Effectiveness of birth control methods

The effectiveness of a birth control method can be expressed as the percentage of unplanned pregnancies that occur while using the method. Employing this criterion, Table 62–1 compares the effectiveness of the major birth control methods. As you can see, the most effective methods are Nexplanon, intrauterine devices (IUDs), and sterilization. Oral contraceptives (OCs), Depo-Provera, the contraceptive ring, and the contraceptive patch are close behind. The least reliable methods include barrier methods, periodic abstinence, spermicides, and withdrawal.

Note that Table 62–1 contains two columns of figures, one labeled perfect use and the other typical use. The perfect use figures represent pregnancy rates when a method of birth control is employed exactly as it should be (ie, consistently and with proper technique). The typical use figures represent pregnancy rates observed in actual practice. The higher pregnancy rates reported in the typical use column are largely an indication that methods of birth control are not always used when and as they should be.

Selecting a birth control method

Figure 62–1 indicates the percentage of users who select a particular form of birth control. Perhaps surprisingly, the method chosen most frequently is sterilization: female sterilization (tubal ligation) plus male sterilization (vasectomy) are selected by 37% of birth control users. OCs or male condoms are chosen by most of the remaining birth control users. Diaphragms, periodic abstinence, IUDs, and other techniques account for a small fraction of birth control use.

Several factors should be considered when choosing a method of birth control. Chief among these are effectiveness, safety, and personal preference. As indicated in Table 62–1, the most effective methods are etonogestrel subdermal implants [Nexplanon], intramuscular medroxyprogesterone acetate [Depo-Provera], sterilization, and IUDs. Three other methods—OCs, the contraceptive ring [NuvaRing], and the contraceptive patch [Ortho Evra]—are close behind. The remaining methods—condoms, the sponge, diaphragm, cervical cap, spermicides, and periodic abstinence—must be used in a near-perfect fashion to afford any reasonable level of protection.

When factoring safety into the selection equation, several guidelines apply. Combination OCs should be avoided by women with certain cardiovascular disorders (see below), as well as by women over 35 years old who smoke. For women in these categories, an alternative method (eg, diaphragm, progestin-only pill, or IUD) is preferable. Although OCs are effective and relatively convenient, they can also cause significant side effects. Accordingly, women who consider the benefit/risk ratio unfavorable should be advised about alternative contraceptive techniques. Women who are not in a mutually monogamous relationship, and hence are at risk for a sexually transmitted disease (STD), should not use an IUD.

Personal preference is a major factor in providing the motivation needed for consistent implementation of a birth control method. Because even the best form of contraception will be less effective if improperly practiced, the importance of personal preference cannot be overemphasized. Practitioners should take pains to educate patients about the contraceptive methods available so that selection and use can be based on understanding.

Additional factors that bear on selecting a birth control method include family planning goals, age, frequency of sexual intercourse, and the individual’s capacity for adherence. If family planning goals have already been met, sterilization of either the male or female partner may be desirable. For women who engage in coitus frequently, OCs or a long-term method (eg, Nexplanon, Depo-Provera, IUD) are reasonable choices. Conversely, when sexual activity is limited, use of a spermicide, condom, or diaphragm may be more appropriate. Since barrier methods combined with spermicides can offer some protection against venereal disease (as well as providing contraception), these combinations may be of special benefit to individuals who have multiple partners. If adherence is a problem (as it can be with OCs, condoms, and diaphragms), use of a long-term method (eg, vaginal contraceptive ring, IUD, Nexplanon, Depo-Provera) can confer more reliable protection.

To help women select the birth control method that suits them best, Planned Parenthood has created a step-by-step computerized selection tool, accessible online at www.plannedparenthood.org/all-access/my-method-26542.htm. This tool accounts for all of the factors noted above.

Oral contraceptives

There are two main categories of OCs: (1) those that contain an estrogen plus a progestin, known as combination OCs, and (2) those that contain just a progestin, known as “minipills” or progestin-only OCs. Of the two groups, combination OCs are by far the more widely used.

