A. Combined Oral Contraceptives
1. Efficacy and methods of use
Combined oral contraceptives have a perfect use failure rate of 0.3% and a typical use failure rate of 8%. Their primary mode of action is suppression of ovulation. The pills can be initially started on the first day of the menstrual cycle, the first Sunday after the onset of the cycle, or on any day of the cycle. If started more than 5 days after the first day of the cycle, a backup method should be used for the first 7 days. If an active pill is missed at any time, and no intercourse occurred in the past 5 days, two pills should be taken immediately and a backup method should be used for 7 days. If intercourse occurred in the previous 5 days, emergency contraception should be offered, and the pills restarted the following day. A backup method should be used for 5 days.
2. Benefits of oral contraceptives
Noncontraceptive benefits of oral contraceptives include lighter menses and improvement of dysmenorrhea symptoms, decreased risk of ovarian and endometrial cancer, and improvement in acne. Functional ovarian cysts are less likely with oral contraceptive use. The frequency of developing uterine myomas is lower in patients who have taken oral contraceptives for longer than 4 years. There is also a beneficial effect on bone mass.
3. Selection of an oral contraceptive
Any of the combination oral contraceptives containing 35 mcg or less of ethinyl estradiol or 3 mg of estradiol valerate are suitable for most women. There is some variation in potency of the various progestins in the pills, but there are essentially no clinically significant differences for most women among the progestins in the low-dose pills. There is insufficient evidence that triphasic oral contraceptives provide any benefit compared to monophasic oral contraceptives in terms of effectiveness, bleeding patterns or discontinuation rates. Therefore, monophasic pills are recommended as a first choice for women starting oral contraceptive use. Women who have acne or hirsutism may benefit from treatment with desogestrel, drospirenone, or norgestimate, since they are the least androgenic. A combination regimen with 84 active and 7 inert pills that results in only four withdrawal bleeds per year is available. There is also a combination regimen that is taken continuously with withdrawal bleeds. At the end of 1 year of use of this method, 58% of the women had amenorrhea, and nearly 80% reported no bleeding requiring sanitary protection. Studies have not shown any significant risk from long-term amenorrhea in patients taking continuous oral contraceptives. The low-dose oral contraceptives commonly used in the United States are listed in Table 18–2.
Table 18–2.Commonly used low-dose oral contraceptives (listed within each group in order of increasing estrogen dose). ||Download (.pdf) Table 18–2. Commonly used low-dose oral contraceptives (listed within each group in order of increasing estrogen dose).
|Name ||Progestin ||Estrogen (Ethinyl Estradiol) ||Cost per Month1 |
|Alesse2,3 ||0.1 mg levonorgestrel ||20 mcg ||$35.16 |
|Loestrin 1/202 ||1 mg norethindrone acetate ||20 mcg ||$28.65 |
|Mircette2 ||0.15 mg desogestrel ||20 mcg ||$59.36 |
|Yaz2 ||3 mg drospirenone ||20 mcg ||$70.81 |
|Loestrin 21 1.5/302 ||1.5 mg norethindrone acetate ||30 mcg ||$25.83 |
|Low Ogestrel2 ||0.3 mg norgestrel ||30 mcg ||$30.52 |
|Levora2 ||0.15 mg levonorgestrel ||30 mcg ||$30.94 |
|Desogen2 ||0.15 mg desogestrel ||30 mcg ||$39.34 |
|Yasmin2 ||3 mg drospirenone ||30 mcg ||$76.72 |
|Brevicon2, Modicon2 ||0.5 mg norethindrone ||35 mcg ||$32.20 |
|Demulen 1/352 ||1 mg ethynodiol diacetate ||35 mcg ||$29.96 |
|Ortho-Novum 1/352 ||1 mg norethindrone ||35 mcg ||$29.40 |
|Ortho-Cyclen2 ||0.25 mg norgestimate ||35 mcg ||$32.20 |
|Gildagia2 ||0.4 mg norethindrone ||35 mcg ||$44.80 |
|Combination: Extended-Cycle |
|LoSeasonique (91-day cycle)2 ||0.10 mg levonorgestrel (days 1–84)/0 mg levonorgestrel (days 85–91) ||20 mcg (84 days)/10 mcg (7 days) ||$88.50 |
|Amethyst (28-day pack) ||90 mcg levonorgestrel ||20 mcg ||$59.36 |
|Seasonique (91-day cycle)2 ||0.15 mg levonorgestrel (days 1–84)/0 mg levonorgestrel (days 85–91) ||30 mcg (84 days)/10 mcg (7 days) ||$88.50 |
|Estrostep2 || |
1 mg norethindrone acetate (days 1–5)
1 mg norethindrone acetate (days 6–12)
1 mg norethindrone acetate (days 13–21)
|Cyclessa2 || |
