title: Endometrial expression of epithelial neutrophil-activating peptide-78 during the menstrual cycle or in progestin-only contraceptive users with breakthrough bleeding and the influence of doxycycline therapy.
abstract: BACKGROUND
  Endometrial breakthrough bleeding is characterized by an inflammatory reaction and increased production of proinflammatory mediators, one of which may be epithelial neutrophil-activating peptide-78 (ENA-78), a chemokine with neutrophil-activating properties.
  
  
  RESULTS
  We therefore investigated the endometrial expression of ENA-78 in Norplant users as progestin-only contraceptive with various bleeding patterns (n=35) as compared with non-users with a normal menstrual cycle (n=55). The endometrial stromal cells (ESCs) were the major site of ENA-78 expression with the highest levels found during the secretory phase. The expression of ENA-78 was increased in Norplant users with irregular bleeding as compared with those with regular cycles and amenorrhoea. The levels of ENA-78 detected in uterine washes and sera after the use of Norplant for 3-6 months (n=25) increased compared with baseline (P < 0.05). These levels did not significantly change in Norplant users who received doxycycline (Dox) therapy (25 mg/twice daily for 6 months) when measured midway through or at the conclusion of study when compared with the baseline (n=25). Treatments with medroxyprogesterone acetate (MPA) and tumour necrosis factor-alpha (TNF-alpha) (25 ng/ml), but not 17beta-estradiol (E2) or E2 + MPA (10(-8) M), representing endometrium exposed to contraceptive and inflammatory conditions, respectively, increased the levels of ENA-78 production by ESCs, and this was reduced by co-treatments with Dox (25 microg/ml) (P < 0.05).
  
  
  CONCLUSIONS
  The endometrial production of ENA-78 is altered in progestin-only contraceptive users experiencing breakthrough bleeding and is regulated by MPA and TNF-alpha in ESCs. Although Dox therapy did not alter uterine ENA-78 secretion, its suppression in ESCs suggests that Dox, acting site-specifically and through an anti-inflammatory mechanism, may influence the outcome of breakthrough bleeding in contraceptive users.
authors.affiliation: Department of Obstetrics/Gynecology, University of Florida, Gainesville, FL 32610-0294, USA. cheginin@obgyn.ufl.edu
authors.forename: N
authors.initials: N
authors.lastname: Chegini
authors.forename: X
authors.initials: X
authors.lastname: Luo
authors.forename: Q
authors.initials: Q
authors.lastname: Pan
authors.forename: A
authors.initials: A
authors.lastname: Rhoton-Vlasak
authors.forename: D F
authors.initials: DF
authors.lastname: Archer
mesh_terms: D000293:Adolescent; D000328:Adult; D054365:Chemokine CXCL5; D019743:Chemokines, CXC / Q000096:biosynthesis*; D003271:Contraceptive Agents, Female / Q000627:therapeutic use*; D004318:Doxycycline / Q000627:therapeutic use*; D004717:Endometrium / Q000166:cytology / Q000378:metabolism*; D005260:Female; D005498:Follicular Phase / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D016912:Levonorgestrel / Q000627:therapeutic use*; D008183:Luteal Phase / Q000502:physiology; D017154:Stromal Cells / Q000378:metabolism; D014592:Uterine Hemorrhage / Q000503:physiopathology*
chemical_list: C486263:CXCL5 protein, human; D054365:Chemokine CXCL5; D019743:Chemokines, CXC; D003271:Contraceptive Agents, Female; D016912:Levonorgestrel; D004318:Doxycycline