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New Hormonal Contraceptives Offer Patients More Choices

An overview of recently approved oral and implantable contraceptives

Each year, nearly 2% of U.S. women of reproductive age have an induced abortion.1 This sobering statistic reminds us how important it is for our patients to have access to safe, effective birth control. Toward that end, this article provides an overview of hormonal contraceptives recently approved by the FDA or in development.

ORAL CONTRACEPTIVES (OCS): SUCCESS AND LIMITATIONS

Developed more than four decades ago and representing among the best-studied medications prescribed, oral contraceptives (OCs) continue to be the most popular reversible contraceptive in the U.S.2 OC use is safe for the great majority of women and is associated with numerous noncontraceptive benefits.3,4 Although OCs represent a highly effective birth control method when used correctly and consistently, inconsistent or incorrect use accounts for a surprisingly high annual failure rate of 8% among typical users.5 This statistic underscores the importance of maximizing contraceptive success, whether with OCs or with longer-acting hormonal contraceptives that do not require users’ daily attention.

SHORTENING THE HORMONE-FREE INTERVAL

Traditionally, OC formulations have involved a 28-day regimen, with 21 days of active combined hormone pills followed by a 7-day hormone-free interval. The hormone-free interval results in clearance of exogenous estrogen and progestin 2 to 3 days after completion of active pills. This, in turn, allows for several days during which levels of gonadotropins rise and ovarian follicular growth occurs, with increased risk for ovulation (referred to as "escape ovulation") if the next pack of active pills is not started on time.6 Shortening the hormone-free interval, or using low-dose pills rather than placebo, may decrease the risk for escape ovulation, enhancing contraceptive efficacy.7 Because delays in starting the next active pills are a common cause of accidental pregnancy in OC users, the newly approved formulations have the potential to improve the effectiveness of OC use. Other potential advantages of OC formulations with reduced hormone-free intervals include fewer hormone withdrawal symptoms — such as pelvic pain, headache, breast tenderness, and bloating or swelling8 — and a reduction in intermenstrual7 and scheduled withdrawal bleeding.

Until recently, only one OC regimen with a reduced hormone-free interval (Mircette, 0.15 mg desogestrel/20 µg ethinyl estradiol) substituted low-dose estrogen (10 µg ethinyl estradiol) for five of the seven usual placebo pills. Use of this formulation is associated with less intermenstrual bleeding than other OCs that contain higher doses of estrogen.9 Now, the trend toward reduction or elimination of the hormone-free interval has resulted in the introduction of several new formulations (see Table 1).


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  		Table 1. Oral Contraceptive Formulations That Reduce or Eliminate the Hormone-Free Interval

 

NEW OCS: GREATER EFFICACY, LESS BLEEDING

Two new 28-day OC regimens received FDA approval in the first quarter of 2006: Loestrin 24 Fe (1 mg norethindrone/20 µg ethinyl estradiol) and YAZ (3 mg drospirenone/20 µg ethinyl estradiol). Each provides 24, rather than 21, days of active combined pills followed by 4 days of placebo pills, thus shortening the hormone-free interval. YAZ has also been evaluated in women with premenstrual dysphoric disorder who want to prevent pregnancy. In a placebo-controlled study, significantly more patients who received active OC tablets had improvement in daily mood, physical, and behavioral scores.10

Extended OC regimens that reduce the number of withdrawal bleeding episodes have also become available and continue to increase in popularity. The first approved product to use this approach, Seasonale (150 µg levonorgestrel /30 µg ethinyl estradiol), extends active combined OC use to 84 days (12 weeks) followed by 1 hormone-free week.11 Women interested in this "four periods a year" approach to OCs need to be aware that breakthrough bleeding and spotting during the initial active pill intervals are initially more common than with conventional 28-day regimens. However, over time, unscheduled spotting and bleeding decline substantially.11

