Practical Considerations Regarding the Influence of the Menstrual Cycle on Leukocyte Parameters in Clinical Trials

Abstract

Variations in hormone levels during different phases of the menstrual cycle have been shown to alter the pharmacokinetics of some medications and are known to exert significant effects on seemingly unrelated physiologic parameters. Numerous studies have been undertaken to examine the effects of different phases of the menstrual cycle on leukocyte and differential counts, but results have often been inconclusive and contradictory. This study endeavored to reexamine these parameters, measured by standard laboratory assays, in healthy ovulating females to determine whether the menstrual cycle may have clinically relevant effects on leukocyte counts. Twenty-one women, aged 18 to 35 years and not taking hormonal contraception, were enrolled in an outpatient study within 12 hours after the onset of normal menses. The women reported to the clinical pharmacology unit for a complete blood count with differential on days 1, 2, 7, 10 through 17, 22, and 25 through 32. Blinded duplicate samples were obtained on day 2 to assess variability at the analytic site, and levels of luteinizing hormone and estradiol were measured on days 11 through 16 to determine the day of ovulation. Eighteen women completed the study, with cycle lengths ranging from 24 to 31 days (28.2 +/- 1.9 days, mean +/- SD). Evaluations of the data revealed a trend toward higher leukocyte counts and absolute neutrophil counts at the onset of menses but no significant or clinically relevant effects of different phases of the menstrual cycle on these parameters. Some split samples showed considerable variation in the assays (eg, a 42% increase in absolute neutrophil counts), suggesting that errors at the analytic facility may be a more important consideration than hormonal effects.