title: Endogenous female reproductive hormones and the risk of amyotrophic lateral sclerosis.
abstract: The pathogenesis of amyotrophic lateral sclerosis (ALS) is considered to be multifactorial. Several epidemiological studies showed a lower incidence of ALS in women than in men. This suggests a possible protective effect of female reproductive hormones. The aim of this study was to investigate the association between female reproductive hormones and ALS. We performed a population-based, case-control study in the Netherlands between 1st January 2006 and 1st December 2009. Only women with a natural menopause were included in the analysis. A total of 209 (85 %) of 246 female patients and 672 (93 %) of 719 controls returned a questionnaire on reproductive history to calculate the reproductive time-span and lifetime endogenous estrogen exposure (calculated by subtracting the duration of pregnancies and of oral contraceptive use, and the number of post-ovulatory weeks from the reproductive time-span). 131 (63 %) patients and 430 (64 %) age-matched, population-based controls had experienced a natural menopause. Multivariate analysis showed that increasing the reproductive time-span by a year decreases the risk of ALS with an OR of 0.95 (p = 0.005). Each year longer reproductive time-span [HR 0.90 (p = 0.01)] and lifetime endogenous estrogen exposure [HR 0.96 (p = 0.025)] were associated with a longer survival of ALS patients. The positive association of a longer reproductive time-span and susceptibility and survival of ALS might imply that longer exposure to female reproductive hormones has a neuroprotective effect on motor neurons.
authors.affiliation: Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands. sjong@umcutrecht.nl
authors.forename: Sonja
authors.initials: S
authors.lastname: de Jong
authors.forename: Mark
authors.initials: M
authors.lastname: Huisman
authors.forename: Nadia
authors.initials: N
authors.lastname: Sutedja
authors.forename: Anneke
authors.initials: A
authors.lastname: van der Kooi
authors.forename: Marianne
authors.initials: M
authors.lastname: de Visser
authors.forename: Jurgen
authors.initials: J
authors.lastname: Schelhaas
authors.forename: Yvonne
authors.initials: Y
authors.lastname: van der Schouw
authors.forename: Jan
authors.initials: J
authors.lastname: Veldink
authors.forename: Leonard
authors.initials: L
authors.lastname: van den Berg
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000453:epidemiology* / Q000378:metabolism* / Q000401:mortality; D016022:Case-Control Studies; D018672:Community Health Planning; D003276:Contraceptives, Oral / Q000009:adverse effects; D004967:Estrogens / Q000008:administration & dosage; D005260:Female; D012739:Gonadal Steroid Hormones / Q000378:metabolism*; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D017584:Reproductive History; D012307:Risk Factors; D011795:Surveys and Questionnaires
chemical_list: D003276:Contraceptives, Oral; D004967:Estrogens; D012739:Gonadal Steroid Hormones