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Continuous Hormonal Contraception: An Increasingly Popular Option

Patricia J. Sulak, MD

Emerging data indicate that continuous hormonal contraceptive regimens are not only gaining in patient acceptance, but that they provide better suppression of ovulation and menstrual disorders than regimens with a hormone-free interval.

The most popular method of reversible contraception continues to be combination oral contraceptives (COC) prescribed as a 21/7 regimen (21 days estrogen plus progestin [E+P]/7 days hormone-free). Modifications over the past 4 decades have primarily involved lowering hormone content and utilizing new progestin components. Only recently have changes in the regimen (eg, extended dosing) been considered as a noncontraceptive modification to benefit women by reducing bleeding days or hormone-related side effects.

The 21/7 regimen was created to mimic the average spontaneous menstrual cycle of 28 days. After more than 40 years of use, new regimens are being developed to give women more options with regard to bleeding. Numerous studies over the last decade have documented that lowering the hormone dosage in COCs without altering the standard 7-day hormone-free interval (HFI) compromises ovulation suppression and can induce hormone-withdrawal symptoms.

Although today’s low-dose, 21/7 COCs are very effective in preventing pregnancy, studies have confirmed incomplete inhibition of pituitary-ovarian function.1-5 The resultant follicular growth and endogenous hormone production may increase the potential for follicular cysts and ovulation.1-5 With a standard 7-day HFI, follicle-stimulating hormone (FSH) levels begin to rise on day 3 to 4 of the HFI, allowing follicular recruitment and estradiol production.5 While uncommon, pregnancy can occur because of “escape” ovulation, even in adherent users. Low-dose COCs have also been shown to provide little to no protection from the development of functional ovarian cysts because of the 7-day HFI.6 As most patients are not perfectly adherent, this increases the risk of ovarian cysts and pregnancy.

Today’s standard low-dose COCs often cause “nuisance” side effects. Published data document an increased incidence of menstrual-related symptoms during the 7-day HFI in users, including headache, pelvic pain, bloating/swelling, breast tenderness, and need for pain medication.7 Menstrual-related symptoms such as headache, mood swings, abdominal cramping, bloating, and breast tenderness are well known side effects associated with COCs, and may lead to untimely discontinuation and resultant unintended pregnancy. Modifications in the pill regimen may help to address the issues of follicular development and increased symptomatology.

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SCHEDULED BLEEDING

Women differ regarding their desired menstrual frequency. Determining whether a patient wishes to bleed once a month, once every 3 months, or never will help to dictate which COC regimen to recommend. Currently, there are several approaches to altering the typical 21/7 COC regimen (Table 1). A 24/4 regimen that shortens the 7-day HFI to 4 days can provide greater pituitary-ovarian inhibition, reducing the risk of ovulation, ovarian cyst formation, and common hormone-withdrawal symptoms.1,2,5 Also, a 24/4 regimen has fewer hormone-withdrawal side effects; this is why a 24/4 COC (Yaz) was approved by the FDA for treating premenstrual dysphoric disorder (PMDD), whereas a similar formulation with a 21/7 regimen (Yasmin) was not approved for this indication. Two COC products with 24 days of active hormones and a 4-day HFI were approved by the FDA in 2006: ethinyl estradiol (EE), 20 µg/drospirenone, 3 mg (Yaz); and EE, 20 µg/norethindrone, 1 mg (Loestrin 24FE).

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Table 1. Alterations in the 21/7 Contraceptive Regimen

Extending the active-pill interval beyond the standard 3 weeks to 6, 9, 12 weeks or more is gaining popularity in clinical practice. A survey of US health care providers revealed that the majority thought extended regimens should be offered to women who desired elimination of monthly withdrawal bleeding and associated symptoms.8 The first FDA-approved extended regimen became available in 2003 (Seasonale), consisting of 84 days of levonorgestrel (LNG), 150 µg/EE, 30 µg, followed by a 7-day HFI. However, a 7-day HFI with an extended regimen can lead to the same problems that may occur with a 21/7 regimen.9,10 To provide better pituitary-ovarian suppression, low-dose EE (10 µg) was added to the 7-day HFI (Seasonique); this prevents the risks of increased FSH levels, follicular development, and endogenous estradiol production compared with regimens using a 7-day HFI.9,10

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CONTINUOUS HORMONAL CONTRACEPTION

Continuous hormonal contraception has been available in the United States for more than a decade, primarily consisting of progestin-only injectable methods. Amenorrhea is a primary advantage of some methods of continuous hormonal contraception; studies on women’s attitudes regarding desired frequency of menstruation indicate that with increasing age, the percentage desiring amenorrhea increases as well.11-13 For women who are comfortable with menstrual suppression, numerous options are now available (Table 2).

