Title: Changes in women’s physical function in mid-life by reproductive age and hormones: a
longitudinal study
Version: 1 Date: 16 Aug 2022
Reviewer's report:
Overall comment:
This manuscript describes associations with both chronologic and reproductive aging and
physical function during the menopausal transition. Overall, this paper adds to previous studies
through its longitudinal design, use of a performance-based battery of physical function, and
inclusion of hormones known to change with menopause. However, though the study has a
longitudinal design, the median follow-up in the study was only 2.1 years. As menopause
generally lasts about 7 years (or longer) only a small portion of the menopausal transition was
captured in this study, which is a major limitation. Further, given the relatively young age of
the cohort, it is unlikely we would see major changes in function during this timeframe. The
paper has strengths that add to the literature, but results should be discussed in context of this
short timeframe, particularly as reproductive aging is not accurately captured for women who
have not had their FMP.
Specific comments:
Abstract: The term “Associations of all three reproductive hormones with the composite score
were close to the null” is a little difficult to follow. Could you instead say that there were “no
statistically significant associations between any of the three reproductive hormones with the
composite score”? Same comment for this statement in the Results (line 252).
Background: Grip strength and gait speed (or slowing gait speed) are often used as components
of frailty composites. I recommend removing frailty from the sentence on lines 106-107.
Background: A sentence clearly describing the gap in the literature would improve the flow of
the background leading into the overall research question. (For example, existing longitudinal
studies examined menopausal state, but not the hormonal changes that accompany reproductive
aging.)
Methods: The timeline of the study visits is somewhat unclear. Line 144 mentions that clinic
assessments began in 2009, while line 147 lists 2011 and 2015 as the timeframe. Later, it is
mentioned that the median follow-up was 2.1 years (Results line 239). Why was the follow-up
ultimately so short as it seems like visits could have occurred over the course of 6 years?
Methods: Was the number of pregnancies or number of children birthed considered as a
confounder?
Methods: Line 230-231, what does the “re-invitation” portion mean? How close together were
these repeat measurements and what was the purpose of them?
Discussion: The first line states that physical function declined. However, this isn’t entirely
accurate. Performance improved on some measures.
Discussion: As mentioned above, the duration of follow-up is short in this study, and the visits
appear to be close together. A large portion of women who remained pre-FMP do not truly
have reproductive aging assessed in this study. Given the limitation of this analysis, the focus
on reproductive aging in this paper seems misleading and other results are more important to
emphasize.
Discussion: How much did the hormone levels change during this follow-up? Is it possible that
there were several null associations because there wasn’t sufficient change observed?
Discussion: Line 357-359, if age at menopause has a causal relationship with physical function,
it would not be a confounder.