Abstract

As women search for safe and effective means of birth control, clinicians are challenged to keep abreast of emerging developments in contraceptive choices. Combined oral contraceptives now offer better cycle control, are effective at lower dosing levels, and trigger fewer adverse effects. Use of synthetic progesterone can minimize symptoms such as appetite increase and bloating. Hormonal delivery by transdermal patch or vaginal ring may be suitable for women who are considered poor pill-takers. Improved injectable agents lead to fewer adverse effects than their older counterparts do. Lastly, a new intrauterine system offers a long-term reversible contraceptive choice that may also decrease menstrual bleeding, dysmenorrhea, and anemia.

Introduction

Advances in contraception have led to a broader choice for sexually active women who wish to avoid pregnancy. Today's contraceptives are used not only to prevent pregnancy, but in some instances (particularly combined oral contraceptives) to provide noncontraceptive benefits (see Table 1^[1]).

This article will focus on currently available hormonal contraceptive methods (specifically, low-dose oral contraceptives, oral contraceptives with new progestins, the contraceptive patch, the vaginal ring, injectable agents, and the intrauterine system), their use in current practice, their relative effectiveness, and their advantages and disadvantages. The article's goal is to familiarize clinicians with how these products work and how patients should be counseled in their use, so that each woman can be helped to make the best possible choice.

Since they first became available in the 1960s, oral contraceptives (OCs) have been widely used by US women. Their popularity has been credited to their reliability, convenience, relative safety, low incidence of adverse effects, and limited contraindications. Initially, combined oral contraceptives (COCs -- that is, those containing both estrogen and progestins) contained as much as 150 mg of estrogen. The early, high-dose pills of the 1960s posed significant health risks, including deep venous thrombosis, pulmonary embolism, stroke, and myocardial infarction.^[2]

Today, typical doses of estrogen range from 20 mg to 35 mg, and 98% of all prescribed OCs contain less than 35 mg of estrogen^[3]; even COCs with as little as 20 mg of estrogen are considered effective.^[4] Pills with low estrogen content are considered safer than higher-dose OCs for certain patients, including perimenopausal women, those with a family history of heart disease, and smokers younger than 35 (although women who take OCs and smoke remain at an increased risk of myocardial infarction and stroke due to OC-associated changes in coagulation factors). Lower-dose OCs offer fewer estrogen-related adverse effects (eg, menstrual cycle abnormalities) than do higher-dose pills.^[4]

The progestin component of COCs has also changed dramatically over the years. Today's combination agents contain about 10% of the amount of progesterone found in COCs manufactured in the 1970s. This reduction has led to a decrease in progestin-associated adverse effects (eg, nausea, breast tenderness, bloating).^[2]

In 2000, FDA approval was granted to Yasmin^®, a COC that contains a synthetic progesterone (drospirenone, or DRSP) with antiandrogenic and antimineralocorticosteroid properties. This agent is associated with less water retention than other COCs, less negative emotional affect, and less appetite increase after six months' use. Women who took this pill did not experience statistically significant changes in weight or blood pressure after 13 months' use.^[5]

Because DRSP contains spironolactone, a potassium-sparing diuretic, it should not be used by women with a history of hyperkalemia secondary to renal insufficiency, hepatic dysfunction, or adrenal insufficiency.^[6] Women who take medications that affect serum potassium levels (eg, angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, other potassium-sparing diuretics, heparin, aldosterone antagonists, and nonsteroidal anti-inflammatory agents) should be advised to use a different type of COC or should at least have their serum potassium levels monitored closely.^[5]

Adverse effects widely associated with combined hormonal contraceptive methods are listed in Table 2.^[7]

The Ortho Evra/Evra^® transdermal system is a combination hormonal contraceptive patch, measuring 20 cm square, that the patient applies to the abdomen, buttocks, upper outer arm, or upper torso -- but not to the breast. Each day, the patch releases 150 mg of norelgestromin and 20 mg of ethinyl estradiol.^[3,8,9]

Use is based on a 28-day cycle. On the first day of each of the first three weeks, a new patch is applied and worn for seven days, then discarded. During the fourth week, no patch is worn and withdrawal bleeding occurs.

