Response to Letter to the Editor from Flood and Hackney: Myofibrillar protein synthesis rates do not differ with low and high estradiol concentrations across the menstrual cycle

We thank Flood and Hackney (1) for applauding our novel study design approach (2), which we feel has provided important insight into the role of the menstrual cycle and, specifically, endogenous estradiol in the regulation of muscle mass. The authors highlighted our decision to include participants who presented with elevated progesterone (>6.36 nmol/L−1) or low estradiol concentrations (no specific criteria) during the late (LF) compared to early (EF) follicular phase, and questioned why we did not acknowledge this or consider alternative analyses. We wish to assure the authors that sensitivity analysis excluding participants with either elevated progesterone or lower estradiol concentrations during LF did not alter the primary outcome, and so we did not consider it appropriate to exclude participants. However, although we did not acknowledge this additional analysis in our manuscript, we clearly and transparently stated the limitation of higher progesterone during LF in the Discussion section, despite following the gold standard 3-step approach and a progesterone cutoff of <16 nmol/L−1 recommended by experts elsewhere (3). Given the absence of established estradiol-specific phase cutoffs in the literature, and the inherent challenges of accurately capturing the LF phase due to the short duration and variable timing of the estradiol peak within and between individuals, we feel this study remains a valuable first in the field.