oral contraceptive

Birth Control Safe and effective options.

n.
A pill, typically containing estrogen or progesterone, that inhibits ovulation and thereby prevents conception. Also called birth control pill.

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Background

Oral contraceptives, or birth control pills, have been used by more than 60 million women worldwide, and are considered by many to be the most socially significant medical advance of the twentieth century. The birth control pill is a tablet taken daily by a woman to prevent pregnancy. The birth control pill does this by inhibiting the development of the egg in the woman's ovary during her monthly menstrual cycle. During a woman's menstrual cycle, a low estrogen level normally triggers the pituitary gland to send out a hormone that initiates development of an egg. The birth control pill releases enough synthetic estrogen to keep that hormone from being released during the monthly cycle. The birth control pill also contains a second synthetic hormone, progestin, which increases the thickness of cervical mucus and impedes development of the uterine lining to further prevent pregnancy. Studies have shown that the birth control pill is 99% effective in preventing pregnancy. The results of studies on the safety of the birth control vary. Some studies show that its use increases the risk of certain types of cancer, while others show that risk to be minimal. There are also claims that the birth control pill increases risk of stroke and heart attacks.

History

The Planned Parenthood Federation of America commissioned Dr. Gregory Pincus and Dr. John Rock to develop a simple and reliable form of contraception in 1950. Over the next several years, the doctors worked on formulating a birth control pill at the Worcester Foundation for Experimental Biology in Massachusetts. They tested their invention on 6,000 women in Puerto Rico and Haiti. The invention was then marketed in the United States in 1960 as Enovid-10.

Many attribute the changing social land-scape in the United States during the 1960s to the widespread acceptance and use of the birth control pill. As sexual relations outside of marriage and for reasons other than childbearing became more socially acceptable and women seeking careers sought family planning methods, the environment was ripe for introduction of this discreet, easy-to-use form of contraception.

Despite its popularity, soon after the birth control pill was introduced, the public began to raise concerns about side effects and safety. As early as 1961, reports had begun to circulate that the birth control pill increased a woman's risk of suffering a stroke or a heart attack by causing blood clotting. In 1965, the federal Food and Drug Administration (FDA) provided a scientist at Johns Hopkins School of Hygiene and Public Health to study the side effects of the birth control pill. The agency also established an Advisory Committee on Obstetrics and Gynecology to study the relationship between oral contraceptives and blood clotting, as well as whether the birth control pill increased risk of breast, cervical, or endometrial cancer. The committee, the first-ever advisory committee established by the FDA, reported in 1966 that it had found no evidence to render the birth control pill unsafe for human use.

Unsatisfied, the FDA called for a larger study of the effects of the birth control pill on blood clotting. The agency also determined, however, that the birth control pill had not been in use long enough for a study of its relationship to cancer to be observed. At the same time, the World Health Organization (WHO) also determined that the effects of the birth control pill on blood clotting warranted study. By 1968, a British study revealed an increase in blood clots among women taking oral contraceptives. The FDA required that packages of birth control pills contain warning labels. In 1969, the agency concluded that the amount of estrogen affected the level of blood clotting and that birth control pills containing lower dosages of estrogen were as effective as their high-estrogen counterparts. The agency began advising doctors to prescribe the lowest estrogen dosage possible to their patients.

An oral contraceptive containing only progestin was introduced in the early 1970s. Dubbed the mini-pill, this form of oral contraceptive prevented pregnancy solely by causing changes in the uterus and cervix. An egg was produced, but the changes caused by the mini-pill made it difficult for the egg to unite with sperm from the male. While the mini-pill eliminates the risks posed by estrogen, it has been found to be less effective in preventing pregnancy than pills containing estrogen. Throughout the 1970s, pills containing consistently lower doses of estrogen were introduced on the market.

In 1982 a biphasic birth control pill was introduced, followed by a triphasic pill in 1984. These low-dose pills contained varying ratios of progestin to estrogen. In 1988 all three drug companies still manufacturing high-dose birth control pills withdrew their high-dose products from the market, at the FDA's request. By 1990, the amount of estrogen in birth control pills had been reduced by at least two-thirds. Studies show that the risk of blood clotting in women taking the birth control pill has decreased accordingly. Further studies have shown that high-dose birth control pills actually reduced a woman's risk of ovarian and endometrial cancers, benign cysts of the ovaries and breasts, and pelvic inflammatory disease. The risk of breast or cervical cancer is still disputed.

