Implementing an algorithm for controlling for female MC phase for clinical neuroscience

Background Recent research suggests that hormones and/or menstrual cycle (MC) phase at time of study may significantly affect clinical neuroscience outcomes of interest. Prior research puts forth sound methods for characterizing MC phase in women not using hormonal contraceptives (HC). However, an estimated 40% of premenopausal women in the United States use some form of HC. We developed an algorithm for characterizing hormone levels and MC phase among women both using and not using HC. We have employed this algorithm among female collegiate athletes post-mild traumatic brain injury (mTBI) as female athletes are understudied in the sports mTBI field, MC phase may have important effects on mTBI-related outcomes and controlling for MC phase has not been employed in this population. Methods Thirty female collegiate athletes were studied. Fifteen incurred a mTBI 3-10 days prior to assessment and sixteen were age, ethnicity, and menstrual cycle (MC) phase matched to the injured athletes. MC matching was conducted with retrospective and prospective self-report MC tracking, self-report of HC use, and serum progesterone testing. Results 53% (16/30) of females were on HC and 47% (14/30) were not. Of the non-HC users, seven female pairs were in the follicular and one was in the luteal phase. Among the non-HC users, there was 50% agreement in MC phase identification between self-report and progesterone measures and a κ = 0.138. Of the HC users, eight were in the inactive and six were in the active phase of their medication. Among the HC users, average progesterone levels indicated medication compliance (.58ng/mL). Conclusions This study provides important methodology and proof-of-concept that MC phase can be used as a control variable for time-sensitive prospective clinical neuroscience studies including those involving brain injury. When studying females, it is important to properly examine and control for the sex-specific factor of MC phase in order to have a full understanding of brain behavior relationships in translational research.