Comparison of serum and cervical mucus hormone levels during hormone-free interval of 24/4 vs. 21/7 combined oral contraceptives

Contraception. 2013 Jun;87(6):732-7. doi: 10.1016/j.contraception.2012.12.006. Epub 2012 Dec 19.

Abstract

Background: This study analyzes levels of progesterone, estradiol, norethindrone (NET) and ethinyl estradiol (EE) in serum and levels of NET in cervical mucus on the last day of the hormone-free interval (HFI) in users of 24/4 [norethindrone acetate (NETA)/EE-24] vs. 21/7 (NETA/EE-21) regimens.

Study design: This was a randomized controlled, crossover, equivalency trial. Subjects were randomized to receive NETA/EE-24 or NETA/EE-21 for 2 months and then switched between study drugs. Blood and cervical mucus samples were obtained on Days 12-16 and on the last day of the HFI.

Results: From April 2010 to November 2011, 32 subjects were enrolled with 18 subjects completing all study visits. There were no statistically significant differences in either day 12-16 (p=.54) or last hormone-free day (p=.33) cervical mucus NET concentrations between the regimens. On the last day of the HFI, median serum progesterone levels did not differ significantly; however, users of NETA/EE-24 had higher levels of serum NET (p<.001) and users of NETA/EE-21 had higher levels of serum estradiol (p=.01).

Conclusion: This data supports the fact that inhibition of the pituitary-ovarian axis occurs during oral contraceptive use and during the HFI. We demonstrated that a reduced HFI of 4 days resulted in better suppression of the ovarian hormone production, thereby reducing the risk of ovulation and potential contraceptive failure.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cervix Mucus / drug effects*
  • Cervix Mucus / metabolism
  • Contraceptives, Oral, Combined / blood
  • Contraceptives, Oral, Combined / metabolism
  • Contraceptives, Oral, Combined / pharmacokinetics*
  • Contraceptives, Oral, Combined / pharmacology
  • Contraceptives, Oral, Hormonal / blood
  • Contraceptives, Oral, Hormonal / metabolism
  • Contraceptives, Oral, Hormonal / pharmacokinetics*
  • Contraceptives, Oral, Hormonal / pharmacology
  • Cross-Over Studies
  • Estradiol / analogs & derivatives
  • Estradiol / blood
  • Estradiol / metabolism*
  • Ethinyl Estradiol / blood
  • Ethinyl Estradiol / metabolism
  • Ethinyl Estradiol / pharmacokinetics
  • Ethinyl Estradiol / pharmacology
  • Female
  • Follicular Phase
  • Humans
  • Norethindrone / analogs & derivatives
  • Norethindrone / blood
  • Norethindrone / metabolism
  • Norethindrone / pharmacokinetics
  • Norethindrone / pharmacology
  • Norethindrone Acetate
  • Ovary / drug effects*
  • Ovary / metabolism
  • Ovulation Inhibition / drug effects
  • Patient Dropouts
  • Pituitary Gland / drug effects*
  • Pituitary Gland / metabolism
  • Progesterone / blood
  • Progesterone / metabolism*
  • Single-Blind Method
  • Tissue Distribution
  • Young Adult

Substances

  • Contraceptives, Oral, Combined
  • Contraceptives, Oral, Hormonal
  • Ethinyl Estradiol
  • Progesterone
  • Estradiol
  • Norethindrone Acetate
  • Norethindrone