Omitting the first oral contraceptive pills of the cycle does not automatically lead to ovulation

Am J Obstet Gynecol. 1998 Jul;179(1):41-6. doi: 10.1016/s0002-9378(98)70249-2.


Objective: Our purpose was to test the hypothesis that omitting the first three pills of the contraceptive cycle leads to ovulation.

Study design: Ninety-nine women, randomly assigned to 1 of 3 treatments of combined oral contraceptives, completed the study. Treatments contained ethinyl estradiol and either monophasic gestodene, triphasic gestodene, or monophasic desogestrel. Pituitary-ovarian activity was monitored by ultrasonography of the ovaries and assay of serum concentrations of estradiol, progesterone, and follicle-stimulating hormone over 1 normal cycle (study period 1) and 1 cycle after an extended pill-free interval of 10 days (study period 2).

Results: None of the women experienced normal ovulation as evaluated by ultrasonography and serum progesterone concentrations. However, follicle-stimulating hormone reached a maximal serum concentration in most women during the first 7 pill-free days, indicating complete pituitary recovery, and increases in serum estradiol concentrations were seen in each woman although with marked interindividual variation. During study period 2 we found follicles of >18 mm in 24%, 24%, and 40% of the monophasic gestodene, triphasic gestodene, and monophasic desogestrel groups, respectively.

Conclusions: Follicular growth up to preovulatory size is common in women missing the first one to three pills of their contraceptive cycle. Although this creates the prerequisite for ovulation, normal ovulation did not occur when pill omissions were limited to only 3 days.

PIP: The hypothesis that omission of the first three pills of the oral contraceptive (OC) cycle leads to ovulation by extending further the pill-free period was investigated in 107 healthy women 18-35 years of age recruited from family planning programs in Finland, the Netherlands, and Belgium. Study participants were randomly allocated to one of the following treatment groups: 1) monophasic gestodene--75 mcg of gestodene and 30 mcg of ethinyl estradiol; 2) triphasic gestodene--6 days of 50 mcg gestodene and 30 mcg ethinyl estradiol, 5 days of 70 mcg gestodene and 40 mcg ethinyl estradiol, and 10 days of 100 mcg gestodene and 30 mcg ethinyl estradiol; or 3) monophasic desogestrel--150 mcg desogestrel and 20 mcg ethinyl estradiol. Noncompliance with OC taking was simulated by extending the pill-free period from 7 to 10 days. During or after the extended pill-free interval, follicular growth exceeding 18 mm occurred in 24% of women in the monophasic gestodene group, 24% in the triphasic gestodene group, and 40% in the monophasic desogestrel group. Follicle-stimulating hormone reached a maximum serum concentration in most women during the first 7 pill-free days, indicating complete pituitary recovery. No normal ovulation was observed after either a 7- or 10-day pill-free period as evaluated by ultrasonography of follicles and serum progesterone assays. Since normal ovulation did not occur when pill omissions were limited to 3 days, OC users who forget to take these three tablets can be safely advised to start the pill cycle on day 11.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Contraceptives, Oral, Combined / therapeutic use*
  • Desogestrel / therapeutic use
  • Drug Administration Schedule
  • Estradiol / pharmacology
  • Ethinyl Estradiol / therapeutic use
  • Female
  • Follicle Stimulating Hormone / pharmacology
  • Humans
  • Menstrual Cycle / drug effects*
  • Norpregnenes / therapeutic use
  • Ovarian Follicle / drug effects
  • Ovarian Follicle / growth & development
  • Ovulation / drug effects*
  • Progesterone / pharmacology


  • Contraceptives, Oral, Combined
  • Norpregnenes
  • Gestodene
  • Ethinyl Estradiol
  • Progesterone
  • Estradiol
  • Desogestrel
  • Follicle Stimulating Hormone