Title: Gastrointestinal Functioning and Menstrual Cycle Phase in Emerging Young Adult
Women: A Cross-Sectional Study
Version: 2 Date: 09 Aug 2023
Reviewer's report:
This manuscript presents a survey study in which the authors sought to differentiate between
symptoms arising from variations in the menstrual cycle and disorders related to the gut-brain
interaction. While this research topic is very intriguing, the cross-sectional study design and the
crude menstrual stage categorization method are far from optimal to address the main research
question. Also, the  Detailed comments are below.
1. Background: The authors claimed that few studies have examined the relationship between GI
symptoms and menstrual cycle. This is not true. Many key references are missing regarding GI
symptoms across menstrual cycle and menstrual GI symptoms. Some examples are listed below.
Please better synthesize the literature regarding what is know about the relationship between GI
symptoms and menstrual cycle and its mechanisms.
# Houghton LA, Lea R, Jackson N, et al. The menstrual cycle affects rectal sensitivity in patients
with irritable bowel syndrome but not healthy volunteersGut 2002;50:471-474.
# Heitkemper, Margaret M., et al. "Symptoms across the menstrual cycle in women with irritable
bowel syndrome." The American journal of gastroenterology 98.2 (2003): 420-430.
# Chen, C. X., Ofner, S., Bakoyannis, G., Kwekkeboom, K. L., & Carpenter, J. S. (2018).
Symptoms-based phenotypes among women with dysmenorrhea: A latent class analysis.
Western journal of nursing research, 40(10), 1452-1468.
# Heitkemper, M. M., J. F. Shaver, and E. S. Mitchell. "Gastrointestinal symptoms and bowel
patterns across the menstrual cycle in dysmenorrhea." Nursing research 37.2 (1988): 108-113.
2. Crohn’s disease is a type of IBD. You don’t have to list both IBD and Crohn’s disease as
if they are different.
3. It is not clear why anxiety but not depression was examined. One of the cited references
(Bernstein et al. 2014) has shown higher menstrual/premenstrual GI symptom burden among
those who reported emotional symptoms such as depressive symptoms. Literature has also
connected IBS and depression. Please provide additional justification for why only anxiety was
included. Otherwise, please acknowledge this as a limitation in the discussion.
4. Page 4. In the subsections “objectives of the current study,” what do you mean by
“standardized clinical measures?”
5. Page 5. The statement of the second objective is broad and vague. There have been studies
more comprehensively evaluating PROMIS-GI scales. May be better to say this study examined
if PROMIS-GI scores varied by menstrual stage.
6. (Major).For methods, please describe the study design and justification of the study design.
It seems the authors used cross-sectional design to distinguish GI symptoms due to menstrual
cycle variation and DGBI. The cross sectional design  mixes the within-person differences
and between-person differences and doesn’t really address the main research question. Please
provide rationale for your study design and discuss this as a significant limitation.
7. The authors hypothesized that pain reported during the menses would be in the lower
abdominal region where the female reproductive organs are located (Page 5). It is clinically
and scientifically known that visceral pain including pain related to uterus can be diffused/
poorly located. Referred pain and pain beyond low abdomen have been commonly reported
among women with dysmenorrhea (See some of references above and Brumovsky PR, Gebhart
GF. Visceral organ cross-sensitization - an integrated perspective. Auton Neurosci. 2010
Feb 16;153(1-2):106-15. doi: 10.1016/j.autneu.2009.07.006. Please address this issue in the
discussion.
8. For measures. There are multiple versions of PROMIS GI scales, please be specific which
version was used and what the recall period was. Please provide reference(s) for suggested
PROMIS GI cut of score.
9.  Please provide recall period for abdominal pain scale and map and SHAI.
10. For analysis (page 7), how do you define “irregular cycles?” Also what doe you mean by
“inconsistent in reporting menses onset and ending dates?”
11. It seems to me that the authors only included those who were receiving medical treatment
for DGBI group. What about those with DGBI diagnosis but not receiving treatment?
12. Some texts in results fit better with methods/analysis. This includes types of statistical tests
and how sample matching was achieved.
13. Please organize the results by study aims to increase readability.
14. The lack of differences in GI symptoms across cycle phase can be due to problematic
menstrual cycle categorization approach, mixing within-person and between-person differences,
and selection of measurement tools (e.g., a longer recall period would not reflect the current
symptoms). Please discuss these factors.
15. Please discuss the implications for future research. Given the limitations of the current study,
how future researchers can design better research to address your main research question.
