Serum levels of soluble vascular cell adhesion molecule-1 are decreased in women receiving oral contraceptives compared with normally menstruating women: implications in atherosclerosis

Objective: The primary objective was to assess whether short-term changes in estradiol (E-2), such as those observed in the menstrual cycle, alter serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1), and whether VCAM-1 expression is suppressed in long-term users of exogenous estrogens. The secondary objective was to assess the association, if any, between inflammatory cytokines and expression of sVCAM-1. Design: Prospective collection of serum samples in healthy volunteers. Setting: University hospital. Patients(s): Thirty-one normally menstruating women and 37 oral contraceptive (OC) users. Interventions included serum collection in the early follicular, late follicular, and midluteal phases of the menstrual cycle and once in oral contraceptive users. Main Outcome Measure(s): Samples were assayed for sVCAM-1, tumor necrosis factor alpha (TNF-alpha), and interleukin (IL)-6 by enzyme-linked immunoabsorbent assay (ELISA). Estradiol (E-2) was measured by radioimmunoassay (RIA). Result(s): Oral contraceptive users had significantly lower serum levels of sVCAM-1 compared with normally menstruating women. No significant change was noted in the mean values of sVCAM-1 throughout the menstrual cycle, despite the significant change in 17 beta-estradiol levels. Throughout the menstrual cycle, a significant correlation was noted between the serum levels of TNF-alpha and sVCAM-1. The serum levels of IL-6 correlated with those of sVCAM-1 in the late follicular and midluteal phase of the cycle. Similar correlations were observed in OC users. Conclusion(s): Long-term exposure to exogenous estrogens suppresses serum levels of sVCAM-1. Short-term changes in endogenous estrogens, as observed during the menstrual cycle, may not alter VCAM-1 expression; TNF-alpha and IL-6 may play a role in the regulation of VCAM-1 expression in vivo. (Fertil Steril (R) 2005;83:1480-8. (c) 2005 by American Society for Reproductive Medicine.)