The effects of sex, menstrual cycle, and oral contraceptives on the number and activity of natural killer cells

Objectives. The aim of this study was to study the impact of sex, the menstrual cycle, and the use of oral contraceptives (OC) on the number and activity of natural killer (NK) cells. Methods. Both the number and the activity of NK cells were assessed per milliliter of blood, and NK activity (NKA) per NK cell and per lymphocyte was calculated. NKA was measured in each subject using a whole blood assay, which preserves the plasma and all blood cells, and using a washed blood assay, in which plasma is replaced with an artificial medium. The subjects were young (20-29 years old) women with a regular menstrual cycle (n = 39; 26 tested on both the follicular and the luteal phases), age-matched women who use OC (n = 26), and age-matched men (n = 20). Results. Men showed markedly and significantly higher NKA than women with regular menstrual cycles or women using OC, who had the lowest levels of NKA. No significant differences in blood concentration of NK cell were found. Differences in NKA were of similar magnitude in the whole and washed blood assays per milliliter of blood, per NK cell, or per lymphocyte. The menstrual cycle had no significant effect on activity levels of NK cells, but during the periovulatory phase, the number of NK cells per milliliter of blood increased significantly. Conclusions. The observed differences are independent of the presence of serum factors during the in vitro assessment of NKA, but may be related to chronic exposure to sex steroids and to fluctuation in the NK cell expression of β-adrenoceptors.