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25-Hydroxyvitamin D and Long Menstrual Cycles in a Prospective Cohort Study.

ABSTRACT: BACKGROUND:Vitamin D insufficiency is associated with subfertility and prolonged estrus cycles in animals, but humans have not been well studied. METHODS:A prospective time-to-pregnancy study, Time to Conceive (2010-2015), collected up to 4 months of daily diary data. Participants were healthy, late reproductive-aged women in North Carolina who were attempting pregnancy. We examined menstrual cycle length as a continuous variable and in categories: long (35+ days) and short (?25 days). Follicular phase length and luteal phase length were categorized as long (18+ days) or short (?10 days). We estimated associations between those lengths and serum 25-hydroxyvitamin D (25[OH]D) using linear mixed models and marginal models. RESULTS:There were 1,278 menstrual cycles from 446 women of whom 5% were vitamin D deficient (25[OH]D, <20?ng/ml), 69% were between 20 and 39?ng/ml, and 26% were 40?ng/ml or higher. There was a dose-response association between vitamin D levels and cycle length. Compared with the highest 25(OH)D level (?40?ng/ml), 25(OH)D deficiency was associated with almost three times the odds of long cycles (adjusted odds ratio [aOR] = 2.8 [95% confidence interval (CI) = 1.0, 7.5]). The aOR was 1.9 (1.1, 3.5) for 20 to <30?ng/ml. The probability of a long follicular phase and the probability of a short luteal phase both increased with decreasing 25(OH)D. CONCLUSIONS:Lower levels of 25(OH)D are associated with longer follicular phase and an overall longer menstrual cycle. Our results are consistent with other evidence supporting vitamin D's role in the reproductive axis, which may have broader implications for reproductive success.

SUBMITTER: Jukic AMZ

PROVIDER: S-EPMC5882585 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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25-Hydroxyvitamin D and Long Menstrual Cycles in a Prospective Cohort Study.

Jukic Anne Marie Z AMZ Wilcox Allen J AJ McConnaughey D Robert DR Weinberg Clarice R CR Steiner Anne Z AZ

Epidemiology (Cambridge, Mass.) 20180501 3

<h4>Background</h4>Vitamin D insufficiency is associated with subfertility and prolonged estrus cycles in animals, but humans have not been well studied.<h4>Methods</h4>A prospective time-to-pregnancy study, Time to Conceive (2010-2015), collected up to 4 months of daily diary data. Participants were healthy, late reproductive-aged women in North Carolina who were attempting pregnancy. We examined menstrual cycle length as a continuous variable and in categories: long (35+ days) and short (≤25 d ...[more]

PMID: 29337846

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Project description:BackgroundDespite its importance to women's reproductive health and its impact on women's daily lives, the menstrual cycle, its regulation, and its impact on health remain poorly understood. As conventional clinical trials rely on infrequent in-person assessments, digital studies with wearable devices enable the collection of longitudinal subjective and objective measures.ObjectiveThe study aims to explore the technical feasibility of collecting combined wearable and digital questionnaire data and its potential for gaining biological insights into the menstrual cycle.MethodsThis prospective observational cohort study was conducted online over 12 weeks. A total of 42 cisgender women were recruited by their local gynecologist in Berlin, Germany, and given a Fitbit Inspire 2 device and access to a study app with digital questionnaires. Statistical analysis included descriptive statistics on user behavior and retention, as well as a comparative analysis of symptoms from the digital questionnaires with metrics from the sensor devices at different phases of the menstrual cycle.ResultsThe average time spent in the study was 63.3 (SD 33.0) days with 9 of the 42 individuals dropping out within 2 weeks of the start of the study. We collected partial data from 114 ovulatory cycles, encompassing 33 participants, and obtained complete data from a total of 50 cycles. Participants reported a total of 2468 symptoms in the daily questionnaires administered during the luteal phase and menses. Despite difficulties with data completeness, the combined questionnaire and sensor data collection was technically feasible and provided interesting biological insights. We observed an increased heart rate in the mid and end luteal phase compared with menses and participants with severe premenstrual syndrome walked substantially fewer steps (average daily steps 10,283, SD 6277) during the luteal phase and menses compared with participants with no or low premenstrual syndrome (mean 11,694, SD 6458).ConclusionsWe demonstrate the feasibility of using an app-based approach to collect combined wearable device and questionnaire data on menstrual cycles. Dropouts in the early weeks of the study indicated that engagement efforts would need to be improved for larger studies. Despite the challenges of collecting wearable data on consecutive days, the data collected provided valuable biological insights, suggesting that the use of questionnaires in conjunction with wearable data may provide a more complete understanding of the menstrual cycle and its impact on daily life. The biological findings should motivate further research into understanding the relationship between the menstrual cycle and objective physiological measurements from sensor devices.

