title: Late follicular phase administration of mifepristone suppresses circulating leptin and FSH - mechanism(s) of action in emergency contraception?
abstract: OBJECTIVE
  Low dose mifepristone (RU486) is highly effective in emergency post-coital contraception (EC), although the mechanism(s) of action remains unclear. We studied the endocrine actions of 10 mg mifepristone administered orally as a single dose to eight healthy volunteers (aged 20-45 years) during the late follicular phase.
  
  
  METHODS
  Serum levels of LH, FSH, oestradiol, progesterone, leptin, mifepristone, cortisol, and gluco-corticoid bioactivity (GBA) were measured before and 1, 2, 4 and 8 h after ingestion of mifepristone on cycle day 10 or 11 (study day 1), and follow-up was continued for 10 days. Ovarian ultrasonography was performed on study days 1 and 7. Similar measurements were carried out during a control cycle.
  
  
  RESULTS
  Mifepristone postponed ovulation, as evidenced by a 3.4+/-1.1 day (means+/-s.d.) delay (P < 0.005) in the LH surge and 3.6+/-4.0 day prolongation of the treatment cycle (P = 0.08). During the mifepristone cycle, an LH surge was displayed by five subjects when serum mifepristone levels had declined to 9.5+/-7.1 nmol/l. During the day of mifepristone administration, circulating GBA (P < 0.001) and leptin (P < 0.001) levels declined. On the day after mifepristone administration, mean serum FSH and leptin levels were lower than pretreatment values (3.8+/-1.8 IU/l vs 5.2+/-1.1 IU/l, n = 7, P < 0.05; 28.9+/-6.7 microg/l vs 33.2+/-9.0 microg/l, n = 7, P < 0.05 respectively), and the corresponding difference in the mean serum oestradiol concentration was borderline (452+/-252 pmol/l vs 647+/-406 pmol/l, n = 7, P = 0.056). In contrast to the control cycle, individual leptin levels declined during the follow-up after ingestion of mifepristone (n = 8, P < 0.01).
  
  
  CONCLUSIONS
  These data showed that the commonly employed dose of mifepristone for EC delays ovulation and prolongs the menstrual cycle, when given during the late follicular phase. The mechanism of action of mifepristone may include a reduction of FSH secretion via a decrease in circulating leptin.
authors.affiliation: Department of Obstetrics and Gynecology, University of Helsinki, Helsinki, Finland.
authors.forename: Riikka
authors.initials: R
authors.lastname: Leminen
authors.forename: Taneli
authors.initials: T
authors.lastname: Raivio
authors.forename: Sirpa
authors.initials: S
authors.lastname: Ranta
authors.forename: Joachim
authors.initials: J
authors.lastname: Oehler
authors.forename: Helena
authors.initials: H
authors.lastname: von Hertzen
authors.forename: Olli A
authors.initials: OA
authors.lastname: Jänne
authors.forename: Oskari
authors.initials: O
authors.lastname: Heikinheimo
mesh_terms: D000328:Adult; D044363:Contraception, Postcoital; D003283:Contraceptives, Postcoital, Synthetic / Q000008:administration & dosage* / Q000494:pharmacology; D004334:Drug Administration Schedule; D005260:Female; D005640:Follicle Stimulating Hormone / Q000037:antagonists & inhibitors* / Q000097:blood; D005498:Follicular Phase; D006801:Humans; D020738:Leptin / Q000037:antagonists & inhibitors* / Q000097:blood; D008597:Menstrual Cycle / Q000187:drug effects; D015735:Mifepristone / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D003283:Contraceptives, Postcoital, Synthetic; D020738:Leptin; D015735:Mifepristone; D005640:Follicle Stimulating Hormone