title: Female hormonal exposures and neuromyelitis optica symptom onset in a multicenter study.
abstract: OBJECTIVE
  To study the association between hormonal exposures and disease onset in a cohort of women with neuromyelitis optica spectrum disorder (NMOSD).
  
  
  METHODS
  Reproductive history and hormone use were assessed using a standardized reproductive survey administered to women with NMOSD (82% aquaporin-4 antibody positive) at 8 clinical centers. Using multivariable regression, we examined the association between reproductive exposures and age at first symptom onset (FS).
  
  
  RESULTS
  Among 217 respondents, the mean age at menarche was 12.8 years (SD 1.7). The mean number of pregnancies was 2.1 (SD 1.6), including 0.3 (SD 0.7) occurring after onset of NMOSD symptoms. In the 117 participants who were postmenopausal at the time of the questionnaire, 70% reported natural menopause (mean age: 48.9 years [SD 3.9]); fewer than 30% reported systemic hormone therapy (HT) use. Mean FS age was 40.1 years (SD 14.2). Ever-use of systemic hormonal contraceptives (HC) was marginally associated with earlier FS (39 vs 43 years,p= 0.05). Because HC use may decrease parity, when we included both variables in the model, the association between HC use and FS age became more significant (estimate = 2.7,p= 0.007). Among postmenopausal participants, 24% reported NMOSD onset within 2 years of (before or after) menopause. Among these participants, there was no association between age at menopause or HT use and age at NMOSD onset.
  
  
  CONCLUSIONS
  Overall, age at NMOSD onset did not show a strong relationship with endogenous hormonal exposures. An earlier onset age did appear to be marginally associated with systemic HC exposure, an association that requires confirmation in future studies.
authors.affiliation: Brigham and Women's Hospital (R.B., T.C.), Boston, MA; Harvard Medical School (R.B., F.J.M., E.C.K., T.C.), Boston, MA; The Walton Centre NHS Foundation Trust (L.E., K.M., A.J.), Liverpool, UK; Washington University School of Medicine (E.A., A.H.C.), St. Louis, MO; Charité-Universitätsmedizin Berlin (N.B., K.R., F.P.), Germany; University of Utah Imaging & Neurosciences Center (M.M.C.), Salt Lake City; Massachusetts General Hospital (F.J.M., S.T., E.C.K.), Boston; Johns Hopkins Medical Institute (M.A.M., M.L.), Baltimore, MD; MS Institute at Shepherd Center (G.B.), Atlanta, GA; Mayo Clinic (B.W.), Rochester, MN; and Mayo Clinic (D.M.W.), Scottsdale, AZ.
authors.forename: Riley
authors.initials: R
authors.lastname: Bove
authors.affiliation: Brigham and Women's Hospital (R.B., T.C.), Boston, MA; Harvard Medical School (R.B., F.J.M., E.C.K., T.C.), Boston, MA; The Walton Centre NHS Foundation Trust (L.E., K.M., A.J.), Liverpool, UK; Washington University School of Medicine (E.A., A.H.C.), St. Louis, MO; Charité-Universitätsmedizin Berlin (N.B., K.R., F.P.), Germany; University of Utah Imaging & Neurosciences Center (M.M.C.), Salt Lake City; Massachusetts General Hospital (F.J.M., S.T., E.C.K.), Boston; Johns Hopkins Medical Institute (M.A.M., M.L.), Baltimore, MD; MS Institute at Shepherd Center (G.B.), Atlanta, GA; Mayo Clinic (B.W.), Rochester, MN; and Mayo Clinic (D.M.W.), Scottsdale, AZ.
