Antioxidant Supplementation Reduces Endometriosis-Related Pelvic Pain in Humans

The pathophysiology of endometriosis and mechanisms responsible for its major symptoms, infertility and chronic pelvic pain, are poorly understood. Several studies have suggested that oxidative stress plays an important role in its pathogenesis. Antioxidants have been shown to alleviate animal model markers of pain. A previous study in women reported that deficient intake of antioxidants (vitamin E, vitamin C, zinc, and selenium) was associated with endometriosis pathology. Another human study found that an antioxidant-rich diet improved antioxidant markers in women with endometriosis. This randomized, placebo-controlled trial investigated whether antioxidant supplementation in women with endometriosis would alleviate chronic pain or decrease inflammatory peritoneal fluid biomarkers of oxidation. Fifty-nine women, aged 19 to 41 years, with chronic pelvic pain and history of endometriosis or infertility, were randomly assigned to receive daily oral doses of 1 of the following regimens: combined vitamin E (1200 IU) and vitamin C (1000 mg) (treatment group, n = 46) or placebo (n = 13) for 8 weeks before surgery. Pain scores were obtained before, during (biweekly), and after treatment. At 8 weeks, the peritoneal fluid was collected and used for measurement of the following inflammatory markers: regulated upon activation, normal T-cell expressed and secreted (RANTES), interleukin 6, and monocyte chemotactic protein 1. Antioxidant treatment reduced chronic pelvic pain scores for everyday pain by 43% compared with baseline (P = 0.0055), whereas there was no change in everyday pain in the placebo (100% of baseline score). In the treatment group, dysmenorrhea (pain associated with menstruation) and dyspareunia (pain with sex) decreased by 37% and 24%, respectively. In the placebo group, dysmenorrhea-associated pain decreased in 4 patients, and there was no change in chronic pain or dyspareunia. Antioxidant treatment reduced levels of peritoneal fluid inflammatory markers (RANTES, P ≤ 0.002), interleukin 6 (P ≤ 0.056), and monocyte chemotactic protein 1 (P ≤ 0.016) compared with the placebo. These findings show that administration of antioxidants to women with endometriosis reduces chronic pelvic pain as well as peritoneal inflammatory markers. These data provide in vivo evidence that endometriosis may be a disease of oxidative stress.