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Table 2. Continuous Hormonal Contraception

Continuous Combination Hormonal Contraception

Regimens for COCs that entirely eliminate the HFI have been prescribed in an off-label fashion for decades as a treatment for endometriosis and other menstrual disorders. Acceptance of continuous regimens has been documented in the clinical setting, particularly in patients with menstrual complaints.14-16 Studies have documented a reduction in premenstrual mood swings, headaches, and pelvic pain in patients converted from a 21/7 to a continuous regimen.17-19 One study of 102 patients converted from a 21/7 COC regimen to a continuous regimen showed a statistically significant reduction in severe headaches;18 by contrast, headache severity peaks during the HFI of a 21/7 regimen.18 Importantly, the decrease in menstrual-associated symptoms persists with ongoing use of COCs (Figure).19

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Figure. A sustained improvement in menstrual symptoms with ongoing use of continuous hormonal contraception.

However, although continuous regimens eliminate scheduled bleeding, they can cause irregular, breakthrough “nuisance” bleeding and spotting. Breakthrough bleeding resulting from continuous regimens may be effectively managed by implementing an abbreviated, 3-day HFI.16,20 In a prospective trial of subjects with breakthrough bleeding on a continuous regimen, those randomized to a 3-day HFI experienced less nuisance bleeding than those randomized to a continuous regimen.20

In 2007, the first continuous-regimen COC was approved by the FDA (EE, 20 µg/LNG, 90 µg [Lybrel]). While this is the only continuous COC approved by the FDA, other COCs, the transdermal contraceptive patch, and the contraceptive vaginal ring are often prescribed in a continuous regimen by health care providers in an off-label fashion. Studies are currently ongoing with these methods to further assess benefits and side effects, particularly incidence and management of breakthrough bleeding.

Continuous Progestin Contraception

Continuous progestin-only contraception is available via several routes of administration, including pills, injections, implants, and intrauterine contraception (IUC). Progestin-only oral contraceptives (OCs) contain either levonorgestrel or norethindrone. They are primarily utilized in breast-feeding women and in patients with contraindications to estrogen-containing contraceptives. Depot medroxyprogesterone acetate (DMPA) is a progestin-only contraceptive injection. Approximately 60% of patients who are given intramuscular DMPA injections every 12 weeks will become amenorrheic after the first year, increasing to 80% by 2 years. Because DMPA is highly effective in inhibiting ovarian function, patients are hypoestrogenic, which may lead to decreased bone mineral density. This bone loss reverses after discontinuation.

The only contraceptive implant marketed in the United States (Implanon) contains the progestin etonogestrel, and consists of a single rod approximately the size of a matchstick.21 Placed in the upper arm, the implant is effective for up to 3 years. Because the etonogestrel implant does not completely inhibit ovarian function, patients are not hypoestrogenic and bone loss does not occur. Breakthrough bleeding is the main reason for discontinuation.

The levonorgestrel-containing intrauterine system (LNG-IUS [Mirena]) has been available in this country for more than 5 years. Not only is the LNG-IUS as effective as sterilization, but it also has other advantages, including immediate reversibility upon removal and a significant reduction in menstrual flow and pelvic pain.

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CONCLUSION

Modifications of the standard 21/7 contraceptive regimen—eg, COCs, vaginal ring, transdermal patch—can greatly improve both side-effect profiles and continuation rates. Shortening the HFI, adding estrogen to the standard HFI, and extending the active-component interval are all effective strategies, providing greater ovarian suppression and reducing use of low-dose 21/7 regimens. For patients desiring menstrual suppression, several combination and progestin-only methods are available. With such a wide array of products, matching the method with the patient's needs—so essential for adherence—is now easier. Patients should be educated that monthly withdrawal bleeding is not only medically unnecessary, but can actually induce menstrual-associated side effects. In addition, improvements in contraceptive regimens with more extended/continuous regimens and products have the potential to further decrease unintended pregnancy.

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Patricia J. Sulak, MD, is Professor, Department of Obstetrics and Gynecology, Texas A&M College of Medicine; and Medical Director, Division of Research, Scott & White Memorial Hospital, Temple, TX. She is a board member of The Female Patient.

References

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