Monthly haemostatic factor variability in women and men

Abstract

Background: Hormonal status influences haemostatic factors including fibrinogen, factor VII and plasminogen activator inhibitor (PAI-1), and concentrations differ among men, premenopausal and postmenopausal women. This study examines how phases of the menstrual cycle influence variability of fibrinogen, factor VII and PAI-1.

Design: We studied 103 subjects (39 premenopausal women, 18 postmenopausal women and 46 men) during three, randomized, 8-week energy- and nutrient-controlled experimental diets in the Dietary Effects on Lipids and Thrombogenic Activity (DELTA) Study. Fasting blood samples were collected weekly during the last 4 weeks of each diet period, and haemostatic factors were quantified. Two linear mixed-effects models were used for fibrinogen, factor VII and PAI-1: one to estimate and compare group-specific components of variance, and the other to estimate additional fixed effects representing cyclical functions of day of menstrual cycle in premenopausal women.

Results: Systematic cyclical variation with day of menstrual cycle was observed for fibrinogen (P < 0.0001), factor VII (P = 0.0012) and PAI-1 (P = 0.0024) in premenopausal women. However, the amplitude of cycling was small relative to the total magnitude of intra-individual variability. In addition, the intra-individual variance and corresponding coefficient of variation observed in premenopausal women did not differ from postmenopausal women and men.

Conclusions: The variability in haemostatic factors in premenopausal women is no greater than for postmenopausal women or men. Consequently, premenopausal women can be included in studies investigating haemostatic factor responses without controlling for stage of menstrual cycle.

Keywords: Controlled dietary intervention; factor VII; fibrinogen; menstrual cycle; plasminogen activator inhibitor.

Figure 1. Flow chart for selection of study participants

Figure 2. Variability of Fibrinogen (FIB), Factor VII and Plasminogen Activator Inhibitor-1 (PAI-1) over 28-Days

Data is displayed as deviation from a reference value. The curve or line represents the deviation of the sub-population mean for the analyte at that point in time compared with the overall population mean value for the entire time period (shown on the right y-axis). The circles represent the deviation of a single measurement of fibrinogen (FIB), factor VII or plasminogen activator inhibitor (PAI-1) for an individual from the overall mean value for that individual. Intraindividual variations are computed independently for each diet period. For premenopausal women (Panel A), the first day of menses was the index day - based on self-reported menstrual calendar and confirmed by hormone concentrations (estradiol, progesterone, luteinizing hormone). For postmenopausal women (Panel B) and men (Panel C) the index day was randomly selected for each subject.

Figure 2. Variability of Fibrinogen (FIB), Factor VII and Plasminogen Activator Inhibitor-1 (PAI-1) over 28-Days

Data is displayed as deviation from a reference value. The curve or line represents the deviation of the sub-population mean for the analyte at that point in time compared with the overall population mean value for the entire time period (shown on the right y-axis). The circles represent the deviation of a single measurement of fibrinogen (FIB), factor VII or plasminogen activator inhibitor (PAI-1) for an individual from the overall mean value for that individual. Intraindividual variations are computed independently for each diet period. For premenopausal women (Panel A), the first day of menses was the index day - based on self-reported menstrual calendar and confirmed by hormone concentrations (estradiol, progesterone, luteinizing hormone). For postmenopausal women (Panel B) and men (Panel C) the index day was randomly selected for each subject.