The patient's first patch should be applied on the first day of menses; if it is applied at any other time during the cycle, a backup contraceptive method should be used for the first seven days. Thereafter, the patch should be applied on the same day of each week. The skin should be clean, dry, healthy, and free of lotions or creams. Once the patch is applied, the patient may bathe, shower, or swim while wearing it.^[1,3] The patch can be worn undetected under clothing.

Although patients may express concern about losing the patch, partial or complete detachment has been shown to occur in less than 5% of cases.^[9] If the patch does become loose or fall off, the patient should immediately apply a new patch, then replace it on her regularly scheduled patch change day (thus, when a patient's first prescription for the patch is written, the clinician should also write a prescription for a single replacement patch). If the patch is off for longer than 24 hours, a new cycle must be initiated with a new patch, and a backup birth control method used for the next seven days.^[3]

In an analysis of pooled data from studies involving more than 3,300 women, the overall annual probability of pregnancy in patch users was reported at 0.8%,^[9] suggesting that the transdermal system is comparably effective to the OC.^[3,8] The patch is ideal for women who find it difficult to remember to take a pill at the same time each day; among patch users, the mean proportion of cycles with perfect compliance is 88.2%, compared with 77.7% among OC users.^[8]

Apart from adverse effects generally associated with combined hormonal contraception use, patch users' most frequently reported complaint was application-site reactions, but adverse effects were treatment-limiting in only 1% to 2.4% of study subjects.^[3] Women who weigh 90 kg (198 lb) or more may experience a higher failure rate (ie, pregnancy) with the transdermal system than lower-weight women^[9] and should be encouraged to consider a different method of birth control.

The combination contraceptive vaginal ring (NuvaRing^®; see Figure 1) is a flexible transparent device made of ethylene vinyl that is inserted by the patient into the vagina; there, it releases daily doses of ethinyl estradiol (15 mg) and etonogestrel (120 mg) over three weeks' use.^[1,7,10] It is removed for one week, during which time withdrawal bleeding occurs. A new ring is then inserted.^[1]

Figure 1. The combination contraceptive vaginal ring, which is inserted by the patient, releases daily doses of ethinyl estradiol and etonogestrel over three weeks' use. Image courtesy of Organon USA.

The vaginal ring requires lower hormone doses than COCs because administration by the vaginal route precludes hepatic or gastrointestinal interference.^[1,10] Similarly effective as COCs, the vaginal ring offers more uniform plasma hormone concentrations.^[10] Patients report that it is easy to use, does not require fitting, needs to be administered only once each month, and can be left in place during swimming, bathing, and intercourse.^[1,10]

In combined data from 1,950 North American and European women who used the vaginal ring for at least three months, 96% of those who completed 13 cycles' use were satisfied or very satisfied and 85% of the women and 71% of their sexual partners said they never or rarely felt the ring during intercourse. Eighty-five percent of women reported menses of the same or shorter duration and 85% reported menstrual pain as unchanged or reduced.^[10]

Of 821 women (35.4%) who did not complete the studies, 52.2% gave reasons not related to the device (eg, wishing to become pregnant), 42.7% referred to adverse events (eg, tendency for the ring to fall out), 2.6% said they were pregnant, and 2.3% complained of bleeding irregularities.

Ring-specific adverse effects include vaginal irritation, infections, and discharge, but vaginal medications (such as antifungal cream) can be used while the ring is in place.^[7] Adverse effects associated with other combination contraceptive agents may also occur.

In the United States, use of injectable contraceptives began in 1992 with FDA approval of depot medroxyprogesterone acetate (DMPA or Depo-Provera^®), a three-month progestin-only agent.^[1,11] Though effective, long-acting, reversible, and convenient, this method has been associated with bleeding changes and weight gain, and for some women, headache, dizziness, acne, and moodiness.

