Endometrial effects of intrauterine levonorgestrel.

Local intrauterine delivery of levonorgestrel (LNG) results in extensive decidualization of endometrial stromal cells, atrophy of the glandular and surface epithelium and changes in vascular morphology (suppression of spiral artery formation and presence of large dilated vessels). With endometrial exposure to LNG, there is down-regulation of sex steroid receptors in all cellular components. As a consequence of endometrial sex steroid receptor down-regulation, there is perturbation of progesterone-regulated locally acting mediators, and the integrity of blood vessel walls is disturbed. Thus, intrauterine LNG administration results in modulation of local mediators regulating endometrial function. To date, no single factor has been identified where the expression correlates closely with unscheduled breakthrough bleeding (BTB). BTB is a common side effect and reason for discontinuation of LNG-IUS use. Much remains to be determined about the mechanisms involved in suppression of menstruation, BTB episodes and the local endometrial environment with local LNG administration.