Effect of gonadotropin-releasing hormone agonists on monocyte chemotactic protein-1 production and macrophage infiltration in leiomyomatous uterus

Objective: The level of monocyte chemotactic protein-1 (MCP-1), a potent ch emoattractant for monocytes, is fivefold higher in myometrium than in leiom yoma. We have previously shown that myometrium. from women using GnRH agoni sts (GnRH-a) express the highest levels of MCPA, which has anti proliferati ve effects on leiomyoma cells. We hypothesized that MCP-1 may have a direct paracrine effect in leiomyomatous uterus rather than acting by way of chem oattraction of macrophages. Design: Cross-sectional study. Setting: University medical center. Patient(s): Women with leiomyoma (n=32). Interventiont(s): Immunohistochemical analysis performed in the myometrium, and leiomyoma of women receiving (n=11) and not receiving (n=21) GnRH-a tr eatment. Main Outcome Measure(s): The MCP-1 levels and macrophage counts determined by immunohistochemistry in the myometrium and leiomyoma of women receiving GnRH-a were compared to the levels and counts in women not receiving GnRH-a . Result(s): Samples from all 11 patients using GnRH-a revealed strong MCP-1 staining, whereas staining was only weakly present in 11 and absent in 10 s amples from patients not receiving GnRH-a, revealing a significant differen ce in MCP-1 expression between GnRH-a users versus nonusers (P=.006). The n umber of tissue macrophages between GnRH-a users and nonusers was not signi ficantly different. Conclusion(s): We found that there is an increase in the MCP-1 protein expr ession in the myometrium of women receiving GnRH-a treatment. On the other hand, we have not observed a difference in the macrophage count and distrib ution with GnRH-a treatment, suggesting a potentially direct antiproliferat ive role for MCP-1 rather than acting by means of chemoattraction of macrop hages. (Fertil Steril(R) 2001;76:792-6. (C) 2001 by American Society for Re productive Medicine.).