Combination oral contraceptives

Since their introduction in the late 1950s, combination OCs have become one of our most widely prescribed families of drugs. These drugs are both safe and effective, although minor side effects are common.

Mechanism of action

Combination OCs reduce fertility primarily by inhibiting ovulation. How? The estrogen in combination OCs suppresses release of FSH from the pituitary (and thereby inhibits follicular maturation), and progestin in combination OCs acts in the hypothalamus and pituitary to suppress the midcycle LH surge, which normally triggers ovulation. Secondary mechanisms include thickening of the cervical mucus (creating a barrier to the penetration of sperm), and alteration of the endometrium making it less hospitable for implantation.

Components

Estrogens.

Only three estrogens are employed: ethinyl estradiol, mestranol, and estradiol valerate. Most combination OCs use ethinyl estradiol. A few older products use mestranol, which undergoes conversion to ethinyl estradiol in the body. And one new product—Natazia—uses estradiol valerate, which undergoes conversion to estradiol in the body.

Progestins.

Combination OCs employ eight different progestins, which can be grouped into four generations (Table 62–2). Progestins in all four generations are equally effective. Differences relate to side effects, especially thrombotic events, androgenic effects (acne, hirsutism, dyslipidemia), and hyperkalemia.

TABLE 62–2 

Progestins Used in Combination Oral Contraceptives

Progestins	Comments
First Generation
Ethynodiol diacetate Norethindrone	• Lower risk of thrombosis than with other progestins • Mildly androgenic
Second Generation
Levonorgestrel Norgestrel	• Greater risk of thrombosis than with FGPs • More androgenic than FGPs • Prolonged half-life
Third Generation
Desogestrel Norgestimate	• Greater risk of thrombosis than with FGPs (especially desogestrel) • Less androgenic than FGPs
Fourth Generation
Dienogest Drospirenone	For drospirenone and dienogest: • Greater risk of thrombosis than with other progestins (especially drosperinon) • Less androgenic than FGPs • Low risk of acne and hirsutism For drospirenone only: • Risk of hyperkalemia

FGPs = first-generation progestins.

Drospirenone, a fourth-generation progestin, deserves comment. This unique compound has progestational, antiandrogen, and antialdosterone actions. The drug is a structural analog of spironolactone, a potassium-sparing diuretic that blocks receptors for aldosterone. Drospirenone was developed in an effort to reduce fluid retention caused by the estrogen component in combination OCs. (Estrogens promote fluid retention by activating the renin-angiotensin-aldosterone system. Drospirenone reduces fluid retention by blocking aldosterone receptors, thereby preventing retention of sodium and water. As a result, OCs made with drospirenone may cause less bloating, weight gain, and hypertension than other combination OCs.) The principal concern with drospirenone is venous thromboembolism, which occurs more often than with other progestins. Also, drospirenone can cause hyperkalemia (secondary to renal retention of potassium).

Effectiveness

As indicated in Table 62–1, OCs can be very effective. With perfect use, the failure rate is only 0.3%. However, with typical use, the failure rate is significantly higher: about 8%. Among women who are overweight, efficacy is somewhat reduced. Possible reasons include decreased blood levels of the hormones, sequestration in adipose tissue, and altered metabolism. However, even though efficacy of OCs is slightly reduced in overweight women, these drugs are still more reliable than most of the alternatives.

Overall safety

Determining the relative safety of combination OCs is complex. Part of the difficulty lies with the fact that much of our information on the adverse effects of OCs was gathered when these agents were employed in higher doses than those employed today. Newer data show that today’s OCs, as currently prescribed, are considerably safer than indicated by older studies. An additional complication stems from the fact that the risk of mortality associated with OCs is much smaller than the risk associated with pregnancy and delivery. Keeping the above provisos in mind, we can make the following observations on OC safety. Of the contraceptive methods available, OCs produce the broadest spectrum of adverse effects, ranging from nausea to menstrual irregularity to rare thromboembolic disorders. However, despite their wide variety of undesired actions, when used by healthy women, OCs produce no greater mortality than any other form of birth control.

