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REVIEW

PELIN BATUR, MD JULIE ELDER, DO MARK MAYER, MD Gault Women’s Health and Breast Pavilion, Gault Women’s Health and Breast Pavilion, Department of General Internal Medicine, Department of General Internal Medicine, Department of General Internal Medicine, The Cleveland Clinic The Cleveland Clinic The Cleveland Clinic

Update on contraception: Benefits and risks of the new formulations

■ ABSTRACT OMEN OFTEN STOP using contraception W because of adverse effects, inconve- Several new contraceptives have become available to nience, and cost. Improper use alone leads to women in recent years. These new agents include ultra-low- about 1 million unplanned in the dose oral contraceptives as well as injectable, vaginal, and each year; half end in .1 patch formulations. We review these, with emphasis on the New contraceptives afford women more Yasmin pill (which contains a new progestin), the Lunelle options. Many of the newer agents have fewer once-a-month injection, the Ortho Evra patch, the NuvaRing adverse effects, which may ultimately improve , the Mirena , and emergency compliance and patient satisfaction. Health contraceptive kits. Patient education regarding these options care providers need to be well informed about is essential for patient compliance and satisfaction. these options so that patients can make sound decisions about contraception. ■ KEY POINTS This article reviews the newest develop- ments in contraception, including: Contraception is used both for protection against unwanted • Low and ultra-low dosing of and for a variety of noncontraceptive health • New progestins benefits, including improvements in dysmenorrhea, anemia, • Risks and benefits of oral contraceptives acne, and others. including drug interactions, health bene- fits, and potential adverse effects • New contraceptive options, including a Various drugs, including some antibiotics, anticonvulsants, new progestin, a patch, a once-a-month anti-HIV protease inhibitors, and herbal products, can affect shot, a vaginal ring, emergency contracep- the metabolism of oral contraceptives. tion, and an experimental device for surgery-free . Blood pressure should be closely monitored for several months after a women starts taking oral contraceptives, and ■ OVERVIEW OF ORAL CONTRACEPTIVES followed yearly thereafter. Oral contraceptives have been used for more If an Ortho Evra becomes partially or than 40 years in the United States and are the completely detached, the patient should replace it second most popular contraceptive choice for 2 immediately, but if it has been off for more than 1 day she women (after sterilization). About 35 million women in the United may not be protected against pregnancy. States use some form of contraception, and PATIENT INFORMATION 95% of all sexually active women have used it New contraceptives for women, page 697 at some point.3,4 Contraception is used both

This paper discusses therapies that are experimental or that are not approved by the US Food for protection against unwanted pregnancy and Drug Administration for the use under discussion. and, in the case of oral contraceptives, for

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T ABLE 1 Monophasic oral contraceptives

PRODUCTS ESTROGEN PROGESTIN

Necon 1/50, Nelova 1/50 M, 50 µg Norethindrone 1.0 mg Norinyl 1+50, Ortho-Novum 1/50 Demulen 1/50, Zovia 1/50 Ethinyl 50 µg Ethynodiol diacetate 1.0 mg Ovral, Ogestrel Ethinyl estradiol 50 µg 0.5 mg Ovcon-50 Ethinyl estradiol 50 µg Norethindrone 1.0 mg LOW-DOSE Demulen 1/35, Zovia 1/35 Ethinyl estradiol 35 µg Ethynodiol diacetate 1.0 mg Necon 1/35, Nelova 1/35, Ethinyl estradiol 35 µg Norethindrone 1.0 mg Norinyl 1+35, Nortrel 1/35, Ortho-Novum 1/3 Brevicon, Modicon, Ethinyl estradiol 35 µg Norethindrone 0.5 mg Necon 0.5/35, Nelova 0.5/35, Nortrel 0.5/35 Ovcon-35 Ethinyl estradiol 35 µg Norethindrone 0.4 mg Ortho-Cyclen Ethinyl estradiol 35 µg 0.25 mg Apri, Desogen, Ortho-Cept Ethinyl estradiol 30 µg 0.15 mg Yasmin Ethinyl estradiol 30 µg 3.0 mg Levlen, Levora, Nordette Ethinyl estradiol 30 µg Levonoregestrel 0.15 mg Loestrin 1.5/30 Ethinyl estradiol 30 µg Norethindrone acetate 1.5 mg µ The true failure Lo/Ovral, Low-Ogesterel Ethinyl estradiol 30 g Norgestrel 0.3 mg ULTRA-LOW-DOSE rate of oral Alesse, Aviane, Levlite Ethinyl estradiol 20 µg 0.1 mg contraceptives Loestrin 21 1/20 Ethinyl estradiol 20 µg Norethindrone acetate 1.0 mg is 3% PROGESTIN-ONLY Ovrette — Norgestrel 0.075 mg Ortho Micronor, Nor-Q.D. — Norethindrone 0.35 mg

