated the basal enzymatic activity observed in both cell types. Our findings confirm the presence of aromatase in endometriosis and probably the existence of a local estrogen production that may be stimulated by some factors such as cytokines present in the PF of these patients. Therefore, the use of aromatase inhibitors combined with immunomodulator agents could be a novel approach to be investigated in future clinical trials.
These results suggest that alteration in the production of cytokines in the PF, especially IL-6, besides contributing to the endometriosis and its evolution, probably increases embryotoxicity. However, no correlation was found between the latter and associated infertility.
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