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  • Title: Cytokeratin 8, 18 and 19 in endometrial epithelium of Norplant and norethisterone enanthate injectable progestogen contraceptive users.
    Author: Wonodirekso S, Hadisaputra W, Affandi B, Siregar B, Rogers PA.
    Journal: Hum Reprod; 1996 Oct; 11 Suppl 2():144-9. PubMed ID: 8982756.
    Abstract:
    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. All endometrial epithelium contain the cytoskeletal intermediate filaments cytokeratins 8, 18, and 19. The aim of this study was to observe changes in the expressions of these cytokeratins in endometrial epithelial cells from Indonesian women receiving norethindrone enanthate and to compare them with the patterns of expression reported for Norplant users. Study subjects received 2 norethindrone enanthate injections (150 mg) spaced 8 weeks apart. Regardless of bleeding pattern or histopathologic finding, epithelial tissues from these 7 women stained either strongly or intensely for cytokeratin, including isolated epithelial fragments from unclassified biopsies. Surface and glandular epithelia from norethindrone enanthate users consisted of a single layer of high columnar cells, with no obvious differences between proliferative-like and secretory-like endometria. In contrast, surface epithelial tissue from 37 Norplant users showed weaker immunostaining and epithelial cells were rounded and stratified. No relationship between cytokeratin expression and breakthrough bleeding pattern was detected. These findings suggest that norethindrone enanthate and Norplant act differently on endometrial epithelial cytokeratin, with women receiving the former contraceptive agent showing a cytokeratin distribution similar to that seen in the normal menstrual cycle. The capability of norethindrone enanthate to preserve epithelial integrity may have implications for reducing the incidence of progestogen-related breakthrough bleeding.
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