Cytokeratin 8, 18 and 19 expressions, epithelial shedding, and stromal extravasation in endometrium of norethisterone enanthate (NET-EN) progestogen contraceptive users: (A preliminary report)

Cytokeratins 8, 18 and 19 are members of the cytoskeletal intermediate filament (IF) 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. Progestogen contraceptives including levonorgestrel (LNG, Norplant®) implant, injectable depot-medroxyprogesterone acetate (DMPA) and norethisterone-enanthate (NET-EN) are known to cause bleeding problems among users that are responsible for more than 50% of the withdrawals from these methods. The aim of this study was to explore any changes in the expression and distribution of epithelial cytokeratin 8, 18 and 19, also changes in endometrial stroma and epithelium in NET-EN users compared to LNG users and normal subjects that could be related to the bleeding problems. Fourteen NET-EN endometrial biopsies were paraffin embedded and stained routinely using hematoxyllin and eosin (HE) for histological dating and observing any stromal and epithelial changes. The slides were then stained immunohisto-chemically to find any changes in the cytokeratin expression and distribution which were then compared with the LNG and normal endometrium from previous study. The results showed that women who had received NET-EN for 3-4 months have a cytokeratin distribution similar to that seen in normal menstrual cycle. This is in contrast to endometrium from LNG users where cytokeratin expression was reduced and the epithelial cells more rounded. In addition, sub-epithelial and deeper stromal extravasations were observed among NET-EN endometrium but no such data available from LNG tissues, thus no comparison can be made. No relationship between cytokeratin expression and stromal extravasations with bleeding patterns were found.