Title: Progestins in the symptomatic management of endometriosis: A meta-analysis on their
effectiveness and safety.
Version: 0 Date: 31 Aug 2022
Reviewer:  Noemi Salmeri
Reviewer's report:
I was asked to revise the Manuscript entitled "The Effectiveness of the Use of Progestins in the
Symptomatic Management of Endometriosis: A Systematic Review" for publication in BMC
Women's Health.
The meta-analysis topic has not much novelty, since it has been extensively discussed in
literature. However, it still remains highly debated so a systematic overview  may still rise some
interest in readers.
The title of the Manuscript does not summarize the main outcomes investigated in the study
((1) determine the effect of progestins in providing pain relief in women diagnosed with
endometriosis, and (2) determine the occurrence of adverse effects in patients receiving
progestins). It also does not provide information on the quantitative synthesis provided by
the authors. I would suggest to change it as "Progestins in the symptomatic management of
endometriosis: a meta-analysis on their effectiveness and safety" or "Effectiveness and Safety
on the use of progestins in endometriosis-related pain: A meta-analysis" (No capital letters).
English language revisions are required.
Background:
Table  1 is too simplistic to summarize endometriosis staging according to r-AFS classification.
Please add at the least the score required to be classified in each stage and maybe also some
examples.
"At present, the only definite way to diagnose and stage endometriosis is through visualisation
during surgery. " - I do not agree. Please, provide more references. According to World
Endometriosis Society (WES) either deep endometriosis or ovarian endometriosis can be
diagnosed with high accuracy and sensitivity by US-scans performed by skilled operators. Please
specify it in your manuscript.
"Endometriosis affects approximately 6-10% of women of reproductive age [9]. Ghiasi,
Kulkarni, and Missmer in 2020 [10], conducted a review of the global prevalence of
endometriosis between January 1989 and June 2019. Amongst the 28 research papers that
reported prevalence, 17 provided prevalence estimations in women with infertility, showing
a total prevalence of endometriosis of 27%. Likewise, 11 studies looked at the prevalence
of endometriosis in females presenting with persistent pelvic pain, showing a 29% overall
prevalence of endometriosis. Twelve studies looked at the prevalence of endometriosis in
patients who have had a hysterectomy, ovarian cancer, and tubal sterilization reported a
prevalence of 16%, 10%, and 5% respectively. This study also reported the range prevalence of
endometriosis in different geographical regions. In Africa, the prevalence ranged from 0.2-48%,
and in Australia, the range was 3.4-3.7%. The prevalence estimations ranges were much larger in
America, Asia, and Europe, being 0.7-70%, 1-72%, and 0.8-70% respectively. A large limitation
of this review is the complexity in endometriosis diagnosis, creating challenges in defining a
true population prevalence [10]." - I would move this paragraph after the current first (it is the
epidemiological background).
Methods:
Please add more information on exclusion criteria (i.e. studies on animals, case series, case
reports...).
Why did you choose to adopt the CASP tools to assess the quality of the research? Please add
more explanation on your choice.
Please provide more information on the statistical approach you've chosen. How did you
modeled the fixed or the random effect approach?
Also, did you performed a small-study effect analysis to assess publication biases?
Results:
Table 2: please add columns for N of treated, N of untreated and for year of enrollment (not year
of publication); also, localization of endometriosis disease and a description on main symptoms
in original studies should be provided.
Figure 4: quality of the figure is very poor.
Table 3: please add absolute values (not only percentages)
Figure 5: please rename "events" columns with "no events" referring to no AE.
Overall: Please specify that 96 to 99% heterogeneity is very high rather than considerable. Please
add publication bias analysis (or even only a funnel plot for visual inspection).
Discussion:
Please add more personal comments: how your results may impact clinical practice?
Overall:
I suggest to perform also subgroup analysis to investigate the high heterogeneity of the pooled
risk estimates.