Reviewer’ s report
Title: Effects of oral contraceptives and natural menstrual cycling on environmental learning
Version: 0Date: 16 Mar 2018
Reviewer: Christian Josef Merz
Reviewer's report:
Manuscript number: BMWH-D-17-00463Effects of oral contraceptives and natural menstrual
cycling on environmental learningIn this report, the authors describe a study conducted in womentaking oral contraceptives and naturally cycling women undergoing a test of topographicalmemory on two testing days: once during active pill intake or the mid-luteal-phase and onceduring inactive pill intake or the early follicular phase. Results showed that OC users had betterimmediate memory compared to naturally cycling women at both testing points, but comparablememory for a delayed recall task. The manuscript contributes to a vast literature concerning sexdifferences on memory processes. In my opinion, it is not ready for publication at this stage, I haveseveral substantial points, which need to be addressed by the authors.1. Abstract: topographicmemory should be described in more detail. The conclusion section should be re-writtencompletely; the mentioned sex difference was not tested here, the same applies for cortisol effects,I would not call the intake of oral contraceptives hormone THERAPY , the fact that OC containsynthetic hormones does not belong to the conclusion and it is not explained how this fact canexplain the enhancement of topographic memory.2. In the introduction and/or discussion, theauthors should also cite the prominent review of Montoya & Bos, published 2017 in TICS. Inaddition, negative feedback processes of the HPG-axis should be mentioned leading to lowendogenous sex hormone availability in OC users. Furthermore, the included pill should be
characterized as androgenic or anti-androgenic.3. In total, the introduction is quite long, not
focussed and unstructured. Please reduce the length substantially and delete non-important details(e.g., here and also in the discussion, I am wondering why there is a detour on cortisol effects).Please also think of whee to put a new paragraph.4. Methods: A negative t-value does not exist,please correct and also add the degrees of freedom.5. Since only one pill was included for thewhole OC group, it should be mentioned in the limitations that the results cannot be generalized toother pills, in particular containing different compounds, e.g. mono- or biphasic compositions. Infact, triphasic pills are not used that often compared to other pills, so the authors investigated aquite exclusive sample.6. The dependent variable derived from the WalCT test should be betterdescribed. What does 144 means as a maximum score? What is the minimum score? How is itcalculated?7. The factor order of testing sessions should be included in the statistical model toaccount for the variance related to this factor. The authors should also be more precise what itmeans that order of testing sessions was randomized across participants: how many women testedfirst during the off- vs. on-phase and during the midluteal vs. early follicular phase?8. The twophases are named 4th-5th and 20th-21st days, but this does not reflect the testing points for OCwomen, please correct.9. The delayed recall data should also be depicted in a figure, so that thereader can notice why the difference is gone (were OC women worse or naturally cycling womenbetter in delayed vs. immediate recall?). This fact could also be tested in an overall new ANOVA
including immediate vs. delayed recall as an additional factor.10. In the discussion, the authors
should try to speculate on the underlying mechanism of OC effects on topographical memory.
Which brain areas are targeted, which actions do OCs trigger in these brain areas and how areprogestin and estrogen receptors involved? How do low levels of natural estradiol andprogesterone explain the observed enhancement?11. The authors also mention that naturallycycling women have a slower performance, why slower? Were reaction times also measured?12.Under conclusions, no conclusions are given but limitations, please correct the header and insert anew conclusion section. The authors should also be more precise how their results can provideinsights for treatments in women with topographical disorders or visuo-spatial difficulties.13.Women take hormonal contraceptives for different reasons and can vary from naturally cycling
women due to different factors, e.g. related to culture, religion or personality. This discussion
should also be inserted. 14. In figure 1b, SE should be given and not SE, please also indicatesignificant results with an asterisk.15. English language should be checked professionally.
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
NoDoes the work include the necessary controls?
If not, please specify which controls are required in your comments to the authors.
NoAre 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 manuscript or would you recommend an
additional statistical review?If an additional statistical review is recommended, please specify what aspects require furtherassessment in your comments to the editors.
I am able to assess the statisticsQuality of written English
Please indicate the quality of language in the manuscript:
Not suitable for publication unless extensively editedDeclaration of competing interests
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