Morphological and functional features of endometrial decidualization following long-term intrauterine levonorgestrel delivery

Abstract

Irregular bleeding remains a common reason for the discontinuation of progestin-only contraception. The levonorgestrel releasing intrauterine system (LNG-IUS) has profound morphological effects upon the endometrium. Specific features are gland atrophy and extensive decidual transformation of the stroma. Morphological changes in the endometrium may be associated with perturbation of mechanisms regulating normal endometrial function. This study describes endometrial stromal and glandular features prior to and up to 12 months following insertion of the LNG-IUS. Comparison is made with first trimester decidua. In order to elucidate further mechanisms governing endometrial function with local intrauterine delivery of LNG, we here report histological features consistent with decidualization; a significant increase in granulocyte-macrophage colony stimulating factor (GM-CSF) immunoreactivity in decidualized stromal cells; glandular and stromal prolactin receptor expression and an infiltrate of CD56 + large granular lymphocytes and CD68 + macrophages. We are unaware of previous reports which have documented longitudinally both morphological and functional observations in endometrium exposed to local intrauterine levonorgestrel delivery. These studies demonstrate that long-term administration of intrauterine levonorgestrel results in features of altered morphology and function. No correlation was apparent between the end points in the study and the bleeding patterns described by the subjects. Further evaluation of these features in the context of menstrual bleeding experience may contribute to a better understanding of this troublesome side-effect which often leads to dissatisfaction and discontinuation of the intrauterine system.

Morphological and Ultrastructural Changes in Human Endometrium Following Low-Dose Levonorgestrel Contraceptive Intrauterine Systems (LNG-IUS-12) 13.5 mg

“…It releases 12 lg/24 h LNG into uterus cavity and has a life span of 3 years. In this study, the morphological changes of endometrium that is atrophic and inactive were similar to LNG-IUS-20 [1,2,10]. 12 lg of LNG per day proved to be effective in producing the suppression characterized by glandular atrophy and decidualization of stroma.…”

“…It comprises a T-shaped plastic frame, with a cylinder of the synthetic progestogen levonorgestrel (52 mg), enclosed in a silastic sleeve allowing the controlled slow release of 20 lg daily of hormone into the uterine cavity. LNG from this system lead to obvious and profound effects on endometrial morphology and function atrophy of gland and changes in vascular morphology, an extensive decidualization of the stroma, increased stromal inflammatory reaction and dilation of capillaries , occasionally accompanied by thrombosis [1,2]. Moreover, the change of the uterine environment brings efficient contraception.…”

Abnormal Uterine Bleeding during Progestin-Only Contraception May Result from Free Radical-Induced Alterations in Angiopoietin Expression

“…Several studies have shown that levonorgestrel (LNG) administered either locally to the uterine cavity or systemically results in very significant morphological changes in the endometrium including gland atrophy, extensive decidual transformation of the stroma, and increased endometrial vasculature density. [1][2][3] With long-term LNG contraception, the vessels are enlarged, dilated, thinwalled, and fragile, suggesting they are the product of aberrant angiogenesis. 4,5 Indeed, a number of investigators have found a link between LTPOC-associated bleeding and aberrant expression of the angiogenic agent vascular endothelial growth factor (VEGF).…”

Anti-proliferative effects of progesterone antagonists in the primate endometrium: a potential role for the androgen receptor

“…Therapeutic progestogens that are highly androgenic result in endometrial atrophy. For example, marked endometrial atrophy is a feature of the endometrial response among women using a levonorgestrelreleasing intrauterine system (Critchley et al, 1998). As the suppressive effects of androgens on endometrial growth resemble the atrophic effects induced by anti-progestins, the possibility that the androgen receptor (AR) plays a role in anti-progestin action in human and non-human primate endometrium was evaluated using in situ hybridization, immunocytochemistry and ligand binding assays to assess changes in the endometrial AR during anti-progestin treatment .…”