The Effects of Dienogest on Macrophage and Natural Killer Cells in Adenomyosis: A Randomized Controlled Study

Background: Progestin has been used for symptomatic treatment of adenomyosis, although its effect on the immune system has not been studied. The aim of this study was to investigate the changes of macrophage and natural killer (NK) cell infiltration in tissues obtained from women with adenomyosis who did or did not receive oral progestin dienogest. Materials and Methods: In this randomized controlled clinical trial study, 24 patients with adenomyosis who required hysterectomy were enrolled. Twelve patients received dienogest 28-35 days before surgery, and the other 12 patients were not treated with any hormones. The endometrial and myometrial tissue samples were immediately collected after hysterectomy, and immunohistochemistry for a macrophage marker (CD68) and a NK cells marker (CD57) was performed. Results: The number of CD57 cells was significantly increased in endometrial glands of the treated group compared to the untreated group (P=0.005) but not in stroma in the endometrium of the treated patients (P=0.416). The difference in the number of CD68 cells was not statistically significant between treated and untreated groups in the endometrial glands (P=0.055) or stromal tissues (P=0.506). Conclusion: Administration of oral progestin dienogest to patients with adenomyosis increased the number of uterine infiltrating NK cells in glandular structure of eutopic endometrium. The differential effects of progestin on NK cells depended on the site of immune cell infiltration. The effects of oral progestin on uterine NK cells in adenomyosis have the potentials to be beneficial to pregnancies occurring following discontinuation of treatment in terms of embryo implantation and fetal protection (Registration number: TCTR20150921001).