Potential involvement of iron in the pathogenesis of peritoneal endometriosis

Journal of the World Endometriosis Society

Defrère S, Van Langendonckt A, González-Ramos R, Vaesen S, Jouret M, Lousse J-C, Donnez J
Department of Gynaecology, Université Catholique de Louvain, Bruxelles, Belgium

December 2006

Despite an increasing number of studies on endometriosis, its aetiology remains elusive, partly due to its multi-factorial characteristics. Indeed, a growing body of evidence suggests that a combination of genetic, hormonal, environmental, immunological and anatomical factors may play a role in the pathogenesis of this disorder (Giudice and Kao, 2004).

Our hypothesis is that iron may be involved in the pathogenesis of endometriosis.Iron overload in endometriosis patients

Several studies have demonstrated the presence of iron overload in the different compartments of the peritoneal cavity of endometriosis patients (peritoneal fluid, ectopic endometrial tissue, peritoneum adjacent to lesions and macrophages) (Van Langendonckt et al., 2002b, c). In the peritoneum and stroma of endometriotic lesions, cytologic and histochemical data revealed the presence of iron conglomerates (Moen and Halvorsen, 1992; Petrozza et al., 1993; Van Langendonckt et al., 2002c) and macrophages heavily laden with ferric pigment (Gaulier et al., 1983; Stowell et al., 1997). In endometriotic cysts too, iron concentrations in cystic fluid were shown to be an indicator of endometriosis (Sugimura et al., 1992; Takahashi et al., 1996; Iizuka et al., 1998). In the peritoneal fluid of patients with endometriosis, higher levels of iron were detected (Arumugam, 1994; Arumugam and Yip, 1995; Van Langendonckt et al. 2002c; Polak et al., 2006).

Origin of iron
A potential source of iron in body fluids is haemoglobin. In case of endometriosis, the iron could originate from lysis of erythrocytes carried into the pelvic cavity by retrograde menstruation or hemorrhaging foci of ectopic endometrium (Van Langendonckt et al., 2004).

Retrograde menstruation, transporting menstrual reflux through the fallopian tubes into the peritoneal cavity and preserving body iron content in women, is a common physiologic event in all menstruating women with patent tubes (Halme et al., 1984) and an essential step in the pathogenesis of peritoneal endometriosis (Sampson, 1927). However, this phenomenon is often amplified in endometriosis patients. Indeed, menstruation is often longer and heavier in women with endometriosis (Sanfilippo et al., 1986; Darrow et al., 1993; Vercellini et al., 1997; Vinatier et al., 2001) and cycles tend to be shorter (Arumugam and Lim, 1997). Moreover, increased menstrual reflux may be due to certain anatomical dispositions often encountered in endometriosis patients (Sanfilippo et al., 1986; Salamanca and Beltran, 1995; Barbieri, 1998; Vinatier et al., 2001).

While red blood cells are frequently present in the peritoneal fluid of most women, increased concentrations of erythrocytes have been reported in the peritoneal cavity of women with endometriosis during menstruation (D’Hooghe and Debrock, 2002). Halme et al. (1984) demonstrated that women with endometriosis have a greater number of erythrocytes, even during the non-menstrual phase, suggesting that processes other than menstrual reflux, such as lesion bleeding (which is not under hormonal control), may contribute to the accumulation of erythrocytes in peritoneal fluid (Van Langendonckt et al., 2002).

Iron metabolism in the pelvic cavity in case of endometriosis

Our studies, mimicking conditions of retrograde menstrual discharge, allowed us to gather further data on the metabolism of iron in the pelvic cavity in the context of endometriosis pathology (see Figure 1). Our work clearly suggests that peritoneal iron overload encountered in the different compartments of the peritoneal cavity (lesions, peritoneal fluid and peritoneal macrophages) of endometriosis patients may well originate from the lysis of erythrocytes, which have been carried into the pelvic cavity by retrograde menstruation or hemorrhaging foci of ectopic endometrium (Van Langendonckt et al., 2004; Defrère et al., 2006).

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Author: Leslie Carol Botha

Author, publisher, radio talk show host and internationally recognized expert on women's hormone cycles. Social/political activist on Gardasil the HPV vaccine for adolescent girls. Co-author of "Understanding Your Mood, Mind and Hormone Cycle." Honorary advisory board member for the Foundation for the Study of Cycles and member of the Society for Menstrual Cycle Research.