their noncontraceptive health benefits. Products containing mestranol do not con- Most oral agents contain both estrogen tain less than 50 µg because lower doses are and progestin, which suppress gonadotropins, less effective. inhibit ovulation, and alter cervical mucus to Although early oral contraceptives con- make sperm entry difficult. taining ethinyl estradiol had up to 100 µg, cur- In theory, the failure rate is 0.1%, but the rent pills contain an average of 30 to 35 µg. true failure rate is 3% due to incorrect use. Pills containing less than 50 µg of ethinyl estradiol are called “low-dose.” Estrogen dosing: Low or ultra low New “ultra-low-dose” pills contain ethinyl The two estrogen compounds available in the estradiol 20 to 25 µg (TABLE 1, TABLE 2). They are United States are ethinyl estradiol and mes- used mainly during the menopausal transition tranol. Ethinyl estradiol is the most common- to control symptoms and for contraception, ly used; mestranol is a prodrug that is con- but they also can be used in patients who have verted to ethinyl estradiol by the liver. adverse effects with higher doses.

682 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 70 • NUMBER 8 AUGUST 2003 Downloaded from www.ccjm.org on September 30, 2021. For personal use only. All other uses require permission. T ABLE 2 Multiphasic oral contraceptives

PRODUCT DAY ESTROGEN DOSE PROGESTIN DOSE

BIPHASIC Mircette 1–21 Ethinyl estradiol 20 µg Desogestrel 0.15 mg 22–26 10 µg 0.0 mg Jenest 1–7 Ethinyl estradiol 35 µg Norethindrone 0.5 mg 8–21 35 µg 1.0 mg Necon 10/11, Nelova 10/11, 1–10 Ethinyl estradiol 35 µg Norethindrone 0.5 mg Ortho-Novum 10/11 11–21 35 µg 1.0 mg TRIPHASIC Tri-Levlen, Trivora, Triphasil 1–6 Ethinyl estradiol 30 µg Levonorgestrel 0.05 mg 7–11 40 µg 0.075 mg 12–21 30 µg 0.125 mg Ortho Tri-Cyclen 1–7 Ethinyl estradiol 35 µg Norgestimate 0.18 mg 8–14 35 µg 0.215 mg 15–21 35 µg 0.25 mg Ortho-Novum 7/7/7 1–7 Ethinyl estradiol 35 µg Norethindrone 0.5 mg 8–14 35 µg 0.75 mg 15–21 35 µg 0.125 mg Tri-Norinyl 1–7 Ethinyl estradiol 35 µg Norethindrone 0.5 mg 8–14 35 µg 1.0 mg 15–21 35 µg 0.5 mg Cyclessa 1–7 Ethinyl estradiol 25 µg Desogestrel 1.1 mg 8–14 25 µg 0.125 mg 15–21 25 µg 0.150 mg Estrostep 1–5 Ethinyl estradiol 20 µg Norethindrone 1.0 mg 6–12 30 µg 1.0 mg 13–21 35 µg 1.0 mg

The new progestins The efficacy of oral contraceptives that In the 1940s, chemists made structural contain the new progestins is similar to that of changes to testosterone that altered its activi- the older formulations. Compared with levo- ty from an to a progestin. norgestrel-containing pills, which are the Testosterone-derived progestins bind to the most androgenic of the second-generation androgen receptor and have varying degrees oral contraceptives, the third-generation pills of androgenic activity. have less of an effect on carbohydrate and Adverse metabolic effects of highly lipid metabolism and are more effective in androgenic progestins (eg, levonorgestrel) reducing acne and hirsutism in hyperandro- include reductions in serum high-density genic women (TABLE 3). lipoprotein (HDL), increased low-density Unfortunately, data are limited comparing lipoprotein (LDL), and glucose intolerance. the third-generation progestins with second- More-selective, third-generation progestins generation progestins such as norethindrone were developed with structural modifications and ethynodiol diacetate (which are less andro- to lower their androgen activity; examples are genic than levonorgestrel).5 Furthermore, con- norgestimate and desogestrel. troversy has arisen because of reports of

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T ABLE 3 Progestin-only contraceptives Progestin-only oral contraceptives, otherwise Available progestins known as “mini-pills,” are available for women for oral contraceptives who cannot tolerate estrogen (eg, due to a his- First-generation tory of heart disease or thromboembolism). No longer used These pills, however, are associated with more breakthrough bleeding and lower contracep- Second-generation* tive efficacy than combination pills, and they Norgestrel are used mainly in lactating women. In fact, a Ethynodiol diacetate backup contraceptive method must be used for Norethindrone 2 days if a woman is more than 3 hours late Levonorgestrel taking a dose. A backup method also is rec- ommended each month at midcycle to Third-generation improve efficacy. Norgestimate In addition, progestin-only contracep- Desogestrel tives, such as injectable medroxyprogesterone Spironolactone-derived acetate (Depo-Provera), have recently been Drospirenone linked to reversible decreases in bone densi- ty.8,9 The potential role of these agents in osteoporosis risk is still being defined. For this *Second-generation progestins are thought to be more androgenic than third-generation progestins. reason, women taking progestin-only agents should be sure to take in at least 1,200 mg of calcium daily.

