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Oral contraceptives (OCs) mimic ovarian hormones. Once ingested, they inhibit the release of gonadotropin-releasing hormone (GnRH) by the hypothalamus, thus inhibiting the release of the pituitary hormones that stimulate ovulation. OCs also affect the lining of the uterus and cause the cervical mucus to thicken, making it impervious to sperm. If used consistently and correctly, OCs are an effective form of contraception.
OCs may be a combination of the hormone estrogen and a progestin or a progestin alone.
For most combination OCs, an active pill (estrogen plus progestin) is taken daily for 21 to 24 days. Then, an inactive (placebo) pill is taken daily for 4 to 7 days to allow for withdrawal bleeding. In some products, the placebo pill contains iron and folate (folic acid); in others, this pill is not truly inactive but contains 10 mcg of ethinyl estradiol.
Most combination OCs contain 10 to 35 mcg of ethinyl estradiol. This dose is considered low. Low-dose OCs are usually preferred to high-dose OCs (50 mcg of estrogen) because low-dose OCs appear equally effective and have fewer adverse effects, except for a higher incidence of irregular vaginal bleeding during the first few months of use. One new product uses estradiol valerate instead of ethinyl estradiol. The doses of estrogen and progestin are the same throughout the month in some combination OCs (monophasic pills); they change throughout the month in others (multiphasic pills).
All combination OCs have similar efficacy; the pregnancy rate after 1 yr is 0.3% with perfect use and about 9% with typical (ie, inconsistent) use.
To be effective, progestin-only OCs must be taken at the same time of day, every day. No inactive pills are included. Progestin-only OCs provide effective contraception primarily by thickening the cervical mucus and preventing sperm from passing through the cervical canal and endometrial cavity to fertilize the egg. In some cycles, these OCs also suppress ovulation, but this effect is not the primary mechanism of action. Common side effects include irregular bleeding. Progestin-only OCs are commonly prescribed when women wish to take OCs but estrogen is contraindicated. Pregnancy rates with perfect and typical use of progestin-only OCs are similar to those with combination OCs.
OCs may be started at any time in a woman's life up until menopause. However, combination OCs must be used with caution in some women (for more information, see the US Medical Eligibility Criteria for Contraceptive Use, available at US Medical Eligibility Criteria for Contraceptive Use, 2010). Use of combination OCs is contraindicated by the following:
< 21 days postpartum or < 42 days postpartum if risk of venous thromboembolism is high
Smoking > 15 cigarettes/day in women > 35
Current or past breast cancer
Severe decompensated cirrhosis, hepatocellular adenoma, or liver cancer
Venous thromboembolism (deep venous thrombosis or pulmonary embolism), thrombogenic mutation, or SLE with unknown or positive antiphospholipid antibody status
Migraine with aura or migraine of any type in women > 35
Ischemic heart disease
Diabetes for > 20 yr or with vascular disease (eg, neuropathy, nephropathy, retinopathy)
History of malabsorptive bariatric surgery
Valvular heart disorders with complications
Solid-organ transplantation with complications
Current or medically treated gallbladder disease or a history of contraceptive-related cholestasis
Acute viral hepatitis
Although OCs may have some adverse effects, the overall risk of these events is small.
OCs may cause breakthrough bleeding (which may resolve with time or when the estrogen dose is increased) or amenorrhea; amenorrhea, if not acceptable, may resolve when the progestin dose is decreased. In some women, ovulation remains inhibited for a few months after they stop taking OCs. OCs do not adversely affect the outcome of pregnancy when conception occurs during or after their use.
Estrogens increase aldosterone production and cause Na retention, which can cause dose-related, reversible increases in BP and in weight (up to about 2 kg). Weight gain may be accompanied by bloating, edema, and breast tenderness. Most progestins used in OCs are related to 19-nortestosterone and are androgenic. Norgestimate, etonogestrel, and desogestrel are less androgenic than levonorgestrel, norethindrone, norethindrone acetate, and ethynodiol diacetate. Androgenic effects may include acne, nervousness, and an anabolic effect resulting in weight gain. If a woman gains > 4.5 kg/yr, a less androgenic OC should be used. Newer 4th-generation antiandrogenic progestins include dienogest and drospirenone (related to spironolactone, a diuretic).
