Medical Education Library

Alteration of the hormone-free interval during oral contraception

Publish date: November 1, 2008

References

1. Baerwald AR, Olatunbosun OA, Pierson RA. Effects of oral contraceptives administered at defined stages of ovarian follicular development. Fertil Steril. 2006;86:27-35.

2. Willis SA, Kuehl TJ, Spiekerman AM, Sulak PJ. Greater inhibition of the pituitary—ovarian axis in oral contraceptive regimens with a shortened hormone-free interval. Contraception. 2006;74:100-103.

3. Sullivan H, Furniss H, Spona J, Elstein M. Effect of 21-day and 24-day oral contraceptive regimens containing gestodene (60 microg) and ethinyl estradiol (15 microg) on ovarian activity. Fertil Steril. 1999;72:115-120.

4. Killick SR, Fitzgerald C, Davis A. Ovarian activity in women taking an oral contraceptive containing 20 microg ethinyl estradiol and 150 microg desogestrel: effects of low estrogen doses during the hormone-free interval. Am J Obstet Gynecol. 1998;179:S18-S24.

5. The Mircette Study Group. An open-label, multicenter, noncomparative safety and efficacy study of Mircette, a low-dose estrogen-progestin oral contraceptive. Am J Obstet Gynecol. 1998;179:S2-S8.

6. Rosenberg MJ, Meyers A, Roy V. Efficacy, cycle control, and side effects of low- and lower-dose oral contraceptives: a randomized trial of 20 microgram and 35 microgram estrogen preparations. Contraception. 1999;60:321-329.

7. Vandever MA, Kuehl TJ, Sulak PJ, et al. Evaluation of pituitary-ovarian axis suppression with three oral contraceptive regimens. Contraception. 2008;77:162-170.

8. van Heusden AM, Fauser BC. Residual ovarian activity during oral steroid contraception. Hum Reprod Update. 2002;8:345-358.

9. Reape KZ, DiLiberti CE, Hendy CH, Volpe EJ. Effects on serum hormone levels of low-dose estrogen in place of placebo during the hormone-free interval of an oral contraceptive. Contraception. 2008;77:34-39.

10. Coffee AL, Kuehl TJ, Willis S, Sulak PJ. Oral contraceptives and premenstrual symptoms: comparison of a 21/7 and extended regimen. Am J Obstet Gynecol. 2006;195:1311-1319.

11. Coffee AL, Sulak PJ, Kuehl TJ. Long-term assessment of symptomatology and satisfaction of an extended oral contraceptive regimen. Contraception. 2007;75:444-449.

12. Sulak P, Willis S, Kuehl T, Coffee A, Clark J. Headaches and oral contraceptives: impact of eliminating the standard 7-day placebo interval. Headache. 2007;47:27-37.

13. Sulak PJ, Scow RD, Preece C, Riggs MW, Kuehl TJ. Hormone withdrawal symptoms in oral contraceptive users. Obstet Gynecol. 2000;95:261-266.

14. Anderson FD, Gibbons W, Portman D. Safety and efficacy of an extended-regimen oral contraceptive utilizing continuous low-dose ethinyl estradiol. Contraception. 2006;73:229-234.

15. Kaunitz AM, Reape KZ, Portman D, Hait H. The impact of altering the hormone free interval on bleeding patterns in users of a 91-day extended regimen oral contraceptive. Presented at: Annual Meeting of the Association of Reproductive Health Professionals; September 26-29, 2007; Minneapolis, MN. Contraception. 2007;76:157.-

Dr Sulak reports that she has received grant/research support from Duramed, Organon, and Warner Chilcott; has served as a consultant to Duramed and Warner Chilcott; and is a member of the speakers’ bureau of Bayer, Duramed, Warner Chilcott, and Wyeth.

Dr Liu reports that he has received grant/research support from Barr-Duramed, Procter & Gamble, and Solvay; and has served as a consultant to Barr, Novagyn, and Solvay.

DR SULAK: The rise in FSH and 17-beta estradiol during the 7-day HFI continues into the first week of active pills and takes 5 to 7 days to decrease significantly.²

Reducing hormone withdrawal symptoms

DR LIU: Clinicians started extending OC regimens for patients with endometriosis or suspected endometriosis, whose pelvic pain flared up with the onset of bleeding.

DR SULAK: Then we realized that the benefits of extended regimens went beyond endometriosis and could help patients with menstrual migraine headaches or severe premenstrual syndrome. With extended regimens, we have shown reductions in mood swings, pain, headaches, bloating, and swelling.^6,10-12

With a low-dose regimen and a 7-day HFI, we were actually creating estrogen-withdrawal headaches, cramps, bloating, and other symptoms.¹³ In our prospective randomized trial of Seasonale vs Seasonique, we observed a tendency toward fewer headaches during the estrogen-supplemented week.⁷ And we weren’t even looking at headaches in that study! Adding estrogen during that typical week off may have the potential to decrease some of these withdrawal symptoms, but this needs further study.

Bleeding and spotting: Managing expectations

DR LIU: When a patient begins an extended-regimen OC, how do you manage her expectations about spotting and bleeding?

DR SULAK: Any patient on an extended-regimen OC has to be a great pill-taker, so I suggest that she put her pills somewhere she’ll see them at about the same time everyday. I tell patients that particularly during that first cycle, there is a high incidence of unscheduled bleeding. When I prescribe an OC regimen that substitutes a low-dose estrogen pill for the traditional placebo week, I explain that the patient will have a progestin withdrawal bleed during the estrogen-only pills. I also mention that in subsequent packs, the unscheduled bleeding is greatly reduced.^14,15

Conclusions

DR LIU: The modifications to the HFI that we’ve seen in recently approved OCs represent an incremental advance in our understanding of the physiology of ovarian follicle development. Experience and studies have shown how altering the HFI can optimize patient outcomes.

DR SULAK: We do need to see the demise of the 7-day HFI. Practitioners should realize that these changes in OCs are not arbitrary. They are substantiated by real science and will mean a true improvement in the symptoms and quality of life our patients experience.