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

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Abstract

Objective

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.

Methods

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.

Results

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]).

Conclusions

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.

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Acknowledgements

We thank Dr. Aleksander Stanic-Kostic for his expertise and intellectual insight.

Funding

The project described was supported by the Clinical and Translational Science Award (CTSA) program, through the NIH National Center for Advancing Translational Sciences (NCATS), grant UL1TR002373 and KL2TR002374. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

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Author notes

  1. Jeffrey J. VanWormer and Christie  M. Bartels contributed equally as co-last authors.

Authors and Affiliations

  1. Department of Medicine, School of Medicine and Public Health, University of Wisconsin, 1685 Highland Avenue, Madison, WI, 53705-2281, USA

    Sara S. McCoy & Christie M. Bartels

  2. Department of Biostatistics and Medical Informatics, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA

    Scott Hetzel

  3. Department of Population Sciences, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA

    Scott Hetzel

  4. Center for Clinical Epidemiology and Population Health, Marshfield Clinic Research Institute, Marshfield, WI, USA

    Jeffrey J. VanWormer

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  1. Sara S. McCoy
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Correspondence to Sara S. McCoy.

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According to the Declaration of Helsinki, all procedures were approved in advance by the MC Institutional Review Board (IRB-20–699) with a waiver of individual informed consent and HIPAA authorization due to the retrospective nature of this medical record study design.

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McCoy, S.S., Hetzel, S., VanWormer, J.J. et al. Sex hormones, body mass index, and related comorbidities associated with developing Sjögren’s disease: a nested case–control study. Clin Rheumatol 41, 3065–3074 (2022). https://doi.org/10.1007/s10067-022-06226-8

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