Flood, Tess and Hackney, Anthony (2025) 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. The Journal of Clinical Endocrinology & Metabolism, 111 (3). e961-e962. ISSN 0021-972X

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Abstract

To the Editor,

It is with great interest that we read the recent paper by Apicella et al, which assesses myofibrillar protein synthesis rates (MPSR) and estradiol concentrations across the menstrual cycle (MC) (1). Prior research in this area has attempted to use the phases of the MC as the experimental research design to manipulate ovarian hormones (OH) concentrations within subjects (early follicular = low OH levels, luteal = high OH levels) (2, 3). The authors clearly point out that a limitation of such approaches is that the anti-estrogenic actions of progesterone, being elevated in the luteal phase, may counteract the actions of estradiol on MPSR (4). To offset this potential progesterone confounding effect, Apicella et al designed their study to have subjects complete experimental trials at the early follicular (EF) and late follicular (LF) phases of the MC (ie, LF theoretically having elevated estradiol and low progesterone).

We applaud this novel study design approach; however, several issues within the paper raise concerns for us. First, in Figure 2 (panel G), it clearly shows that several of the 17 subjects had substantially elevated LF trial progesterone (greater than the mean values in EF). Recent methodological guidance suggests a progesterone cutoff of 6.36 nmol·L−1 for the LF MC phase; this value was approached (n = 1) or exceeded (n = 3) by these select subjects (5). This indicates that ∼20% of the sample was not in the hormonal conditions desired in the LF trial—potentially confounding their data interpretation. We wonder why the authors did not consider examining their data with alternative approaches, such as conducting sub-analyses, for example, (i) involving excluding the subjects who showed substantial elevations in progesterone during LF, or (ii) perhaps a sensitivity analysis in which those participants who had LF estradiol levels 2 SD lower than the cohort would be removed. At a minimum, the authors should have noted that the elevated LF progesterone levels of certain subjects were a potential limitation within their data.

Item Type:	Article
Identifier:	10.1210/clinem/dgaf678
Subjects:	Medicine and health
Date Deposited:	15 Nov 2025
Dates:	Date Publication status 11 November 2025 Accepted 18 December 2025 Published
School, department or research centre:	School of Human and Social Sciences
URI:	https://repository.uwl.ac.uk/id/eprint/14263
Sustainable Development Goals:	Goal 3: Good Health and Well-Being

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