A number of new products, including two under development, are providing women with a wide range of options in hormonal contraception.
A number of new products, including two under development, are providing women with a wide range of options in hormonal contraception (see table). In addition, new information about administration and dosing will aid physicians in choosing and administering oral contraceptive products.
According to Pat Sulak, M.D., director of the sex education program at Scott and White Clinic/ Memorial Hospital in Temple, Texas, there are two major advances in hormone-based contraception: new modes of administration and elimination of the monthly withdrawal bleeding that occurs during the placebo interval. Sulak said that the optimal method for an individual woman depends on many factors, including: the patient's age, lifestyle, and prior history of contraception and compliance with her drug regimen. Ron Ruggiero, Pharm.D., clinical professor at the college of pharmacy at the University of California at San Francisco, concurs. "Pharmacists minimally need to provide reinforcement on the rational and proper use of hormone-based contraception. This must be done at the initial as well as follow-up encounter to ensure compliance," he said.
Oral contraceptives (OCs) comprise the most common method of reversible birth control. According to the American College of Obstetricians and Gynecologists (ACOG), OCs are used by approximately 16 million women in the United States. The Food & Drug Administration has stated, "In clinical use since the late 1950s, the safety of oral contraceptives has been studied more extensively than any other class of drugs." Despite 50 years of clinical use of OCs, experts agree that room for improvement in both efficacy and safety remains.
Linda Dominguez, a nurse practitioner with Albuquerque-based Planned Parenthood of New Mexico, said, "When a woman chooses one of the many highly effective [hormone-based] contraceptive methods available, she not only achieves her family planning goals but will also likely receive many other health benefits." She added, "The improvement in quality of life should be underscored in counseling. What a boon it is for women not only to be able to control their fertility, but also control their cycles and the symptoms that accompany them."
When a woman receives a new prescription for an oral contraceptive, she is usually instructed to wait to begin taking the pills until after her next menstrual period has started. While specific instructions vary, with recommendations for Sunday-starts or first-day starts, women may delay initiation of their OCs for several days to up to three weeks.
According to Carolyn Westhoff, M.D., professor of Obstetrics and Gynecology at Columbia University College of Physicians and Surgeons, the historical reasoning behind these instructions was to avoid inadvertent OC exposure in a woman who might already be pregnant and to link the first OC withdrawal bleeding to a four-week cycle, mimicking the regular menstrual cycle. This approach often results in confusion and an increased risk of conception during the wait to begin the pill.
Westhoff and her Columbia University colleagues have evaluated an alternate approach to the initiation of OC therapy. Using the "Quick Start" method, patients take the first dose at their clinic visit, regardless of where they are in their menstrual cycle. In a study of 250 women, taking the first OC pill in the clinic was strongly associated with continuation of OC therapy to a second pill pack. A subsequent randomized trial of 113 women showed no difference in the rate of breakthrough bleeding or spotting. According to Westhoff, the Quick Start method is being evaluated in an NIH-funded randomized trial of 200 women, aged 25 or younger. "We think this approach might be useful for any woman starting pills or the newer hormonal methods [of contraception]. It [Quick Start] should also be useful for busy clinicians because it simplifies health education," said Westhoff.
According to Victoria Holt, Ph.D., MPH, of the department of epidemiology and the School of Public Health & Community Medicine at the University of Washington, while it is commonly accepted that noncompliance with pill taking is the most common cause of oral contraceptive failure, patient weight may also be a factor. A retrospective cohort analysis conducted at the University of Washington, using data from the Group Health Cooperative of Puget Sound, has shown that women weighing >70.5 kilograms (155 pounds) were at increased risk of OC failure. The increased risk was seen with both low-dose (ethinyl estradiol dose < 50 mcg) and very low dose (ethinyl estradiol dose < 35 mcg) OCs. This observation was also noted in studies of Ortho Evra, a transdermal patch containing combined estrogen/progestin.
Miriam Zieman, M.D., of Emory University School of Medicine, reported that in clinical trials, approximately one-third of the on-treatment pregnancies reported with Ortho Evra occurred in women with a baseline body weight >=90 kilograms (198 pounds). As this increased rate of contraceptive failure in women with a higher body weight has also been reported in studies of OCs, this observation should not be considered unique to transdermal delivery systems, according to the University of Washington study. Anne Moore, RN, NP, a women's health nurse practitioner and professor of nursing at Vanderbilt University, advises counseling heavier women with regard to compliance and encouraging them to continue to use OCs appropriately rather than relying on less effective [barrier] methods of contraception.
Two surveys have reported that the majority of menstruating women (ages 18-50) are willing to decrease the number of menstrual cycles per year or eliminate menstruation entirely. A telephone survey was conducted with over 900 women, ages 18-49, with regard to their views on menstruation and menstrual symptomatology. The authors of the report, Isolde den Tonkelaar and Bjorn Oddens of the International Health Foundation in Utrecht, the Netherlands, reported that greater than 70% of menstruating women would prefer a less painful, shorter, or less heavy period and that the majority (>60% of each age group) preferred a bleeding frequency of once every three months or more. More recently, AF Glasier of the Center for Reproductive Biology at the University of Edinburgh reported the results of a questionnaire-based survey of 1,000 women attending family planning clinics worldwide. As in the Dutch study, women would opt to bleed once every three months, if given the opportunity.
