25-hydroxyvitamin D and long menstrual cycles in a prospective cohort study.
Epidemiology. 2018 Jan 15. doi: 10.1097/EDE.0000000000000804. [Epub ahead of print]
Jukic AMZ, Wilcox AJ1, McConnaughey DR2, Weinberg CR3, Steiner AZ4.
Vitamin D insufficiency is associated with subfertility and prolonged estrus cycles in animals, but humans have not been well studied.
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, as well as 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.
There were 1278 menstrual cycles from 446 women of whom 5% were vitamin D deficient OH)D <20ng/ml), 69% were between 20 and 39ng/ml, and 26% were 40ng/ml or higher. There was a dose-response association between vitamin D levels and cycle length. Compared with the highest 25(OH)D level (≥40ng/ml), 25(OH)D deficiency was associated with almost three times the odds of long cycles (adjusted odds ratio (aOR) (95% confidence interval (CI: 2.8 (1.0, 7.5)). The aOR was 1.9 (1.1, 3.5) for 20-<30ng/ml. The probability of a long follicular phase and the probability of a short luteal phase both increased with decreasing 25(OH)D.
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.
PMID: 29337846 DOI: 10.1097/EDE.0000000000000804
Increasing serum 25-hydroxyvitamin D is associated with reduced odds of long menstrual cycles in a cross-sectional study of African American women
Fertility and Sterility, Available online 18 March 2016, doi:10.1016/j.fertnstert.2016.03.004
Anne Marie Z. Jukic, Ph.D.a, b, , , Kristen Upson, Ph.D.b, Quaker E. Harmon, M.D., Ph.D.b, Donna D. Baird, Ph.D.b
Objective: To examine the association between serum 25-hydroxyvitamin D [25(OH)D] and menstrual cycle length and regularity.
Design: Community-based, cross-sectional study of serum 25(OH)D (adjusted for seasonal differences in timing of blood draw) and menstrual cycle length. Women aged 23–34 years reported their gynecologic history. Menstrual cycles were described with four independent categories (normal, short, long, irregular). We used polytomous logistic regression to estimate the association between a doubling of seasonally adjusted 25(OH)D and the odds of each cycle category.
Patient(s): A total of 1,102 African American women aged 23–3 years.
Main Outcome Measure(s): Self-reported menstrual cycle length over the previous 12 months, excluding women who were using cycle-regulating medications over the entire year. Women who reported that their cycles were “too irregular to estimate” were classified as having irregular cycles. A typical cycle length of <27 days was considered “short,” >34 days was “long,” and 27–34 days was “normal.”
Result(s): The median 25(OH)D level was 14.7 ng/mL (interquartile range, 10.9–19.6 ng/mL). A doubling of 25(OH)D was associated with half the odds of having long menstrual cycles: adjusted odds ratio (aOR) 0.54, 95% confidence interval (CI) 0.32–0.89. 25-Hydroxyvitamin D was not associated with the occurrence of short (aOR 1.03, 95% CI 0.82–1.29) or irregular (aOR 1.46, 95% CI 0.88–2.41) menstrual cycles. Results were robust to several sensitivity analyses.
Conclusion(s): These findings suggest that vitamin D status may influence the menstrual cycle and play a role in ovarian function. Further investigation of 25(OH)D and ovarian hormones, and prospective studies of 25(OH)D and cycle length, are needed.
Lower plasma 25-hydroxyvitamin D is associated with irregular menstrual cycles in a cross-sectional study
Reprod Biol Endocrinol. 2015 Mar 11;13:20. doi: 10.1186/s12958-015-0012-5.
Jukic AM1, Steiner AZ2, Baird DD3.
1Epidemiology Branch, National Institute of Environmental Health Sciences, PO Box 12233, Durham, USA. jukica at niehs.nih.gov.
2Department of Obstetrics and Gynecology, University of North Carolina, Chapel Hill, USA. anne_steiner at med.unc.edu.
3Epidemiology Branch, National Institute of Environmental Health Sciences, PO Box 12233, Durham, USA. baird at niehs.nih.gov.
BACKGROUND: In animals, low levels of vitamin D are associated with estrus cycle disturbances, but there are virtually no human data. We examined the association of 25-hydroxyvitamin D (25(OH)D) (a biomarker for vitamin D status) with menstrual cycle characteristics.
METHODS: Women aged 35-44 were randomly selected from a Washington D.C. health plan and invited to participate in the Uterine Fibroid Study (1996-1999). Our analysis includes 636 women (57% were African-American) who provided a blood sample and completed a telephone interview that included gynecologic history. Women were asked their usual cycle length in the preceding year. Women who reported it was "too irregular to estimate" were classified as having irregular cycles (N=48). Women were excluded if they currently or recently used hormonal contraception or any other medication that influences menstrual cycles. 25(OH)D was measured by radioimmunoassay in stored plasma samples.
RESULTS: The median 25(OH)D level was 12.0 ng/mL (interquartile range: 7.6, 19.7 ng/mL). After controlling for age, race, BMI, education, age of menarche, current smoking, alcohol use, and physical activity, a decrease in 25(OH)D of 10 ng/mL was associated with 1.9 times the odds of irregular cycles (Odds ratio (OR) (95% confidence interval (CI)): 1.9 (1.0, 3.4), p=0.04). 25(OH)D was not associated with the occurrence of short cycles (OR(CI): 1.08 (0.79, 1.48, p=0.6) or long cycles (OR(CI): 1.31 (0.66, 2.60), p=0.4).
CONCLUSIONS: Lower levels of 25(OH)D were associated with irregular cycles, but not with short or long cycles. Vitamin D may play a role in regulating ovulatory function. Further investigation of potential mechanisms is warranted.
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