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Oral Contraceptives

By

Frances E. Casey

, MD, MPH, Virginia Commonwealth University Medical Center

Reviewed/Revised Jul 2023
View PATIENT EDUCATION

Oral contraceptives (OCs) are steroid hormones that 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, decreasing the likelihood of implantation of an embryo, 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 started at any age from menarche until menopause.

OCs may be a combination of the hormone estrogen and a progestin or a progestin alone.

Combination oral contraceptives

For most combination oral contraceptives, 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 a few formulations, the placebo pill contains iron and folate (folic acid); in others, this pill is not truly inactive but contains a lower dose of ethinyl estradiol than the pills used during the other weeks. Combination OCs are also available in extended-cycle formulations (with 84 active pills, one to be taken each day, followed by 7 days of placebo pills) or as continuous-use formulations (active pills every day, with no placebo pills).

Most combination OCs contain 10 to 35 mcg of ethinyl estradiol. Estradiol valerate may be used 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 year is 0.3% with perfect use and about 9% with typical (ie, inconsistent) use.

Contraindications to combined estrogen-progestin contraceptives (pills, patch, vaginal ring)

Combination OCs or other estrogen-progestin contraceptives (patch, vaginal ring) must be used with caution in some women (for more information, see the US Medical Eligibility Criteria for Contraceptive Use, 2016 and Update to US Medical Eligibility Criteria for Contraceptive Use, 2016: Updated recommendations for the use of contraception among women at high risk for HIV infection).

The risk of adverse effects of estrogen-progestin contraceptives varies, depending on the risk factor and associated complications. Estrogen-progestin contraceptive use represents an unacceptable health risk in patients with the following characteristics:

Estrogen-progestin contraceptive use represents a theoretical or proven risk that usually outweighs the advantages in patients with the following characteristics:

  • ≤ 42 days postpartum with risk factors for venous thromboembolism

  • Superficial venous thrombosis (thrombosis associated with a peripheral intravenous catheter may be lower risk)

  • Past breast cancer and no evidence of current disease for 5 years

  • Smoking in women < 35 years old

  • Adequately controlled hypertension

  • Peripartum cardiomyopathy ≥ 6 months

  • Multiple sclerosis with prolonged immobility

  • Inflammatory bowel disease, if risk factors for venous thromboembolism are present

  • Current or medically treated gallbladder disease or a history of contraceptive-related cholestasis

  • Bariatric surgery with a malabsorption due to shortening the functional small intestinal length (eg, Roux-en-Y gastric bypass or biliopancreatic diversion)

  • Current treatment with fosamprenavir, rifampin, rifabutin, lamotrigine, or certain antiseizure medications

Progestin-only oral contraceptives

To be effective, progestin-only OCs must be taken at the same time of day, every day. The same dose is taken daily, and no inactive pills are included. Breakthrough bleeding is a common adverse effect.

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. Pregnancy rates with perfect and typical use of progestin-only OCs are similar to those with combination OCs.

Contraindications to progestin-only contraceptives (pills, implants, injections)

Progestin-only OCs are commonly prescribed when women wish to take OCs but estrogen is contraindicated.

Women with current breast cancer should not take progestin-only pills, implants, or injections.

Progestin-only contraceptive use represents a theoretical or proven risk that usually outweighs the advantages in patients with the following characteristics:

  • Past breast cancer and no evidence of current disease for 5 years

  • Unexplained vaginal bleeding

  • Current and history of ischemic heart disease

  • Severe (decompensated) cirrhosis, hepatocellular adenoma, or liver cancer

  • History of jejunal bypass surgery (for progestin-only pills)

  • Current treatment with rifampin, rifabutin, or certain antiseizure medications (for progestin-only pills)

  • Ischemic heart disease, severe hypertension, or multiple risk factors for atherosclerotic cardiovascular disease (for progestin contraceptive injections)

  • Vascular disease, including due to diabetes or systematic lupus erythematosus (for progestin contraceptive injections)

Adverse Effects of Oral Contraceptives

Although oral contraceptives may have some adverse effects, the overall risk of these effects is small. Bloating, breast tenderness, nausea, and headache are the most common adverse effects.

Patients on combined OCs may develop amenorrhea or breakthrough bleeding (bleeding while taking the active pills) with prolonged duration of use. Either of these effects may be managed by changing to a pill with a higher estrogen dose. Progestin-only pills often cause irregular vaginal bleeding.

In some women, ovulation remains inhibited for a few months after they stop taking OCs, but there is no long-term effect on fertility. OCs do not adversely affect the outcome of pregnancy when conception occurs during or after their use.

