Neurotrauma Rep. 2026 Jul 10;7:2689288X261463039. doi: 10.1177/2689288X261463039. eCollection 2026 Jan-Dec.
ABSTRACT
Females of reproductive age with concussion often report greater symptom severity and duration than age-matched males; the mechanisms underlying female symptomology remain unclear. This study investigated the association between hormone profiles and time to return to learn/work (RTL/W) following concussion. A secondary aim was to explore differences in symptom severity and salivary miR-27a-5p/miR-30a-3p expression between hormone profile groups. Based on an a priori power calculation, 36 females aged 28.8 ± 7.5 (17-44 years) presenting to an emergency department within 72 h of a confirmed concussion were recruited. Participants were classified into three hormone profile groups: n = 20 natural menstrual cycle (NMC); n = 8 progestin-only hormonal contraception (PROG); and n = 8 oral contraception (Oral Contraceptive Pill; OCP). Saliva samples were collected for measurement of miR-27a-5p/miR-30a-3p, and participants completed weekly online surveys reporting symptom scores until achieving RTL/W. The mean initial symptom score was 47.0 ± 23.7 (8-100), and mean time to RTL/W was 27.3 ± 33.1 (2-179 days). Cox hazard regression revealed a statistically significant association of hormone profile with time to RTL/W. PROG (hazard ratio [HR]: 2.5, 95% confidence interval [CI]: 1.0-6.1, p = 0.048) and OCP (HR: 2.7, 95% CI: 1.1-6.4, p = 0.027) were significantly associated with increased likelihood of RTL/W compared with NMC. Initial symptom score was not significantly associated with time to RTL/W (p = 0.628). Exploratory analysis showed no statistically significant mean differences between groups for initial symptom score [F(2, 33) = 1.755, p = 0.189]. Fourteen saliva samples provided complete miR-27a-5p/miR-30a-3p data; mean miR-27a-5p/miR-30a-3p was 0.84 ± 0.06 (0.75-0.92). No statistically significant mean differences in miR-27/miR-30 expression were observed between hormone profile groups (F 2, 11 = 0.519, p = 0.609). Females using PROG or OCP were between 1.0 and 6.7 times more likely to achieve RTL/W than NMC at any given time. Hormone profile, but not initial symptom score, was predictive of time to RTL/W. Salivary miR-27a-5p/miR-30a-3p may be a useful biomarker in females with concussion and warrants further research.
PMID:42539337 | PMC:PMC13422596 | DOI:10.1177/2689288X261463039