Reviewer's report 
 Melatonin effects on luteinizing hormone in postmenopausal women: A pilot clinical trial Title: 
NCT00288262 
 2  30 March 2006 Version: Date: 
 Alfred J Lewy Reviewer: 
Reviewer's report: 
General 
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Major Compulsory Revisions (that the author must respond to before a decision on publication can 
be reached) 
The authors have not made it easy to determine what changes have actually been made in the 
manuscript, since they have not identified them by line and page number. Nor have they restated my 
suggestions for improvement in their entirety. Perhaps this is one reason why they have not 
addressed these concerns more completely. 
1) The prospective hypotheses have been clarified. 
2) The rank-order correlation between blood and urine LH was provided but not the parametric 
correlation. 
3) The figures greatly improve the ms. 
4) By way of clarification, I requested the power analysis to determine the number of subjects 
needed to provide more than marginal statistical significance should the difference between means 
remain the same, which is expected. Instead, the authors have used the power analysis to predict 
what difference between means would be significant given the same sample size. The authors 
conclude that their results calls for a larger study; with all of the hard work and good intentions that 
went into this study, it would be worthwhile if they could come up with some of their own ideas for 
improving the methodology of the proposed larger study -- if they think that they know why some 
studies show positive results and others do not, would it not be advisable to test both methodologies in this larger, proposed study; also, given that the recently identified Bellipanni study found the predicted decrease in LH in younger women, but not menopausal women, would the new study 
continue to include only older women (especially if one of the goals is to test the safety of melatonin 
in women of child-bearing potential)? Also, one very important question for the next study that is not 
discussed is the age group: if the authors are mainly interested in hot flashes, then the older group is 
more appropriate; if it is LH that is of most interest, then a younger group should be studied. The 
authors continue to think that the changes in the placebo group, though larger than in the 
experimental groups, may not be real or otherwise worth discussing in the text. 
5) The authors have elected not to use the opportunity of publishing this paper to more carefully 
review the literature. The literature cited continues to be rather uncritical: for example, although 
Suhner published an abstract in 2003, why is there no full paper on this study published three years later? 
Finally, I agree with the authors about the importance of publishing the results from a clinical trial, 
whether they are positive, negative or equivocal. The authors recommend a larger trial based on the 
fact that in many ways their study falls into the latter category. However, they make no suggestions 
for changes in methodology. It would be very useful for the authors to tell us what they would 
suggest for changes of methodology in future studies that they have learned from their study (or from the recently identified 2001 publication). 
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Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the author can be trusted to correct) 
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Discretionary Revisions (which the author can choose to ignore) 
 Unable to decide on acceptance or rejection until the authors have responded to the What next?: 
major compulsory revisions 
 An article of importance in its field Level of interest: 
 Acceptable Quality of written English: 
 No Statistical review: 
Declaration of competing interests: 
I am co-inventor on several melatonin use-patents owned by my university currently not licensed by 
any company.