Title: Gastrointestinal Functioning and Menstrual Cycle Phase in Emerging Young Adult
Women: A Cross-Sectional Study
Version: 2 Date: 09 Aug 2023
Reviewer's report:
This manuscript presents a survey study in which the authors sought to differentiate between
symptoms arising from variations in the menstrual cycle and disorders related to the gut-brain
interaction. While this research topic is very intriguing, the cross-sectional study design and the
crude menstrual stage categorization method are far from optimal to address the main research
question. Also, the  Detailed comments are below.
1. Background: The authors claimed that few studies have examined the relationship between GI
symptoms and menstrual cycle. This is not true. Many key references are missing regarding GI
symptoms across menstrual cycle and menstrual GI symptoms. Some examples are listed below.
Please better synthesize the literature regarding what is know about the relationship between GI
symptoms and menstrual cycle and its mechanisms.
# Houghton LA, Lea R, Jackson N, et al. The menstrual cycle affects rectal sensitivity in patients
with irritable bowel syndrome but not healthy volunteersGut 2002;50:471-474.
# Heitkemper, Margaret M., et al. "Symptoms across the menstrual cycle in women with irritable
bowel syndrome." The American journal of gastroenterology 98.2 (2003): 420-430.
# Chen, C. X., Ofner, S., Bakoyannis, G., Kwekkeboom, K. L., & Carpenter, J. S. (2018).
Symptoms-based phenotypes among women with dysmenorrhea: A latent class analysis.
Western journal of nursing research, 40(10), 1452-1468.
# Heitkemper, M. M., J. F. Shaver, and E. S. Mitchell. "Gastrointestinal symptoms and bowel
patterns across the menstrual cycle in dysmenorrhea." Nursing research 37.2 (1988): 108-113.
2. Crohn’s disease is a type of IBD. You don’t have to list both IBD and Crohn’s disease as
if they are different.
3. It is not clear why anxiety but not depression was examined. One of the cited references
(Bernstein et al. 2014) has shown higher menstrual/premenstrual GI symptom burden among
those who reported emotional symptoms such as depressive symptoms. Literature has also
connected IBS and depression. Please provide additional justification for why only anxiety was
included. Otherwise, please acknowledge this as a limitation in the discussion.
4. Page 4. In the subsections “objectives of the current study,” what do you mean by
“standardized clinical measures?”
5. Page 5. The statement of the second objective is broad and vague. There have been studies
more comprehensively evaluating PROMIS-GI scales. May be better to say this study examined
if PROMIS-GI scores varied by menstrual stage.
6. (Major).For methods, please describe the study design and justification of the study design.
It seems the authors used cross-sectional design to distinguish GI symptoms due to menstrual
cycle variation and DGBI. The cross sectional design  mixes the within-person differences
and between-person differences and doesn’t really address the main research question. Please
provide rationale for your study design and discuss this as a significant limitation.
7. The authors hypothesized that pain reported during the menses would be in the lower
abdominal region where the female reproductive organs are located (Page 5). It is clinically
and scientifically known that visceral pain including pain related to uterus can be diffused/
poorly located. Referred pain and pain beyond low abdomen have been commonly reported
among women with dysmenorrhea (See some of references above and Brumovsky PR, Gebhart
GF. Visceral organ cross-sensitization - an integrated perspective. Auton Neurosci. 2010
Feb 16;153(1-2):106-15. doi: 10.1016/j.autneu.2009.07.006. Please address this issue in the
discussion.
8. For measures. There are multiple versions of PROMIS GI scales, please be specific which
version was used and what the recall period was. Please provide reference(s) for suggested
PROMIS GI cut of score.
9.  Please provide recall period for abdominal pain scale and map and SHAI.
10. For analysis (page 7), how do you define “irregular cycles?” Also what doe you mean by
“inconsistent in reporting menses onset and ending dates?”
11. It seems to me that the authors only included those who were receiving medical treatment
for DGBI group. What about those with DGBI diagnosis but not receiving treatment?
12. Some texts in results fit better with methods/analysis. This includes types of statistical tests
and how sample matching was achieved.
13. Please organize the results by study aims to increase readability.
14. The lack of differences in GI symptoms across cycle phase can be due to problematic
menstrual cycle categorization approach, mixing within-person and between-person differences,
and selection of measurement tools (e.g., a longer recall period would not reflect the current
symptoms). Please discuss these factors.
15. Please discuss the implications for future research. Given the limitations of the current study,
how future researchers can design better research to address your main research question.