The incidence of deep venous thrombosis and thromboembolism (eg, pulmonary embolism) increases as the estrogen dose is increased. With OCs that contain 10 to 35 mcg of estrogen, risk is 2 to 4 times the risk at baseline. However, this increased risk is still much lower than the risk associated with pregnancy. A wide variety of progestins in combination OCs may also affect this risk. OCs that contain levonorgestrel appear to lower this risk, and OCs that contain drospirenone or desogestrel may increase it. Risk is probably increased because production of clotting factors in the liver and platelet adhesion are increased. If deep vein thrombosis or pulmonary embolism is suspected in a woman taking OCs, OCs should be stopped immediately until results of diagnostic tests can confirm or exclude the diagnosis. Also, OCs should be stopped as soon as possible before any major surgery that requires immobilization for a long time. Women with a family history of idiopathic venous thromboembolism should not use OCs that contain estrogen.
Current use of OCs does not increase the risk of breast cancer, nor does former use in women aged 35 to 65. Also, risk is not increased in high-risk groups (eg, women with certain benign breast disorders or a family history of breast cancer).
Risk of cervical cancer is slightly increased in women who have used OCs for > 5 yr, but this risk decreases to baseline 10 yr after stopping OCs. Whether this risk is related to a hormonal effect or to behaviors (ie, not using barrier contraception) is unclear.
Although increased stroke risk has been attributed to OCs, low-dose combination OCs do not appear to increase risk of stroke in healthy, normotensive, nonsmoking women. Nonetheless, if focal neurologic symptoms, aphasia, or other symptoms that may herald stroke develop, OCs should be stopped.
CNS effects of OCs include nausea, vomiting, headache, depression, and sleep disturbances.
Although progestins may cause reversible, dose-related insulin resistance, use of OCs with a low progestin dose rarely results in hyperglycemia. Serum high-density lipoprotein (HDL) cholesterol levels may decrease when OCs with a high progestin dose are used but usually only increase when OCs with low progestin and estrogen doses are used. The estrogen in OCs increases triglyceride levels and can exacerbate preexisting hypertriglyceridemia. Most alterations in serum levels of other metabolites are not clinically significant. Thyroxine-binding globulin capacity may increase in OC users; however, free thyroxine levels, thyroid-stimulating hormone levels, and thyroid function are not affected.
Levels of pyridoxine, folate, B complex vitamins, ascorbic acid, Ca, manganese, and zinc decrease in OC users; vitamin A levels increase. None of these effects is clinically significant, and vitamin supplementation is not advised as an adjunct to OC use.
Recent evidence indicates that low-dose OCs do not increase the risk of developing gallstones. However, women who previously developed cholestasis when they were using OCs should not take OCs again. Women who have had cholestasis of pregnancy (idiopathic recurrent jaundice of pregnancy) may become jaundiced if they take OCs, and OCs should be used cautiously in these women.
Rarely, benign hepatic adenomas, which can spontaneously rupture, develop. Incidence increases as duration of use and OC dose increase; adenomas usually regress spontaneously after OCs are stopped.
Melasma occurs in some women; it is accentuated by sunlight and disappears slowly after OCs are stopped. Because treatment is difficult (see Melasma (chloasma)), OCs are stopped when melasma first appears. OCs do not increase risk of melanoma.
OCs have some very important health benefits. High- and low-dose combination OCs decrease the risk of endometrial and ovarian cancers by about 50% for at least 20 yr after OCs are stopped. They also decrease the risk of benign ovarian tumors, abnormal vaginal bleeding, dysmenorrhea, osteoporosis, premenstrual dysphoric disorder, iron deficiency anemia, benign breast disorders, and functional ovarian cysts. Ectopic pregnancy and salpingitis, which can impair fertility, occur less frequently in OC users.