Adverse effects

Combination OCs can cause a variety of adverse effects. However, although many types of effects may occur, severe effects are rare. Hence, when compared with the serious risks associated with pregnancy and childbirth, the risks of OCs are low. Nonetheless, because OCs are usually taken by women who are healthy, and because OCs represent a potential health hazard (albeit small), we must take steps to minimize risk. To this end, a full medical history should be obtained. If the history reveals an absolute contraindication to OC use (Table 62–3), OCs should not be prescribed. In women with relative contraindications, OCs should be used with caution. Should candidates for OCs undergo a thorough physical examination? Possibly, but the need is questionable.

TABLE 62–3 

Absolute and Relative Contraindications to the Use of Combination OCs

Absolute Contraindications

Thrombophlebitis, thromboembolic disorders, cerebral vascular disease, coronary occlusion, or a past history of these conditions, or a condition that predisposes to these disorders

Abnormal liver function

Known or suspected breast cancer

Undiagnosed abnormal vaginal bleeding

Known or suspected pregnancy

Smokers over the age of 35

Relative Contraindications

Hypertension

Cardiac disease

Diabetes

History of cholestatic jaundice of pregnancy

Gallbladder disease

Uterine leiomyoma

Epilepsy

Migraine

Thromboembolic disorders.

Combination OCs have been associated with an increased risk of venous thromboembolism (VTE), arterial thromboembolism, pulmonary embolism, myocardial infarction (MI), and thrombotic stroke. Among OC users, the relative risk of a thrombotic event is 2 to 3 times the risk in nonusers. However, the absolute risk is still very small: about 8 to 10 events per 10,000 woman-years of OC use. Furthermore, the risk of thrombosis associated with OCs is considerably lower than the risk associated with pregnancy and delivery. How do OCs promote thrombosis? At least in part by raising levels of clotting factors. Thrombosis is not due to atherosclerosis.

Until the mid-1990s, we believed that thrombotic events were caused solely by the estrogen in combination OCs. However, it is now clear that the progestin can contribute too. Two newer progestins—drospirenone and desogestrel—appear to carry the greatest risk.

Fortunately, the risk of thrombotic events with OCs used today is much lower than with the OCs used in the past. Why? Because the amount of estrogen in OCs has been reduced. When combination OCs first became available, they contained high doses of estrogens (eg, 100 mcg ethinyl estradiol). Today’s OCs contain no more than 50 mcg ethinyl estradiol (and usually less), and hence the risk of thromboembolism is quite low.

Major factors that increase the risk of thromboembolism are heavy smoking, a history of thromboembolism, and thrombophilias (genetic disorders that predispose to thrombosis). Additional risk factors include diabetes, hypertension, cerebral vascular disease, coronary artery disease, and surgery in which immobilization increases the risk of postoperative thrombosis.

In the past, OCs were not recommended for women over the age of 35. Why? Because earlier studies indicated an increase in the risk of myocardial infarction for this group. However, re-analysis showed that the risk was limited to older women who smoked. With today’s low-estrogen OCs, nonsmokers may continue usage until menopause, with no greater risk of MI than among younger women.

Several measures can help minimize thromboembolic phenomena. Specifically:

• The estrogen dose in OCs should be no greater than required for contraceptive efficacy.

• OCs containing drospirenone or desogestrel should generally be avoided.

• OCs should not be prescribed for heavy smokers, women with a history of thromboembolism, or women with other risk factors for thrombosis.

• OCs should be discontinued at least 4 weeks prior to surgery in which postoperative thrombosis might be expected.

• Women should be informed about the symptoms of thrombosis and thromboembolism (eg, leg tenderness or pain, sudden chest pain, shortness of breath, severe headache, sudden visual disturbance) and instructed to consult the prescriber if these occur.

What about the cardiovascular risk for former OC users? Data from the Women’s Health Initiative suggest that use of OCs in the past may protect against cardiovascular disease. Among women with a history of OC use, there was an 8% decrease in the overall incidence of cardiovascular disease, including a reduced risk of angina, myocardial infarction, peripheral vascular disease, transient ischemic attacks, and elevation of cholesterol.

