Evaluation of pituitary-ovarian axis suppression with three oral contraceptive regimens

Contraception. 2008 Mar;77(3):162-70. doi: 10.1016/j.contraception.2007.11.005. Epub 2008 Jan 11.


Background: The study was conducted to evaluate follicular development and hormone patterns with three oral contraceptive (OC) regimens before, during and after the 7-day hormone-free interval (HFI) or 7-day ethinyl estradiol (EE)-supplemented interval.

Study design: The study is a single-center, open-label, prospective, randomized trial to evaluate pituitary-ovarian suppression with three OC regimens containing identical hormones: 30 mcg of EE and 150 mcg of levonorgestrel (LNG).

Methods: After a standard 21/7 OC baseline cycle, subjects were randomized to one of three treatment groups: (1) three 21/7-day cycles of 150 mcg LNG/30 mcg EE for 21 days followed by 7 days of placebo (n=10); (2) one 84/7-day cycle of 150 mcg LNG/30 mcg EE for 84 days followed by 7 days of placebo (n=12) and (3) one 84/7EE-day cycle of 150 mcg LNG/30 mcg EE for 84 days followed by 7 days of 10 mcg EE (n=11). Estradiol; follicle-stimulating hormone (FSH); luteinizing hormone and inhibin-B levels, ovarian follicles and daily symptom diaries were collected.

Results: Compared to subjects receiving placebo during the 7-day HFI, those receiving EE demonstrated reductions (p<.05) in both FSH and estradiol. Number of developing follicles was less after the 7-day EE interval compared to that after 7-day HFI. Subjects on the 84/7 and 84/7EE regimens reported less (p=.03) daily menstrual flow than those on the 21/7-day regimen. A trend (p=.06) toward reduced headaches during the 7-day EE-supplemented interval was noted.

Conclusions: Supplementation of the standard 7-day HFI with 10 mcg EE after 84 days of an extended OC decreased FSH levels and decreased the number of developing follicles.

Publication types

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

MeSH terms

  • Adult
  • Contraceptives, Oral, Combined / administration & dosage*
  • Contraceptives, Oral, Synthetic / administration & dosage
  • Drug Administration Schedule
  • Estradiol / blood
  • Ethinyl Estradiol / administration & dosage*
  • Female
  • Follicle Stimulating Hormone / blood
  • Humans
  • Inhibins / blood
  • Levonorgestrel / administration & dosage*
  • Luteinizing Hormone / blood
  • Ovarian Follicle / diagnostic imaging
  • Ovarian Follicle / drug effects*
  • Ovarian Follicle / physiology
  • Pituitary Gland / drug effects*
  • Pituitary Gland / physiology
  • Prospective Studies
  • Ultrasonography


  • Contraceptives, Oral, Combined
  • Contraceptives, Oral, Synthetic
  • inhibin B
  • Ethinyl Estradiol
  • Estradiol
  • Inhibins
  • Levonorgestrel
  • Luteinizing Hormone
  • Follicle Stimulating Hormone