In May 2006, a second extended regimen OC, Seasonique, was approved.12 Seasonique is identical to Seasonale except that low-dose estrogen (10 µg ethinyl estradiol) is substituted for placebo. While Seasonale and Seasonique have not been compared head-to-head, data from clinical trials of the 91-day extended regimens with12 and without11 low-dose estrogen during the hormone free interval suggest that Seasonique may be associated with less unscheduled bleeding. In addition, an OC in development administers combined OCs without any hormone-free interval for one year.13

SINGLE-ROD CONTRACEPTIVE IMPLANT

A single-rod implantable contraceptive (Implanon) that releases the progestin etonogestrel for 3 years was approved in July 2006. Efficacy is high, with some clinical trials reporting no failures.14 Because Implanon is a progestin-only contraceptive, it can be used by women for whom contraceptive does of estrogen are contraindicated (e.g., a 37-year-old smoker). As with all continuous progestin-only contraceptive methods, side effects most likely to result in discontinuation relate to changes in bleeding patterns, including persistent or unpredictable spotting and bleeding. In contrast with the older six-implant Norplant system, Implanon is easily and rapidly inserted and removed.14

CONCLUSION

New OC formulations that reduce or eliminate the hormone-free interval have the potential to reduce not only accidental pregnancies, but also hormone withdrawal symptoms and bleeding. One new OC has demonstrated efficacy in the treatment of premenstrual dysphoric disorder. The single-rod progestin-only contraceptive implant represents a convenient, highly effective method of birth control that is quicker and easier to insert and remove than the older six-rod system. These recently approved hormonal contraceptives represent attractive birth control options for our patients.

— Andrew M. Kaunitz, MD

Published in Journal Watch Women's Health August 31, 2006

Citation(s):

1. Jones RK et al. Contraceptive use among U.S. women having abortions in 2000-2001. Perspect Sex Reprod Health 2002 Nov/Dec; 34:294-303.

2. Mosher WD et al. Use of contraception and use of family planning services in the United States: 1982–2002. Accessed August 10, 2006 at http://www.cdc.gov/nchs/data/ad/ad350.pdf.

3. Petitti DB. Combination estrogen-progestin oral contraceptives. [Erratum in: N Engl J Med 2004 Jan 1; 350:92.] N Engl J Med 2003 Oct 9; 349:1443-50.

4. Kaunitz AM. Beyond the pill: New data and options in hormonal and intrauterine contraception. Am J Obstet Gynecol 2005 Apr; 192:998-1004.

5. Trussell J. Contraceptive failure in the United States. Contraception 2004 Aug; 70:89-96.

6. Baerwald AR et al. Ovarian follicular development is initiated during the hormone-free interval of oral contraceptive use. Contraception 2004 Nov; 70:371-7.

7. Mishell DR Jr. Rationale for decreasing the number of days of the hormone-free interval with use of low-dose oral contraceptive formulations. Contraception 2005 Apr; 71:304-5.

8. Sulak PJ et al. Hormone withdrawal symptoms in oral contraceptive users. Obstet Gynecol 2000 Feb; 95:261-6.

9. Rosenberg MJ et al. Efficacy, cycle control, and side effects of low- and lower-dose oral contraceptives: A randomized trial of 20 micrograms and 35 micrograms estrogen preparations. Contraception 1999 Dec; 60:321-9.

10. Yonkers KA et al. Efficacy of a new low-dose oral contraceptive with drospirenone in premenstrual dysphoric disorder. Obstet Gynecol 2005 Sep; 106:492-501.

11. Anderson FD and Hait H. A multicenter, randomized study of an extended cycle oral contraceptive. [Erratum in: Contraception 2004 Feb; 69:175.] Contraception 2003 Aug; 68:89-96.

12. Anderson FD et al. Safety and efficacy of an extended-regimen oral contraceptive utilizing continuous low-dose ethinyl estradiol. Contraception 2006 Mar; 73:229-34.

13. Davis AR et al. Return to menses after continuous use of a low-dose oral contraceptive. Obstet Gynecol 2006 Apr; 107:3S.

14. Funk S et al. Safety and efficacy of Implanon, a single-rod implantable contraceptive containing etonogestrel. Contraception 2005 May; 71:319-26.

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Copyright © 2006. Massachusetts Medical Society. All rights reserved.