Lower estrogen exposure linked to increased risk for Sjögren's syndrome in women
Primary Sjögren’s syndrome in women is associated with lower estrogen exposure and cumulative menstrual cycling, according to data published in Arthritis Care & Research.
“Sjögren’s syndrome is the most female-predominant systemic autoimmune disease with typical onset around the time of menopause,” Sara S. McCoy, MD, of the University of Wisconsin School of Medicine and Public Health, told Healio Rheumatology. “The female predominance and timing of Sjögren’s syndrome indicated a likely role for sex hormones in Sjogren’s pathogenesis.”
To evaluate whether estrogen exposure — determined by age at menarche, age at menopause, hormone use, hysterectomy and parity — impacts the development of primary Sjögren’s syndrome, McCoy and colleagues conducted a case-control study of participants from the Sjögren’s International Collaborative Clinical Alliance (SICCA) registry. According to the researchers, the SICCA is an NIH-funded international registry that enrolled women aged 21 years and older with suspected or confirmed primary Sjögren’s syndrome from 2003 to 2012.
McCoy and colleagues included 1,320 SICCA participants with primary Sjögren’s syndrome, based on EULAR 2016 criteria, and 1,360 individuals with symptoms but no key features of the disease, with the latter group acting as the control. The researchers calculated participants’ estrogen scores based on early menarche, defined as 10 year or younger; late menopause, defined as older than 53 years; having more than three pregnancies; hysterectomy; and the use of hormone therapy. In addition, they calculated cumulative menstrual cycling by taking the number of years menstruating and subtracting the time while pregnant.
According to the researchers, there was an inverse trend between primary Sjögren’s syndrome and composite estrogen scores, after adjusting for age, recruitment site, ethnicity, education, employment status and smoking. Odds ratios for the SICCA control group were 0.8 for composite estrogen score 1 (95% CI, 0.67-0.99), 0.7 for composite estrogen score 2 (95% CI, 0.57-0.97) and 0.5 for composite estrogen score 3 (95% CI, 0.3-0.86).
In addition, at the highest level of cumulative menstrual cycling among patients who were postmenopausal and had primary Sjögren’s syndrome, the researchers noted a 24% reduction in cumulative sex hormone exposure compared with the control participants.
“This cross-sectional study, utilizing the Sjogren’s International Collaborative Clinical Alliance registry, is the largest to date studying sex hormone exposure and Sjögren’s syndrome,” McCoy said. “We found that progressive increase of estrogen exposure leads to a stepwise reduction in the odds of Sjogren’s syndrome.”
“This study highlights a role of estrogen balance in the pathogenesis of Sjögren’s syndrome and indicates that greater lifetime cumulative estrogen exposure might be protective against Sjögren’s syndrome,” she added. “Estrogen exposure is likely to influence Sjögren’s syndrome development, however the exact role of estrogen in the pathogenesis of Sjögren’s syndrome remains to be defined.” – by Jason Laday
Disclosure: The researchers report no relevant financial disclosures.