Sex hormones, body mass index, and related comorbidities associated with developing Sjögren’s disease: a nested case–control study

Sjögren's disease (SjD), a highly female predominant systemic autoimmune disease, peaks in perimenopause. Prior studies lack details on timing or type of sex hormone exposure. We examined SjD risk using endogenous and exogenous hormone exposure and related comorbidities.We performed a retrospective case-control study of adult women, nested within a population cohort. Cases had SjD diagnosed by a rheumatology provider or two SjD diagnoses from a non-rheumatology provider with a positive anti-SSA antibody or salivary gland biopsy. Cases were age-matched to three SjD-free controls. We calculated modified composite estrogen scores (mCES) and collected demographics, comorbidities, and endogenous and exogenous hormone exposures. Risk ratios were adjusted for demographics.Of 546 SjD cases and 1637 age-matched controls, mCES was not significantly associated with SjD in adjusted models. The top individual hormone exposures associated with SjD included estrogen replacement therapy (ERT; RR 1.78 [95% CI 1.47-2.14]), polycystic ovarian syndrome (1.65 [1.28-2.12]), and hysterectomy without bilateral oophorectomy (1.51 [1.13-2.03]). We identified comorbidities preceding SjD including fibromyalgia, pulmonary disease, diabetes, lymphoma, osteoporosis, peripheral vascular disease, and renal disease. Taking comorbidities into account, we developed a predictive model for SjD that included fibromyalgia (2.50 [1.93-3.25]), osteoporosis (1.84 [1.27-2.66]), hormone replacement therapy (HRT) (1.61 [1.22-2.12]), diabetes (0.27 [0.13-0.50]), and body mass index (BMI) (0.97 [0.95-0.99]).We report a novel algorithm to improve identifying patients at risk for SjD and describe sex hormone association with SjD. Finally, we report new comorbidities associated with SjD decrease, BMI and diabetes, and increase, lymphoma and osteoporosis.. Key Points •Given female predominance and typical perimenopausal onset, sex hormones should be considered when studying comorbidities in Sjögren's disease. •The top exposures associated with developing Sjögren's disease included fibromyalgia, osteoporosis, and use of hormone replacement therapy. Possible protective factors included prior diabetes and higher body mass index. •We used our newly identified exposures to generate a predictive algorithm, which has potential to improve diagnosis and pathogenic insights into Sjögren's disease.