The most recently developed injectable contraceptive, Lunelle^TM, combines 25 mg of medroxyprogesterone acetate with 5 mg of estradiol cypionate.^[1] Administered every 28 days (± 5 days) by intramuscular injection, this method offers excellent cycle control after the first few cycles and is less often associated with abnormal bleeding patterns than the progestin-only injectable. Fertility has been reported to return rapidly after injections are discontinued.^[12]

Adverse effects associated with the monthly injectable's use include amenorrhea, weight gain (though less weight gain than with the original three-month agent), fluid retention, and other effects associated with combination contraceptives. It should be noted that the manufacturer of Lunelle voluntarily recalled all prefilled syringes -- but not vials -- in October 2002, because of "a lack of assurance of full potency" in certain lots.^[13] (Go to www.lunelle.com.)

For some patients, a significant disadvantage to any injectable agent is that it requires monthly or quarterly administration by a health care professional, including the time and expense of scheduled office visits. This should be discussed with patients before injectables are initiated. Nevertheless, injectable contraceptives may be preferable to COCs for women who forget to take daily pills.

Like the traditional copper T intrauterine device, Mirena^® is inserted by the clinician into the patient's uterine cavity to prevent pregnancy (see Figure 2). Yet this new intrauterine system (IUS), a T-shaped device about the size of a quarter and made of soft, flexible plastic, contains 52 mg of the progestin levonorgestrel in a release-controlling membrane with a monofilament removal thread.^[1,14] As levonorgestrel is released at 20 mg/d into the uterine lining, it thickens the cervical mucus, suppresses ovarian function, and inhibits sperm movement. It also thins the uterine lining, making it an unfavorable environment for implantation.^[7] The IUS is inserted during an office visit and is approved for as long as five years' continuous use.^[1]

Figure 2. The intrauterine system, inserted into the uterine cavity by a clinician, gradually releases levonorgestrel for as long as five years' continuous use. Image courtesy of Berlex Laboratories, Inc.

Because the IUS contains no estrogen component, it is appropriate for women in whom estrogen is contraindicated. The IUS may also be an effective treatment for women with dysmenorrhea, menorrhagia, and anemia^[7,15] and may serve as an effective transition from contraception to hormone replacement therapy.^[1]

The IUS requires only low maintenance; the patient must be instructed to check its strings after each menstrual period to ensure that the device is in place. For women who choose to become pregnant, the device can be removed by the clinician at any time; no waiting period is required before conception, and IUS use is not associated with a decline in fertility.

In a study of 165 women, 90% completed three years' use of the IUS. Marked improvements in menstrual pain were reported, and complete or temporary amenorrhea (occurring in 20% and 56% of patients, respectively, within one year's use) was generally well accepted, with fear of unwanted pregnancy decreasing with continued IUS use. Bleeding irregularities rarely led to discontinuation of use.^[1,7,14]

For clinicians who wish to prescribe the IUS, education on insertion and management is offered by the manufacturer. According to the product prescribing information, the IUS is contraindicated in women with multiple sexual partners and is not recommended for those who have not had at least one term pregnancy.

Conclusion

As contraceptive methods continue to evolve, women will have a growing array of choices to meet their individual needs and preferences. Hormonal birth control methods are relatively safe and highly effective; the variety of hormone delivery methods makes these agents easier than ever to prescribe and manage. Clinicians should be familiar with each method's advantages and disadvantages in order to help each patient make the most appropriate choice (see "Why Women Discontinue Contraceptive Use,"^[1,7,14]). Practitioners are urged to stay abreast of new developments in contraception.

CME Information

The print version of this article was originally certified for CE credit. For accreditation details, contact the publisher. Jobson Publishing, LLC, 100 Avenue of the Americas, New York, NY 10013-1678, phone (973) 954-9237, email: editor@clinicianreviews.com.

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An important aspect of counseling women regarding their choice of birth control is to explain in advance the adverse or unexpected effects that may occur. Women who use the intrauterine system (IUS), for example, may be alarmed at first by amenorrhea (which occurs in 20% of users by the end of the first year; 56% experience occasional or temporary absence of menses).^[1,7,14] Eventually, 81% of IUS users consider amenorrhea a positive change.^[14]

Among all women who use hormonal contraceptives, 12% discontinue use because of irregular bleeding. Other reasons they give^[7] are:

Michele R. Davidson is Assistant Professor at George Mason University College of Nursing and Health Science and practices as a nurse-midwife at Women's Healthcare Associates of Loudoun in Landsdowne, Virginia. She is also a member of the Clinician Reviews Editorial Board.