title: A prospective, randomized, pharmacodynamic study of quick-starting a desogestrel progestin-only pill following ulipristal acetate for emergency contraception.
abstract: OBJECTIVE
  Is there a pharmacodynamic interaction between ulipristal acetate (UPA) 30 mg for emergency contraception and a daily progestin-only contraceptive pill, desogestrel (DSG) 0.75 mg, when initiated the next day?
  
  
  CONCLUSIONS
  In this study, DSG impaired the ability of UPA to delay ovulation, but UPA had little impact on the onset of contraceptive effects due to DSG.
  
  
  BACKGROUND
  UPA is a progesterone receptor modulator used for emergency contraceptive (EC) at the dose of 30 mg. UPA delays ovulation by at least 5 days when administered in the mid to late follicular phase. In theory, potent progestins could reactivate progesterone signaling that leads to follicle rupture, thereby impacting the effectiveness of UPA as EC. In addition, UPA could alter the onset of the contraceptive effect of progestin-containing contraceptives started immediately after UPA.
  
  
  METHODS
  A single-blind (for observer), placebo-controlled, partial crossover study was conducted in two sites [Dominican Republic (DR) and the Netherlands (NDL)] over 11 months from October 2012 to September 2013. Healthy female volunteers participated in two of the three treatment cycles separated by a washout cycle. Treatment combinations studied were as follows: (i) a single 30 mg dose of UPA followed by 75 µg per day DSG for 20 days, (ii) a single 30 mg dose of UPA followed by 20 days of placebo matching that of DSG (PLB2) or (iii) one tablet of placebo-matching UPA (PLB1) followed by 75 µg per day DSG for 20 days. Participants were randomized to one of the three treatment sequences (UPA + DSG/UPA + PLB2, PLB1 + DSG/UPA + DSG and UPA + PLB2/PLB1 + DSG) when a lead follicle was ≥ 14 to <16 mm diameter on transvaginal ultrasound imaging (TVU).
  
  
  METHODS
  A total of 71 women were included, and 49 were randomized to a first treatment combination of the three period sequences (20 in the DR and 29 in the NDL); 41 of the 49 continued and completed two treatment combinations (20 in the DR and 21 in the NDL).
  
  
  RESULTS
  Initiating DSG treatment the day after UPA significantly reduced the ovulation delaying effect of UPA (P = 0.0054). While ovulation occurred in only one of the 29 UPA-only cycles (3%) in the first 5 days, it occurred in 13 of the 29 (45%) UPA + DSG cycles.
  
  
  CONCLUSIONS
  This was a small, descriptive, pharmacodynamic study in which some findings differed by study site. Distinguishing between a cystic corpus luteum and a luteinized unruptured follicle (LUF) by TVU was difficult in some cases; however, the investigators reached consensus, when the study was still blinded, regarding ovulation based on hormone levels and careful review of daily TVU images.
  
  
  CONCLUSIONS
  Initiating the use of a DSG progestin-only pill (POP) immediately after UPA reduces the ability of UPA to delay ovulation and thus may decrease its efficacy as EC. If starting a DSG POP after using UPA for EC, and possibly any progestin-only method, consideration should be given to delaying for at least 5 days after UPA intake in order to preserve the ovulation delaying effects of UPA.
authors.affiliation: PROFAMILIA, Ave. Nicolás de Ovando & Calle 16, Santo Domingo 10401, Dominican Republic vbrache@gmail.com.
authors.forename: V
authors.initials: V
authors.lastname: Brache
authors.affiliation: PROFAMILIA, Ave. Nicolás de Ovando & Calle 16, Santo Domingo 10401, Dominican Republic.
authors.forename: L
authors.initials: L
authors.lastname: Cochon
authors.affiliation: Dinox, Hanzeplein 1, Entrance 53, Groningen 9713 GZ, The Netherlands.
authors.forename: I J M
authors.initials: IJ
authors.lastname: Duijkers
authors.affiliation: HRA Pharma, 15, rue Béranger, Paris 75 003, France.
authors.forename: D P
authors.initials: DP
authors.lastname: Levy
authors.affiliation: HRA Pharma, 15, rue Béranger, Paris 75 003, France.
authors.forename: N
authors.initials: N
authors.lastname: Kapp
authors.affiliation: HRA Pharma, 15, rue Béranger, Paris 75 003, France.
authors.forename: C
authors.initials: C
authors.lastname: Monteil
authors.affiliation: HRA Pharma, 15, rue Béranger, Paris 75 003, France.
authors.forename: J L
authors.initials: JL
authors.lastname: Abitbol
authors.affiliation: Dinox, Hanzeplein 1, Entrance 53, Groningen 9713 GZ, The Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Klipping
mesh_terms: D000293:Adolescent; D000328:Adult; D044363:Contraception, Postcoital / Q000379:methods*; D003280:Contraceptives, Oral, Synthetic / Q000008:administration & dosage* / Q000627:therapeutic use; D018592:Cross-Over Studies; D017135:Desogestrel / Q000008:administration & dosage* / Q000627:therapeutic use; D004293:Dominican Republic; D005260:Female; D006801:Humans; D009426:Netherlands; D009649:Norpregnadienes / Q000627:therapeutic use*; D010060:Ovulation / Q000187:drug effects*; D011446:Prospective Studies; D016037:Single-Blind Method; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D003280:Contraceptives, Oral, Synthetic; D009649:Norpregnadienes; D017135:Desogestrel; C555622:ulipristal acetate
keywords: UPA; emergency contraception; progesterone receptor modulator; progestin-only pills; quickstart