Reviewer ’s report  
 
Title: Stool frequency and form and gastrointestinal symptoms  differ by day of the menstrual 
cycle in healthy adult women taking oral contraceptives: a prospective observational study  
 
Version: 1 Date: 03 Feb 2020  
 
Reviewer: Andrea Rapkin  
 
Reviewer's report:  
 
Please i nclude all comments for the authors in this box rather than uploading your report as an 
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Please overwrite this text when adding your comments to the authors.Abstract, page 1 Line 23: 
Menstrual pain and pain from GI symptoms can't be separated  
 
Abstract, page 2 Line 35: Misleading did not differ by day of the menstrual cycle.  Symptoms 
differed only between days of menstrual bleeding and other times of the cycle. Abstract should 
be clear, unfortunately many  never get past the abstract.  
 
Page 3, Line 41 -42: Not clear if this is days 12, 8, 6, 4 and 2 of menstrual cycle and why t hese 
days were chosen?  
 
Page 3, Line 46:  Suggest rephrase "Bowel habits appear to differ between the day 1 of menstrual 
bleeding and the remainder of the cycle.  
 
Page 3, line 47: Sentence  is misleading:  increased abdominal discomfort day 1 of bleeding is 
not necessarily due to GI sx  
 
Usual menstrual pain severity and location were not ascertained.  
 
Page 3, Line 50: Remove Premenstrual syndrome, the paper has nothing to do with PMS  
 
Page 4, Line 59:  The introduction  focuses  on hormonal changes across the cy cle when the  
study design precludes this evaluation. The study can only assess the effects of menstruation vs 
rest of cycle as its completely unknown when the hormone withdrawal occurred w r t menses in 
these women on OC s  
 
Ref 11 related to the diuretic effect of continuous DRSP containing OC, not sensory changes  
 
Page 6, Line 111 -114: Unrelated to current study. You have no information on which days are 
premenstrual as some women may have been taking 24 4 cycleand some 21 7 cycle pills. . 
Suggest removal of information related to PMS  or also  note effects of cyclic OCs on PMS  
 
 Line 118: effect of menstrual cycle in women taking OCs  
 
Page 7, Line 121: Why did you hypothesize this when women were taking OCPS and do not 
have day to day hormonal changes? You can hypothesize changes w hormone withdrawal or 
menses only but design did not allow AU to determine how symptoms varied with hormone 
withdrawal compared with menses  
 
 Were women taking nsaids excluded? This can confound res ults as NSAIDS can affect GI tract  
 
Page 7, Line 140: What is meant by appropriate time points in light of the above ?  
 
Page 10, Line 186: No ovulation  
 
Page 12. Line 242: not reproductive hormones, 17 B estradiol and progesterone,  only synthetic 
hormones ethinyl estradiol and a progestin  
 
Page 12, line 244: Incorrect interpretation: Progesterone has been suppressed by OCPS, there is 
progestin throughout the cycle until last day of pill pack but AU do not know when that was 
compared t o day 1 of bleeding  
 
In fact the 2 days prior to menses have little to no progestin, depending on the half life of the 
progestin in the particular formulation  
 
 
Discussion:  
 
Compare w other studies of GI  function and menstrual cycle. For ex Heitcemper et al  did 
include women on OCs and controls in her IBS and IBD studies.  
 
Am J Gastroenterol. 2003 Feb;98(2):420 -30.A daily diary was used to assess symptoms across 
one menstrual cycle. Repeated -measures analysis of covariance, controlling for age and body 
mass i ndex, was used to compare patterns of symptoms across the menstrual cycle by oral 
contraceptive use and predominant bowel pattern (diarrhea, constipation, alternating). Data from 
control women are presented for comparison.. The pattern of symptoms over the  menstrual cycle 
did not differ by predominant bowel pattern or by oral contraceptive use.Many of the symptoms 
examined differed by predominant bowel pattern and menstrual cycle phase, not just the GI 
symptoms. The menstrual cycle variation was similar reg ardless of oral contraceptive use or 
predominant bowel pattern.  
 
 
Flaws of study:  
 
unknown which days pts were taking active pills  
 
whether nsaids were taken  
 
 If PMS was a topic of study , mood was not assessed throughout cycle  
 
Dose, formulation and regimen o f pills unknown  
 
Usual menstrual pain not noted so inc abdominal pain w day 1 of bleeding isn't necessarily due 
to GI sx  
 
 Intake of nsaids not noted , could inc indigestion be due to NSAIDs?  
Extended cycle pills not noted as a possible solution , why just d ietary and lifestyle?  
 
Are the methods appropriate a nd well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
No 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
Are you able to assess any statistics in the manus cript or would you recommend an 
additional statistical review?  
If an additional s tatistical review is recommended, please speci fy what aspects require further 
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
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futur e? 
 
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