authors.forename: Liene
authors.initials: L
authors.lastname: Elsone
authors.affiliation: Brigham and Women's Hospital (R.B., T.C.), Boston, MA; Harvard Medical School (R.B., F.J.M., E.C.K., T.C.), Boston, MA; The Walton Centre NHS Foundation Trust (L.E., K.M., A.J.), Liverpool, UK; Washington University School of Medicine (E.A., A.H.C.), St. Louis, MO; Charité-Universitätsmedizin Berlin (N.B., K.R., F.P.), Germany; University of Utah Imaging & Neurosciences Center (M.M.C.), Salt Lake City; Massachusetts General Hospital (F.J.M., S.T., E.C.K.), Boston; Johns Hopkins Medical Institute (M.A.M., M.L.), Baltimore, MD; MS Institute at Shepherd Center (G.B.), Atlanta, GA; Mayo Clinic (B.W.), Rochester, MN; and Mayo Clinic (D.M.W.), Scottsdale, AZ.
authors.forename: Enrique
authors.initials: E
authors.lastname: Alvarez
authors.affiliation: Brigham and Women's Hospital (R.B., T.C.), Boston, MA; Harvard Medical School (R.B., F.J.M., E.C.K., T.C.), Boston, MA; The Walton Centre NHS Foundation Trust (L.E., K.M., A.J.), Liverpool, UK; Washington University School of Medicine (E.A., A.H.C.), St. Louis, MO; Charité-Universitätsmedizin Berlin (N.B., K.R., F.P.), Germany; University of Utah Imaging & Neurosciences Center (M.M.C.), Salt Lake City; Massachusetts General Hospital (F.J.M., S.T., E.C.K.), Boston; Johns Hopkins Medical Institute (M.A.M., M.L.), Baltimore, MD; MS Institute at Shepherd Center (G.B.), Atlanta, GA; Mayo Clinic (B.W.), Rochester, MN; and Mayo Clinic (D.M.W.), Scottsdale, AZ.
authors.forename: Nadja
authors.initials: N
authors.lastname: Borisow
authors.affiliation: Brigham and Women's Hospital (R.B., T.C.), Boston, MA; Harvard Medical School (R.B., F.J.M., E.C.K., T.C.), Boston, MA; The Walton Centre NHS Foundation Trust (L.E., K.M., A.J.), Liverpool, UK; Washington University School of Medicine (E.A., A.H.C.), St. Louis, MO; Charité-Universitätsmedizin Berlin (N.B., K.R., F.P.), Germany; University of Utah Imaging & Neurosciences Center (M.M.C.), Salt Lake City; Massachusetts General Hospital (F.J.M., S.T., E.C.K.), Boston; Johns Hopkins Medical Institute (M.A.M., M.L.), Baltimore, MD; MS Institute at Shepherd Center (G.B.), Atlanta, GA; Mayo Clinic (B.W.), Rochester, MN; and Mayo Clinic (D.M.W.), Scottsdale, AZ.
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Cortez
authors.affiliation: Brigham and Women's Hospital (R.B., T.C.), Boston, MA; Harvard Medical School (R.B., F.J.M., E.C.K., T.C.), Boston, MA; The Walton Centre NHS Foundation Trust (L.E., K.M., A.J.), Liverpool, UK; Washington University School of Medicine (E.A., A.H.C.), St. Louis, MO; Charité-Universitätsmedizin Berlin (N.B., K.R., F.P.), Germany; University of Utah Imaging & Neurosciences Center (M.M.C.), Salt Lake City; Massachusetts General Hospital (F.J.M., S.T., E.C.K.), Boston; Johns Hopkins Medical Institute (M.A.M., M.L.), Baltimore, MD; MS Institute at Shepherd Center (G.B.), Atlanta, GA; Mayo Clinic (B.W.), Rochester, MN; and Mayo Clinic (D.M.W.), Scottsdale, AZ.
authors.forename: Farrah J
authors.initials: FJ
authors.lastname: Mateen
authors.affiliation: Brigham and Women's Hospital (R.B., T.C.), Boston, MA; Harvard Medical School (R.B., F.J.M., E.C.K., T.C.), Boston, MA; The Walton Centre NHS Foundation Trust (L.E., K.M., A.J.), Liverpool, UK; Washington University School of Medicine (E.A., A.H.C.), St. Louis, MO; Charité-Universitätsmedizin Berlin (N.B., K.R., F.P.), Germany; University of Utah Imaging & Neurosciences Center (M.M.C.), Salt Lake City; Massachusetts General Hospital (F.J.M., S.T., E.C.K.), Boston; Johns Hopkins Medical Institute (M.A.M., M.L.), Baltimore, MD; MS Institute at Shepherd Center (G.B.), Atlanta, GA; Mayo Clinic (B.W.), Rochester, MN; and Mayo Clinic (D.M.W.), Scottsdale, AZ.