Estrogens increase aldosterone production and cause sodium retention, which can cause dose-related, reversible increases in blood pressure (BP) and in weight (up to about 2 kg). Weight gain may be accompanied by bloating and edema.

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/year, 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 Deep Venous Thrombosis (DVT) Deep venous thrombosis (DVT) is clotting of blood in a deep vein of an extremity (usually calf or thigh) or the pelvis. DVT is the primary cause of pulmonary embolism. DVT results from conditions... read more Deep Venous Thrombosis (DVT) and thromboembolism Overview of Thrombotic Disorders In healthy people, homeostatic balance exists between procoagulant (clotting) forces and anticoagulant and fibrinolytic forces. Numerous genetic, acquired, and environmental factors can tip... read more (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. The progestins in combination OCs may also affect this risk. OCs that contain levonorgestrel appear to have a lower risk than OCs that contain drospirenone or desogestrel. Risk is probably increased because steroid hormones increase production of clotting factors in the liver and increase platelet adhesion. 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 at least 1 month before any major surgery that requires immobilization for a long time and should not be taken again until 1 month afterward. Women with a history of or at high risk for venous thromboembolism should not use OCs that contain estrogen.

Central nervous system effects of OCs may include nausea, vomiting, headache, depression, and sleep disturbances. Although increased stroke Ischemic Stroke Ischemic stroke is sudden neurologic deficits that result from focal cerebral ischemia associated with permanent brain infarction (eg, positive results on diffusion-weighted MRI). Common causes... read more Ischemic 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 immediately. Smokers over 35 should not use contraceptives that contain estrogen because of the increased risk of myocardial infarction and/or stroke.

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 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, calcium, 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.

Risk of developing gallstones does not appear to be increased by use of low-dose OCs.

Rarely, benign hepatic adenomas Hepatocellular Adenoma Benign liver tumors are relatively common. Most are asymptomatic, but some cause hepatomegaly, right upper quadrant discomfort, or intraperitoneal hemorrhage. Most are detected incidentally... read more , which can spontaneously rupture, develop. Incidence increases as duration of use and OC dose increase; adenomas usually regress spontaneously after OCs are stopped.

Melasma Drug Interactions Oral contraceptives (OCs) are steroid hormones that inhibit the release of gonadotropin-releasing hormone (GnRH) by the hypothalamus, thus inhibiting the release of the pituitary hormones that... read more occurs in some women; it is accentuated by sunlight and disappears slowly after OCs are stopped. Because treatment is difficult, OCs are stopped when melasma first appears. OCs do not increase risk of melanoma.

Adverse effects references

Benefits of Oral Contraceptives

They also decrease the risk of functional ovarian cysts Functional ovarian cysts Benign ovarian masses include functional cysts (eg, corpus luteum cysts) and neoplasms (eg, benign teratomas). Most are asymptomatic; some cause pelvic pain. Evaluation includes pelvic examination... read more , benign ovarian tumors Benign Ovarian Masses Benign ovarian masses include functional cysts (eg, corpus luteum cysts) and neoplasms (eg, benign teratomas). Most are asymptomatic; some cause pelvic pain. Evaluation includes pelvic examination... read more , abnormal uterine bleeding Abnormal Uterine Bleeding Abnormal uterine bleeding (AUB) in patients of reproductive age is a bleeding pattern that is not consistent with normal menstrual cycle parameters (frequency, regularity, duration, and volume)... read more due to ovulatory dysfunction, dysmenorrhea Dysmenorrhea Dysmenorrhea is uterine pain around the time of menses. Pain may occur with menses or precede menses by 1 to 3 days. Pain tends to peak 24 hours after onset of menses and subside after 2 to... read more , premenstrual dysphoric disorder Premenstrual dysphoric disorder Depressive disorders are characterized by sadness severe enough or persistent enough to interfere with function and often by decreased interest or pleasure in activities. Exact cause is unknown... read more , iron deficiency anemia Iron Deficiency Anemia Iron deficiency is the most common cause of anemia and usually results from blood loss; malabsorption, such as occurs in celiac disease, is a much less common cause. Symptoms are usually nonspecific... read more Iron Deficiency Anemia , and benign breast disorders Evaluation of Breast Disorders Breast symptoms (eg, masses, nipple discharge, pain) are common, accounting for millions of medical visits every year. Although the great majority of symptoms have benign causes, breast cancer... read more Evaluation of Breast Disorders . Salpingitis Acute salpingitis Pelvic inflammatory disease (PID) is a polymicrobial infection of the upper female genital tract: the cervix, uterus, fallopian tubes, and ovaries; abscess may occur. PID may be caused by sexually... read more , which can impairs fertility, occur less frequently in OC users.