Although OCs can slow the metabolism of certain drugs (eg, meperidine), these effects are not clinically important.
Some drugs can induce liver enzymes (eg, cytochrome P-450 enzymes) that accelerate transformation of OCs to less biologically active metabolites. Women who take these drugs should not be given OCs concurrently unless other contraceptive methods are unavailable or unacceptable. These drugs include certain anticonvulsants (most commonly phenytoin, carbamazepine, barbiturates, primidone, topiramate, and oxcarbazepine), ritonavir-boosted protease inhibitors, rifampin, and rifabutin. Lamotrigine should not be used with OCs because OCs can decrease lamotrigine levels and affect seizure control.
Before OCs are started, clinicians should take a thorough medical, social, and family history to check for potential contraindications to use. BP is measured, and a urine pregnancy test is done. OCs should not be prescribed unless BP is normal and results of the urine pregnancy test are negative. A physical examination, although often done when OCs are started, is not required. However, a physical examination is recommended within 1 yr of OC initiation. A follow-up visit in 3 mo may be useful for discussing potential adverse effects and for rechecking BP. OCs can be prescribed for 13 mo at a time.
OCs may be started on the same day as the contraceptive office visit (often called the quick-start method). The day of the week and time in the menstrual cycle are not important to when OCs are started. However, if OCs are started > 5 days after the first day of menses, women should use a backup contraceptive method (eg, condoms) for the first 7 days of OC use.
Progestin-only OCs must be taken every day, at the same time every day. If > 27 h elapse between doses of a progestin-only OC, women should use a backup contraceptive method for 7 days in addition to taking the OC daily. For combination OC, timing is not as stringent. However, if combined OC users miss taking a pill, they are advised to take 2 pills the next day. If they forget to take a pill for 2 days, they should resume taking the OC each day and should use a backup contraceptive method for 7 days.
After a 1st-trimester spontaneous or induced abortion, combination OCs may be started immediately. For deliveries at 12 to 28 wk gestation, combination OCs may be started within 1 wk. After a delivery at > 28 wk, combination OCs should not be started until > 21 days after delivery because risk of thromboembolism is additionally increased during the postpartum period. If women are exclusively breastfeeding (feeding on demand including night feedings and not supplementing with other foods) or if their risk of venous thromboembolism is increased (eg, because of a recent cesarean delivery), use of combination OCs should be delayed 42 days. In 98% of women who are exclusively breastfeeding and in whom menses does not resume, pregnancy does not occur for 6 mo postpartum even when no contraception is used. However, these women are often advised to start using contraception within 3 mo after delivery.
Progestin-only OCs may be used immediately postpartum.
If women have a history of a liver disorder, tests to confirm normal liver function should be done before OCs are prescribed. Women at risk of diabetes (eg, those who have a family history, who have had gestational diabetes, who have had high-birth-weight infants, or who have physical signs of insulin resistance such as acanthosis nigricans) require plasma glucose screening and a complete serum lipid profile annually. Use of low-dose OCs is not contraindicated by abnormal glucose or lipid test results, except for triglycerides > 250 mg/dL. Most women with diabetes mellitus may take combination OCs; exceptions are those who have vascular complications (eg, neuropathy, retinopathy, nephropathy) and those who have had diabetes for > 20 yr.
All combination OCs (estrogen plus a progestin) are equally effective; formulations with a low estrogen dose are preferred because they have fewer adverse effects.
Progestin-only OCs may cause irregular bleeding and must be taken at the same time every day.
Women may take OCs continuously until menopause if they have no contraindications.
Combination OCs increase the risk of thrombotic disorders, but this risk is less than that associated with pregnancy.
OCs do not increase the overall risk of breast cancer.
Before OCs are prescribed, a thorough patient history is required; a physical examination is not required but ideally should be done within 1 yr after OCs are started.
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