Endometrial epithelial integrity and subepithelial reticular fibre expression in progestin contraceptive acceptors

Long-acting progestin contraceptives have been available in many countries for a number of years with a large number of women now using them. Although some improvements in delivery systems have been made, the major problem with progestin-only contraceptives remains unpredictable endometrial breakthrough bleeding (BTB), which is responsible for more than 50% of drop-outs from this form of contraception. Using hysteroscopy, endometrial petechiae and ecchymoses are a common finding among Norplant users, although these features do not always correlate with BTB. It has been postulated that epithelial and subepithelial tissues may provide a barrier to BTB, as long as epithelial integrity is maintained. The aim of this pilot study is to explore structural changes in the endometrial surface epithelium, and subepithelial collagen III fibres. Endometrial biopsies from noresthisterone-enanthate (Net-En) users (n = 6) and controls (n = 6) were assessed using routine haematoxylin and eosin staining and immunohistochemical staining for cytokeratins 8, 18 and 19, and collagen III. A conventional silver impregnation method was also used to identify subepithelial collagen III fibres. Most of the Net-En tissues showed reduced surface epithelial cell height compared to controls (P = 0.002). Cytokeratin staining was weaker (P = 0.04) and distributed evenly between basal and apical parts of the cell in Net-En tissue, compared to more apically in controls. Both immunohistochemical and conventional silver staining methods revealed that the subepithelial collagen III meshwork remained unchanged in Net-En compared to control endometrium. Both staining methods identified collagen fibres with equal sensitivity. In conclusion, atrophic changes remain the dominant appearance for progestin-exposed endometrium, with reduced cytokeratin staining, but apparently there is little change in subepithelial collagen III expression.