title: Comparison of a 24-day and a 21-day pill regimen for the novel combined oral contraceptive, nomegestrol acetate and 17β-estradiol (NOMAC/E2): a double-blind, randomized study.
abstract: BACKGROUND Nomegestrol acetate/17β-estradiol (NOMAC/E(2)) is a new monophasic oral contraceptive combining NOMAC (2.5 mg), a highly selective progesterone-derived progestogen, with E(2) (1.5 mg), which is structurally identical to endogenous estrogen. The objective of this study was to compare the effects on ovarian activity of two different NOMAC/E(2) regimens. METHODS This was a double-blind, randomized study. Healthy, premenopausal women (aged 18-38 years, previous menstrual cycle length 28 ± 7 days) were randomized by computer-generated code to once-daily NOMAC/E(2) for three consecutive 28-day cycles: either 24 days with a 4-day placebo interval (n = 40) or 21 days with a 7-day placebo interval (n = 37) per cycle. Follicular growth (primary outcome measure), plasma hormone profiles and bleeding patterns were assessed. RESULTS There was no evidence of ovulation during treatment with either NOMAC/E(2) regimen. The largest follicle diameter was significantly smaller in the 24-day group than in the 21-day group [mean (SD) mm in cycle 2: 9.0 (3.0) versus 11.3 (5.3) (P = 0.02); in cycle 3: 9.2 (3.0) versus 11.5 (6.0) (P = 0.04)]. Mean FSH plasma levels were significantly lower in the 24-day versus the 21-day group on Day 24 of cycles 1 and 2. Withdrawal bleeding duration was significantly shorter in the 24-day than in the 21-day group [mean (SD) days after cycle 1: 3.5 (1.3) versus 5.0 (2.6) (P = 0.002); after cycle 2: 3.9 (1.6) versus 4.8 (1.7) (P = 0.03)]. CONCLUSIONS The 24-day NOMAC/E(2) regimen was associated with greater inhibition of follicular growth and shorter duration of withdrawal bleeding than the 21-day regimen, suggesting the shorter pill-free interval results in a greater margin of contraceptive efficacy and tolerability, and fewer withdrawal symptoms.
authors.affiliation: Endocrine Unit, Hôpital Saint Antoine AP-HP, 75571 Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Christin-Maitre
authors.forename: D
authors.initials: D
authors.lastname: Serfaty
authors.forename: N
authors.initials: N
authors.lastname: Chabbert-Buffet
authors.forename: E
authors.initials: E
authors.lastname: Ochsenbein
authors.forename: D
authors.initials: D
authors.lastname: Chassard
authors.forename: J-L
authors.initials: JL
authors.lastname: Thomas
mesh_terms: D003277:Contraceptives, Oral, Combined / Q000008:administration & dosage*; D004311:Double-Blind Method; D004958:Estradiol / Q000008:administration & dosage*; D006801:Humans; D008535:Megestrol / Q000008:administration & dosage*; D009649:Norpregnadienes / Q000008:administration & dosage*
chemical_list: D003277:Contraceptives, Oral, Combined; D009649:Norpregnadienes; D004958:Estradiol; C038501:nomegestrol acetate; D008535:Megestrol