Estrogen Replacement Improves Verbal Memory and Executive Control in Oligomenorrheic/Amenorrheic Athletes in a Randomized Controlled Trial

J Clin Psychiatry. 2017 May;78(5):e490-e497. doi: 10.4088/JCP.15m10544.


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.

Trial registration: identifier: NCT00946192.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Cutaneous
  • Administration, Oral
  • Adolescent
  • Amenorrhea / drug therapy*
  • Amenorrhea / psychology*
  • Athletes*
  • Estrogen Replacement Therapy*
  • Executive Function / drug effects*
  • Female
  • Follow-Up Studies
  • Humans
  • Mental Recall / drug effects*
  • Neuropsychological Tests
  • Oligomenorrhea / drug therapy*
  • Oligomenorrhea / psychology*
  • Verbal Learning / drug effects*
  • Young Adult

Associated data