Title: Systematic Review and Meta-Analysis of the Etiology of Menorrhagia in 2,770 adolescent
females
Version: 1 Date: 18 Nov 2023
Reviewer:  Phuc Nhon Nguyen
Reviewer's report:
Dear authors,
I read with the great interest in your research since menorrhagia is affecting to 37% of
adolescents. Thank you for your work. The main findings of menorrhagia according to PALM-
COEIN classification in adolescent females are "A half of the cases had no identifiable
etiology (45.9%, 95%CredI 43.8–47.9). Ovarian Uterine Disorders (23.7%; 95% CredI 22-25.5),
Coagulation Disorders (19.4%; 95% CredI 17.8–21.1), and Platelet Disorders (6.23%; 95%
CredI 5.27–7.27)". The identifiable and structural etiologies are not the major cause in this
period.
However, I have alot of corcerns in your  database.
- Regarding inclusion criteria, you search the term " abnormal uterine bleeding (AUB)", "
menorrhagia", and " HMB" on internet database. But "AUB" is not the same to "menorrhagia",
and the authors did not exclude other etiologies in AUB  in Study flowchart (Fig 1).
- In table 1, criteria III, children are age from 0-21 years old. Please remember the aldolescent age
is from 10 to 19 years old following definition of WHO. How the authors include 0-9 and 20-21
years old in inclusion criteria? Even the child of 0-9 years old has not already the menstrual
period. Thus, it is not reality.
- In table 2, I try to reveal 2 studies with the high percentage of number including  the
studies of first author such as Khamees and Rose. But the data remains unclear. In study of
Khamees,  I found that  although the study included 673 young women, 16% of whom met the
study definition for severe heavy menstrual bleeding.  In the study of Rose, "There were 258
adolescents who sought care for HMB in the ED during the study period. A total of 44 patients
(17%) were admitted to the hospital, whereas 214 (83%) were discharged. In the admitted group,
the mean initial hemoglobin (Hgb) was 6.3 g/dL compared to 12.0 g/dL in the discharged group
(P < .0001).  Anovulation was the etiology of HMB in the majority (56%) of both inpatients and
outpatients. Of the 44 adolescents admitted to the hospital for HMB, 12 (27%) had a bleeding
disorder (BD) and 32 (73%) did not". I really concern that what is the benefit when the authors
included the total number of the study? Meanwhile, the rational etiology has a smaller number.
Therefore, the number of 2770 adolescent females is not true.
This is only 2 studies that I took a look, I don't be sure of other studies which the authors included.
-  Regardless of other Tables, I agree with the causes relating to platelet abmormalities, and
coagulation disorder bleeding since the laboratory tests are commonly easy to assess. However,
the  anovulation was the  most common etiology of HMB in the majority . This is the final
diagnosis after excluding other etiologies. In practice, we need to perform the ultrasonography,
the serum qualification of FSH, TSH, estroges, progesterone, even TSH, FT3, FT4, etc. It's not
easy under the gynecologist's eyes.
- The topic will be more significant when the authors discuss about menorrhagia in adolescent
in rural and urban region, at tertiary referral hospital and frontline hospital. Since the knowledge
of the patients and parents, the assessment of management are different.
-Some important documents  related to this subject should be included in your manuscript as
below:
+Munro MG, Critchley HOD, Fraser IS; FIGO Menstrual Disorders Committee. The two
FIGO systems for normal and abnormal uterine bleeding symptoms and classification of
causes of abnormal uterine bleeding in the reproductive years: 2018 revisions [published
correction appears in Int J Gynaecol Obstet. 2019 Feb;144(2):237]. Int J Gynaecol Obstet.
2018;143(3):393-408. doi:10.1002/ijgo.12666
+ Fraser IS, Critchley HO, Broder M, Munro MG. The FIGO recommendations on
terminologies and definitions for normal and abnormal uterine bleeding. Semin Reprod Med.
2011;29(5):383-390. doi:10.1055/s-0031-1287662
+Graham RA, Davis JA, Corrales-Medina FF. The Adolescent with Menorrhagia: Diagnostic
Approach to a Suspected Bleeding Disorder. Pediatr Rev. 2018;39(12):588-600. doi:10.1542/
pir.2017-0105
Best regards,