title: Changes in vaginal morphology, steroid receptor and natural antimicrobial content following treatment with low-dose mifepristone.
abstract: BACKGROUND
  We have previously shown that the antigestagen mifepristone is contraceptive when given in a daily dose of 5 mg, po. Epidemiological studies suggest that gestagen-only contraceptives may increase the risk of transmission of human immunodeficiency virus (HIV) due to effects on the vaginal defenses to infection. We investigate the effects of mifepristone on vaginal thickness, steroid receptor and natural antimicrobial content and pharmacokinetics of mifepristone.
  
  
  METHODS
  In a pilot study, eight women were given mifepristone 5 mg/day for an average of 33 days. Ovarian function was assessed by measurement of estradiol and progesterone in blood and their metabolites in urine and by serial ultrasound of their ovaries. Vaginal biopsies were collected before (late proliferative) and after taking mifepristone.
  
  
  RESULTS
  All subjects showed a similar pattern of descending serum concentrations of mifepristone. The elimination phase half-life was 18+/-5.1 h (mean+/-SD). Mean Cmax measured at 1 h was 641.7 nmol/L (range, 502-740 nmol/L). All eight women reported amenorrhea for the duration of treatment and seven of eight women showed biochemical and ultrasound evidence of anovulation. There was no significant change in vaginal thickness following treatment [342+/-40 microm pretreatment, 303+/-69 microm posttreatment (mean+/-SEM); p>.05]. Estrogen (ERalpha, ERbeta) and androgen receptor were expressed in both vaginal epithelium and subepithelial stroma, whereas progesterone receptor was expressed predominantly in the subepithelial stroma. There was no change in receptor content and distribution following mifepristone treatment. Natural antimicrobial mRNA [secretory leukocyte protease inhibitor, human beta defensins mRNA (HBD1, HBD2, HBD3, HBD5), granulysin and elafin] was extracted from the vaginal tissues, and the content was unaffected by mifepristone treatment.
  
  
  CONCLUSIONS
  The absence of changes in vaginal thickness, steroid receptor and natural antimicrobial content and its distribution in this preliminary study suggests that in contrast to other estrogen-free contraceptives, mifepristone is unlikely to be associated with the increased risk of transmission of HIV and other sexually transmitted infections.
authors.affiliation: Contraceptive Development Network, Centre for Reproductive Biology, University of Edinburgh, The Queen's Medical Research Institute, 47 Little France Crescent, EH16 4TJ Edinburgh, UK.
authors.forename: Nitish
authors.initials: N
authors.lastname: Narvekar
authors.forename: Fatim
authors.initials: F
authors.lastname: Lakha
authors.forename: Hilary O D
authors.initials: HO
authors.lastname: Critchley
authors.forename: Anna F
authors.initials: AF
authors.lastname: Glasier
authors.forename: Alistair R W
authors.initials: AR
authors.lastname: Williams
authors.forename: Riikka
authors.initials: R
authors.lastname: Leminen
authors.forename: Oskari
authors.initials: O
authors.lastname: Heikinheimo
authors.forename: Rodney W
authors.initials: RW
authors.lastname: Kelly
authors.forename: David T
authors.initials: DT
authors.lastname: Baird
mesh_terms: D000328:Adult; D000890:Anti-Infective Agents; D000945:Antigens, Differentiation, T-Lymphocyte / Q000187:drug effects; D003280:Contraceptives, Oral, Synthetic / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D053492:Elafin / Q000187:drug effects; D004717:Endometrium / Q000187:drug effects; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D015735:Mifepristone / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D010053:Ovary / Q000187:drug effects; D010865:Pilot Projects; D012333:RNA, Messenger / Q000378:metabolism; D011987:Receptors, Steroid / Q000187:drug effects* / Q000378:metabolism; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000187:drug effects; D014621:Vagina / Q000187:drug effects* / Q000378:metabolism; D023083:beta-Defensins / Q000187:drug effects
chemical_list: D000890:Anti-Infective Agents; D000945:Antigens, Differentiation, T-Lymphocyte; D003280:Contraceptives, Oral, Synthetic; D053492:Elafin; C075005:GNLY protein, human; D012333:RNA, Messenger; D011987:Receptors, Steroid; D053481:Secretory Leukocyte Peptidase Inhibitor; D023083:beta-Defensins; D015735:Mifepristone