What is the role of immunologic dysfunction in the etiology of endometriosis?

Updated: May 10, 2021
  • Author: G Willy Davila, MD; Chief Editor: Michel E Rivlin, MD  more...
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Answer

Relatively recent research has suggested involvement of the immune system in the pathogenesis of endometriosis. An altered immune response to the displaced endometrial tissue has been shown to play an important role as well. Women with this disorder appear to exhibit increased humoral immune responsiveness and macrophage activation while showing diminished cell-mediated immunity with decreased T-cell and natural killer cell responsiveness. Humoral antibodies to endometrial tissue have also been found in sera of women with endometriosis. [15]

Intriguing nonhuman primate studies have demonstrated a strong association between dioxane exposure and the development of endometriosis, implying further that dysfunction of the immune system may contribute to this disease. However, epidemiologic investigations have not been able to confirm this association in humans.

Studies in recent years have focused on assessing the differences between eutopic endometrium and endometriosis. In endometriosis, an aberrantly expressed factor SF-1 activates the expression of the enzyme aromatase, which converts C19 steroids to estrogens. Consequently, estrogen increases the synthesis of prostaglandin E2, which exerts a positive feedback effect, resulting in increased aromatase activity. Additionally, endometriotic tissue is deficient in the enzyme 17-beta hydroxy steroid dehydrogenase type 2, which converts E2 in eutopic endometrium to the less potent E1 under the direction of progestins.

One study found a higher number of endometriomas, more bilateral disease, and a higher incidence of significant pain in women with aromatase positive disease. [16] However, other studies have shown increased cyclooxygenase-2 (COX-2) expression in the stromal cells [17] and aberrant aromatase expression [18] in eutopic endometrium of women with endometriosis.

Although successful treatment has been described with the aromatase inhibitor anastrozole in women with severe postmenopausal endometriosis, [19] more recent studies have also shown it to be effective in cases of severe endometriosis in premenopausal women. [20, 21] Additional data are needed before recommending this as primary treatment.


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