Manipulation of the pill-free interval in oral contraceptive pill users: the effect on follicular suppression

Am J Obstet Gynecol. 2004 Apr;190(4):943-51. doi: 10.1016/j.ajog.2004.02.012.


Objective: The purpose of this study was to compare follicular suppression that was produced by 3 different oral contraceptive regimens that differ by treatment in the pill-free interval.

Study design: In a university setting, 54 women were assigned randomly to receive either 20 microg ethinyl estradiol+100 microg levonorgestrel followed by 7 pill-free days, 20 microg ethinyl estradiol+150 microg desogestrel followed by 2 days of placebo then 10 microg ethinyl estradiol for 5 days, or 28 days of 20 microg ethinyl estradiol plus 150 microg desogestrel. Follicular suppression was evaluated by serial ultrasound scans and by serum and urinary hormone levels during a 2-month study period. Data were analyzed by nonparametric statistical tests.

Results: There was a significant difference in follicle count among the 3 groups (P=.005). Women who were treated with a 7-day pill-free interval experienced the least suppression. Estrogen levels were more variable and led to an observation that overweight (body mass index, >25 kg/m(2)) was associated with reduced follicle suppression (relative risk, 1.6; 95% CI, 1.0, 2.7) and higher estrogen levels (relative risk, 5.3; 95% CI, 1.3, 21).

Conclusion: Contraceptive pill users who were treated with a 7-day pill-free interval demonstrated less follicular suppression than women who were supplemented with either estrogen alone or estrogen plus progestin. Overweight women were less suppressed than women of normal weight.

Publication types

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

MeSH terms

  • Adult
  • Body Mass Index
  • Contraceptives, Oral, Combined / administration & dosage*
  • Desogestrel / administration & dosage
  • Double-Blind Method
  • Drug Administration Schedule
  • Ethinyl Estradiol / administration & dosage
  • Female
  • Humans
  • Levonorgestrel / administration & dosage
  • Menstrual Cycle / drug effects
  • Ovarian Follicle / drug effects*


  • Contraceptives, Oral, Combined
  • Ethinyl Estradiol
  • Levonorgestrel
  • Desogestrel