The pill is still unsafe for certain groups of women, including those who smoke; are obese; have a history of health problems such as diabetes, high blood pressure, or high cholesterol; or have a history of blood clots heart attack, stroke, liver disease, breast cancer or cancer of the reproductive organs.

In addition to preventing pregnancy, the birth control pill can also relieve symptoms associated with premenstrual syndrome. There are at least 30 varieties of birth control pills on the market today.

Rvaw Materials

The main ingredients of the birth control pill are powders containing synthetic versions of the hormones estrogen and progestin.

The Manufacturing
Process

1. Using a process known as the wet granulation method, the active ingredients—the powders containing synthetic versions of estrogen and progestin—are mixed together with a dilutant and a disintegrant (products that dilute the powders and cause them to dissolve in liquid) in a large mixer resembling the mixmaster found in many kitchens. For larger batches, a device known as a twin-shell blender may be used.
2. Solutions carrying a binding agent (the material that will cause the contents of the tablet to cohere) are stirred into the powder mass, which is wetted until it takes on the consistency of brown sugar.
3. The powder mass (known as wet granulation) is forced through a mesh screen.
4. The moist material is then placed on shallow trays covered with large sheets of paper and placed in drying cabinets.
5. A lubricant, in the form of a fine powder, is screened onto the dried material (known as dry granulation).
6. The lubricant and the dry granulation are then mixed in a blender, using a turnbling-type action.
7. Tablets are formed from the mixture, typically using a method known as direct compression. Direct compression uses steel punches and dies in large machines, which press tablets directly from the powdered mixture. The physical composition of the powdered mixture is not altered in any way. The punch and die system is often computerized.
8. The tablets are inspected to ensure compliance with federal regulations and packaged for shipment to pharmacies.

Quality Control

Like medications, birth control pills are subject to strict regulations set forth by the FDA. Production of birth control pills occurs in a highly sterile environment and samples are taken throughout the production process to ensure each batch of pills meets federal regulations. Factors examined include weight, coloration, and other cosmetic concerns. Many computerized tablet machines can provide weight information. The tablet punch and die systems are regularly inspected as well. In addition, the environment in which the tablets are produced is heavily controlled to avoid the influx of contaminants.

The Future

A relatively recent innovation in the field of birth control is the introduction of Norplant, a contraceptive that works on the same time-release concept as the pill but is inserted under the skin of the upper arm and releases the proper dosage into the body's system each day. Another innovation that is new in the United States, although it has been used in Europe, is RU486, a type of birth control that can be taken after intercourse to prevent pregnancy.

Where to Learn More

Books

Gennaro, Alfonso R., ed. Remington:The Science and Practice of Pharmacy. Eaton, PA: Mack Publishing Co., 1995.

Harris, Carla D. "The Birth Control Pill Revisited." In NAACOG's Clinical Issues, 1992: pp. 246-50.

Ketzung, Bertram. Basic and Clinical Pharmacology. Stamford, CT: Appleton and Lange, 1998.

[Article by: Kristin Palm]

