title: The effects on ovarian activity of ulipristal acetate when 'quickstarting' a combined oral contraceptive pill: a prospective, randomized, double-blind parallel-arm, placebo-controlled study.
abstract: OBJECTIVE
  What is the effect on ovarian activity of a preceding intake of ulipristal acetate (UPA) when starting a combined oral contraceptive (COC) in the mid- to late-follicular phase of the cycle?
  
  
  CONCLUSIONS
  This study shows that UPA does not affect the ability of the COC to induce ovarian quiescence.
  
  
  BACKGROUND
  UPA is a progesterone receptor modulator that is available for emergency contraception (EC). In theory, UPA could alter the effectiveness of hormonal contraception started immediately following it and vice versa. Current guidelines regarding quick starting a COC following UPA are based on expert opinion only.
  
  
  METHODS
  A double-blind, randomized, placebo-controlled trial was conducted at three separate sites, Edinburgh (Scotland), Stockholm (Sweden) and Groningen (the Netherlands), over a 5-month period in 2012. Healthy female volunteers were randomized to take either UPA or an identically packaged placebo, at mid-cycle (once a lead ovarian follicle was determined to be >13 mm on transvaginal ultrasound imaging). Participants were randomized by a computer-generated randomization schedule, allocated by sequential, sealed envelopes. All women then started 21 days of the same COC the following day. The study was designed to show non-inferiority of UPA compared with placebo in terms of the proportion of women attaining ovarian quiescence, as measured by the Hoogland scoring system, while taking COC.
  
  
  METHODS
  A total of 76 women were recruited over the three sites, Edinburgh (n = 18), Stockholm (n = 13), Groningen (n = 45) and received either UPA (n = 39) or placebo (n = 37).
  
  
  RESULTS
  There were no significant differences in demographic characteristics of women in the UPA and placebo groups. Among the 76 participants treated, 47 (61.8%) reached quiescence and 25 (32.9%) ovulated. There were no significant differences between the groups in the odds ratio (OR) of reaching ovarian quiescence or not; OR 0.97 (95% CI: 0.39-2.46). All women who reached quiescence had done so after taking COCs for 14 days.
  
  
  CONCLUSIONS
  The main limitations of the study were that measurements of follicle size and blood tests were performed every 2-3 days and so it was not possible to determine the actual day that follicle rupture occurred for the women who ovulated. Furthermore, the ultrasonography was conducted by a number of investigators at the sites which may introduce error in the form of inter-observer variability in measurements of follicle growth. Finally, the findings of the study cannot be extrapolated to other combined hormonal methods of contraception such as the patch or ring, nor to progestogen- only methods of contraception.
  
  
  CONCLUSIONS
  This study provides evidence to suggest that UPA does not affect the ability of the COC to induce ovarian quiescence. However, this study design cannot determine whether the COC affects the ability of UPA to delay ovulation.
  
  
  BACKGROUND
  Funding was provided by HRA Pharma Paris, France. C.K., S.T.C. and K.G.D. have received funds for conducting research studies and lectures for HRA Pharma. C.K. is director of a contract research organization (Dinox). The remaining authors declare no conflicts of interests.
  
  
  BACKGROUND
  Clinicaltrials.gov: NCT01569113.
authors.affiliation: Chalmers Sexual Health Clinic, 2a Chalmers Street, Edinburgh EH3 9ES, UK Obstetrics and Gynaecology, University of Edinburgh, Royal Infirmary of Edinburgh, Edinburgh EH16 4SU, UK sharon.cameron@ed.ac.uk.
authors.forename: S T
authors.initials: ST
authors.lastname: Cameron
authors.affiliation: Karolinska University Hospital Solna, Stockholm SE-171 76, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Berger
authors.affiliation: Chalmers Sexual Health Clinic, 2a Chalmers Street, Edinburgh EH3 9ES, UK.
authors.forename: L
authors.initials: L
authors.lastname: Michie
authors.affiliation: Dinox, Hanzeplein 1, Entrance 53, Groningen 9713 GZ, The Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Klipping
authors.affiliation: Karolinska University Hospital Solna, Stockholm SE-171 76, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Gemzell-Danielsson
mesh_terms: D000328:Adult; D003267:Contraception / Q000379:methods*; D044363:Contraception, Postcoital / Q000379:methods; D003277:Contraceptives, Oral, Combined / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008597:Menstrual Cycle / Q000187:drug effects; D009649:Norpregnadienes / Q000494:pharmacology*; D010053:Ovary / Q000187:drug effects*; D010060:Ovulation / Q000187:drug effects*; D011446:Prospective Studies; D011980:Receptors, Progesterone; D055815:Young Adult
chemical_list: D003277:Contraceptives, Oral, Combined; D009649:Norpregnadienes; D011980:Receptors, Progesterone; C555622:ulipristal acetate
keywords: combined oral contraceptive; emergency contraceptive; progesterone receptor modulator; quickstart; ulipristal acetate