Can women with a history of thrombosis use drugs for birth control? Yes. Although these women should avoid estrogen/progestin products, they can still use a progestin-only method. Options include the levonorgestrel intrauterine system [Mirena], medroxyprogesterone acetate injection [Depo-Provera], the etonogestrel subdermal implant [Nexplanon], and the “minipill”—all of which are discussed below.

Cancer.

Oral contraceptives present no known risk of cancer—with the important exception of promoting (not causing) breast cancer growth. The effects of OCs on cancers of the ovaries, endometrium, cervix, and breast have been studied extensively. Effects on three of these cancers are clear: OCs protect against ovarian and endometrial cancer, and have no impact (positive or negative) on cervical cancer, which is caused by human papillomaviruses.

What about breast cancer? Until a decade ago, the question was unresolved: some studies found a link between OC use and breast cancer; others did not. Now we seem to have a definitive answer: OCs do not increase the risk of breast cancer for most women. This conclusion is based on data from the Women’s Contraceptive and Reproductive Experience (Women’s CARE) study, published in 2002. This major study, involving over 9000 women, found no association between present or past use of OCs and the development of breast cancer. This conclusion applied not only to study participants as a whole, but also to women in the following subgroups:

• Those who used OCs with high estrogen content

• Those who used OCs for a prolonged time

• Those who began OC use during adolescence

• Those with a first-degree relative with breast cancer

These results should reassure women who are OC users.

However, although this study shows that OCs do not increase risk for most women, the results of another large recent study show that OCs do increase risk for some women, specifically, women who have the BRCA1 gene mutation. Even without taking OCs, these women have a very high—50% to 80%—lifetime risk of breast cancer. OCs increase this risk by one-third. The same study found that OCs do not increase risk in women with the BRCA2 mutation.

It is important to note that, although OCs do not cause breast cancer, estrogens can promote the growth of existing breast carcinoma. Accordingly, women with this disease should not take OCs.

Hypertension.

Combination OCs can cause hypertension, but the risk with today’s low-estrogen preparations is very low. How do OCs raise blood pressure? By increasing blood levels of two compounds: angiotensin (a potent vasoconstrictor) and aldosterone (a hormone that promotes salt and water retention). If hypertension develops, and if OCs are determined to be the cause, two options are open: (1) discontinue the OC or (2) continue the OC and manage the hypertension with drugs.

Abnormal uterine bleeding.

By altering the endometrium, OCs may decrease or eliminate menstrual flow. In addition, breakthrough bleeding and spotting may occur, especially with the use of extended-cycle OCs (eg, Seasonique, Seasonale). Spotting and bleeding can also occur with monthly-cycle OCs, most often during the first 3 months when low-estrogen OCs are used. If a period is missed while taking monthly-cycle OCs, the possibility of pregnancy should be assessed. Following discontinuation of OCs, normal menstruation usually resumes, although the first period may be delayed. Women with a pretreatment history of irregular menses will return to their previous pattern when OCs are discontinued.

Use in pregnancy and lactation.

OCs have no therapeutic role during pregnancy, and hence are contraindicated for use by pregnant women. Pregnancy should be ruled out prior to starting OC use, and, if pregnancy should occur despite OC use, dosing should stop immediately. Woman should be assured, however, that inadvertant use of OCs during early pregnancy poses no risk of fetal harm. Because OCs have no role in pregnancy—and not because they are harmful—these drugs are classified in FDA Pregnancy Risk Category X.

Combination OCs enter breast milk and reduce milk production, especially in the early stages of lactation. In contrast, progestin-only OCs have little or no effect on milk production, and hence are preferred for contraception during lactation, at least early on. (Later, when the milk supply is well established, and especially with the addition of solids to the infant’s diet, use of combination OCs may resume.)

Stroke in women with migraine.

When used by women who experience migraine headaches, OCs may increase the risk of thrombotic stroke. However, the absolute increase is low: only 8 cases per 100,000 women at age 20, and rising to 80 cases per 100,000 women at age 40. Because the risk is low, OCs are generally considered safe for women with migraine, provided they are under age 35, don’t smoke, and are healthy, and provided their headaches are not preceded by visual changes known as an aura (migraine with aura has a greater risk of stroke than migraine without aura). Migraine and its management are discussed at length in Chapter 30.