Tablets consisting of one or more synthetic female sex hormones taken by women to prevent pregnancy. Most oral contraceptives are combined pills (known colloquially as 'the pill'), consisting of an oestrogen and a progestogen, which suppress ovulation by, respectively, blocking the release of follicle-stimulating hormone and blocking the release of luteinizing hormone from the pituitary gland (see gonadotrophins). Progestogens also alter the lining of the uterus and the viscosity of mucus in the cervix, so that conception is less likely. The oestrogens used in combined pills are ethinylestradiol, mestranol (which is converted to ethinylestradiol in the body), and estradiol; a variety of progestogens are used, including desogestrel, etonogestrel, gestodene, levonorgestrel, norgestimate, and norethisterone. Biphasic and triphasic pills are taken in two or three phases during the menstrual cycle. The tablets in each phase contain different amounts of oestrogen and progestogen to be taken on different days of the cycle; therefore the pills must be taken in the right order: packaging usually makes this a simple procedure. Phasic pills are designed to reduce the total amount of hormones taken, but still retain the same efficacy. Combined pills are usually taken for 21 days, with a gap of 7 days before starting the next cycle during which the 'period' occurs. Some combined pills, known as everyday (ED) pills, are packaged with placebo (dummy) pills for these 7 days so that a tablet is taken every day and thus the need to remember when to start the next pack is eliminated. It is best to take combined pills at the same time every day to maintain their efficacy. A pill that is taken more than 12 hours late is regarded as 'missed', and the normal cycle of pill taking should be resumed as soon as possible by taking the missed pill and continuing with the rest of the pack; in addition, extra contraception should be used for 7 days. If the 7 days of extra precautions run past the end of a pack, a new pack should be started immediately; i.e. without the usual 7-day gap in pill taking or without taking the 7 dummy pills in ED preparations. Most of the side effects of the pill (see below) are related to the oestrogen content. There is a small risk that blood clots may form in the veins, especially the deep veins of the legs (deep-vein thrombosis), which may be carried in the bloodstream and block a blood vessel in another part of the body (thromboembolism), most often in the lungs. This risk is greater with some oral contraceptives than with others, depending on which progestogen is used in the preparation. However, the risk of a thromboembolism is actually higher during pregnancy.

Progestogen-only pills contain only a synthetic progestogen and no oestrogen. In some women these pills suppress ovulation completely; in others the normal menstrual cycle occurs. Because they cause fewer side effects than the combined pill, progestogen-only pills are more acceptable to some women, especially those who are breastfeeding, who have diabetes, who are at risk of developing thromboembolism (see precautions below), or who cannot take oestrogens. These pills should be taken every day of the cycle, at the same time each day – preferably several hours before intercourse. A pill should be regarded as missed if only 3 hours late, in which case the pills should be resumed as soon as possible and extra contraception should be used for the following week.

A progestogen-only pill containing a high dose of levonorgestrel is available for postcoital (emergency) contraception – the so-called 'morning-after pill'.

Oral contraceptives may also be given to regulate the menstrual cycle, to relieve very heavy or painful periods, and to treat premenstrual tension. They are available on prescription only.

Side effects:
with combined pills, these include breast enlargement, fluid retention with a bloated feeling, weight gain, cramps and pains in the legs, headache, nausea, vomiting, depression, loss of libido, vaginal discharge, skin changes (including brown patches on the face), and breakthrough bleeding. There may be changes in libido, depression, an increase in blood pressure, and irritation from contact lenses. The occurrence of a migraine-like headache for the first time, frequent severe headaches, or visual disturbance should be reported immediately to a doctor. For side effects of progestogen-only pills, see progestogens.

Precautions:
combined pills should not be used during breastfeeding or by women with a history of thrombosis, heart disease, or angina, sickle-cell anaemia, a history of jaundice during pregnancy or any liver disease, breast or genital cancer, or undiagnosed vaginal bleeding; they should not be taken during pregnancy and must be stopped if pregnancy occurs. Combined pills should be used with caution by women with high blood pressure, Raynaud's syndrome, diabetes, varicose veins, asthma, severe depression, or multiple sclerosis and by those on dialysis. The risk of thombosis is increased with age, smoking, and obesity. Breast examination should be carried out before and during treatment. For precautions with progestogen-only pills, see progestogens.

Interactions with other drugs (of combined pills):

angiotensin-converting enzyme inhibitors: their effect in lowering blood pressure is reduced.
Antibiotics ampicillin, tetracycline, rifabutin, and rifampicin reduce the contraceptive effect of combined pills. Additional contraception should be used while taking a short course of broad-spectrum antibiotics and for 7 days after stopping treatment; for women taking rifampicin, additional contraception should be continued for 4–8 weeks after stopping this drug. Women taking a longer course of these antibiotics are advised to use an oral contraceptive containing a higher dose (50 micrograms) of ethinylestradiol; for women taking a longer course of rifampicin, an alternative method of contraception may be advised.
Anticoagulants the effects of warfarin, acenocoumarol, and phenindione are antagonized.
Antiepileptic drugs: carbamazepine, oxcarbazepine, phenobarbital, phenytoin, primidone, rufinamide, and topiramate reduce the contraceptive effect of combined pills. Additional contraception should be used while taking a short course of these drugs and for 7 days after stopping treatment. Women taking a longer course of these drugs are advised to use an oral contraceptive containing a higher dose (50 micrograms) of ethinylestradiol.
Antifungal drugs griseofulvin, fluconazole, itraconazole, and ketoconazole can reduce the contraceptive effect of combined pills. Additional contraception should be used while taking a short course of these drugs and for 7 days after stopping treatment. Women taking a longer course of these drugs are advised to use an oral contraceptive containing a higher dose (50 micrograms) of ethinylestradiol.
Aprepitant reduces the contraceptive effect of combined pills.
Antiviral drugs reduce the contraceptive effect of combined pills.
Bosentan reduces the contraceptive effect of combined pills.
Ciclosporin: combined pills increase the plasma concentration (and therefore side effects) of ciclosporin.
Modafinil reduces the contraceptive effect of combined pills.
St John's wort: reduces the contraceptive effect of combined pills and should not be taken with them.