Extended-cycle oral contraceptive regimens have long been used for the management of menstrual disorders such as endometriosis and as a lifestyle intervention when withdrawal bleeding proved inconvenient. Up to now, extension of the active cycle required women to refill prescriptions prematurely or rely on the use of sample packs.
A new OC product under review at the FDA may change that. The Seasonale regimen consists of 84 days of active combination OC pills (ethinyl estradiol 30 mcg with levonorgestrel 150 mcg) followed by seven days of placebo in a 91-day cycle. Use of Seasonale results in women having their hormone withdrawal ("period") only four times per year as opposed to 13 times per year associated with the conventional 28-day OC regimens.
The preliminary results from a controlled clinical trial showed that Seasonale was >99% effective in preventing pregnancy. As with all OC formulations, unscheduled bleeding (that which occurs during active pill therapy) appeared to decrease with continued use. The extent of withdrawal bleeding in the patient who received Seasonale was comparable to conventional 28-day regimens and may improve with long-term (>one year) therapy. According to Andy Anderson, M.D., principal investigator of the study, Seasonale is the only oral contraceptive regimen that decreases the number of menstrual cycles from 13 to four per year. "In addition to providing contraception, Seasonale will be an option for any woman who wants greater control over her menstrual cycle."
Sulak agrees. "The use of extended OCs will become more popular once a product that provides a greater number of active pills per pack becomes available." Seasonale is under development by Barr Laboratories and may be available as early as late summer 2003.
Mirena (levonorgestrel-releasing intrauterine system, Berlex Laboratories) is a levonorgestrel-releasing intrauterine system containing 52 mg of levonorgestrel released at a rate of approximately 20 mcg per day. The system, similar to an intrauterine device, is inserted into the uterine cavity, where it provides intrauterine contraception for up to five years. Berlex recommends its use in women who have had at least one child, no history of pelvic inflammatory disease, ectopic pregnancy, or have risk for ectopic pregnancy.
In addition to its use as a contraceptive, several studies have reported the successful use of Mirena as a therapeutic intervention in women with menorrhagia. In these women, Mirena has been shown to be as effective as endometrial ablation in women and has also improved iron status in women with heavy menstrual bleeding. Sulak indicated that the intrauterine system might be optimal for women who have difficulty complying with a contraceptive regimen, as it is "years of contraception with nothing to do [on the part of the patient]."
Nuva Ring (etonogestrel/ethinyl estradiol vaginal ring; Organon) is a vaginal ring designed to release 0.120 mg etonogestrel and 0.015 mg ethinyl estradiol per day. It is self-inserted once every three weeks. Although it is not a daily contraceptive method, like combination oral contraceptives, there is a seven-day hormone withdrawal at the end of every 21-day interval to allow for withdrawal bleeding. The efficacy and adverse events associated with Nuva Ring are similar to those seen with combination OCs. Patients should be counseled regarding timely insertion of the ring and instructed on what to do if there is accidental slippage or expulsion.
Ortho Evra (norelgestromin/ ethinyl estradiol transdermal system; Ortho-McNeil) is a hormone-containing transdermal patch applied to the abdomen, buttock, upper outer arm, or upper torso (excluding the breasts) once per week for three weeks in a four-week (28-day) cycle. Similar to that in other 28-day contraceptive methods, the fourth week is hormone free to allow for withdrawal bleeding.
The patch is a three-layer matrix, where the middle layer holds and releases the active hormones norelgestromin (150 mcg per day) and ethinyl estradiol (20 mcg per day). Norelgestromin is the active metabolite of norgestimate. Although not administered orally, it provides combination hormone therapy with a side-effect profile that is generally comparable to combination OCs. However, breast symptoms (breast discomfort, engorgement, and pain) were reported in significantly more women treated with Ortho Evra as compared with oral contraceptives (P<0.001). Application-site reactions (skin irritation) were reported in approximately 18% to 20% of patients.
In clinical trials, approximately one-third of the on-treatment pregnancies reported occurred in women with a baseline body weight of >90 kilograms (198 pounds). The increased rate of contraceptive failure in women with a higher body weight has also been reported in studies of oral contraceptives and may not be unique to transdermal delivery systems.
A new progestin-only implant, under review by the FDA, may soon provide physicians with another option for women who prefer long-term contraceptive protection. Implanon (etonogestrel implant system; Organon) is a small, flexible rod inserted under the skin of the upper arm. The rod contains 68 mg of etonogestrel (the active metabolite of desogestrel) that is released slowly over three years. The initial rod insertion and eventual removal is performed during an office visit.
The use of Implanon does not eliminate the need for routine gynecologic checkups. In clinical studies, Implanon was highly effective in preventing pregnancy; there were no pregnancies reported in 1,200 women-years of exposure. As with other progestin-only-based contraceptives, irregular bleeding patterns were the most commonly reported side effect. Until Implanon becomes available in the United States, Vanderbilt's Moore reminds practitioners that "Depo-Provera [medroxyprogesterone] Injection for birth control; Pharmacia] is still considered one of the most effective, but underutilized, methods of contraception available."
Regarding the new contraceptive options, Ruggiero said he believes that "contraceptive methods that limit patient noncompliance by their design will replace OCs for many patients, but may also increase oral contraceptive use for those who become disenchanted with their side effects or costs."
Dominguez added, "The nearly simultaneous appearance of these new products has refreshed the dialogue clinicians have with women who are seeking contraception, as well as conversation between women and their partners. These conversations are the cornerstone to success with any of these methods."