Benign hepatic adenoma.

Hepatic adenoma is a rare complication seen in women who use OCs that contain mestranol. These highly vascular, nonmalignant tumors are usually picked up as incidental findings on a computed tomography scan or magnetic resonance imaging. If hepatic adenoma is diagnosed, discontinuing OCs usually results in spontaneous tumor regression.

Effects related to estrogen or progestin imbalance.

Many of the mild side effects of combination OCs result from an excess or deficiency of estrogen or progestin. Effects that can result from an excess of estrogen include nausea, breast tenderness, and edema. Progestin excess can increase appetite and cause fatigue and depression. A deficiency in either hormone can cause menstrual irregularities. Side effects related to hormonal imbalance are summarized in Table 62–4.

TABLE 62–4 

Side Effects Caused by an Excess or Deficiency in the Estrogen or Progestin Content of an Oral Contraceptive Regimen

Estrogen	Progestin
Excess	Deficiency	Excess	Deficiency
Nausea Breast tenderness Edema Bloating Hypertension Migraine Cervical mucorrhea Polyposis	Early or midcycle breakthrough bleeding Increased spotting Hypomenorrhea	Increased appetite Weight gain Depression Tiredness Fatigue Hypomenorrhea Breast regression Monilial vaginitis Acne, oily scalp* Hair loss* Hirsutism*	Late breakthrough bleeding Amenorrhea Hypermenorrhea

^*Caused by progestins that have strong androgenic activity.

Quite often, these effects can be reduced by adjusting the estrogen/progestin balance of an OC regimen. With most women, therapy is initiated with an OC containing 30 to 35 mcg of ethinyl estradiol. If significant nausea occurs, it can be managed by dosing at bedtime or, if needed, switching to an OC with less estrogen. Using less estrogen can also reduce breast discomfort. During the first 3 months of use, spotting and breakthrough bleeding are common, and usually resolve on their own. If they don’t, they can be managed by increasing the estrogen dosage, or by using a product that contains a different progestin. For women who experience androgenic effects (eg, acne, hirsutism), switching to an OC that has drospirenone or dienogest can help. Other side effects can be reduced by making similar adjustments. When substituting one combination OC for another, the change is best made at the beginning of a new cycle.

Hyperkalemia.

Drospirenone, a fourth-generation progestin, promotes renal retention of potassium, and can thereby cause hyperkalemia. Accordingly, the drug is inappropriate for women with conditions that predispose to hyperkalemia (eg, renal insufficiency, adrenal insufficiency, liver disease). Furthermore, drospirenone should be used with caution in women taking other drugs that can elevate serum potassium. Important among these are angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, potassium-sparing diuretics, potassium supplements, and nonsteroidal anti-inflammatory drugs (when taken daily). If women taking these drugs are using a drospirenone-containing OC, potassium levels should be checked during the first cycle of use.

Glucose intolerance.

Oral contraceptives can elevate blood glucose levels. This diabetogenic effect is caused by the progestin in OCs. Glucose intolerance is most likely in patients who are already diabetic or have experienced gestational diabetes. Because hypoglycemic agents (eg, insulin) can control glucose elevations induced by OCs, the presence of diabetes does not preclude OC use. Prediabetic women should be monitored for development of hyperglycemia. Glucose intolerance may occur less with OCs that contain desogestrel or norgestimate.

Other adverse effects.

Rarely, OCs may precipitate gallbladder disease in women who already have gallstones or a history of gallbladder disease. OCs can occasionally cause ocular injury (eg, retinal vascular occlusion, retinal edema, optic neuropathy). Accordingly, if visual changes occur, OCs should be discontinued until the underlying cause is diagnosed. Combination OCs have been associated with an increased risk of systemic lupus erythematosus, primarily in women who recently began OC use. Rarely, OCs cause melasma, characterized by dark brown patches on the face.

