Contraception means to prevent conception, but in common medical usage, it also refers to methods that prevent implantation. The goal of contraception is to make every child a wanted child. Most methods of contraception (e.g., barrier methods and hormone preparations) also reduce the risk of sexually transmitted diseases (STDs), but intrauterine devices (IUDs) may increase the risk of STDs or their consequences.
Contraceptive methods are generally categorized as reversible [see Table I] or irreversible. Irreversible methods are often referred to as sterilization procedures. Pregnancy termination is not typically regarded as contraception, but the availability of medical methods of abortion has blurred this distinction. Emergency postcoital contraceptive methods are also available.
Most methods of contraception are designed for use by women. Hormonal methods of male contraception are under development, but they are not yet commercially available.1 In any case, unless such products prove to be almost free of side effects, their acceptance by men is likely to be limited.
Historically, methods to prevent or terminate pregnancy have been subject to intense legal regulation. In the United States, legal regulations vary widely from state to state regarding the provision of services to minors, waiting periods for termination and sterilization, husband and parental consent, reporting of complications and deaths, and restrictions on advance directives by pregnant or potentially pregnant women. Some states also have regulations regarding the type of practitioner or the type of facility in which contraceptive and fertility management procedures can be provided, but no state currently bans the use of reversible contraceptives. Medical insurance coverage for contraception varies widely.
The percentage of women using a contraceptive method rose from 56% in 1982 to 64% in 1995.2 The most widely used methods in 1995 were female sterilization, combined estrogen and progestin oral contraceptives (COCs), and the male condom. Male condom use is common among unmarried couples; this popularity is due in part to the protection its use affords against certain STDs, particularly HIV infection.
Combined Estrogen-Progestin Contraceptives
COCs are formulated with estrogen (in the form of ethinyl estradiol), in doses ranging from 20 to 35 |ig, and a variety of progestins derived from 19-nortestosterone. Individual formulations may have a fixed dose of progestin (monophasic) or may have doses that vary by cycle phase (triphasic). Two preparations contain varying estrogen doses.
Efficacy and mechanism of action
Combined estrogen and progestin oral contraceptives are a highly effective method of birth control. Theoretical efficacy is about 99.9%, but the typical efficacy is around 97%.3 The contraceptive effect of COCs derives principally from the suppression of the hypothalamic release of gonadotropin-releasing hormone (GnRH) and the concomitant suppression of the pituitary release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). The decrease in LH reduces ovarian an-drogen secretion. The suppression of GnRH is primarily caused by the progestin component. Estrogen also independently suppresses FSH at the pituitary level, thereby retarding folliculogenesis.
COCs are progestin dominant. Progestin exposure causes endometrial decidualization and atrophy, rendering the en-dometrium unfavorable for implantation and thickening of the cervical mucus, thereby blocking the entry of sperm and bacteria into the upper genital tract. There are three generations of progestins. Third-generation progestins, which are theoretically less androgenic, include desogestrel, gestodene, and norges-timate. The clinical superiority of one progestin over any other has not been demonstrated.
Reduction of androgen exposure
All COC preparations reduce androgen exposure by two mechanisms: (1) suppression of ovarian androgen production, as a result of the reduction in LH stimulation of the ovarian theca compartment and (2) elevation of the level of sex hormone-binding globulin protein, which binds androgens and thereby lowers the unbound fraction of circulating androgens. COCs reduce facial or androgen-dependent hair growth and acne by reducing the circulating concentrations of androgens available to occupy androgen receptors on the pilosebaceous unit. Although women with polycystic ovary syndrome have elevated GnRH and LH levels, COCs containing 30 to 35 |ig of estrogen adequately suppress their androgen secretion.4
Continuous versus cyclic coc regimens
Traditional COCs follow a 28-day cycle, with 21 days of active pills and 7 days of placebo pills. The 7-day placebo window permits significant follicular development, and higher estrogen and progestin doses are then needed to inhibit further folliculo-genesis and ovulation. Further, if there is a delay in starting the next pill pack, a so-called escape ovulation may result.
In patients taking COCs to effect ovarian suppression for medical purposes, this 28-day cycle may be ineffective. These patients may benefit from a long-cycle regimen—42 to 105 days of active pills, and then 1 week off—or a continuous regimen.
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Table 1 Categories of Commercially Available Reversible Contraceptives |
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Barrier methods |
Progestin preparations |
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Condoms |
Oral |
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Diaphragms |
Injectable |
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Cervical caps |
Implantable |
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Hormonal |
Intrauterine devices |
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Combined estrogen- |
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progestin preparations |
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Oral |
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Vaginal ring |
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Transdermal |
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Injectable |
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For long-cycle regimens, patients use the active pills from several packs; however, a commercial long-cycle preparation that includes 63 days’ worth of active pills is under development. The use of continuous COC regimens has not been well studied, but it is common to omit the placebo week in women undergoing hormonal treatment for disorders such as polycystic ovary syndrome or endometriosis, as well as in those who desire amenor-rhea or have headaches or other symptoms provoked by estrogen withdrawal during the placebo week. There are several advantages to a continuous approach, including better suppression of ovarian function. Persistent ovarian cysts may be less likely with a continuous regimen than with a cyclic regimen.