0.1 mg desogestrel (days 1–7)
0.125 mg desogestrel (days 8–14)
0.15 mg desogestrel (days 15–21)
|25 mcg ||$33.60 |
|Ortho-Tri-Cyclen Lo || |
0.18 norgestimate (days 1–7)
0.215 norgestimate (days 8–14)
0.25 norgestimate (days 15–21)
|25 mcg ||$61.60 |
|Trivora2,3 || |
0.05 mg levonorgestrel (days 1–6)
0.075 mg levonorgestrel (days 7–11)
0.125 mg levonorgestrel (days 12–21)
|Ortho-Novum 7/7/72,3 || |
0.5 mg norethindrone (days 1–7)
0.75 mg norethindrone (days 8–14)
1 mg norethindrone (days 15–21)
|35 mcg ||$32.20 |
|Ortho-Tri-Cyclen2,3 || |
0.18 mg norgestimate (days 1–7)
0.215 mg norgestimate (days 8–14)
0.25 mg norgestimate (days 15–21)
|35 mcg ||$39.20 |
|Tri-Norinyl2,3 || |
0.5 mg norethindrone (days 1–7)
1 mg norethindrone (days 8–16)
0.5 mg norethindrone (days 17–21)
|35 mcg ||$39.35 |
|Progestin-Only Minipill |
|Ortho Micronor2,3 ||0.35 mg norethindrone to be taken continuously ||None ||$39.60 |
Several medications interact with oral contraceptives to decrease their efficacy, typically by causing induction of microsomal enzymes in the liver. Some commonly prescribed medications in this category are phenytoin, phenobarbital (and other barbiturates), primidone, topiramate, carbamazepine, rifampin, and St. John’s wort. Women taking these medications should use another means of contraception for maximum safety.
Antiretroviral medications, specifically ritonavir-boosted protease inhibitors, may significantly decrease the efficacy of combined oral contraceptives. Other antiretrovirals, such as nonnucleoside reverse transcriptase inhibitors have smaller effects on oral contraceptive efficacy, while nucleoside reverse transcriptase inhibitors do not appear to have an effect on contraceptive efficacy.
5. Contraindications and adverse effects
Oral contraceptives have been associated with many adverse effects; they are contraindicated with some conditions and should be used with caution in others (Table 18–3).
Table 18–3.Contraindications to use of oral contraceptives. ||Download (.pdf) Table 18–3. Contraindications to use of oral contraceptives.
Thrombophlebitis or thromboembolic disorders (past or present)
Stroke or coronary artery disease (past or present)
Cancer of the breast (known or suspected)
Undiagnosed abnormal vaginal bleeding
Estrogen-dependent cancer (known or suspected)
Hepatocellular adenoma (past or present)
Diabetes mellitus with vascular disease
Age over 35 and smoking > 15 cigarettes daily
Migraine with aura
Surgery or orthopedic injury requiring prolonged immobilization
Migraine without aura
Heart or kidney disease
Cholestasis during pregnancy
Sickle cell disease (S/S or S/C type)
The risk of heart attack is higher with use of oral contraceptives, particularly with pills containing 50 mcg of estrogen or more. Cigarette smoking, obesity, hypertension, diabetes mellitus, or hypercholesterolemia increases the risk. Young nonsmoking women have minimal increased risk. Smokers over age 35 and women with other cardiovascular risk factors should use other non-estrogen–containing methods of birth control.
B. THROMBOEMBOLIC DISEASE
An increased rate of venous thromboembolism is found in oral contraceptive users, especially if the dose of estrogen is 50 mcg or more. While the overall risk is very low (5–6 per 100,000 woman-years compared to 50–300 per 100,000 pregnancies), several studies have reported a twofold increased risk in women using oral contraceptives containing the progestins, gestodene (not available in the United States), drospirenone, or desogestrel, compared with women using oral contraceptives with levonorgestrel and norethindrone. Women in whom thrombophlebitis develops should stop using this method, as should those at increased risk for thrombophlebitis associated with surgery, fracture, serious injury, hypercoagulable condition, or immobilization. Women with a known thrombophilia should not use estrogen-containing contraceptives.
C. CEREBROVASCULAR DISEASE
Overall, a small increased risk of hemorrhagic stroke and subarachnoid hemorrhage and a somewhat greater increased risk of thrombotic stroke have been found; smoking, hypertension, and age over 35 years are associated with increased risk. Women should stop using estrogen-containing contraceptives if such warning symptoms as severe headache, blurred or lost vision, or other transient neurologic disorders develop.
