Sonya S Dasharathy’s research while affiliated with Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health and other places

Study question: Do uric acid levels across the menstrual cycle show associations with endogenous estradiol (E2) and reproductive hormone concentrations in regularly menstruating women? Summary answer: Mean uric acid concentrations were highest during the follicular phase, and were inversely associated with E2 and progesterone, and positively associated with FSH. What is known already: E2 may decrease serum levels of uric acid in post-menopausal women; however, the interplay between endogenous reproductive hormones and uric acid levels among regularly menstruating women has not been elucidated. Study design, size, duration: The BioCycle study was a prospective cohort study conducted at the University at Buffalo research centre from 2005 to 2007, which followed healthy women for one (n = 9) or 2 (n = 250) menstrual cycle(s). Participants/materials, setting, methods: Participants were healthy women aged 18-44 years. Hormones and uric acid were measured in serum eight times each cycle for up to two cycles. Marginal structural models with inverse probability of exposure weights were used to evaluate the associations between endogenous hormones and uric acid concentrations. Main results and the role of chance: Uric acid levels were observed to vary across the menstrual cycle, with the lowest levels observed during the luteal phase. Every log-unit increase in E2 was associated with a decrease in uric acid of 1.1% (β = -0.011; 95% confidence interval (CI): -0.019, -0.004; persistent-effects model), and for every log-unit increase in progesterone, uric acid decreased by ≈ 0.8% (β = -0.008; 95% CI: -0.012, -0.004; persistent-effects model). FSH was positively associated with uric acid concentrations, such that each log-unit increase was associated with a 1.6% increase in uric acid (β = 0.016; 95% CI: 0.005, 0.026; persistent-effects model). Progesterone and FSH were also associated with uric acid levels in acute-effects models. Of 509 cycles, 42 were anovulatory (8.3%). Higher uric acid levels were associated with increased odds of anovulation (odds ratio 2.39, 95% CI: 1.25, 4.56). Limitations, reasons for caution: The change in uric acid levels among this cohort of healthy women was modest, and analysis was limited to two menstrual cycles. The women in this study were healthy and regularly menstruating, and as such there were few women with high uric acid levels and anovulatory cycles. Wider implications of the findings: These findings demonstrate the importance of taking menstrual cycle phase into account when measuring uric acid in premenopausal women, and confirm the hypothesized beneficial lowering effects of endogenous E2 on uric acid levels. These findings suggest that there could be an underlying association affecting both sporadic anovulation and high uric acid levels among young, regularly menstruating women. Further studies are needed to confirm these findings and elucidate the connection between uric acid and reproductive and later cardiovascular health.

Menstrual bleeding patterns are considered relevant indicators of reproductive health, though few studies have evaluated patterns among regularly menstruating premenopausal women. The authors evaluated self-reported bleeding patterns, incidence of spotting, and associations with reproductive hormones among 201 women in the BioCycle Study (2005-2007) with 2 consecutive cycles. Bleeding patterns were assessed by using daily questionnaires and pictograms. Marginal structural models were used to evaluate associations between endogenous hormone concentrations and subsequent total reported blood loss and bleeding length by weighted linear mixed-effects models and weighted parametric survival analysis models. Women bled for a median of 5 days (standard deviation: 1.5) during menstruation, with heavier bleeding during the first 3 days. Only 4.8% of women experienced midcycle bleeding. Increased levels of follicle-stimulating hormone (β = 0.20, 95% confidence interval: 0.13, 0.27) and progesterone (β = 0.06, 95% confidence interval: 0.03, 0.09) throughout the cycle were associated with heavier menstrual bleeding, and higher follicle-stimulating hormone levels were associated with longer menses. Bleeding duration and volume were reduced after anovulatory compared with ovulatory cycles (geometric mean blood loss: 29.6 vs. 47.2 mL; P = 0.07). Study findings suggest that detailed characterizations of bleeding patterns may provide more insight than previously thought as noninvasive markers for endocrine status in a given cycle.

Understanding variations in lipoprotein cholesterol levels throughout the menstrual cycle is important because there may be clinical implications regarding the appropriate timing of measurement and implications on the design and interpretation of studies in women of reproductive age. Our objective was to review the evidence comparing lipoprotein cholesterol levels throughout the menstrual cycle among premenopausal women. Overall, lipoprotein cholesterol levels were observed to vary in response to changing estrogen levels. Taken together, the evidence suggests that total cholesterol and LDL-C tend to be highest during the follicular phase and to decline during the luteal phase, with HDL C highest around ovulation. Based on these findings, the menstrual cycle phase should be taken into account when evaluating lipoprotein cholesterol levels among reproductive-aged women. Measuring cholesterol levels during menses is recommended for consistent comparisons as this phase can be more reliably identified than other phases, although women within National Cholesterol Education Program acceptable ranges, but near the boundaries when tested during menses, should undergo additional tests.