Endometriosis and rheumatoid arthritis

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A couple of recent studies have indicated that those with endometriosis might have a higher risk of rheumatoid arthritis (RA) (Xue et al., 2021; Chen et al., 2021). One study even suggested “in the clinical management of patients with RA, rheumatologists should be especially mindful of the possibility of underlying endometriosis” (Xue et al., 2021). This is echoed by Shigesi et al. (2019) who states that “the observed associations between endometriosis and autoimmune diseases suggest that clinicians need to be aware of the potential coexistence of endometriosis and autoimmune diseases when either is diagnosed.”

Harris et al. (2016) cautions that “it remains to be understood whether and how endometriosis itself, or hysterectomy or other factors associated with endometriosis, is related to risk of…RA.” Alpízar-Rodríguez  et al. (2017) found that “laparoscopically confirmed endometriosis was found to be significantly associated with subsequent RA…However, this association was attenuated after adjustment by hysterectomy and oophorectomy, suggesting a possible confounding effect by surgically induced menopause.” This effect of menopause on RA has been noted before- “the peak incidence in females coincides with menopause when the ovarian production of sex hormones drops markedly” (Islander et al., 2011). The effect of female hormones has been noted to influence RA symptoms as well. For instance, one study noted “decreased joint pain during times when estrogen and progesterone levels are high” (Costenbader et al., 2008). Estrogen can have “both stimulatory and inhibitory effects on the immune system” and it has been noted that “the rapid decline in ovarian function and in circulating oestrogens at menopause is associated with spontaneous increases in pro-inflammatory cytokines” (Alpízar-Rodríguez et al., 2017). Part of the effect may be seen in the estrogen receptors, with an increase of ER-β over ER-α receptors in RA synovial tissue (Alpízar-Rodríguez et al., 2017). This increased expression of ER-β receptors is also seen in endometriosis lesions (which can cause increased inflammation) (Bulun et al., 2012).  

References

Alpízar-Rodríguez, D., Pluchino, N., Canny, G., Gabay, C., & Finckh, A. (2017). The role of female hormonal factors in the development of rheumatoid arthritis. Rheumatology56(8), 1254-1263. https://doi.org/10.1093/rheumatology/kew318

Bulun, S. E., Monsavais, D., Pavone, M. E., Dyson, M., Xue, Q., Attar, E., … & Su, E. J. (2012, January). Role of estrogen receptor-β in endometriosis. In Seminars in reproductive medicine (Vol. 30, No. 01, pp. 39-45). Thieme Medical Publishers. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4034571/…

Chen, S. F., Yang, Y. C., Hsu, C. Y., & Shen, Y. C. (2021). Risk of Rheumatoid Arthritis in Patients with Endometriosis: A Nationwide Population-Based Cohort Study. Journal of Women’s Health30(8), 1160-1164. https://doi.org/10.1089/jwh.2020.8431

Costenbader, K. H., & Manson, J. E. (2008). Do female hormones affect the onset or severity of rheumatoid arthritis?. Arthritis Care & Research, 59(3), 299-301. https://onlinelibrary.wiley.com/doi/epdf/10.1002/art.23324

Harris, H. R., Costenbader, K. H., Mu, F., Kvaskoff, M., Malspeis, S., Karlson, E. W., & Missmer, S. A. (2016). Endometriosis and the risks of systemic lupus erythematosus and rheumatoid arthritis in the Nurses’ Health Study II. Annals of the rheumatic diseases75(7), 1279-1284. http://dx.doi.org/10.1136/annrheumdis-2015-207704

Islander, U., Jochems, C., Lagerquist, M. K., Forsblad-d’Elia, H., & Carlsten, H. (2011). Estrogens in rheumatoid arthritis; the immune system and bone. Molecular and cellular endocrinology, 335(1), 14-29. DOI: 10.1016/j.mce.2010.05.018

Xue, Y. H., You, L. T., Ting, H. F., Chen, Y. W., Sheng, Z. Y., Xie, Y. D., … & Wei, J. C. C. (2021). Increased risk of rheumatoid arthritis among patients with endometriosis: a nationwide population-based cohort study. Rheumatology60(7), 3326-3333. https://doi.org/10.1093/rheumatology/keaa784

Shigesi, N., Kvaskoff, M., Kirtley, S., Feng, Q., Fang, H., Knight, J. C., … & Becker, C. M. (2019). The association between endometriosis and autoimmune diseases: a systematic review and meta-analysis. Human reproduction update25(4), 486-503. https://doi.org/10.1093/humupd/dmz014