title: Bleeding pattern and cycle control with estetrol-containing combined oral contraceptives: results from a phase II, randomised, dose-finding study (FIESTA).
abstract: This study aims to assess vaginal bleeding patterns and cycle control of oral contraceptives containing estetrol (E4) combined with either drospirenone (DRSP) or levonorgestrel (LNG).
  
  
  
  An open-label, multicentre, randomised, dose-finding study lasting six cycles in healthy women aged 18-35 years was used. Four treatments (15 mg or 20 mg E4, combined with either 3 mg DRSP or 150 mcg LNG) were administered in a 24/4-day regimen. A marketed dosing regimen of estradiol valerate with dienogest (E2V/DNG) served as reference since it contains (like E4) a natural oestrogen.
  
  
  
  A total of 396 women were randomised, of whom 389 received study medication, and 316 completed the study. By cycle 6, the frequencies of unscheduled bleeding and/or spotting and absence of withdrawal bleeding were the lowest in the 15 mg E4/DRSP group (33.8% and 3.5%, respectively). In the E2V/DNG reference group, these frequencies were 47.8% and 27.1%, respectively. By cycle 6, the frequency of women with absence of withdrawal bleeding was <20% for all E4 treatment groups: 3.5-3.8% combined with DRSP and 14.0-18.5% combined with LNG. By cycle 6, unscheduled intracyclic bleeding was reported by <20% of women in the 20 mg E4/LNG group (18.9%) and in the 15 mg E4/DRSP group (16.9%).
  
  
  
  This study showed that, of the four treatment modalities investigated, the 15 mg E4/DRSP combination has the most favourable bleeding pattern and cycle control.
  
  
  
  Due to its favourable bleeding pattern and cycle control, the 15 mg E4/DRSP combination is the preferred combination for further phase III clinical development.
authors.affiliation: Sexual Health Clinic (Väestöliitto), 00100 Helsinki, Finland.
authors.forename: Dan
authors.initials: D
authors.lastname: Apter
authors.affiliation: Pantarhei Bioscience BV, 3700 AL Zeist, the Netherlands.
authors.forename: Yvette
authors.initials: Y
authors.lastname: Zimmerman
authors.affiliation: Pantarhei Bioscience BV, 3700 AL Zeist, the Netherlands.
authors.forename: Louise
authors.initials: L
authors.lastname: Beekman
authors.affiliation: Estetra SPRL, 4000 Liège, Belgium. Electronic address: mmawet@mithra.com.
authors.forename: Marie
authors.initials: M
authors.lastname: Mawet
authors.affiliation: Estetra SPRL, 4000 Liège, Belgium.
authors.forename: Catherine
authors.initials: C
authors.lastname: Maillard
authors.affiliation: Estetra SPRL, 4000 Liège, Belgium; University of Liège, 4000 Liège, Belgium.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Foidart
authors.affiliation: Pantarhei Bioscience BV, 3700 AL Zeist, the Netherlands.
authors.forename: Herjan J T
authors.initials: HJ
authors.lastname: Coelingh Bennink
mesh_terms: D000736:Androstenes / Q000008:administration & dosage / Q000009:adverse effects; D003271:Contraceptive Agents, Female / Q000008:administration & dosage* / Q000737:chemistry; D003277:Contraceptives, Oral, Combined / Q000008:administration & dosage* / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004953:Estetrol / Q000008:administration & dosage / Q000009:adverse effects; D004958:Estradiol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D016912:Levonorgestrel / Q000008:administration & dosage / Q000009:adverse effects; D008796:Metrorrhagia / Q000188:drug therapy / Q000209:etiology; D009277:Nandrolone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives
chemical_list: D000736:Androstenes; D003271:Contraceptive Agents, Female; D003277:Contraceptives, Oral, Combined; C023635:dienogest; D004958:Estradiol; D016912:Levonorgestrel; D009277:Nandrolone; D004953:Estetrol; C035144:drospirenone
keywords: Bleeding pattern; Cycle control; Dienogest; Estetrol; Estradiol valerate