Reproductive and hormonal risk factors for sarcoidosis: a nested case–control study

Abstract

Background: Sarcoidosis incidence peaks in females around the fifth decade of life, which coincides with menopause, suggesting hormonal factors play a role in disease development. We investigated whether longer exposure to reproductive and hormonal factors is associated with reduced sarcoidosis risk. Methods: We conducted a matched case–control study nested within the Mammography Screening Project. Incident sarcoidosis cases were identified via medical records and matched to controls on birth and questionnaire date (1:4). Information on hormonal factors was obtained through questionnaires prior to sarcoidosis diagnosis. Multilevel modelling was used to estimate adjusted odds ratios with 95% credible intervals (OR; 95% CI). Results: In total, 32 sarcoidosis cases and 124 controls were included. Higher sarcoidosis odds were associated with older age at menarche (OR 1.19: 95% CI 0.92–1.55), natural menopause versus non-natural (OR 1.53: 95% CI 0.80–2.93), later age at first pregnancy (OR 1.11: 95% CI 0.76–1.63) and ever hormone replacement therapy (HRT) use (OR 1.40: 95% CI 0.76–2.59). Lower odds were associated with older age at menopause (OR 0.90: 95% CI 0.52–1.55), longer duration of oral contraceptive use (OR 0.70: 95% CI 0.45–1.07), longer duration of HRT use (OR 0.61: 95% CI 0.22–1.70), ever local estrogen therapy (LET) use (OR 0.83: 95% CI 0.34–2.04) and longer duration of LET use (OR 0.78: 95% CI 0.21–2.81). However, the CIs could not rule out null associations. Conclusion: Given the inconsistency and modest magnitude in our estimates, and that the 95% credible intervals included one, it still remains unclear whether longer estrogen exposure is associated with reduced sarcoidosis risk.