title: Estrogen Replacement Improves Verbal Memory and Executive Control in Oligomenorrheic/Amenorrheic Athletes in a Randomized Controlled Trial.
abstract: OBJECTIVE
  Both estrogen and exercise may have cognition enhancing benefits; however, young oligomenorrheic/amenorrheic athletes (OA) with estrogen deficiency have not been evaluated for cognitive deficits. Our objective was to determine whether 6 months of estrogen replacement will impact cognitive domains in OA. We hypothesized that estrogen replacement would improve verbal memory and executive control in OA.
  
  
  METHODS
  We performed cognitive assessments at baseline and after 6 months in 48 OA (14-25 years) randomized to estrogen (EST+) (oral 30 µg ethinyl estradiol [n = 16] or transdermal 100 µg 17-β-estradiol patch [n = 13]) or no estrogen (EST-) (n = 19) in an ongoing clinical trial. Neurocognitive testing included California Verbal Learning Test-Second Edition (CVLT-II) (for verbal memory) and Delis-Kaplan Executive Function System Color-Word Interference Test (D-KEFS-CWIT) (executive control).
  
  
  RESULTS
  On average, subjects (mean ± SEM age: 19.9 ± 3.1 years, body mass index: 20.6 ± 2.3 kg/m²) participated in 10.3 ± 5.9 hours per week of weight-bearing activities of their lower limbs. The EST+ group performed better for CVLT-II verbal memory scores for immediate recall over 6 months of therapy compared to EST- (P < .05) even after controlling for baseline scores and age. Changes in D-KEFS-CWIT scores over 6 months did not differ between the groups. However, the EST+ group had greater improvements in inhibition-switching completion time over 6 months compared with the EST- group after controlling for baseline scores and age (P = .01).
  
  
  CONCLUSIONS
  OA show improvements in verbal memory and executive control following 6 months of estrogen replacement. These findings in athletes, who are in their prime of neurocognitive development, underscore the need for future studies exploring cognition in OA.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT00946192.
authors.affiliation: Pediatric Endocrinology, Massachusetts General Hospital for Children, 101 Merrimac, Ste 615, Boston, MA 02114. cbaskaran@mgh.harvard.edu.|Pediatric Endocrine Unit, Massachusetts General Hospital for Children and Harvard Medical School, Boston, Massachusetts, USA.|Neuroendocrine Unit, Massachusetts General Hospital for Children and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Charumathi
authors.initials: C
authors.lastname: Baskaran
authors.affiliation: Neuroendocrine Unit, Massachusetts General Hospital for Children and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Brooke
authors.initials: B
authors.lastname: Cunningham
authors.affiliation: Neuroendocrine Unit, Massachusetts General Hospital for Children and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Franziska
authors.initials: F
authors.lastname: Plessow
authors.affiliation: Pediatric Endocrine Unit, Massachusetts General Hospital for Children and Harvard Medical School, Boston, Massachusetts, USA.|Neuroendocrine Unit, Massachusetts General Hospital for Children and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Vibha
authors.initials: V
authors.lastname: Singhal
authors.affiliation: Neuroendocrine Unit, Massachusetts General Hospital for Children and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Woolley
authors.affiliation: Neuroendocrine Unit, Massachusetts General Hospital for Children and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Ackerman
authors.affiliation: Neuroendocrine Unit, Massachusetts General Hospital for Children and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Meghan
authors.initials: M
authors.lastname: Slattery
authors.affiliation: Department of Biostatistics, Massachusetts General Hospital for Children and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Hang
authors.initials: H
authors.lastname: Lee
authors.affiliation: Neuroendocrine Unit, Massachusetts General Hospital for Children and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Lawson
authors.affiliation: Eating Disorders Clinical and Research Program, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Kamryn
authors.initials: K
authors.lastname: Eddy
authors.affiliation: Pediatric Endocrine Unit, Massachusetts General Hospital for Children and Harvard Medical School, Boston, Massachusetts, USA.|Neuroendocrine Unit, Massachusetts General Hospital for Children and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Madhusmita
authors.initials: M
authors.lastname: Misra
mesh_terms: D000279:Administration, Cutaneous; D000284:Administration, Oral; D000293:Adolescent; D000568:Amenorrhea / Q000188:drug therapy* / Q000523:psychology*; D056352:Athletes; D015914:Estrogen Replacement Therapy; D056344:Executive Function / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D011939:Mental Recall / Q000187:drug effects*; D009483:Neuropsychological Tests; D009839:Oligomenorrhea / Q000188:drug therapy* / Q000523:psychology*; D014706:Verbal Learning / Q000187:drug effects*; D055815:Young Adult