Proprietary preparations:
see table.

See also depot contraceptives.

Proprietary preparation	Ingredients	Formulation (per 28-day pack)
Combined pills
Brevinor	†ethinylestradiol norethisterone	21 active tablets
Cilest	ethinylestradiol norgestimate	21 active tablets
Femodene	ethinylestradiol gestodene	21 active tablets
Femodene ED	ethinylestradiol gestodene	21 active tablets + 7 dummy tablets
Femodette	ethinylestradiol gestodene	21 active tablets
Loestrin 20	ethinylestradiol (20 micrograms) norethisterone	21 active tablets
Loestrin 30	ethinylestradiol (30 micrograms) norethisterone	21 active tablets
Marvelon	ethinylestradiol desogestrel	21 active tablets
Mercilon	ethinylestradiol (20 micrograms) desogestrel	21 active tablets
Microgynon 30	ethinylestradiol levonorgestrel	21 active tablets
Microgynon 30 ED	ethinylestradiol levonorgestrel	21 active tablets + 7 dummy tablets
Norimin	ethinylestradiol norethisterone	21 active tablets
Norinyl-1	mestranol (50 micrograms) norethisterone	21 active tablets
Ovranette	ethinylestradiol levonorgestrel	21 active tablets
Ovysmen	ethinylestradiol norethisterone	21 active tablets
Qlaira	estradiol dienogest	21 active tablets
Sunya 20/75	ethinylestradiol gestodene	21 active tablets
Yasmin	ethinylestradiol drospirenone	21 active tablets
Phasic combined pills
BiNovum	ethinylestradiol norethisterone	2 phases (7 + 14) of active tablets
Logynon	ethinylestradiol levonorgestrel	3 phases (6 + 5 + 10) of active tablets
Logynon ED	ethinylestradiol levonorgestrel	3 phases (6 + 5 + 10) of active tablets + 7 dummy tablets
Synphase	ethinylestradiol norethisterone	3 phases (7 + 9 + 5) of active tablets
Triadene	ethinylestradiol gestodene	3 phases (6 + 5 + 10) of active tablets
TriNovum	ethinylestradiol norethisterone	3 phases (7 + 7 + 7) of active tablets
Progestogen-only pills
Cerazette	desogestrel	28 active tablets
Femulen	ethynodiol diacetate	28 active tablets
Micronor	norethisterone	28 active tablets
Norgeston	levonorgestrel	28 active tablets
Noriday	norethisterone	28 active tablets

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Definition

Oral contraceptives are medicines taken by mouth to help prevent pregnancy. They are also known as the pill, OCs, or birth control pills.

Description

Oral contraceptives, or birth control pills, contain synthetic forms of two hormones produced naturally in the body. These hormones, estrogen and progestin, regulate the female menstrual cycle. Some types of oral contraceptives use only progestational hormones, but most use a combination of estrogen and progestin. As of 2004, there were three types of oral contraceptives marketed:

• Monophasic use a fixed dose of both estrogen and progestin during the entire cycle.
• Biphasic oral contraceptives use a constant amount of estrogen during the full cycle, but the amount of progestin is lower during the first half of the cycle and increases in the second half. This shift in dosage is intended to mimic the natural ovarian cycle.
• Triphasic oral contraceptives may vary both the estrogen and progestin levels at different times during the cycle.

