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

Objective Inflammation plays an important role in endometriosis and adenomyosis. Progestin has been used for symptomatic treatment of adenomyosis, although its effect on inflammation has not been studied. We conducted a randomized controlled study to investigate the changes of immune cell expression, i.e. macrophages and natural killer cells, in the tissue obtained from women with adenomyosis who did or did not receive oral progestin dienogest. MaterialsAndMethods Twenty-four patients with adenomyosis who required hysterectomy were enrolled and were divided into two groups by block randomization method with a block size of four. Twelve patients received dienogest 28-35 days before surgery, and the other 12 patients were not treated with any hormone. The endometrial and myometrial tissue samples were immediately collected after hysterectomy, and we then performed immunohistochemistry for a macrophage marker (CD68) and natural killer cells antibody (CD57). Results The number of CD57 cells were significantly increased in endometrial glands (p=0.005, treated vs. untreated group; median (range 25%, 75%), 4.37 (0.31, 14.68) vs. 0 (0, 0)), but not in stroma in the endometrium of the treated patients (p=0.416, treated vs. untreated group; median (range 25%, 75%), 21.87(10, 68.81), 10 (8.75, 15.93)). The number of CD68 cells were not statistically significant different between treated and untreated groups in the endometrial glands (p=0.055, treated vs. untreated group; median (range 25%, 75%), 4.37 (0, 9.06), 0 (0, 1.56)) or stromal tissues (p=0.506, treated vs. untreated group; median (range 25%, 75%), 64.37 (20.62, 92.5), 44.37 (22.18, 50.93)). Conclusion Administration of oral progestin dienogest to patients with adenomyosis increased the number of uterine natural killer cells in glandular structure of eutopic endometrium. The differential effects of progestin on NK cells depended upon the site of immune cell infiltration. The enhancing effect of oral progestin on uterine NK cells in adenomyosis would be beneficial to pregnancies occurring following discontinuation of treatment in terms of embryo implantation and fetal protection.