Folic acid supplement use and menstrual cycle characteristics: a cross-sectional study of Danish pregnancy planners

Abstract

Purpose To examine the association between folic acid (FA) supplementation obtained through either single FA tablets or multivitamins (MVs) and menstrual cycle characteristics among 5,386 women aged 18–40 years, enrolled in an Internet-based study of Danish women attempting pregnancy during 2007–2011. Methods In a cross-sectional study, we used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations of FA supplementation with menstrual cycle regularity, short (<27 days), long (30–33 days), and very long (≥34 days) cycle length, and duration and intensity of menstrual bleeding. Results Compared with non-use, FA supplementation was associated with reduced odds of short cycle length [OR=0.80, 95% CI: 0.68–0.94], and a trend towards increased odds of very long cycle length [OR=1.21, 95% CI: 0.87–1.68] compared with cycle length of 27–29 days. The inverse association with short cycle length was stronger among 18–30 year-old women [OR=0.68, 95% CI: 0.53–0.87], nulliparous women [OR=0.66, 95% CI: 0.52–0.84], and women who used both FA and MVs [OR=0.75, 95% CI: 0.60–0.95]. We found no clear association between FA supplementation and cycle regularity and duration and intensity of menstrual bleeding. Conclusion FA supplementation was inversely associated with short menstrual cycle length. This association was strongest among women aged 18–30 years, nulliparous women, and women who used both FA and MVs.

The Effect of Folic Acid Supplementation in the Ovary and Upon Embryo Development

“…Alteration of one-carbon metabolism cycle has been shown to induce dysregulation of gonadotropin (Kanakkaparambil et al, 2009) and steroid hormones levels (Gaskins et al, 2012;Li et al, 2015;Michels et al, 2017). Moreover, the use of FA supplementation was associated with an increased length of the oestrus cycles (Cueto et al, 2015). This suggests that hormonal disruption could be involved in the gene expression changes observed in this project.…”

“…In this project, oestrus cycle was detected just at the end of the supplementation; however, longer examination of the cycles can provide information whether there is any alteration that could explain the difference in the mating process. Folate intake in women have shown an increase in the cycle length, and folate serum was associated with an increase in progesterone during the luteal phase, suggesting that FA can have some effect in the ovarian cycle (Cueto et al, 2015;Michels et al, 2017).…”

Folate, homocysteine and the ovarian cycle among healthy regularly menstruating women

“…Dietary folate or use of or supplements containing folic acid has been examined in the few studies of one-carbon metabolism and the menstrual cycle that we identified (Chavarro et al, 2008;Gaskins et al, 2012;Cueto et al, 2015). The Danish Pregnancy Planning Study found that folic acid supplementation was associated with reduced odds of short cycle length (Cueto et al, 2015).…”

“…Folate and homocysteine are often studied in the context of reproductive health, particularly among women undergoing fertility treatment (Boxmeer et al, 2009;Gaskins et al, 2015). Very few studies explore the effects of folate and homocysteine on menstrual cycle characteristics and these studies focus on associations with dietary or supplemental folate, rather than serum or plasma biomarkers which may more accurately reflect individual bioavailability and metabolism (Chavarro et al, 2008;Gaskins et al, 2012;Cueto et al, 2015). In our previous work, we found higher intakes of folic acid from foods were protective against sporadic anovulation and were associated with an increase in luteal phase progesterone (Gaskins et al, 2012), but we were unable to assess biomarkers of folate status at that time.…”

High maternal folic acid intake around conception alters mouse blastocyst lineage allocation and expression of key developmental regulatory genes

“…Mice fed the high FA diet for 4 weeks showed a delay in mating time. In humans, higher intake of FA has been associated with changes in the hormonal control of the menstrual cycle; with higher intake of synthetic folate significantly associated with higher luteal progesterone levels (Gaskins et al, 2012), while women taking FA supplementation have a shorter menstrual cycle length (Cueto et al, 2015). The delay in mating time observed in this study may result from HFA intake disrupting the estrus cycle, but further analysis of the effect of FA intake on the estrus cycle and hormonal regulation is required to determine the mechanism by which FA intake influence time to conception.…”