The goal of the biphasic and triphasic formulations is to achieve adequate control of the menstrual cycle while using lower doses of both estrogens and progestins, thereby reducing the risk of adverse effects. Reviews of controlled studies have not demonstrated a clear advantage of the newer formulations over the older monophasic drugs.

General Use

When taken in the proper amounts, following a specific schedule, oral contraceptives are very effective in preventing pregnancy. Studies show that fewer than one of every 100 females who use oral contraceptives correctly becomes pregnant during the first year of use.

These pills have several effects that help prevent pregnancy. For pregnancy to occur, an egg must become mature inside a woman's ovary, be released, and travel to the fallopian tube. Sperm must travel through the reproductive track to fertilize the egg in the fallopian tube. Then the fertilized egg must travel to the woman's uterus (womb), where it lodges in the uterus lining and develops into a fetus.

The main way that oral contraceptives prevent pregnancy is by keeping an egg from ripening fully. Eggs that do not ripen fully cannot be fertilized. In addition, birth control pills thicken mucus in the woman's body through which the sperm has to swim. Thus it is more difficult for the sperm to reach the egg. Oral contraceptives also change the uterine lining so that a fertilized egg cannot lodge there to develop.

Although contraception is the primary use of these medications, they may also be used to treat adolescent and post-adolescent acne in girls. Some products have this as part of their official indications, but others may be used as well.

Precautions

No form of birth control (except abstinence from sexual intercourse) is 100 percent effective. However, oral contraceptives can be highly effective when used properly. Teens and young women who anticipate having sexual intercourse should discuss the options with a healthcare professional.

Oral contraceptives do not protect against AIDS or other sexually transmitted diseases. For some protection against such diseases, teenage males and young men need to use a latex condom. Also, oral contraceptives are not effective immediately after a young woman begins taking them. Physicians recommend using other forms of birth control for the first one to three weeks. Then users should follow the instructions of the physician who prescribed the medicine.

Smoking cigarettes while taking oral contraceptives greatly increases the risk of serious side effects. Females who take oral contraceptives should not smoke cigarettes.

Seeing a physician regularly while taking this medicine is very important. The physician will note unwanted side effects, and patients should follow his or her advice on how often they should be seen.

Young women who take oral contraceptives should be sure to tell the healthcare professional in charge before they undergo surgical or dental procedures, laboratory tests, or emergency treatment.

This medicine may increase sensitivity to sunlight. Females using oral contraceptives should avoid too much sun exposure and should not use tanning beds, tanning booths, or sunlamps until they know how the medicine affects them. Some females taking oral contraceptives may get brown splotches on exposed areas of their skin. These usually go away over time after the women stop taking birth control pills.

Oral contraceptives may cause the gums to become tender and swollen or to bleed. Careful brushing and flossing, gum massage, and regular cleaning may help prevent this problem. Users should check with a physician or dentist if gum problems develop.

Side Effects

Serious side effects are rare in healthy females who do not smoke cigarettes. In women with certain health problems, however, oral contraceptives may cause problems such as liver cancer, noncancerous liver tumors, blood clots, or stroke. Healthcare professionals can help prospective users weigh the benefits of being protected against unwanted pregnancy against the risks of possible health problems.

The most common minor side effects are nausea, vomiting, abdominal cramping or bloating, breast pain, tenderness or swelling, swollen ankles or feet, tiredness, and acne. These problems usually go away as the body adjusts to the drug and do not need medical attention unless they continue or they interfere with normal activities. Other side effects should be brought to the attention of the physician who prescribed the medicine. Teens and young women should check with the physician as soon as possible if any of the following side effects occur:

• menstrual changes, such as lighter periods or missed periods, longer periods, or bleeding or spotting between periods
• headaches
• vaginal infection, itching, or irritation
• increased blood pressure

Women who have any of the following symptoms should get emergency help right away. These symptoms may be signs of blood clots:

• sudden changes in vision, speech, breathing, or coordination
• severe or sudden headache
• coughing up blood
• sudden, severe, or continuing pain in the abdomen or stomach
• pain in the chest, groin, or leg (especially in the calf)
• weakness, numbness, or pain in an arm or leg

The adverse effects of oral contraceptives can be impossible to predict. Other than avoiding smoking, there are no effective means of preventing side effects. All observed adverse effects should be reported to a physician promptly.

