Reviewer's report
Title:Plasma 25-hydroxyvitamin D and risk of premenstrual syndrome in a
prospective cohort study
Version:1Date:17 January 2014
Reviewer: Sunni Mumford
Reviewer's report:
Major Compulsory Revisions
1. The authors point out that the median duration between blood collection and
later diagnosis in one cohort is 28 months and 22 months between diagnosis and
later blood collection in the other cohort. Unfortunately, given the half-life of
25(OH)D of only 3-4 weeks, the over two year and close to two year time frame
in between collection and later diagnosis or previous diagnosis of PMS, could be
seen as a major flaw in the design of the study. Vitamin D stores, as the authors
eluded to in their manuscript by accounting for season of blood draw, are
seasonal/temporal. For any given women, without taking into account
supplementation or dietary changes over the course of two years, the potential
for drastically different vitamin D stores exist. The authors report “Specifically,
each 10 nmol/L increase in 25OHD was associated with a 13% higher risk of
PMS (95% CI = 1.03 – 1.25). In contrast, 25OHD levels were not associated with
risk in cases with blood collected before diagnosis.” The authors go on to report
“Relations of 25OHD levels with individual menstrual symptoms also varied by
timing of blood collection. Among women with 25OHD measured before they
were diagnosed with PMS, plasma 25OHD levels were inversely related to risk of
developing breast tenderness, fatigue, diarrhea and/or constipation, and
depression (all P < 0.05; Table 3).”
In light of the aforementioned, these results are difficult to interpret. The authors
do, in the discussion, give an intraclass correlation comparing three
measurements of 25(OH)D over three years and a comparison prior to and after
menopause. However, given the major potential for significant intra-woman
variability, please elaborate on the impact this has on interpreting the results.
2. Materials and Methods, first paragraph under Laboratory measurement:
There is a recent trend in vitamin D measurement changing from the combination
of the two isoforms (25(OH)D2 and 25(OH)D3 ) to give a 25(OH)D level, to
measurement of 25(OH)D3 isoform alone. Also Vitamin D binding globulin
(VDBG) levels effect measurement of 25(OH)D level. Please clearly state 1.
What 25(OH)D level was measured and reasoning behind the specific
measurement chosen, for example assay/laboratory availability vs inherently low
levels of 25(OH)D2 across populations making negligible impact on total
25(OH)D level, and 2. How did the authors account for VDBG levels?
3. Materials and Methods, first paragraph under Laboratory measurement:
Please also refer to comment 6 below, the laboratory measurement of total
calcium is inherently flawed given that 40% of calcium is protein bound. Total
calcium, therefore, has to be adjusted for protein stores. An ionized calcium level
is a more accurate determination of serum calcium in the absence of protein
(albumin) information. Please state 1. The actual calcium level measured, and 2.
if total calcium measured, explain the lack of adjustment for albumin.
4. Materials and Methods, first paragraph under Laboratory measurement:
Please clarify if PTH drawn was an intact PTH (iPTH) level.
5. Materials and Methods, second paragraph under Statistical Analysis:
The authors state that the number of moles on lower leg was used as a measure
of skin tone. On one hand, this has the potential to carry more weight in the
statistical analysis, as out of all the matching factors listed, this has the potential
for the most direct association with sun light exposure. On the other hand, this
reviewer is unaware of any literature directly linking number of moles on lower
leg and measure of skin tone, or of direct sunlight exposure. Please provide
reference for the linkage. If indeed, number of moles on lower leg is a proven
marker of sunlight exposure, hence vitamin D exposure, please make the
appropriate adjustments in the statistical analysis.
6. Materials and Methods, last paragraph under Statistical Analysis:
The authors adjusted for season of lab draw in the unconditional logistic
regression, but not other factors known to influence vitamin D measurements,
including physical activity (indoor vs outdoor time activity and exposure to
sunlight) and protein stores, which impact both vitamin D and calcium levels.
Please take into consideration indoor vs outdoor physical activity and report
adjustments accordingly.
7. The authors return frequently in their manuscript to the concept that the
association between calcium, vitamin D, pth and PMS could be related to use of
calcium and vitamin D supplements to treat existing PMS, and also report in the
discussion that the positive association was limited to women taking
supplements. If data is available, please comment on the range of type and
amount of supplement. If able to, statistical analysis should be perform based on
Endocrine Society or other guidelines for supplement amounts based on age.
- Minor Essential Revisions
1. Materials and Methods, first paragraph under Assessment of Premenstrual
Syndrome, last sentence: Please clearly state: 1. what type of cancer was part of
exclusion criteria, 2. how infertility was defined in the questionnaire used for
exclusion criteria, and 3. how “highly irregular” menstrual cycles were defined in
the questionnaire used for exclusion criteria
2. Materials and Methods, first paragraph under Assessment of Premenstrual
Syndrome:
The authors state that women who did not report a diagnosis of PMH in 1989 or
1991 were “thus at risk for being diagnosed with PMS during follow-up.” The use
of the word “risk” is misleading. As it is used now, it implies that all nurses
responding to the questionnaires had inherent risk to develop PMS.
3. Results section, second paragraph
Authors state “25OHD (91.6 nmol/L) was 1.26 (95% CI = 0.79 – 2.02) compared
to the lowest quintile (median = 42.4 nmol/L). “ Please be consistent with
reporting of 25OHD levels, i.e. comparing median to median so if report (median
= 42.4 nmol/L) then report (median = 91.6 nmol/L).
4. Results section and Table 1 :
Please be consistent when reporting P values out number of decimal spaces.
- Discretionary Revisions
None
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests