Greater inhibition of the pituitary--ovarian axis in oral contraceptive regimens with a shortened hormone-free interval

Contraception. 2006 Aug;74(2):100-3. doi: 10.1016/j.contraception.2006.02.006. Epub 2006 Apr 27.


Objective: Our objective was to test the hypothesis that shortening the hormone-free interval (HFI) between cycles of 21 days of oral contraceptives (OCs) reduces pituitary secretion of gonadotropins and ovarian production of estradiol and inhibin-B.

Design: We used a prospective trial design comparing the standard 7-day HFI and shortened HFI during cycles, with an OC containing 0.03 mg of ethinyl estradiol and 3 mg of drospirenone.

Methods: Twelve current OC users initially utilized an OC in the standard fashion, with 21 days of active pills and a 7-day HFI, followed by 21 days of active pills with randomization to either a 3-day or a 4-day HFI. Nine daily blood samples were obtained for the measurement of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol and inhibin-B, beginning with active pill 21 days before each HFI of the two cycles. Analysis of variance was used to compare hormones for 9 days bracketing the standard 7-day HFI and to compare, within individuals, the 7-day HFI and the subsequent shortened HFI.

Results: During the 7-day HFI, all four hormones significantly (p>.001) increased from baseline. FSH increased beginning on HFI Day 4, inhibin-B increased beginning on HFI Day 5, and LH and estradiol increased beginning on HFI Day 6. Subjects randomized to the 3-day or the 4-day HFI did not differ with regard to age and body size (p=.88) or initial hormone level (p=.67). Greater pituitary and ovarian suppression was seen with the shortened HFI for all four hormones (p<.001). Hormone levels in the 7 days after the last active pill of the second cycle did not differ (p>.4) between the 3-day and the 4-day HFI groups.

Conclusions: Shortening the HFI from 7 days to 3 or 4 days blunts increases in the pituitary-ovarian axis during cycles of OC use.

Publication types

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

MeSH terms

  • Adult
  • Contraceptives, Oral / administration & dosage*
  • Estradiol / blood
  • Female
  • Follicle Stimulating Hormone / blood
  • Humans
  • Inhibins / blood
  • Luteinizing Hormone / blood
  • Ovary / drug effects
  • Ovary / physiology*
  • Pituitary Gland / drug effects
  • Pituitary Gland / physiology*
  • Prospective Studies


  • Contraceptives, Oral
  • inhibin B
  • Estradiol
  • Inhibins
  • Luteinizing Hormone
  • Follicle Stimulating Hormone