Increased breakthrough bleeding is a potential side effect of a continuous regimen as compared with a cyclic regimen. The increase in breakthrough bleeding is attributable partly to the development of fragile endometrial vessels coursing along the surface of the endometrium and partly to impaired local hemo-stasis.5 The only near-continuous COC preparation that avoids the increase in breakthrough bleeding while increasing follicu-lar suppression is Mircette, which has 2 placebo days, 5 days of 10 |ig estrogen, and 21 days of 20 |ig estrogen plus 150 |ig deso-gestrel.6 One objective of these modifications is to lower overall sex steroid exposure and minimize the unwanted consequences of pill use while minimizing breakthrough bleeding.
Nonoral combined contraceptives
Several combined estrogen-progestin contraceptives that do not use the oral route have recently been developed. All offer the convenience of less-frequent dosing.
The hormonal vaginal contraceptive ring (NuvaRing) was approved by the Food and Drug Administration in October 2001. This product is a flexible polymer ring, about 2 in. in diameter, which the patient inserts in her vagina. The ring releases a continuous low dose of estrogen and etonogestrel. The ring is left in place for 3 weeks, then removed for the week during which the patient will have her menstrual period. Neither patients nor their partners can tell that the ring is in place. Comparison of the vaginal ring with a COC has shown a lower incidence of irregular bleeding and a higher incidence of a normal intended bleeding pattern with the ring.7
The transdermal contraceptive patch (Ortho Evra) was approved by the FDA in November 2001. The patch delivers estrogen and norelgestromin over the course of a week. Patches are applied once a week for 3 consecutive weeks to the skin of the buttocks, the abdomen, the upper torso, or the upper outer arm.8 In general, the efficacy and cycle control provided by the patch are comparable to those of COCs, but the efficacy of the patch may be lower in women who weigh 198 lb (90 kg) or more.9 The overall rate of patch detachment is about 4%; about 2% of users experience skin irritation at the site of application.
An injectable estrogen-progestin contraceptive (Lunelle) is available in the United States. The preparation, which is given intramuscularly once a month, contains medroxyprogesterone acetate and estradiol cypionate in a timed-release form. In clinical trials, efficacy and patient satisfaction have been comparable to that seen with COCs.10
Side effects
A myriad of serious and nuisance side effects are associated with COCs [see Table 2]. Smoking markedly increases the risk of venous thromboembolism. Smoking is a relative contraindication to COC use, particularly in women older than 35 years.
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Table 2 Potential Side Effects of Oral Contraceptives |
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Serious side effects |
Metabolic changes |
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Decreased insulin action |
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Increase in clotting factors |
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Elevation of triglyceride levels |
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Increase in the metabolic work load |
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of the liver |
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Increase in renin substrate |
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Clinical manifestations* |
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Venous thromboembolic events |
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Fatty liver or hepatoma |
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Cholestasis or cholecystitis |
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Diabetes mellitus |
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Hypertension |
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Cardiovascular events |
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Exacerbation of depression |
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Drug interactions |
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Nuisance side effects |
Mastodynia |
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Reduced libido |
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Reduced vaginal lubrication |
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Increased appetite |
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Weight gain |
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Fatigue |
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Bloating |
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*These events are rare in healthy women younger than 50 years.
The crucial clinical issue is to convince the woman who smokes to stop smoking rather than deny her access to an acceptable form of contraception. For nonsmokers who take COCs containing 35 |ig or less of estrogen, the risk of nonfatal venous thromboembolism is approximately one half that of pregnancy (60 per 100,000 women) but greater than that observed in healthy women who do not take oral contraceptives (5 per 100,000 women). The alleged excess mortality from venous thromboembolism attributable to third-generation progestins as compared with other progestins is less than two per million women per year.12 However, women with familial throm-bophilia caused by factor V Leiden or prothrombin mutation 20210A have a greatly increased risk of venous thromboembolism when using any oral contraceptive13 [see 5:XIV Thrombotic Disorders]. In white women, the carrier rate of factor V Leiden is approximately 3% and that of prothrombin mutation 20210A is less than 2%, so screening has not been routinely advised.14 Also, there are other known causes of thrombophilia, but not all the thrombophilias can be detected.
