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For conception to occur, a sperm must fertilize a mature egg. Specific hormones stimulate the ripening of the egg and its movement from an ovary to the uterus. Hormones are substances formed by one organ that are carried, in the bloodstream, to another organ, where they stimulate that target organ to function. During conception, there is considerable interchange between the ovaries and the pituitary gland located in the brain.
The ovaries produce estrogen, the principal female hormone. It is carried to the pituitary gland, where it stimulates the secretion of follicle-stimulating hormone (FSH). FSH travels to the ovaries where it stimulates the maturation of an unripened egg, or ovum. As the ovum develops, the ovary releases more estrogen.
Increased estrogen in the bloodstream stimulates the pituitary gland to produce large amounts of luteinizing hormone (LH). Increased levels of LH cause a mature egg to be released from an ovary. The process is called ovulation.
After ovulation, the egg passes down the fallopian tube, where it may be fertilized by a sperm. The fertilized egg continues to the uterus, where it attaches to the wall or lining (endometrium). When the ovary releases an egg, its protective coating, the follicle, remains behind, forming the corpus luteum, which produces both estrogen and another hormone, progesterone. The combination of estrogen and progesterone stops production of FSH and LH by the pituitary gland and thickens and strengthens the endometrium, allowing the fertilized egg to develop in the uterus.
If an egg is fertilized, the corpus luteum increases in size, persists for several months, and is critical for sustaining pregnancy. If pregnancy does not occur, the declining levels of progesterone at the end of the normal menstrual cycle cause a complex process in the inner layer of the uterus, the endometrium. As a result, it becomes necrotic and is then shedded, leading to menstruation. With the first day of menstruation, the next cycle in a woman's reproductive life starts.
How Do Oral Contraceptives Prevent Pregnancies?
Oral contraceptives employ synthetic hormones that mimic the properties of natural estrogens and/or progesterone to "fool" the female reproductive system. They provide constant levels of an estrogen and/or progestin in the blood, thus suppressing the release of both FSH and LH. Suppression of FSH inhibits maturation of an egg in an ovary. Suppression of LH inhibits release of an egg from the ovary. In addition to the inhibition of ovulation, the constant level of an estrogen and progestin in the body cause insufficient thickening of the endometrium, which prevents attachment of the egg. Progestins also promotes production of thick, opaque mucus, which acts as a barrier to sperm, as sperm can only pass through clear, thin mucus. Progestin is also thought to produce changes in the fallopian tubes that impede movement of the egg toward the uterus. Estrogen and progestin may also alter the pattern of muscle contractions in the tubes and uterus. This effect may interfere with implantation. In case ovulation does occur, which is rare but can happen, these additional effects also help to prevent pregnancies.
Types of Oral Contraceptives
A. Combination (estrogen/progestin) OCs
Combination OCs contain both estrogen and progestin, and are classified as either monophasic, triphasic, or biphasic. Synthetic rather than natural hormones are used in OCs because their greater potency allows for more predictable results. The two estrogens used in OCs are ethinyl estradiol and mestranol (see Table 1 below). In the body, mestranol breaks down to ethinyl estradiol.
Progestins used in OCs are synthetic progesterones, or in other words, produced in laboratories. Seven different progestins are used in OC formulations (see Table 1 below). Different progestins have different strengths and side effects. They were developed to give physicians more choices for each woman to see which OC is tolerated best.
Table 1. Hormones Used in OCs
Most combination OCs are given as active pills for 21 days followed by a 7-day hormone-free period to allow for withdrawal bleeding. Some packets of combination OCs contain only 21 pills all of which are active. Others also include seven placebos, hormone-free pills in another color. Many users prefer the 28-day packets since they do not need to make a calendar notation as to when to begin their next cycle of pills. One brand of pills contains estrogen-only pills in the fourth week.
The amount of estrogen and progestin in individual pills, of a combination OC packet may vary depending on when in the cycle the pill is taken.
Monophasic OCs contain the same dosage of each hormone in each active pill.
Biphasic OCs alter the progestin/estrogen ratio in 2 phases.
Triphasic OCs alter the progestin/estrogen ratio in three multi-day phases by varying the amounts of progestin, estrogen, or both.
Biphasic and triphasic OCs are thought to approximate a woman's natural hormonal fluctuations more closely by varying the progestin/estrogen ratios. The aim of these formulations is to minimize the occurence of breakthrough bleeding and amenorrhea while maintaining efficacy. However, some physicians and patients prefer monophasic OCs because they are less confusing (all active pills are the same color and have the same dose of hormones).
C. Progestin-Only OCs
Also called minipills, progestin-only pills (POPs) are indicated for women who should not take estrogen containing pills. These include women who are breastfeeding, who are hypertensive, or who are at risk for developing blood clots. Minipills are estrogen-free oral contraceptive tablets that provide a continuous flow of low dose progestin. Unlike combination OCs, progestin-only pills must be taken continuously without a hormone-free period. Minipills are slightly less effective than regular pills and often cause irregular menstrual patterns. Minipills prevent pregnancies mainly by making the cervical mucus impermeable to sperm and by making it more difficult for an egg to attach to the uterus lining.
