Title: Differential symptom relief profiles of menopausal therapies: an online survey study
Version: 0 Date: 31 May 2025
Reviewer's report:
Dear Authors,
Thank you for the opportunity to review your manuscript.
Comments below-
BACKGROUND
Lines 70-88 – background knowledge about menopause, symptoms and its impact could be more
concise (as most likely, the larger audience for this study will have a baseline understanding
of menopause)
Lines 89-120 – as per previous point, suggest providing a summary statement of this issue in
the introduction, and moving the more detailed literature review to the discussion
Lines 126-7 – This statement is an assessment of your results – suggest moving this to your
discussion
METHODS
Line 142-143 – Study materials developed in consultation with a psychiatrist. Please outline the
background of the other team members involved in survey design. Was there consultation of
e.g. a gynaecologist or endocrinologist who frequently manages menopause symptoms?
Line 158-162 – MENQOL questionnaire is validated for this indication, however you have not
administered the MENQOL, but adapted the symptom list for your assessment. Please justify
why.
“Participants were required to select the symptoms that had improved by ticking a box” - How
was ‘symptom relief’ defined to the survey participant (e.g. any improvement vs. substantive
improvement vs. complete resolution of symptoms)? Were all participants with any level of
improvement considered a ‘responder’?
Later use of ‘response rate’ e.g. in Table 2 and throughout manuscript should be clarified if this is
referring to % of participants who respond, rather than mean quantitative (amount of) response.
Line 166-7 – Further to above, please justify how you have scaled scoring in this area.
Please justify combination of categorical data (yes/no for symptom relief) into a continuous/
quantitative measure (scaled scoring) and subsequently selected statistical tests. This may not
be appropriate management of the outcome and would suggest a test suitable for comparison
of categorical data.
Furthermore, please discuss whether equal weighting of a categorical yes/no for ‘symptom
relief’ is an accurate depiction of overall impact to a patient suffering these symptoms.
Other considerations -
Was there any reimbursement to participants?
How was missing data, ‘speeders’ and inaccurate entries assessed for?
RESULTS
TABLE 1 - An inclusion criteria is >3 months of treatment duration, but was length of treatment
and compliance assessed? What effect could this have on perceived efficacy of each respective
treatment? (e.g. as a hypothetical example – Psychotherapy once a month for 3 months vs.
HRT daily for 3 months would be expected to have quite different effects, and it would not be
unreasonable to need to pursue psychological therapies to see benefit)
Line 193-4 – How was symptom relief attributed when women reported several concurrent
therapies?
Supplementary Figure 1 - How was oral HRT defined? It seems clinically unlikely that patients
were on concurrent transdermal and oral oestrogen (and certainly not that proportion).
DISCUSSION
International guidelines for menopause (including the NICE guidelines in the UK) already
recommend personalised, wholistic patient approach for management of menopause, involving
multi-modal therapies and multidisciplinary models. How do your results fit with current
evidence and guidelines?
Lines 257-271 – Opening sentence of this paragraph does not align with the rest of this
paragraph.  I think the authors are highlighting that psychological therapies are suggested
to have a more substantial benefit in the psychosocial domain, but minimal in others. The
data from this study does not suggest that all women should be recommended psychotherapy
in combination with their transdermal HRT. It is also worth considering the multi-factorial
influences that contribute to ‘psychosocial’ symptoms.  E.g. is past history of mental health
condition considered in the analysis?
The discussion regarding accessibility is valid and crucial - the other consideration for
psychotherapy in most countries is cost, and cost-effectiveness and patient acceptability is a
consideration.
Lines 272-279 – Please discuss how your results fit and contribute to the current available
evidence for these treatments.
The NICE guidelines suggest testosterone can be considered for low sexual desire but is not a
first line therapy and evidence (see below) only supports its use in HSDD (hypoactive sexual
desire disorder/dysfunction) which is a specific diagnosis and not generalisable to a menopause
population or all of the ‘sexual’ domain symptoms assessed.
See: Susan R Davis, Rodney Baber, Nicholas Panay, Johannes Bitzer, Sonia Cerdas Perez,
Rakibul M Islam, Andrew M Kaunitz, Sheryl A Kingsberg, Irene Lambrinoudaki, James Liu,
Sharon J Parish, JoAnn Pinkerton, Janice Rymer, James A Simon, Linda Vignozzi, Margaret E
Wierman, Global Consensus Position Statement on the Use of Testosterone Therapy for Women,
The Journal of Clinical Endocrinology & Metabolism, Volume 104, Issue 10, October 2019,
Pages 4660–4666, https://doi.org/10.1210/jc.2019-01603
Lines 280-7 – A checklist can be a useful adjunct to clinical care and may be time-saving in
some regards, but is there evidence to support that identifies more information than a clinical
consult? Again, how do your findings fit with this discussion point?
Also, it is crucial to consider how bothersome a symptom is to a patient in their management
also – experience alone does not necessarily indicate a negative impact on quality of life.
Management needs to consider treatment side effects, tolerance and patient acceptability of
treatment (which were not assessed in this study).  See above comment about yes/no for
symptom relief vs. using the complete validated MENQOL questionnaire which quantifies how
bothersome each symptom is.