Cancer Morbidity in Rheumatoid Arthritis: Role of Estrogen Metabolites

Abstract

Estrogen metabolites have been implicated in rheumatoid arthritis (RA) and cancer, although the mechanism remains unestablished. Some estrogen metabolites, which are used for the assessment of cancer risk, play an important role in RA. The pathways by which malignancies associated with RA remain elusive. Possible mechanism involves enzymatic or nonenzymatic oxidation of estrogen into catecholestrogen metabolites through semiquinone and quinone redox cycle to produce free radicals that can cause DNA modifications. Modifications of DNA alter its immunogenicity and trigger various immune responses leading to elevated levels of cancer and RA antibodies. However, the role of different estrogen metabolites as a mediator of immune response cannot be ruled out in various immune-related diseases.

Autoimmune diseases and breast cancer risk by tumor hormone‐receptor status among elderly women

“…In spite of the female excess of rheumatoid arthritis, the peak incidence in women occurs at the time of menopause, which is associated with decreased production of estrogens; in many women with rheumatoid arthritis, disease activity diminishes during pregnancy, when levels of female sex hormones are high. Furthermore, there is some evidence that menopausal hormone therapy decreases disease activity in postmenopausal rheumatoid arthritis patients . Thus, lower hormone levels might be associated with increased risk of rheumatoid arthritis but decreased risk of hormone sensitive breast cancers.…”

“…Furthermore, there is some evidence that menopausal hormone therapy decreases disease activity in postmenopausal rheumatoid arthritis patients. 22,23 Thus, lower hormone levels might be associated with increased risk of rheumatoid arthritis but decreased risk of hormone sensitive breast cancers. The relationships between pernicious anemia and psoriasis and hormonal factors are unclear.…”

Prevalence of Cancer in Rheumatoid Arthritis: Epidemiological Study Based on the National Health and Nutrition Examination Survey (NHANES)

“…Some studies have also shown that estrogen metabolites can modulate the immune response and play a role. Estrogen metabolites, as reactive oxygen species, could be causing DNA damage, which can lead to elevated levels of RA and cancer autoantibodies [20].…”

Roundoc Rx: Rheumatoid Arthritis—A Functional Medicine Approach

“…In addition, the oxidized quinone metabolite of 4-OHE forms depurinating adducts with DNA, which potentially stimulates autoantibody production by B-lymphocytes. 22 For all of these reasons, I frequently measure reproductive hormones and estrogen metabolites in patients with RA.…”