Reviewer ’s report  
 
Title: Effects of oral contraceptives and natural menstrual cycling on  environmental learning  
 
Version: 0 Date: 15 Mar 2018  
 
Reviewer: MARIE -FRANCE MARIN  
 
Reviewer's report:  
 
Summary: The authors investigated whether naturally -cycling women and oral contraceptive 
users differ in their learning and recall of a topographical memory task. They assess this at two 
time points (at day 4 -5 and day 20 -21 of the menstr ual cycle for the naturally cycling women; 
day 2 -4 and day 20 -21 for the oral contraceptive users). They found that women using oral 
contraceptives are better at learning the 8 -step sequence path relative to OC users. No effects 
were found for delayed reca ll and no effect of testing time was found.  
 
 
Topic is interesting: I am unclear on certain points (see below). In my opinion, more information 
and some specification are needed from the authors to improve the manuscript.  
 
 
 
Comments:  
 
In the abstract, the authors seem to refer to 'oestrogens' to discuss the endogenous production of 
sex hormones and refer to 'estradiol' for the exogenous administration (given that exogenous 
methods can specifically target E2). However, in the manuscript, both estradiol and o estrogens 
are used to refer to endogenous production (for example, page 8: line 7, line 28, line 39, line 58). 
It might be good to harmonize the text or to specify the use of the terms in different contexts.  
 
 
There is one sentence about cortisol in the in troduction. This lacks justification and integration in 
the current literature (mostly focused on sex hormones and memory/cognitive functions).  
 
 
Sentence to break down or elaborate because it is difficult to follow:  
 
In general, low (early follicular and the entire follicular for oestrogens and progesterone, 
respectively) and high (mid - and late -luteal phase for both estrogens and progesterone)  
 
 
Please reword: 'Being hormonal fluctuations controlled in OC users'.  
 
 
The idea about the athletes (page 9, line 7) lacks integration in the literature. There is no context. 
If the same study was done in athletes, the authors need to explain it a little bit more and most 
importantly, state how their study is different (what ques tion is addressed specifically in their 
study that could not be answered from study #37).  
 
 
It is mentioned that NCW reported a regular menstrual cycle. Would be important to state how 
the authors define 'regular' menstrual cycle (for example, duration).  
 
 
Do the authors have information about previous use of OC in for the NCW group?  
 
 
What is the anamnesis questionnaire? What does it assess?  
 
 
In the methods, the authors mention that Day 4 -5 refer for the first day of the inactive pill phase - 
whereas they st ate Day 6 in the introduction (for OC group).  
 
 
I thought that each woman was tested twice (once in the follicular phase and once in the luteal 
phase for the NCW group, for example). However, the last sentence of the methodology section 
is a little confusin g to me. The authors state that the phases were randomized across participants. 
Do they mean that the order of the phase in which participants are tested (follicular before luteal 
vs. luteal before follicular) is counterbalanced across participants OR that  participants are 
randomly assigned to be tested either in the luteal phase or the follicular phase.  
 
 
The statistics used are not clear for me. Why are two ANOVAs necessary (one for learning and 
one for recall)? They could treat memory as a repeated -measu re (with immediate vs. delayed 
recall) and therefore only perform one ANOVA (and decompose significant interaction, if 
necessary).  
 
 
It would have been interesting to assess other memory domains in order to test whether some 
effects are specific to certain  types of memory (in the same sample). This could be discussed in 
the limitation section. Also, it would have been interesting to add a group of men in order to have 
a better understanding about sex differences and hormonal difference.  
 
 
The authors refer t o cortisol in their discussion to explain their findings. The study that they cite 
has shown that the impact of cortisol (exogenously administered) was attenuated for women 
using OC. I do not think that this is relevant in the context of the current study,  where the 
participants were not stressed and they did not receive exogenous cortisol. At this point, the 
discussion is weak and required further elaboration.  
 
Are the methods appropriate and well described?  
If not, p lease 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.  
 
Yes 
 
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 statistical review is recommended, please specify 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:  
 
Needs some language corrections before being published  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, f ees, funding, or salary from an 
organisation that may in any way gain or lose financially from the publi cation of this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation t hat may in any way gain or lose 
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you curr ently applying for any patents  relating to the content of the 
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any  other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
If you can answer no to all of the above, write 'I declare that I have  no competing interests' 
below. If your reply is yes to any, please give details below.  
 
I declare that I have no competing inter ests 
 
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