There is no increased risk of breast cancer in women aged 35–64 who are current or former users of oral contraceptives. Women with a family history of breast cancer or women who started oral contraceptive use at a young age are not at increased risk. Combination oral contraceptives reduce the risk of endometrial carcinoma by 40% after 2 years of use and 60% after 4 or more years of use. The risk of ovarian cancer is reduced by 30% with pill use for less than 4 years, by 60% with pill use for 5–11 years, and by 80% with use for 12 or more years. Oral contraceptives have been associated with the development of benign hepatocellular adenomas and peliosis hepatis (blood-filled cavities) (but not focal nodular hyperplasia or hepatocellular carcinoma); hepatocellular adenomas may rarely cause rupture of the liver, hemorrhage, and death. The risk of hepatocellular adenoma increases with higher dosage, longer duration of use, and older age.
Oral contraceptives may cause hypertension in some women; the risk is increased with longer duration of use and older age. Women in whom hypertension develops while using oral contraceptives should use other non-estrogen–containing contraceptive methods. However, with regular blood pressure monitoring, nonsmoking women with well-controlled mild hypertension may use oral contraceptives.
Migraine or other vascular headaches may occur or worsen with pill use. If severe or frequent headaches develop while using this method, it should be discontinued. Women with migraine headaches with an aura should not use oral contraceptives.
Combined oral contraceptives can impair the quantity and quality of breast milk. While it is preferable to avoid the use of combination oral contraceptives during lactation, the effects on milk quality are small and are not associated with developmental abnormalities in infants. Combination oral contraceptives should be started no earlier than 6 weeks postpartum to allow for establishment of lactation. Progestin-only pills, levonorgestrel implants, and DMPA are alternatives with no adverse effects on milk quality.
Depression may occur or be worsened with oral contraceptive use. Fluid retention may occur. Patients who had cholestatic jaundice during pregnancy may develop it while taking birth control pills.
Obese and overweight women have generally been excluded from oral contraceptive trials until recently. Obesity is an independent risk factor for thromboembolic complications. However, it is important that obese women are not denied effective contraception as a result of concerns about complications or efficacy of oral contraceptives. Current evidence suggests that efficacy is similar for normal weight as well as for overweight and obese women.
Nausea and dizziness may occur in the first few months of pill use. Spotting or breakthrough bleeding between menstrual periods may occur, especially if a pill is skipped or taken late; this may be helped by switching to a pill of slightly greater potency. Missed menstrual periods may occur, especially with low-dose pills. A pregnancy test should be performed if pills have been skipped or if two or more expected menstrual periods are missed. Fatigue and decreased libido can occur. Chloasma may occur, as in pregnancy, and is increased by exposure to sunlight.
1. Efficacy and methods of use
A formulation containing 0.35 mg of norethindrone alone is available in the United States. The efficacy is similar to that of combined oral contraceptives but is highly dependent on consistent use (eg, taking the pill within the same 3-hour window every day). The minipill is believed to prevent conception by causing thickening of the cervical mucus to make it hostile to sperm, by causing alteration of ovum transport (which may account for the slightly higher rate of ectopic pregnancy with these pills), and by causing inhibition of implantation. Ovulation is inhibited inconsistently with this method. The minipill is begun on the first day of a menstrual cycle and then taken continuously for as long as contraception is desired; there is no “placebo week.”
The low dose of progestin and absence of estrogen make the minipill safe during lactation; it may increase the flow of milk. It is often tried by women who want minimal doses of hormones and by patients who are over age 35. The minipill lacks the cardiovascular side effects of combination pills. It can be safely used by women with sickle cell (S/S or S/C) disease.
3. Complications and contraindications
Minipill users often have bleeding irregularities (eg, prolonged flow, spotting, or amenorrhea); such patients may need regular pregnancy tests if there is a concern about contraceptive effectiveness. Many of the absolute contraindications and relative contraindications listed in Table 18–3 apply to the minipill; however, the contraceptive benefit of the minipill may outweigh the risks for patients who smoke, who are over age 35, or who have conditions such as superficial or deep venous thrombosis or known thromboembolic disorders or diabetes mellitus with vascular disease. Minor side effects of combination oral contraceptives such as mild headache may also occur with the minipill.
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D. Update on contraceptive contraindications. J Gynecol Obstet Hum Reprod. 2019 May;48(5):297–307.
et al. Update to CDC’s U.S. Medical Eligibility Criteria for Contraceptive Use, 2016: revised recommendations for the use of hormonal contraception among women at high risk for HIV infection. MMWR Morb Mortal Wkly Rep. 2017 Sep 22;66(37):990–4.