James P K Rooney1, Anne E Visser2, Fabrizio D'Ovidio2, Roel Vermeulen2, Ettore Beghi2, Adriano Chio2, Jan H Veldink2, Giancarlo Logroscino2, Leonard H van den Berg2, Orla Hardiman. 1. From the Academic Unit of Neurology (J.P.K.R., O.H.), Trinity Biomedical Sciences Institute, Trinity College Dublin, Ireland; Department of Neurology and Neurosurgery (A.E.V., J.H.V., L.H.v.d.B.), Brain Center Rudolf Magnus, University Medical Center Utrecht, the Netherlands; Department of Neuroscience (F.D., A.C.), ALS Centre, University of Torino, Turin, Italy; Institute for Risk Assessment Sciences (R.V.), Department of Environmental Epidemiology, University of Utrecht, the Netherlands; Department of Neurosciences (E.B.), IRCSS, Mario Negri Institute of Pharmacological Research, Milan; and Department of Neuroscience (G.L.), University of Bari, Italy. jrooney@rcsi.ie. 2. From the Academic Unit of Neurology (J.P.K.R., O.H.), Trinity Biomedical Sciences Institute, Trinity College Dublin, Ireland; Department of Neurology and Neurosurgery (A.E.V., J.H.V., L.H.v.d.B.), Brain Center Rudolf Magnus, University Medical Center Utrecht, the Netherlands; Department of Neuroscience (F.D., A.C.), ALS Centre, University of Torino, Turin, Italy; Institute for Risk Assessment Sciences (R.V.), Department of Environmental Epidemiology, University of Utrecht, the Netherlands; Department of Neurosciences (E.B.), IRCSS, Mario Negri Institute of Pharmacological Research, Milan; and Department of Neuroscience (G.L.), University of Bari, Italy.
Abstract
OBJECTIVE: To investigate the role of hormonal risk factors for amyotrophic lateral sclerosis (ALS) among women from 3 European countries. METHODS: ALS cases and matched controls were recruited over 4 years in Ireland, Italy, and the Netherlands. Hormonal exposures, including reproductive history, breastfeeding, contraceptive use, hormonal replacement therapy, and gynecologic surgical history, were recorded with a validated questionnaire. Logistic regression models adjusted for age, education, study site, smoking, alcohol, and physical activity were used to determine the association between female hormones and ALS risk. RESULTS: We included 653 patients and 1,217 controls. Oral contraceptive use was higher among controls (odds ratio [OR] 0.65, 95% confidence interval [CI] 0.51-0.84), and a dose-response effect was apparent. Hormone replacement therapy (HRT) was associated with a reduced risk of ALS only in the Netherlands (OR = 0.57, 95% CI 0.37-0.85). These findings were robust to sensitivity analysis, but there was some heterogeneity across study sites. CONCLUSIONS: This large case-control study across 3 different countries has demonstrated an association between exogenous estrogens and progestogens and reduced odds of ALS in women. These results are at variance with previous findings, which may be partly explained by differential regulatory, social, and cultural attitudes toward pregnancy, birth control, and HRT across the countries included. Our results indicate that hormonal factors may be important etiologic factors in ALS; however, a full understanding requires further investigation.
OBJECTIVE: To investigate the role of hormonal risk factors for amyotrophic lateral sclerosis (ALS) among women from 3 European countries. METHODS: ALS cases and matched controls were recruited over 4 years in Ireland, Italy, and the Netherlands. Hormonal exposures, including reproductive history, breastfeeding, contraceptive use, hormonal replacement therapy, and gynecologic surgical history, were recorded with a validated questionnaire. Logistic regression models adjusted for age, education, study site, smoking, alcohol, and physical activity were used to determine the association between female hormones and ALS risk. RESULTS: We included 653 patients and 1,217 controls. Oral contraceptive use was higher among controls (odds ratio [OR] 0.65, 95% confidence interval [CI] 0.51-0.84), and a dose-response effect was apparent. Hormone replacement therapy (HRT) was associated with a reduced risk of ALS only in the Netherlands (OR = 0.57, 95% CI 0.37-0.85). These findings were robust to sensitivity analysis, but there was some heterogeneity across study sites. CONCLUSIONS: This large case-control study across 3 different countries has demonstrated an association between exogenous estrogens and progestogens and reduced odds of ALS in women. These results are at variance with previous findings, which may be partly explained by differential regulatory, social, and cultural attitudes toward pregnancy, birth control, and HRT across the countries included. Our results indicate that hormonal factors may be important etiologic factors in ALS; however, a full understanding requires further investigation.