Abstract
BackgroundSarcoidosis 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.MethodsWe 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).ResultsIn 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.ConclusionGiven 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.
Highlights
Sarcoidosis incidence peaks in females around the fifth decade of life, which coincides with menopause, suggesting hormonal factors play a role in disease development
The results from this nested case–control study in women in Västerbotten County indicate that older age at menopause, longer duration of Oral contraceptives (OC), hormone replacement therapy (HRT) or local estrogen therapy (LET) use and ever use of LET may be associated with reduced sarcoidosis risk
Evidence indicates that estrogens inhibit the production of Th1 proinflammatory cytokines, whereas they stimulate the production of Th2 anti-inflammatory cytokines [3, Table 2 Characteristics of sarcoidosis cases and controls included from the Mammography Screening Project, 1995–2006
Summary
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. In Sweden, 1100 new cases are diagnosed every year in adults, with a peak incidence in males between ages 30–50 years, and in females between 50 and 60 years [2] These two different peaks suggest that sex-specific factors play a role in disease onset. We are aware of only one epidemiological study that has investigated the association between reproductive and hormonal factors and risk of incident sarcoidosis [6]. A higher age at menopause, later age at first birth and having a more recent birth (indicators of longer exposure to estrogen) were associated with a lower risk of sarcoidosis in black women from the United States [6]. Further investigation is needed to determine if estrogens are etiologically linked to sarcoidosis
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