Noncontraceptive benefits of OCs

OCs decrease the risk of several disorders, including ovarian cancer, endometrial cancer, ovarian cysts, pelvic inflammatory disease (PID), benign breast disease, iron deficiency anemia, and acne. In addition, OCs favorably affect menstrual symptoms: cramps are reduced, menstrual flow is reduced in volume and duration, and menses are more predictable. In women with premenstrual syndrome or premenstrual dysphoric disorder, OCs can reduce symptom intensity. In some women with menstrually associated migraine, OCs can reduce migraine frequency. Surprisingly, OCs may even benefit women with rheumatoid arthritis.

Drug interactions

Drugs and herbs that reduce the effects of OCs.

Products that induce hepatic cytochrome P450 can accelerate OC metabolism, and can thereby reduce OC effects. Products that induce P450 include rifampin (used for tuberculosis), ritonavir (used for HIV infection), several antiepileptic agents (carbamazepine, phenobarbital, phenytoin, and primidone), and St. John’s wort (an herb used widely for depression). Women taking OCs in combination with any of these agents should be alert for indications of reduced OC blood levels, such as breakthrough bleeding or spotting. If these signs appear, it may be necessary to either (1) increase the estrogen dosage of the OC, (2) combine the OC with a second form of birth control (eg, condom), or (3) switch to an alternative form of birth control.

Drugs whose effects are reduced by OCs.

OCs can decrease the benefits of warfarin and hypoglycemic agents. By increasing levels of clotting factors, OCs can decrease the effectiveness of warfarin, an anticoagulant. By increasing levels of glucose, OCs can counteract the benefits of insulin and other hypoglycemic agents used in diabetes. Accordingly, when combined with OCs, warfarin and hypoglycemic agents may require increased dosage.

Drugs whose effects are increased by OCs.

OCs can impair the hepatic metabolism of several agents, including theophylline, tricyclic antidepressants, diazepam, and chlordiazepoxide. Because of reduced clearance, these drugs may accumulate to dangerous levels. If signs of toxicity appear, dosage of these drugs should be reduced.

Preparations

The combination OCs in current use are listed in Table 62–5. As you can see, nearly all of these products contain the same estrogen: ethinyl estradiol. In contrast, eight different progestins are employed. Products in the table are listed in order of increasing estrogen content. The OCs with low estrogen are safer. As a rule, high-estrogen OCs are reserved for women taking drugs that induce P450. Products with unique properties are discussed immediately below.