authors.forename: Maureen A
authors.initials: MA
authors.lastname: Mealy
authors.affiliation: Brigham and Women's Hospital (R.B., T.C.), Boston, MA; Harvard Medical School (R.B., F.J.M., E.C.K., T.C.), Boston, MA; The Walton Centre NHS Foundation Trust (L.E., K.M., A.J.), Liverpool, UK; Washington University School of Medicine (E.A., A.H.C.), St. Louis, MO; Charité-Universitätsmedizin Berlin (N.B., K.R., F.P.), Germany; University of Utah Imaging & Neurosciences Center (M.M.C.), Salt Lake City; Massachusetts General Hospital (F.J.M., S.T., E.C.K.), Boston; Johns Hopkins Medical Institute (M.A.M., M.L.), Baltimore, MD; MS Institute at Shepherd Center (G.B.), Atlanta, GA; Mayo Clinic (B.W.), Rochester, MN; and Mayo Clinic (D.M.W.), Scottsdale, AZ.
authors.forename: Kerry
authors.initials: K
authors.lastname: Mutch
authors.affiliation: Brigham and Women's Hospital (R.B., T.C.), Boston, MA; Harvard Medical School (R.B., F.J.M., E.C.K., T.C.), Boston, MA; The Walton Centre NHS Foundation Trust (L.E., K.M., A.J.), Liverpool, UK; Washington University School of Medicine (E.A., A.H.C.), St. Louis, MO; Charité-Universitätsmedizin Berlin (N.B., K.R., F.P.), Germany; University of Utah Imaging & Neurosciences Center (M.M.C.), Salt Lake City; Massachusetts General Hospital (F.J.M., S.T., E.C.K.), Boston; Johns Hopkins Medical Institute (M.A.M., M.L.), Baltimore, MD; MS Institute at Shepherd Center (G.B.), Atlanta, GA; Mayo Clinic (B.W.), Rochester, MN; and Mayo Clinic (D.M.W.), Scottsdale, AZ.
authors.forename: Sean
authors.initials: S
authors.lastname: Tobyne
authors.affiliation: Brigham and Women's Hospital (R.B., T.C.), Boston, MA; Harvard Medical School (R.B., F.J.M., E.C.K., T.C.), Boston, MA; The Walton Centre NHS Foundation Trust (L.E., K.M., A.J.), Liverpool, UK; Washington University School of Medicine (E.A., A.H.C.), St. Louis, MO; Charité-Universitätsmedizin Berlin (N.B., K.R., F.P.), Germany; University of Utah Imaging & Neurosciences Center (M.M.C.), Salt Lake City; Massachusetts General Hospital (F.J.M., S.T., E.C.K.), Boston; Johns Hopkins Medical Institute (M.A.M., M.L.), Baltimore, MD; MS Institute at Shepherd Center (G.B.), Atlanta, GA; Mayo Clinic (B.W.), Rochester, MN; and Mayo Clinic (D.M.W.), Scottsdale, AZ.
authors.forename: Klemens
authors.initials: K
authors.lastname: Ruprecht
authors.affiliation: Brigham and Women's Hospital (R.B., T.C.), Boston, MA; Harvard Medical School (R.B., F.J.M., E.C.K., T.C.), Boston, MA; The Walton Centre NHS Foundation Trust (L.E., K.M., A.J.), Liverpool, UK; Washington University School of Medicine (E.A., A.H.C.), St. Louis, MO; Charité-Universitätsmedizin Berlin (N.B., K.R., F.P.), Germany; University of Utah Imaging & Neurosciences Center (M.M.C.), Salt Lake City; Massachusetts General Hospital (F.J.M., S.T., E.C.K.), Boston; Johns Hopkins Medical Institute (M.A.M., M.L.), Baltimore, MD; MS Institute at Shepherd Center (G.B.), Atlanta, GA; Mayo Clinic (B.W.), Rochester, MN; and Mayo Clinic (D.M.W.), Scottsdale, AZ.