Please review this paper.
user
Title: Gastrointestinal Functioning and Menstrual Cycle Phase in Emerging Young Adult
Women: A Cross-Sectional Study
Version: 2 Date: 09 Aug 2023
Reviewer's report:
This manuscript presents a survey study in which the authors sought to differentiate between
symptoms arising from variations in the menstrual cycle and disorders related to the gut-brain
interaction. While this research topic is very intriguing, the cross-sectional study design and the
crude menstrual stage categorization method are far from optimal to address the main research
question. Also, the  Detailed comments are below.
1. Background: The authors claimed that few studies have examined the relationship between GI
symptoms and menstrual cycle. This is not true. Many key references are missing regarding GI
symptoms across menstrual cycle and menstrual GI symptoms. Some examples are listed below.
Please better synthesize the literature regarding what is know about the relationship between GI
symptoms and menstrual cycle and its mechanisms.
# Houghton LA, Lea R, Jackson N, et al. The menstrual cycle affects rectal sensitivity in patients
with irritable bowel syndrome but not healthy volunteersGut 2002;50:471-474.
# Heitkemper, Margaret M., et al. "Symptoms across the menstrual cycle in women with irritable
bowel syndrome." The American journal of gastroenterology 98.2 (2003): 420-430.
# Chen, C. X., Ofner, S., Bakoyannis, G., Kwekkeboom, K. L., & Carpenter, J. S. (2018).
Symptoms-based phenotypes among women with dysmenorrhea: A latent class analysis.
Western journal of nursing research, 40(10), 1452-1468.
# Heitkemper, M. M., J. F. Shaver, and E. S. Mitchell. "Gastrointestinal symptoms and bowel
patterns across the menstrual cycle in dysmenorrhea." Nursing research 37.2 (1988): 108-113.
2. Crohn’s disease is a type of IBD. You don’t have to list both IBD and Crohn’s disease as
if they are different.
3. It is not clear why anxiety but not depression was examined. One of the cited references
(Bernstein et al. 2014) has shown higher menstrual/premenstrual GI symptom burden among
those who reported emotional symptoms such as depressive symptoms. Literature has also
connected IBS and depression. Please provide additional justification for why only anxiety was
included. Otherwise, please acknowledge this as a limitation in the discussion.
4. Page 4. In the subsections “objectives of the current study,” what do you mean by
“standardized clinical measures?”
5. Page 5. The statement of the second objective is broad and vague. There have been studies
more comprehensively evaluating PROMIS-GI scales. May be better to say this study examined
if PROMIS-GI scores varied by menstrual stage.
6. (Major).For methods, please describe the study design and justification of the study design.
It seems the authors used cross-sectional design to distinguish GI symptoms due to menstrual
cycle variation and DGBI. The cross sectional design  mixes the within-person differences
and between-person differences and doesn’t really address the main research question. Please
provide rationale for your study design and discuss this as a significant limitation.
7. The authors hypothesized that pain reported during the menses would be in the lower
abdominal region where the female reproductive organs are located (Page 5). It is clinically
and scientifically known that visceral pain including pain related to uterus can be diffused/
poorly located. Referred pain and pain beyond low abdomen have been commonly reported
among women with dysmenorrhea (See some of references above and Brumovsky PR, Gebhart
GF. Visceral organ cross-sensitization - an integrated perspective. Auton Neurosci. 2010
Feb 16;153(1-2):106-15. doi: 10.1016/j.autneu.2009.07.006. Please address this issue in the
discussion.
8. For measures. There are multiple versions of PROMIS GI scales, please be specific which
version was used and what the recall period was. Please provide reference(s) for suggested
PROMIS GI cut of score.
9.  Please provide recall period for abdominal pain scale and map and SHAI.
10. For analysis (page 7), how do you define “irregular cycles?” Also what doe you mean by
“inconsistent in reporting menses onset and ending dates?”
11. It seems to me that the authors only included those who were receiving medical treatment
for DGBI group. What about those with DGBI diagnosis but not receiving treatment?
12. Some texts in results fit better with methods/analysis. This includes types of statistical tests
and how sample matching was achieved.
13. Please organize the results by study aims to increase readability.
14. The lack of differences in GI symptoms across cycle phase can be due to problematic
menstrual cycle categorization approach, mixing within-person and between-person differences,
and selection of measurement tools (e.g., a longer recall period would not reflect the current
symptoms). Please discuss these factors.
15. Please discuss the implications for future research. Given the limitations of the current study,
how future researchers can design better research to address your main research question.
assistant