Title: Loneliness and analgesic overuse among low-dose estrogen-progestin users in Japan
Version: 3 Date: 19 May 2025
Reviewer's report:
I appreciate the opportunity to review this paper and trust that my comments will contribute to
the refinement of the manuscript.
Introduction
The Introduction of this manuscript does not adequately fulfill its crucial role of clearly
conveying the study's background, research gap, and its aims and significance to the reader.
While the information presented on various topics (e.g., loneliness, pain, medication overuse
headache (MOH), use of low-dose estrogen-progestin (LEP), and menstrual symptoms) is
pertinent, the logical thread that should connect these pieces of information, integrate them, and
lead to the central research questions and hypotheses of this study is unclear.
l.45 Regarding the statement in the Introduction, 'Loneliness is associated with morbidity and
mortality,' it is unclear: morbidity and mortality from what specific conditions or causes? And
is this an association with an increase or a decrease in these outcomes?
l.51-56 The method for measuring loneliness, as well as details concerning its validity, should
be described in the Methods section.
Methods
The Methods section should precisely and thoroughly describe the specific procedures used to
test the study's hypotheses, enabling readers to evaluate the research and replicate it if necessary.
In this manuscript, however, the Methods section lacks clarity, comprehensiveness, and
appropriate organization in several key areas. This raises concerns regarding the transparency
and reproducibility of the study. Moreover, some background information that belongs in the
Introduction appears to be included in the Methods, while conversely, some methodological
details are either insufficiently described or are missing from the Methods section where they
are expected.
l.108 The manuscript states that healthcare professionals were excluded. How were these
individuals identified (e.g., what specific question or criterion was used)? This is unclear, as
the information provided in the manuscript does not seem to suggest a method for determining
their profession.
l.121 - 131 Some of the discussion on migraine and sleep, particularly the aspects that form
the rationale for including sleep-related variables or hypotheses in this study, belongs in the
Introduction section to provide necessary background, rather than in the Methods.
Results
The rationale for comparing age groups as 20s versus 30s should be provided. Furthermore,
routinely calculating p-values for differences in baseline characteristics is not recommended by
epidemiological reporting guidelines such as STROBE. If, despite this, such tests are conducted,
appropriate adjustments for multiple comparisons (e.g., Bonferroni correction) must be applied
to avoid an inflated false positive rate.
Results from logistic regression analyses, including odds ratios (ORs), 95% confidence intervals
(CIs), and p-values, should primarily be presented in a comprehensive and well-organized table.
Discussion
A meaningful Discussion must be built upon a sound Introduction, appropriate Methods, and
robust Results. Given the fundamental deficiencies identified in the preceding sections of this
manuscript, the foundation for a constructive Discussion is critically undermined. As such, a
meaningful critique of the Discussion section cannot be undertaken.