Benefits reference

  • 1. Iversen L, Sivasubramaniam S, Lee AJ, et al: Lifetime cancer risk and combined oral contraceptives: the Royal College of General Practitioners' Oral Contraception Study. Am J Obstet Gynecol 216(6):580.e1-580.e9, 2017. doi:10.1016/j.ajog.2017.02.002

Drug Interactions of Oral Contraceptives

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 antiseizure drugs (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.

Initiation of Oral Contraceptives

Before oral contraceptives are started, clinicians should take a thorough medical, social, and family history to check for potential contraindications to use. Blood pressure is measured, and a urine pregnancy test is done. OCs should not be prescribed unless blood pressure 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 year of OC initiation. A follow-up visit in 3 months may be useful for discussing potential adverse effects and for rechecking blood pressure. OCs can be prescribed for 13 months at a time.

OCs may be started on the same day as the contraceptive 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 hours 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 OCs, timing is not as stringent. However, if combined OC users miss taking a pill one day, 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. If they forget to take a pill for 2 days and have had unprotected sex in the 5 days before forgetting to take the pill, they can consider taking emergency contraception.

The timing for starting combination OCs after pregnancy varies:

  • After a 1st-trimester spontaneous or induced abortion: Started immediately

  • For deliveries at 12 to 28 weeks gestation: Started within 1 week if women have no other significant risk factors for thromboembolism

  • After a delivery at > 28 weeks: Not started until > 21 days postpartum because risk of thromboembolism is additionally increased during the postpartum period (however, should be delayed 42 days 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]

In 98% of women who are exclusively breastfeeding and in whom menses does not resume, pregnancy does not occur for 6 months postpartum even when no contraception is used. However, these women are often advised to start using contraception within 3 months 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 (2.8 mmol/L). 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 years.

Key Points

  • Oral contraceptives (OCs) are generally well tolerated but may cause headache, nausea, bloating, or breast tenderness.

  • Progestin-only OCs may cause irregular bleeding and must be taken at the same time every day to be effective.

  • OCs may be taken from menarche until menopause if they have no contraindications.

  • Combination OCs increase the risk of venous thromboembolism to 2 to 4 times the risk at baseline, but this risk is less than that associated with pregnancy.

  • Study results vary regarding use of OCs and risk of breast cancer, but some studies have found a small increased risk in current or recent users; OCs decrease the risk of ovarian cancer and endometrial cancer.

  • Before OCs are prescribed, a thorough patient history is required; a physical examination is not required but ideally should be done within 1 year after OCs are started.

Drugs Mentioned In This Article

Drug Name Select Trade
Folacin , Folicet, Q-TABS
Alora, Climara, Delestrogen, Depgynogen, Depo-Estradiol, Depogen, Divigel, DOTTI, Elestrin, Esclim, Estrace, Estraderm, Estrasorb, Estring, EstroGel, Evamist, FemPatch, Femring, Femtrace, Gynodiol , Gynogen LA, Imvexxy, LYLLANA, Menostar, Minivelle, Vagifem, Valergen, Vivelle, Vivelle-Dot, Yuvafem
Lexiva
Rifadin, Rifadin IV, Rimactane
Mycobutin
Lamictal, Lamictal CD, Lamictal ODT, Lamictal XR, Subvenite
Implanon, Nexplanon
AfterPill, EContra EZ, EContra One-Step, Fallback Solo, Kyleena , LILETTA, Mirena, My Choice, My Way, Next Choice, Next Choice One Dose, Norplant, Opcicon One-Step, Plan B, Plan B One-Step , Preventeza, React, Skyla, Take Action
Aygestin, Camila, Deblitane 28-Day, Errin , Heather, Jencycla, Jolivette , Lyza, Nora-BE, Norlyroc, Nor-QD, Ortho Micronor, Sharobel 28-Day
Slynd
Aldactone, CAROSPIR
B-Natal, Neuro-K-500
Acerola C, Ascor, Ascor L-500 , Betac, Cecon, Cenolate, YumVs Kids, YumVs ZERO
No brand name available
A Mulsin, Aquasol A, Dofsol-A
Demerol, Meperitab
Dilantin, Dilantin Infatabs, Dilantin-125, Phenytek
Carbatrol, Epitol , Equetro, Tegretol, Tegretol -XR
Mysoline
EPRONTIA, Qudexy XR, Topamax, Topamax Sprinkle, Topiragen , Trokendi XR
Oxtellar XR, Trileptal
Norvir
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