D. Effects of Different OCs
There are many different OC brands. In some cases, different brands are identical except for packaging. In other cases, brands have different hormones in slightly differing amounts. When prescribing a pill, physicians may consider estrogen dose, progestin dose,type of progestin and relative potency as important factors. The risk of serious side effects is higher among women who take more than 50 mcg of estrogen. Most physicians now recommend that women take pills containing 35 mcg or less. Thus, the ideal pill is the one with the lowest estrogen and progestin doses that will be effective in preventing pregnancy and minimize adverse effects.
Oral contraceptives (OCs), also known as the pill, have been available in the United States since 1960. They have become the most widely used types of reversible contraception in this country. In 1995, some 27% of American woman of childbearing age (15 to 44 years of age) who used contraception used OCs. Over the last 2 decades, the amount of both estrogen and progestin contained in the pills have been reduced considerably compared with the early OCs.
Benefits of Oral Contraceptives
OCs are among the most effective means of contraception (Table 1). When used correctly, combination OCs have a failure rate of only 0.1% in the first year of use. This is 60 times more effective than using a diaphragm and 30 times more effective than relying on a condom. In contrast to sterilization, the effect of OCs is more easily reversed.
Progestin-only OCs are somewhat less effective than combination OCs, with a 0.5% pregnancy rate after 1 year of correct use. Even when patients use OCs incorrectly (eg, by forgetting to take a pill or taking a pill out of sequence), the failure rate for both combination and progestin-only OCs is still just 5%.
Table 1. Risk of Pregnancy After 1 Year of Use
Pregnancy Rate (%) When Used Correctly
Depot medroxyprogesterone acetate
Intrauterine device (IUD)
9 - 26
1 - 9
9 - 20
In addition to contraception, OCs provide other noncontraceptive benefits to users. OC use has been associated with a lower incidence of ovarian cancer (Table 2). Women who use OCs have about half the risk of developing ovarian cancer as do women who never used them. Each successive year of OC use reduces the risk of even further ovarian cancer. The incidence of nonmalignant ovarian cysts is also lower in OC users. Progestin in both combination and progestin-only OCs contributes to a lowered incidence of endometrial cancer and benign breast cysts and tumors. The incidence of endometrial cancer is reduced by 50% after at least 1 year of use.
Women who use OCs have more regular and predictable menstrual cycles, with a reduction in the days and amount of menstrual flow, which in turn reduces the risk of iron deficiency anemia. The incidence of premenstrual syndrome (PMS) may also decrease some in women using oral contraceptives.
Use of OCs has also been shown to lower the incidence of ectopic pregnancy and pelvic inflammatory disease (PID). OC use may also increase bone mineral density, have a modest positive effect on cholesterol levels, raising HDL-cholesterol (the "good" cholesterol) and lowering LDL-cholesterol (the "bad" cholesterol). This is a result of the estrogen component, as some progestins alone have a modest negative effective on cholesterol levels.
Table 2. Non-contraceptive Benefits of OCs
Decreased Incidence of:
Benign breast tumors and cysts
Menstrual regularity; predictable cycle
Reduced duration of flow
Reduced amount of flow
Minor Adverse Effects
Major Adverse Effects
Today's OCs contain one fourth or less of the amount of estrogen and one tenth or less of the amount of progestin as the original OCs introduced in the 1960s. As the amount of estrogen and progestin in OCs has been decreased, the risk of certain adverse effects has also fallen dramatically. Low-dose products are defined as those containing less than 50 mcg of estrogen. The lowest estrogen dose currently available in an OC is 20 mcg.
Minor Adverse Effects
Common minor adverse effects linked to the use of OCs include nausea and breast tenderness (both of which often decrease after several months of use), fluid retention, and depression. Some women also may experience increases in blood pressure, so it should be measured annually.
Progestin in OCs have been linked to weight gain, nervousness, and absence of, or abnormal, menstruation. Both estrogens and progestins appear to contribute to breakthrough bleeding.
Major Adverse Effects
The use of OCs has been linked historically to the incidence of cardiovascular disease--including clogged arteries (atherosclerosis), blood clots (thromboembolism), and heart attacks (myocardial infarction) as well as breast cancer, gallbladder disease, cervical cancer, and benign liver tumors. However, as pills with lower estrogen and progestin content have replaced earlier high-dose formulations, the risks of some of these conditions may not be as great as with older OCs. For example:
As currently formulated, OCs actually do not promote the development of atherosclerosis. As noted earlier, the positive impact of estrogen on cholesterol levels appears to counter any potential negative impact of progestin.
The most recent and thorough data suggest that OC use is not linked to breast cancer.
Currently available OCs do not increase the risk for gallbladder disease.
Some health risks may still exist for users of OCs. These include the following:
High doses of estrogen may contribute to formation of blood clots that can result in heart attacks and strokes. For the vast majority of woman taking OCs, the amounts of estrogen in today's OCs pose no risk of heart attack or stroke. However, the risk apparently increases dramatically in women who smoke. Other factors that increase the risk are:
>35 years of age
It is recommended that women older than 35 years of age who smoke do not use OCs.
OC users may be at increased risk of developing cervical cancer. These women should receive a yearly examination of cervical tissue, especially if they have been using OCs for at least 5 years.
Women who have used OCs for longer than 4 years are at increased risk of developing benign liver tumors, although this condition is rare. The tumors disappear if use of the OC is discontinued.