Title: Differential symptom relief profiles of menopausal therapies: an online survey study
Version: 0 Date: 30 May 2025
Reviewer's report:
This interesting paper focused on menopausal symptoms, listed according to MENQOL, in order
to appreciate efficacy  of different therapeutic interventions for menopausal symptoms relief.
This  was also done  before  in the literature, but the strength of this study is to review in a large
menopausal population recurring to different types of treatment for symptomatic relief, and how
these treatments COMPARE in terms of effectiveness to one another.
However, focusing on the relief of symptoms is important, but it relates ONLY to the
emerging part of the iceberg. In fact, the BASAL cause of menopause is the progressive
disappearance of estrogens ( and partly of androgens), and the protecting effect they have
on diverse important functions: cardiovascular, cerebral, metabolic, immunologic...without
NECESSARILY accompanying symptoms (Yang , Stanczyk et al Menopause, 2024) :
menopausal bone catabolism is not symptomatic until fracture occurs!... 30% of diabetes type 2
occurrence is avoided by estrogen administration, etc..SO, treating symptoms is NOT sufficient,
and treating menopause INCIPIENTLY by hormonal therapy is optimal if there is no estrogen
contraindication; many symptoms will be relieved altogether. Then, IN A SECOND TIME,
appreciating if HR-QoL can be optimized in these HRT users is very useful and refining
aspects of the menopausal treatment. What I suggest is that in some words you explain in your
Introduction that you are not looking for the best, more complete therapy of the menopausal state
but focusing on the comparative efficacy of treatment of symptoms between different therapeutic
interventions. Indeed, this hierarchy is just partly suggested in the last lines of your conclusion
and should clearly find a place in the introduction, as well (see further)
More specific points of review
Background: lines 69 and following :In order to characterize the different stages of menopause,
the most appreciated ref that you can cite is Harlow S et al "STRAW + 10" Climacteric 2012; 15:
105-114)-- Ibidem description of different interventions is OK, but, one fear : Probable over-use
of antidepressants, which is NOT a treatment for menopause -BUT for depression (of course,
both can overlap) -- Ibidem :remarks on CBT and Androgens are really welcome
Methods p6, line 138-140 : The participants had received a treatment: not clear if a 2d therapeutic
advice  from a HCP was forbidden or not ?
Materials  and procedure p7, line 156-7 :Not clear about Hysterectomy : menopause occurs if
ovaries (preserved during hysterectomy) are both non functional
Results p9, line 192 : Reviewer positively surprised that HRT treatment was transdermal, in as
much as 69% (usually  less than 20% in many countries, alas): TTS-HRT is effective and safer
(for risk of VTE and stroke) vs oral HRT/ Negatively surprised by high level of antidepressants
used...--Ibidem p9-10 up to line 231 : Recent studies of HR-QoL with different current/new
treatments are in good agreement with the 4 domains of MENQOL studied. However, your
description and corresponding figs 1 and 2 (and Tables) of treatments and differential responses
shown in pairwise comparison reach a useful level of comparison that helps to ascertain
comparisons of treatment effects and of associations of therapeutic interventions which improve
symptoms and QoL. For example, concerning sexual domain, transdermal HRT can be improved
by E-vag addition, and/or by testosterone addition : the clinician knows about it-but you add a
quantification which is welcome.
Discussion ,l. 249~298 :  explains well your data and confirms therapeutic attitude of specialized
clinicians
Conclusion p 14, l.314 : HCPs should prioritize the use of transdermal HRT [and also oral HRT]
" for the alleviation of more global menopausal symptoms" : rather : "not only for basal hormonal
replacement of estrogen deficiency which harms womens' health, but also improves menopausal
symptoms, upgrading, in total, health-related quality of life.