Transactions of the annual meeting of the american gynecological and obstetrical society
Manipulation of the pill-free interval in oral contraceptive pill users: the effect on follicular suppression

https://doi.org/10.1016/j.ajog.2004.02.012Get rights and content

Abstract

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 μg ethinyl estradiol + 100 μg levonorgestrel followed by 7 pill-free days, 20 μg ethinyl estradiol + 150 μg desogestrel followed by 2 days of placebo then 10 μg ethinyl estradiol for 5 days, or 28 days of 20 μg ethinyl estradiol plus 150 μg 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/m2) 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.

Section snippets

Study design

This randomized, investigator-blinded study was approved by the Colorado Multiple Institutional Review Board. Subjects were recruited between July 2000 and March 2002 by broadcast e-mail messages on the University of Colorado Health Sciences Center campus and print advertising. Interested women were screened for eligibility by telephone call to a study co-ordinator. Subjects were required to be between 18 and 38 years old and to report a history of regular menstrual periods at 28 ± 5-day

Results

Fifty-four women were assigned randomly to 1 of the 3 groups. One woman became pregnant before starting the study drug, and 8 women elected not to continue in the study during their first month of OCP treatment for a variety of personal reasons. The baseline characteristics of the 45 remaining women are shown in Table I. Women in the continuous group were older than women in the other 2 groups (P = .01), although the mean age was still only 31.4 years. There was no difference in the mean BMI

Comment

Our data demonstrate that manipulation of the traditional pill-free interval affects folliculogenesis in users of the common 20-μg EE combination OCPs. Women who were supplemented with 5 days of 10 μg EE had fewer and smaller follicles than woman who had a 7-day pill-free interval. In turn, women who were treated with 7 days of 20 μg EE plus 150 μg desogestrel had even fewer and smaller follicles. The obvious concern resulting from these observations is that women who have a 7-day pill-free

Acknowledgments

We thank Dr James R. Murphy for statistical consultation.

References (30)

Cited by (104)

  • Ovarian function during hormonal contraception assessed by endocrine and sonographic markers: a systematic review

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    The continuous LNG + EE regimen (28 days for 3 cycles) completely suppressed ovulation, with poor follicular growth documented by ultrasound and with fast recovery of ovulation after interrupting COC use (Archer et al., 2009). Three randomized studies (Schlaff et al., 2004; Seidman et al., 2015; Vandever et al., 2008) and one prospective study (Kroll et al., 2015) evaluated the suppression of ovarian function after the supplementation of EE during HFI. In 2004, Schlaff et al. randomly assigned 54 women to receive one of these three different regimens: either 20 µg EE + 100 µg LNG followed by seven pill-free days, or 20 µg EE + 150 µg DSG followed by 2 days of placebo then 10 µg EE for 5 days, or 28 days of 20 µg EE + 150 µg DSG.

  • Rationale for eliminating the hormone-free interval in modern oral contraceptives

    2016, International Journal of Gynecology and Obstetrics
  • Ovulatory effects of three oral contraceptive regimens: A randomized, open-label, descriptive trial

    2015, Contraception
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    Shortening the HFI may increase the efficacy of low-estrogen-dose contraceptive regimens [4,8,11,12]. Alternatively, the addition of low-dose estrogen during the usual 7-day HFI has produced greater ovarian suppression, less risk of escape ovulation and improvements in hormone-related symptoms and breakthrough bleeding, and has been shown to be safe and efficacious [8,13,14]. The current study examined ovulation inhibition and ovarian activity in a 21/7-active COC regimen of 150 mcg desogestrel (DSG)/20 mcg EE followed by 7 days of 10 mcg EE.

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Presented at the Twenty-Second Annual Meeting of the American Gynecological and Obstetrical Society, Napa, California, September 18-20, 2003.

Supported in part by an investigator-initiated grant from Organon, Inc, West Orange, NJ.

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