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Endometriosis is a puzzling and sometimes debilitating disease that affects millions of women around the world. Women suffering from endometriosis experience a variety of symptoms, with lower abdominal pain being most common. Pain can be especially intense before and during menstrual periods. Some women experience pain throughout the menstrual cycle; some during sex. The disease forces more than 100,000 hysterectomies each year in the United States alone, and the costs of the disease exceed $1 billion annually.

Endometriosis develops when endometrial-like tissue starts growing in places where it shouldn’t be, away from the lining of the uterus, often in the abdominal cavity or pelvic region, but sometimes in lungs or arms, and elsewhere. These tissue growths respond to hormonal signals in the menstrual cycle in the same way that uterine lining does, building up and breaking down each month. But while the uterine lining can be flushed out of the body during menstruation, the tissue remains of endometrial growths have no place to go. Internal bleeding, inflammation and other problems result.

While these facts about endometriosis are clear, the causes of the disease are much more obscure and debated. There are four key parts to the puzzle.

• First, how does endometrial tissue wind up in inappropriate locations? One suggestion is that endometrial cells are transported by reverse flow off blood during menstruation into the abdominal cavity, or through the blood stream and lymphatic system to more remote sites. Another is that cells in the remote locations are transformed from their original condition into endometrial cells. These explanations are not mutually exclusive.
• Second, why doesn’t the immune system prevent endometrial tissue from becoming established and growing? Recent research has revealed that women with endometriosis are also likely to experience an array of immune system problems, suggesting that immune system dysfunction may be the proximal cause of endometriosis. The challenge then is to understand what has happened to the endometriosis victim's immune system.
• Third, what would lead some women to develop severe endometriosis, while others none at all? There appears to be some heriditary component to the risk of endometriosis, possibly involving multiple genes, but environmental factors are also implicated. The most telling evidence on environment comes from animal studies in which dioxin increases the risk of endometriosis in Rhesus monkeys, and also increases the likelihood that endometrial implants will thrive in rodents. Monkeys exposed to radiation also are more likely to develop endometriosis.
• And fourth, what are the patterns of the disease over time? It is widely believed that endometriosis is more common now than mid-20th century, and data also suggest that more cases are now developing earlier in life than before and becoming more severe.

While we still lack scientific certainty about the causes of endometriosis, exposures to environmental factors that undermine the immune system are emerging as one of the most likely causative agents. Both dioxin (and other dioxin-like compounds) and radiation harm immune system action, in monkeys as well as in people. Widespread exposures to dioxins increased during the 20th century, as most likely did endometriosis. Other contaminants also are toxic to the immune system including a variety of pesticides and industrial compounds.