Endometriosis: interaction of immune and endocrine systems

Endometriosis is a common gynecologic disorder characterized by the presence of endometrial tissue outside the uterine cavity. Although no single theory can explain all cases of endometriosis, the most commonly accepted theory is Sampson's theory of retrograde menstruation. Retrograde menstruation occurs in 76 to 90% of women. The much lower prevalence of endometriosis suggests that additional factors determine susceptibility to endometriosis. Endometriosis is associated with changes in both cell-mediated and humoral immunity. Impaired natural killer cell activity resulting in inadequate removal of refluxed menstrual debris may play a role in the development of endometriotic implants. Moreover, although the peritoneal fluid of women with endometriosis contains increased numbers of immune cells, these seem to facilitate rather than inhibit the development of endometriosis. Macrophages that would be expected to clear endometrial cells from the peritoneal cavity appear to enhance their proliferation by secreting growth factors and cytokines. Although it is unclear whether these immunologic alterations induce endometriosis or are a consequence of its presence, they appear to play an important role in allowing endometriosis implants to persist and progress and contribute to the development of associated infertility and pelvic pain. Danazol and gonadotropin-releasing hormone (GnRH) agonists are commonly used for the medical treatment of endometriosis. These medications seem to down-regulate cellular and humoral immune responses concomitant with their effect on endometriotic implants. Immunomodulatory effects of danazol and GnRH agonists are likely to contribute to the observed clinical improvement associated with their use.