Project description:BACKGROUND:Vitamin D deficiency during pregnancy is associated with adverse pregnancy outcomes, although the association between preconception vitamin D concentrations and livebirth is unknown. We aimed to assess the association between preconception vitamin D and pregnancy outcomes among women with proven fecundity. METHODS:We did a secondary analysis of a prospective cohort from the block-randomised, double-blind, placebo-controlled EAGeR trial. Women aged 18-40 years with one to two previous pregnancy losses were recruited from June 15, 2007, to July 15, 2011, at four clinical sites in the USA and followed up for up to six menstrual cycles while attempting pregnancy and throughout pregnancy if they conceived. Serum 25-hydroxyvitamin D was measured at baseline (preconception) and 8 weeks of gestation. Outcomes of interest included clinical pregnancy, time to pregnancy, pregnancy loss, and livebirths. Risk ratios (RRs) and 95% CIs for livebirths, pregnancy, and pregnancy loss were estimated with weighted log-binomial regression. To assess time to pregnancy, we used discrete time Cox proportional hazards models to calculate fecundability odds ratios (FORs) with 95% CIs. EAGeR is registered with ClinicalTrials.gov, number NCT00467363. FINDINGS:1191 women had available data on preconception 25-hydroxyvitamin D concentrations. 555 (47%) women were classified as having sufficient concentrations (≥75 nmol/L) and 636 (53%) as having insufficient concentrations (<75 nmol/L). Women with sufficient preconception 25-hydroxyvitamin D were more likely to achieve clinical pregnancy (adjusted RR 1·10 [1·01-1·20]) and livebirth (1·15 [95% CI 1·02-1·29]) than were women with insufficient concentrations. Among women who achieved pregnancy, sufficient preconception 25-hydroxyvitamin D, but not that at 8 weeks of gestation, was associated with reduced risk of pregnancy loss (preconception RR per 25 nmol/L 0·88 [95% CI 0·77-0·99]; 8 weeks of gestation 0·98 [0·95-1·01]). No association was observed with fecundability in women with sufficient versus those with insufficient preconception 25-hydroxyvitamin D concentrations (adjusted FOR 1·13 [95% CI 0·95-1·34]). INTERPRETATION:Sufficient preconception 25-hydroxyvitamin D (≥75 nmol/L) was associated with increased likelihood of pregnancy and livebirth. Increased vitamin D concentrations before conception, but not in early pregnancy, were associated with reduced pregnancy loss. FUNDING:National Institutes of Health and Doris Duke Charitable Foundation.

Project description:UnlabelledIn exploring relationships between vitamin D status in childhood and cortical bone, little relationship was observed with plasma concentrations of 25-hydroxyvitamin-D(2) [25(OH)D(2)], whereas 25-hydroxyvitamin-D(3) [25(OH)D(3)] was positively related to cortical bone mineral content (BMC(C)) and cortical thickness, suggesting D(3) exerts a beneficial effect on cortical bone development in contrast to D(2).IntroductionThe study is aimed to determine whether vitamin D status in childhood is related to cortical bone development by examining prospective relationships between plasma concentrations of 25(OH)D(2) and 25(OH)D(3) at 7.6, 9.9 or 11.8 years and peripheral quantitative computed tomography (pQCT) measurements of the mid-tibia at age 15.5 years, in children from the Avon Longitudinal Study of Parents and Children.MethodsRelationships between vitamin D status and pQCT outcomes were analysed by bootstrap linear regression, adjusted for age, sex, body composition, socioeconomic position and physical activity, in 2,247 subjects in whom all covariates were available. 25(OH)D(3) was also adjusted for season and 25(OH)D(2), and 25(OH)D(2) for 25(OH)D(3).Results25(OH)D(3) was positively related to BMC(C) [0.066(0.009,0.122), P?=?0.02], whereas no association was seen with 25(OH)D(2) [-0.008(-0.044,0.027), P?=?0.7] [beta (with 95% CI) represents SD changes per doubling of vitamin D], P?=?0.03 for difference in associations of 25(OH)D(2) and 25(OH)D(3) with BMC(C). There were also differences in associations with cortical geometry, since 25(OH)D(3) was positively related to cortical thickness [0.11(0.04, 0.19), P?=?0.002], whereas no association was seen with 25(OH)D(2) [-0.04(-0.08,0.009), P?=?0.1], P?=?0.0005 for difference. These relationships translated into differences in biomechanical strength as reflected by buckling ratio, which was positively related to 25(OH)D(2) [0.06(0.01,0.11), P?=?0.02] indicating less resistance to buckling, but inversely related to 25(OH)D(3) [-0.1(-0.19,-0.02), P?=?0.03], P?=?0.001 for difference.ConclusionsIn contrast to 25(OH)D(2), 25(OH)D(3) was positively related to subsequent cortical bone mass and predicted strength. In vitamin D-deficient children in whom supplementation is being considered, our results suggest that D(3) should be used in preference to D(2).

Dataset Information

25-Hydroxyvitamin D and Long Menstrual Cycles in a Prospective Cohort Study.

Publications

25-Hydroxyvitamin D and Long Menstrual Cycles in a Prospective Cohort Study.

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