authors.forename: Guy
authors.initials: G
authors.lastname: Buckle
authors.affiliation: Brigham and Women's Hospital (R.B., T.C.), Boston, MA; Harvard Medical School (R.B., F.J.M., E.C.K., T.C.), Boston, MA; The Walton Centre NHS Foundation Trust (L.E., K.M., A.J.), Liverpool, UK; Washington University School of Medicine (E.A., A.H.C.), St. Louis, MO; Charité-Universitätsmedizin Berlin (N.B., K.R., F.P.), Germany; University of Utah Imaging & Neurosciences Center (M.M.C.), Salt Lake City; Massachusetts General Hospital (F.J.M., S.T., E.C.K.), Boston; Johns Hopkins Medical Institute (M.A.M., M.L.), Baltimore, MD; MS Institute at Shepherd Center (G.B.), Atlanta, GA; Mayo Clinic (B.W.), Rochester, MN; and Mayo Clinic (D.M.W.), Scottsdale, AZ.
authors.forename: Michael
authors.initials: M
authors.lastname: Levy
authors.affiliation: Brigham and Women's Hospital (R.B., T.C.), Boston, MA; Harvard Medical School (R.B., F.J.M., E.C.K., T.C.), Boston, MA; The Walton Centre NHS Foundation Trust (L.E., K.M., A.J.), Liverpool, UK; Washington University School of Medicine (E.A., A.H.C.), St. Louis, MO; Charité-Universitätsmedizin Berlin (N.B., K.R., F.P.), Germany; University of Utah Imaging & Neurosciences Center (M.M.C.), Salt Lake City; Massachusetts General Hospital (F.J.M., S.T., E.C.K.), Boston; Johns Hopkins Medical Institute (M.A.M., M.L.), Baltimore, MD; MS Institute at Shepherd Center (G.B.), Atlanta, GA; Mayo Clinic (B.W.), Rochester, MN; and Mayo Clinic (D.M.W.), Scottsdale, AZ.
authors.forename: Dean M
authors.initials: DM
authors.lastname: Wingerchuk
authors.affiliation: Brigham and Women's Hospital (R.B., T.C.), Boston, MA; Harvard Medical School (R.B., F.J.M., E.C.K., T.C.), Boston, MA; The Walton Centre NHS Foundation Trust (L.E., K.M., A.J.), Liverpool, UK; Washington University School of Medicine (E.A., A.H.C.), St. Louis, MO; Charité-Universitätsmedizin Berlin (N.B., K.R., F.P.), Germany; University of Utah Imaging & Neurosciences Center (M.M.C.), Salt Lake City; Massachusetts General Hospital (F.J.M., S.T., E.C.K.), Boston; Johns Hopkins Medical Institute (M.A.M., M.L.), Baltimore, MD; MS Institute at Shepherd Center (G.B.), Atlanta, GA; Mayo Clinic (B.W.), Rochester, MN; and Mayo Clinic (D.M.W.), Scottsdale, AZ.
authors.forename: Friedemann
authors.initials: F
authors.lastname: Paul
authors.affiliation: Brigham and Women's Hospital (R.B., T.C.), Boston, MA; Harvard Medical School (R.B., F.J.M., E.C.K., T.C.), Boston, MA; The Walton Centre NHS Foundation Trust (L.E., K.M., A.J.), Liverpool, UK; Washington University School of Medicine (E.A., A.H.C.), St. Louis, MO; Charité-Universitätsmedizin Berlin (N.B., K.R., F.P.), Germany; University of Utah Imaging & Neurosciences Center (M.M.C.), Salt Lake City; Massachusetts General Hospital (F.J.M., S.T., E.C.K.), Boston; Johns Hopkins Medical Institute (M.A.M., M.L.), Baltimore, MD; MS Institute at Shepherd Center (G.B.), Atlanta, GA; Mayo Clinic (B.W.), Rochester, MN; and Mayo Clinic (D.M.W.), Scottsdale, AZ.
authors.forename: Anne H
authors.initials: AH
authors.lastname: Cross
authors.affiliation: Brigham and Women's Hospital (R.B., T.C.), Boston, MA; Harvard Medical School (R.B., F.J.M., E.C.K., T.C.), Boston, MA; The Walton Centre NHS Foundation Trust (L.E., K.M., A.J.), Liverpool, UK; Washington University School of Medicine (E.A., A.H.C.), St. Louis, MO; Charité-Universitätsmedizin Berlin (N.B., K.R., F.P.), Germany; University of Utah Imaging & Neurosciences Center (M.M.C.), Salt Lake City; Massachusetts General Hospital (F.J.M., S.T., E.C.K.), Boston; Johns Hopkins Medical Institute (M.A.M., M.L.), Baltimore, MD; MS Institute at Shepherd Center (G.B.), Atlanta, GA; Mayo Clinic (B.W.), Rochester, MN; and Mayo Clinic (D.M.W.), Scottsdale, AZ.
authors.forename: Brian
authors.initials: B
authors.lastname: Weinshenker
authors.affiliation: Brigham and Women's Hospital (R.B., T.C.), Boston, MA; Harvard Medical School (R.B., F.J.M., E.C.K., T.C.), Boston, MA; The Walton Centre NHS Foundation Trust (L.E., K.M., A.J.), Liverpool, UK; Washington University School of Medicine (E.A., A.H.C.), St. Louis, MO; Charité-Universitätsmedizin Berlin (N.B., K.R., F.P.), Germany; University of Utah Imaging & Neurosciences Center (M.M.C.), Salt Lake City; Massachusetts General Hospital (F.J.M., S.T., E.C.K.), Boston; Johns Hopkins Medical Institute (M.A.M., M.L.), Baltimore, MD; MS Institute at Shepherd Center (G.B.), Atlanta, GA; Mayo Clinic (B.W.), Rochester, MN; and Mayo Clinic (D.M.W.), Scottsdale, AZ.
authors.forename: Anu
authors.initials: A
authors.lastname: Jacob
authors.affiliation: Brigham and Women's Hospital (R.B., T.C.), Boston, MA; Harvard Medical School (R.B., F.J.M., E.C.K., T.C.), Boston, MA; The Walton Centre NHS Foundation Trust (L.E., K.M., A.J.), Liverpool, UK; Washington University School of Medicine (E.A., A.H.C.), St. Louis, MO; Charité-Universitätsmedizin Berlin (N.B., K.R., F.P.), Germany; University of Utah Imaging & Neurosciences Center (M.M.C.), Salt Lake City; Massachusetts General Hospital (F.J.M., S.T., E.C.K.), Boston; Johns Hopkins Medical Institute (M.A.M., M.L.), Baltimore, MD; MS Institute at Shepherd Center (G.B.), Atlanta, GA; Mayo Clinic (B.W.), Rochester, MN; and Mayo Clinic (D.M.W.), Scottsdale, AZ.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Klawiter
authors.affiliation: Brigham and Women's Hospital (R.B., T.C.), Boston, MA; Harvard Medical School (R.B., F.J.M., E.C.K., T.C.), Boston, MA; The Walton Centre NHS Foundation Trust (L.E., K.M., A.J.), Liverpool, UK; Washington University School of Medicine (E.A., A.H.C.), St. Louis, MO; Charité-Universitätsmedizin Berlin (N.B., K.R., F.P.), Germany; University of Utah Imaging & Neurosciences Center (M.M.C.), Salt Lake City; Massachusetts General Hospital (F.J.M., S.T., E.C.K.), Boston; Johns Hopkins Medical Institute (M.A.M., M.L.), Baltimore, MD; MS Institute at Shepherd Center (G.B.), Atlanta, GA; Mayo Clinic (B.W.), Rochester, MN; and Mayo Clinic (D.M.W.), Scottsdale, AZ.
authors.forename: Tanuja
authors.initials: T
authors.lastname: Chitnis