COCs may decrease insulin action, an effect that has been attributed to the progestin component. The use of COCs does not increase the risk of diabetes mellitus in women who do not have other risk factors for the disease. However, in a nonrandomized clinical trial that followed Latin-American women with gesta-tional diabetes for 7.5 years post partum, the rate of development of diabetes mellitus was 8.7% for those given nonhormon-al contraception, 10.4% for those who used COCs, and 26.5% for those who used progestin-only pills. Life-table analysis showed an increase in diabetes mellitus within 2 years in the progestin-only group.15 Given these considerations, it is prudent to avoid prescribing any progestin-only form of contraception in women predisposed to diabetes mellitus or in frankly diabetic women. Fortunately, COC use by insulin-dependent diabetic women does not increase the risk of diabetic retinopathy or nephropathy.16
COCs have a negligible effect on the overall risk of cancer.17 Among women who take oral contraceptives for 8 years, the estimated increase in the number of cases of cancer is 125 per 100,000 for cervical cancer and 41 per 100,000 for liver cancer; those increases are offset, however, by decreases in endometri-al cancer and ovarian cancer [see Benefits, below].17 Oral contraceptive use does not appear to increase the risk of breast cancer significantly—regardless of the dose, duration of use, or age at use—even in women with a family history of breast cancer.18 However, the effect of oral contraceptive use on risk of breast cancer in carriers of BRCA1 and BRCA2 has not been defined.
Exposure to high doses of estrogen or progestin may provoke depression and mood disturbances, but this effect is limited to women with an underlying diathesis.19 It is not known whether oral contraceptive use increases the lifetime risk of depression or hastens its onset in women so predisposed.
Progestins have mineralocorticoid activity that results in the retention of up to 2 lb of water in sensitive women. The pro-gestins also increase plasma renin activity; in predisposed women, hypertension may result.
Oral contraceptive use can cause drug interactions by increasing liver production of proteins that bind other drugs, by inhibiting oxidative metabolism in the liver by the P-450 and P-448 cytochrome systems, and by competing for or accelerating conjugation. Conversely, drugs that stimulate the hepatic mi-crosomal system, such as oral antifungal agents or rifampin, may decrease plasma levels of contraceptive steroid and lead to unintended pregnancy. Antibiotics such as ampicillin, tetra-cyclines, and metronidazole do not interfere with COC efficacy.
Contraindications
There are specific contraindications to oral contraceptives [see Table 3]. Lactating women should probably not take COCs. Women with hypertension, epilepsy, depression, hepatitis, gallbladder disease, migraine, or premenstrual syndrome (PMS) need to be carefully monitored. Fibroids are not a contraindication to COC use.
Benefits
Women use oral contraceptives primarily for birth control. If side effects are tolerable, they are pleased to gain the other benefits [see Table 4]. Women generally appreciate the lighter and predictable menses. The option of long cycles or continuous use to schedule or skip bleeding episodes is a major advantage for any busy woman, particularly one who travels or spends time outdoors. Other women use oral contraceptives to treat an underlying disorder, such as polycystic ovary syndrome, dys-menorrhea, endometriosis, or idiopathic hirsutism. In general, the same benefits accrue.
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Table 3 Contraindications to Oral Contraceptives |
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Active liver or gallbladder disease |
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Medically significant hypertriglyceridemia |
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Active or past venous thromboembolic events |
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Atherosclerotic heart disease |
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Undiagnosed vaginal bleeding |
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Estrogen-dependent neoplasia |
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Breast cancer |
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Endometrial cancer |
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Symptomatic mitral valve prolapse |
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Smoking after 35 years of age |
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Table 4 Potential Benefits of Oral Contraceptives |
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Reduced risk of the following disorders: |
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Ectopic pregnancy |
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Benign breast disease |
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Anemia |
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Ovarian cysts and cancer |
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Endometrial cancer |
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Lighter and predictable menses |
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Reduction or elimination of dysmenorrhea |
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Bone accretion |
One of the major benefits of COC use is bone accretion. One study showed that as little as 10 |ig of estrogen was bone sparing in women older than 40 years, and 5 |ig of estrogen plus 1 mg of norethindrone caused bone accretion.20 Women who are hyperandrogenic but eumenorrheic have greater bone mass than do hyperandrogenic women who are oligomenor-rheic. The latter have slightly higher bone mass than eumenor-rheic, nonhirsute women. Women with polycystic ovary syndrome or idiopathic hirsutism who take oral contraceptives will have a decrement in endogenous androgen exposure, but COC use in this setting is expected to be bone sparing. Women with hypothalamic hypogonadism, particularly those with an eating disorder, have underlying metabolic disturbances that render their bones less responsive to exogenous steroid exposure. These women may continue to lose or not accrue bone even if they use COCs.
Long-term use of COCs reduces the incidence of endometri-al cancer and ovarian cancer. Among women who take oral contraceptives for 8 years, it is estimated that there will be 197 fewer cases of endometrial cancer per 100,000 users and 193 fewer cases of ovarian cancer per 100,000 users.17 Newer COCs, which contain 20 |ig of estrogen, appear to provide identical risk reduction for ovarian cancer as did older formulations, which contained 50 |ig or more of estrogen.21 A recent study showed that oral contraceptives also markedly reduce the risk of ovarian cancer in carriers of BRCA1 and BRCA2 mutations (who are at increased risk for ovarian cancer and pre-menopausal breast cancer). The longer the duration of use, the greater is the protection from ovarian cancer.