Oral contraceptives may continue to affect the menstrual cycle for some time after a young woman stops taking them. Women who miss periods for several months after stopping this medicine should check with their physicians. Other rare side effects may occur. Anyone who has unusual symptoms while taking oral contraceptives should get in touch with her physician.

Interactions

Oral contraceptives may interact with a number of other medicines. When interaction occurs, the effects of one or both of the drugs may change or the risk of side effects may be greater. Anyone who takes oral contraceptives should let the physician know all other medicines she is taking and should ask whether possible interactions can interfere with drug therapy.

These drugs may make oral contraceptives less effective in preventing pregnancy. Anyone who takes these drugs should use an additional birth control method for the entire cycle in which the medicine is used:

• ampicillin
• penicillin V
• rifampin (Rifadin)
• tetracyclines
• griseofulvin (Gris-PEG, Fulvicin)
• corticosteroids
• barbiturates
• carbamazepine (Tegretol)
• phenytoin (Dilantin)
• primidone (Mysoline)
• ritonavir (Norvir)

In addition, taking the following medicines with oral contraceptives may increase the risk of side effects or interfere with the medicine's effects:

• Theophylline: Effects of this medicine may increase, along with the chance of unwanted side effects.
• Cyclosporine: Effects of this medicine may increase, along with the chance of unwanted side effects.
• Troleandomycin (TAO): Chance of liver problems may increase. Effectiveness of oral contraceptive may also decrease, raising the risk of pregnancy.

The list above does not include every drug that may interact with oral contraceptives. Women should be sure to check with a physician or pharmacist before combining oral contraceptives with any other prescription or nonprescription (over-the-counter) medicine. As with any medication, the benefits and risks should be discussed with a physician.

Parental Concerns

Parents become concerned that teens who use oral contraceptives are at risk of becoming sexually active. Although studies have been limited, they have failed to show that availability of oral contraceptives leads to an increase in sexual activity among adolescent girls.

Oral contraceptives do not protect against sexually transmitted diseases. When used for contraception, they should be limited to monogamous relationships.

Although the list of potential side effects and adverse effects is very long and contains some severe risks, the actual frequency of these risks is low. In most cases, oral contraceptives have a very high safety margin.

Resources

Books

Mcevoy, Gerald K., et al. AHFS Drug Information 2004. Bethesda, MD: American Society of Healthsystems Pharmacists, 2004.

Siberry, George K., and Robert Iannone, eds. The Harriet Lane Handbook, 15th ed. Philadelphia: Mosby, 2000.

Periodicals

Kaunitz, Andrew M. "Enhancing oral contraceptive success: The potential of new formulations." American Journal of Obstetrics & Gynecology 190, no. 4, Suppl. (April 2004): S23–S29.

Organizations

American Academy of Dermatology. PO Box 4014, Schaumburg, IL 60168–4014. Web site: www.aad.org.

American Board of Obstetrics and Gynecology. 2915 Vine Street, Dallas, TX 75204. Web site: www.abog.org.

Planned Parenthood Federation of America. 434 West 33rd St., New York, NY 10001. Web site: www.plannedparenthood.org.

Web Sites

"Update on Oral Contraceptives." American Family Physician. Available online at www.aafp.org/afp/991101ap/html (accessed September 28, 2004).

[Article by: Deanna M. Swartout-Corbeil, R.N. Samuel Uretsky, PharmD]

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A pill designed for contraception by preventing ovulation.

The Pill was introduced in the 1950s, and its possible side effects are still being investigated. It nonetheless offered an ease of use and reliability of result that no other method of contraception had ever before supplied. In this way, it contributed greatly to the sexual revolution.

n.pl

trade names: Demulen, Loestrin, Lo/Ovral, Nordett; drug class: estrogen/progestin combinations; action: prevents ovulation by suppressing folliclestimulating and luteinizing hormones; uses: pregnancy prevention, endometriosis, hypermenorrhea, hypogonadism. Also called estrogens, mestranol androgens, ethinyl estradiol, levonorgestrel.

For a list of words related to oral contraceptive, see:

• PHARMACOLOGY - oral contraceptive: medication that contains synthetic female sex hormones and prevents conception when taken daily; birth-control pill

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