Cytokeratin 8, 18 and 19 in endometrial epithelium of Norplant® and norethisterone enanthate injectable progestogen contraceptive users

Cytokeratins 8, 18 and 19 are members of the cytoskeletal intermediate filament family found in all simple epithelia. Intermediate filaments are dynamic intracytoplasmic structures that can be influenced by a number of external factors. Norethisterone enanthate (NET-EN) is a long-acting progestogen contraceptive that has been found to arrest endometrial growth in the rat. Both Norplant® and NET-EN cause bleeding problems among users which are responsible for >50% of withdrawals with these methods. The aim of this study was to explore changes in the expression and distribution of cytokeratins 8, 18 and 19 in NET-EN- and Norplant-exposed endometrial epithelium which could be related to bleeding disturbances. Seven NET-EN and 37 Norplant endometrial biopsies were paraffin-embedded and stained immunohistochemically to evaluate cytokeratin expression and distribution. The results showed that women who had received NET-EN for 3-4 months had a cytokeratin distribution similar to that seen in the normal menstrual cycle. This is in contrast to endometrium from Norplant users in which cytokeratin expression was reduced and the epithelial cells were more rounded. No relationship between cytokeratin expression and breakthrough bleeding pattern was found. NET-EN and Norplant may act differently on endometrial epithelial cytokeratin.