title: Inhibition of ovulation by administration of estetrol in combination with drospirenone or levonorgestrel: Results of a phase II dose-finding pilot study.
abstract: OBJECTIVE
  The aim of the study was to evaluate the efficacy of different dosages of estetrol (E4) combined with one of two progestins in suppressing the pituitary-ovarian axis and ovulation in healthy premenopausal women.
  
  
  METHODS
  This was an open, parallel, phase II, dose-finding, pilot study performed in healthy women aged 18 to 35 years with a documented ovulatory cycle before treatment. For three consecutive cycles in a 24/4-day regimen, participants received 5 mg or 10 mg E4/3 mg drospirenone (DRSP); 5 mg, 10 mg or 20 mg E4/150 μg levonorgestrel; or 20 μg ethinylestradiol (EE)/3 mg DRSP as comparator. Pituitary-ovarian axis activity and the occurrence of ovulation were evaluated by monitoring follicular size, serum levels of follicle-stimulating hormone, luteinising hormone, estradiol and progesterone during treatment cycles 1 and 3. Endometrial thickness was evaluated throughout the trial, and the return of ovulation was evaluated after the last intake of medication.
  
  
  RESULTS
  A total of 109 women were included in the trial. No ovulation occurred in any treatment group. Ovarian activity inhibition seemed proportional to the E4 dosage: the highest suppression was observed in the 20 mg E4 group and was very similar to that observed with EE/DRSP. Endometrial thickness was suppressed to the same extent in all groups. Post-treatment ovulation occurred in all participants between 17 and 21 days after the last active treatment. The study combinations were well tolerated and safe.
  
  
  CONCLUSIONS
  Combined with a progestin, E4 adequately suppresses ovarian activity, particularly when given at a dosage above 10 mg/day.
authors.affiliation: a * Dinox BV , Groningen , the Netherlands.
authors.forename: Ingrid J M
authors.initials: IJ
authors.lastname: Duijkers
authors.affiliation: a * Dinox BV , Groningen , the Netherlands.
authors.forename: Christine
authors.initials: C
authors.lastname: Klipping
authors.affiliation: b Pantarhei Bioscience BV , Zeist , the Netherlands.
authors.forename: Yvette
authors.initials: Y
authors.lastname: Zimmerman
authors.affiliation: b Pantarhei Bioscience BV , Zeist , the Netherlands.
authors.forename: Nicole
authors.initials: N
authors.lastname: Appels
authors.affiliation: c Estetra SPRL , Liège , Belgium.
authors.forename: Maud
authors.initials: M
authors.lastname: Jost
authors.affiliation: c Estetra SPRL , Liège , Belgium.
authors.forename: Catherine
authors.initials: C
authors.lastname: Maillard
authors.affiliation: c Estetra SPRL , Liège , Belgium.
authors.forename: Marie
authors.initials: M
authors.lastname: Mawet
authors.affiliation: c Estetra SPRL , Liège , Belgium.|d University of Liège , Liège , Belgium.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Foidart
authors.affiliation: b Pantarhei Bioscience BV , Zeist , the Netherlands.
authors.forename: Herjan J T
authors.initials: HJ
authors.lastname: Coelingh Bennink
mesh_terms: D000293:Adolescent; D000328:Adult; D000736:Androstenes / Q000008:administration & dosage* / Q000009:adverse effects; D003277:Contraceptives, Oral, Combined / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004717:Endometrium / Q000000981:diagnostic imaging; D004953:Estetrol / Q000008:administration & dosage* / Q000009:adverse effects; D004958:Estradiol / Q000097:blood; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D016912:Levonorgestrel / Q000008:administration & dosage* / Q000009:adverse effects; D007986:Luteinizing Hormone / Q000097:blood; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D006080:Ovarian Follicle / Q000000981:diagnostic imaging; D010060:Ovulation / Q000187:drug effects; D034445:Ovulation Inhibition; D010865:Pilot Projects; D010902:Pituitary Gland / Q000187:drug effects / Q000502:physiology; D011374:Progesterone / Q000097:blood; D014463:Ultrasonography; D055815:Young Adult
chemical_list: D000736:Androstenes; D003277:Contraceptives, Oral, Combined; D000451:Mineralocorticoid Receptor Antagonists; D004997:Ethinyl Estradiol; D011374:Progesterone; D004958:Estradiol; D016912:Levonorgestrel; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D004953:Estetrol; C035144:drospirenone
keywords: Estetrol; Estrogen; Oral contraception; Ovulation inhibition; Progestin