Current Issue

Volume 11, Number 4, Jan-Mar 2018 Pages: 279-286

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


Saowapak Prathoomthong, M.D, 1, Yada Tingthanatikul, M.D, 2, Srithean Lertvikool, M.D, 2, Nittaya Rodratn, M.Sc, 2, Wanwisa Waiyaput, M.Sc, 3, Kanthanadon Dittharot, M.Sc, 3, Morakot Sroyraya, Ph.D, 4, 5, Areepan Sophonsritsuk, M.D., Ph.D., 2, *,
Department of Obstetrics and Gynecology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
Reproductive Endocrinology and Infertility Unit, Department of Obstetrics and Gynecology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
Office of Research Academic and Innovation, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
Department of Anatomy, Faculty of Science, Mahidol University, Bangkok, Thailand
Mahidol University Nakhon Sawan Campus, Nakhon Sawan, Thailand
*Corresponding Address: Reproductive Endocrinology and Infertility Unit Department of Obstetrics and Gynecology Ramathibodi Hospital Mahidol University Rama VI Rd. Bangkok Thailand 10400 Email:areepan.sop@mahidol.ac.th

Abstract

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 re- quired 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 differ- ence in the number of CD68 cells was not statistically significant between treated and untreated groups in the endo- metrial 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 im- plantation and fetal protection (Registration number: TCTR20150921001).