TABLE 62–5 

Composition of Combination Oral Contraceptives

Trade Name	mcg	Estrogen	mg	Progestin
28-DAY-CYCLE OCs
Monophasic
Loestrin Fea	10	Ethinyl estradiol	1	Norethindrone
Junel 1/20	20	Ethinyl estradiol	1	Norethindrone
Junel Fe 1/20
Loestrin 21 1/20
Loestrin Fe 1/20
Loestrin 24 Feb
Microgestin 1/20
Microgestin Fe 1/20
Aviane-28	20	Ethinyl estradiol	0.1	Levonorgestrel
Lessina
Lutera
Sronyx
Gianvic	20	Ethinyl estradiol	3	Drospirenone
YAZc
Beyazc,d
Generess Fee	25	Ethinyl estradiol	0.8	Norethindrone
Levora	30	Ethinyl estradiol	0.15	Levonorgestrel
Nordette-28
Portia-28
Cryselle	30	Ethinyl estradiol	0.3	Norgestrel
Low-Ogestrel-21
Low-Ogestrel-28
Lo/Ovral-28
Junel 1.5/30	30	Ethinyl estradiol	1.5	Norethindrone
Junel Fe 1.5/30
Loestrin 21 1.5/30
Loestrin Fe 1.5/30
Microgestin 1.5/30
Microgestin Fe 1.5/30
Apri	30	Ethinyl estradiol	0.15	Desogestrel
Desogen
Ortho-Cept
Reclipsen
Solia
Ocella	30	Ethinyl estradiol	3	Drospirenone
Safyrald
Yasmin
Kelnor 1/35	35	Ethinyl estradiol	1	Ethynodiol diacetate
Zovia 1/35
Balziva	35	Ethinyl estradiol	0.4	Norethindrone
Femcon Fee
Ovcon-35e
Zenchent
Brevicon-28	35	Ethinyl estradiol	0.5	Norethindrone
Modicon-28
Necon 0.5/35
Nortrel 0.5/35
Necon 1/35	35	Ethinyl estradiol	1	Norethindrone
Norinyl 1 + 35
Nortrel 1/35
Ortho-Novum 1/35
MonoNessa	35	Ethinyl estradiol	0.25	Norgestimate
Ortho-Cyclen-28
Previfem
Sprintec
Ovcon-50	50	Ethinyl estradiol	1	Norethindrone
Ogestrel 0.5/50	50	Ethinyl estradiol	0.5	Norgestrel
Zovia 1/50	50	Ethinyl estradiol	1	Ethynodiol diacetate
Necon 1/50	50	Mestranol	1	Norethindrone
Norinyl 1 + 50
Biphasic
Necon 10/11	35	Ethinyl estradiol	0.5	Norethindrone (phase 1)
	35	Ethinyl estradiol	1	Norethindrone (phase 2)
Azurette	20	Ethinyl estradiol	0.15	Desogestrel (phase 1)
Kariva	10	Ethinyl estradiol	0	Desogestrel (phase 2)
Mircette
Triphasic
Caziant	25	Ethinyl estradiol	0.1	Desogestrel (phase 1)
Cesia	25	Ethinyl estradiol	0.125	Desogestrel (phase 2)
Cyclessa
Velivet	25	Ethinyl estradiol	0.15	Desogestrel (phase 3)
Aranelle	35	Ethinyl estradiol	0.5	Norethindrone (phase 1)
Leena	35	Ethinyl estradiol	1	Norethindrone (phase 2)
Tri-Norinyl	35	Ethinyl estradiol	0.5	Norethindrone (phase 3)
Ortho-Novum 7/7/7	35	Ethinyl estradiol	0.5	Norethindrone (phase 1)
Necon 7/7/7	35	Ethinyl estradiol	0.75	Norethindrone (phase 2)
Nortrel 7/7/7	35	Ethinyl estradiol	1	Norethindrone (phase 3)
Enpresse	30	Ethinyl estradiol	0.05	Levonorgestrel (phase 1)
Trivora	40	Ethinyl estradiol	0.075	Levonorgestrel (phase 2)
	30	Ethinyl estradiol	0.125	Levonorgestrel (phase 3)
Ortho Tri-Cyclen Lo	25	Ethinyl estradiol	0.18	Norgestimate (phase 1)
Tri LoSprintec	25	Ethinyl estradiol	0.215	Norgestimate (phase 2)
	25	Ethinyl estradiol	0.25	Norgestimate (phase 3)
Ortho Tri-Cyclen	35	Ethinyl estradiol	0.18	Norgestimate (phase 1)
TriNessa	35	Ethinyl estradiol	0.215	Norgestimate (phase 2)
Tri-Previfem
Tri-Sprintec	35	Ethinyl estradiol	0.25	Norgestimate (phase 3)
Estrostep Fe	20	Ethinyl estradiol	1	Norethindrone (phase 1)
Tilia	30	Ethinyl estradiol	1	Norethindrone (phase 2)
Tilia Fe	35	Ethinyl estradiol	1	Norethindrone (phase 3)
Tri-Legest Fe
Quadriphasic
Natazia	3	Estradiol valerate	0	Dienogest (phase 1)
	2	Estradiol valerate	2	Dienogest (phase 2)
	2	Estradiol valerate	3	Dienogest (phase 3)
	1	Estradiol valerate	0	Dienogest (phase 4)
EXTENDED-CYCLE OCs
Introvalef	30	Ethinyl estradiol	0.15	Levonorgestrel
Jolessaf
Quasensef
Seasonalef
Seasoniqueg
LoSeasoniqueg	20	Ethinyl estradiol	0.1	Levonorgestrel
CONTINUOUS OC
Lybrelh	20	Ethinyl estradiol	0.09	Levonorgestrel

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