Bcl-2, Fas and caspase 3 expression in endometrium from levonorgestrel implant users with and without breakthrough bleeding

Women using the progestin-only contraceptive Norplant(R) often suffer from unpredictable bouts of breakthrough bleeding, which usually occurs from a t hin atrophic endometrium, The role of cellular apoptosis in the endometrial response to Norplant has not been investigated. The aim of the present stu dy was to use immunohistochemistry to produce semi-quantitative scores for expression of the apoptosis-related proteins Bcl-2, Fas and caspase 3 in en dometrium from 16 controls and 42 women using Norplant with minimal or majo r breakthrough bleeding problems. The results showed no difference in endom etrial immunostaining for any of the three proteins between Norplant users with and without breakthrough bleeding. There was also no evidence of endom etrial endothelial cell immunostaining for any of the proteins. Bcl-2 was t he only protein to show a cyclical pattern, with higher expression in the p roliferative compared to secretory glands. All three proteins showed differ ent expression levels in control functionalis versus basalis, with the surv ival protein Bcl-2 being higher in basalis, and the death receptor Fas and the proteolytic enzyme caspase 3 being higher in the functionalis, Overall, the results suggest that apoptosis is regulated differently in functionali s compared to basalis, and that atrophic Norplant-exposed endometrium appea rs more like functionalis than basalis with respect to expression of Fas an d caspase 3, There was no evidence for a role for apoptosis in the mechanis ms that underlie progestin-induced endometrial breakthrough bleeding.