title: Bcl-2, Fas and caspase 3 expression in endometrium from levonorgestrel implant users with and without breakthrough bleeding.
abstract: Women using the progestin-only contraceptive Norplant often suffer from unpredictable bouts of breakthrough bleeding, which usually occurs from a thin atrophic endometrium. The role of cellular apoptosis in the endometrial response to Norplant has not been investigated. The aim of the present study was to use immunohistochemistry to produce semi-quantitative scores for expression of the apoptosis-related proteins Bcl-2, Fas and caspase 3 in endometrium from 16 controls and 42 women using Norplant with minimal or major breakthrough bleeding problems. The results showed no difference in endometrial immunostaining for any of the three proteins between Norplant users with and without breakthrough bleeding. There was also no evidence of endometrial endothelial cell immunostaining for any of the proteins. Bcl-2 was the only protein to show a cyclical pattern, with higher expression in the proliferative compared to secretory glands. All three proteins showed different expression levels in control functionalis versus basalis, with the survival 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 functionalis compared to basalis, and that atrophic Norplant-exposed endometrium appears more like functionalis than basalis with respect to expression of Fas and caspase 3. There was no evidence for a role for apoptosis in the mechanisms that underlie progestin-induced endometrial breakthrough bleeding.
authors.affiliation: Department of Obstetrics and Gynaecology, Monash University, Victoria, Australia. peter.rogers@med.monash.edu.au
authors.forename: P A
authors.initials: PA
authors.lastname: Rogers
authors.forename: F
authors.initials: F
authors.lastname: Lederman
authors.forename: D
authors.initials: D
authors.lastname: Plunkett
authors.forename: B
authors.initials: B
authors.lastname: Affandi
mesh_terms: D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000032:analysis*; D003271:Contraceptive Agents, Female / Q000009:adverse effects*; D004343:Drug Implants; D004717:Endometrium / Q000737:chemistry* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016912:Levonorgestrel / Q000009:adverse effects*; D045167:Progesterone Congeners / Q000009:adverse effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*; D014018:Tissue Distribution; D014592:Uterine Hemorrhage / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D019014:fas Receptor / Q000032:analysis*
chemical_list: D003271:Contraceptive Agents, Female; D004343:Drug Implants; D045167:Progesterone Congeners; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor; D016912:Levonorgestrel; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases