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.

Trial registration: ClinicalTrials.gov identifier: NCT00946192.

Conflict of interest statement

Conflict of interest: Authors involved in the study report no conflict of interest to disclose.

© Copyright 2017 Physicians Postgraduate Press, Inc.

Figures

Figure 1:. Changes in cognitive scores in estrogen-replaced and no-therapy groups after adjusting for age and baseline scoresa

a The figure shows the changes in CVLT-II and D-KEFS Color Word Interference test scores over six months adjusted for age and baseline value by treatment group. Immediate recall scores (Trial 1 and Trial B) and scores for cognitive flexibility assessed by Inhibition Switching Completion time were significantly improved in the EST+ compared with EST- groups. * p value <0.05 Abbreviations: CVLT-II: California Verbal Learning Test, Edition II, D-KEFS: Delis Kaplan Executive Function System, EST-: No estrogen replacement, EST+: Estrogen replacement