increased risk of deep venous thrombosis with Drug interactions third-generation pills compared with second- Various drugs can influence the metabolism of generation pills.6 oral contraceptives. Unintended pregnancy or Third- Given this debate, our approach is to pre- breakthrough bleeding can result when oral generation oral scribe pills containing norethindrone, a less contraceptives are taken with: androgenic second-generation progestin, • Antimicrobials (eg, penicillins, tetracy- contraceptives when starting a patient on an oral contracep- clines, griseofulvin, rifampin) are more tive for the first time. However, women doing • Anticonvulsants (eg, phenytoin, carba- well on a third-generation progestin do not mazepine, felbamate, topiramate) effective in need to change preparations. • Anti-HIV protease inhibitors reducing acne • Herbal products. For example, in women Monophasic or multiphasic? taking oral contraceptives and St. John’s and hirsutism To further lower the total steroid dose, in the wort (Hypericum perforatum), bleeding late 1970s pharmaceutical companies intro- irregularities may occur 1 week after start- duced multiphasic preparations—pill packs ing St. John’s wort, with regular cycles that vary the dose at different times in the returning when the herb is stopped.10 (TABLE 2). Trials have not con- The incidence of accidental pregnancy in sistently shown significant differences women taking these with oral between monophasic, biphasic, and triphasic contraceptives is unknown, but women using oral contraceptives regarding bleeding pat- the lowest-dose preparations may be at highest tern, symptoms, or efficacy, however.7 risk. This is an important consideration, given Because most clinical experience and the large number of ultra-low-dose regimens available studies are with the monophasic for- on the market (TABLE 1).11 mulations, these are often preferred. However, as for patient satisfaction, our clinical observa- Safety of oral contraceptives tion is that the choice of progestin is probably The safety profile of oral contraceptives has more important than whether the regimen is been demonstrated in millions of women, and monophasic or multiphasic. taking them is considered safer than pregnan-

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cy.12 A recent study13 found similar mortality In women over age 35, smoking 15 or rates in 23,000 users and nonusers of oral con- more cigarettes per day increases the risk of traceptives. MI.23 Studies have not defined how other car- diovascular risk factors affect the incidence of Noncontraceptive benefits MI in oral contraceptive users. Concomitant of oral contraceptives hypertension, dyslipidemia, diabetes, or obesi- Most women are unaware of the many non- ty may further increase the risk. contraceptive benefits of oral contraceptives, Venous thromboembolism. Studies con- which include improvements in or decreased sistently show that the risk of venous throm- risk of: boembolism (VTE) is two to six times higher • Dysmenorrhea in oral contraceptive users than in nonusers.24 • Anemia However, the incidence of VTE in otherwise • Acne healthy women is low, at about 1 or 2 persons • Hirsutism in 1,000 to 10,000, depending on age. The • primary factor contributing to VTE is estro- • Benign breast disease gen; however, there are conflicting reports • Endometrial cancer about the potentially additive risk with the • Ovarian cysts14 third-generation progestins.25,26 • (newly recognized: a 50% Risk factors for VTE include increasing decrease in ovarian cancer risk, including age, obesity, family history of VTE, surgery, cases associated with mutations in the BRCA and the factor V Leiden mutation. Patients genes15,16) with this mutation have six to seven times the • Colorectal cancer (an 18% to 40% reduc- risk of VTE, which increases up to 35 times tion17,18) with oral contraceptive use. Women with a • Pelvic inflammatory disease (a 10% to documented history of VTE that is unex- 70% lower incidence) plained or associated with pregnancy should • Osteopenia, osteoporosis. Because oral avoid oral contraceptives. Oral contraceptives provide a consistent dose of Hypertension. Many women have an contraceptives estrogen, they may increase bone mineral increase in blood pressure with oral contra- density by promoting higher peak bone ceptive use, although readings usually remain may increase mass.19 This benefit has been reported with within the normal range. The risks of preg- bone mineral ultra-low-dose formulations, and the positive nancy in women with hypertension should be effect increases with higher doses and longer weighed against the risks of oral contraceptive density use. A 25% reduction in hip fractures has use. been demonstrated.20 Low-dose oral contraceptives are not con- • Dyslipidemia. Oral contraceptives that traindicated in otherwise healthy women with contain third-generation progestins improve well-controlled hypertension, but women serum lipoprotein profiles by increasing HDL over age 35 who have hypertension and who and decreasing LDL, although the clinical sig- smoke or have end-organ vascular disease nificance of these changes is not clear.21 should not use oral contraceptives. Blood pressure should be closely moni- Risks of oral contraceptive use tored for several months after starting oral The benefits of oral contraceptives must be contraceptives and followed yearly thereafter. weighed against the potential risks. Stroke. Studies evaluating oral contra- Coronary artery disease. Low-dose oral ceptives and stroke are difficult to interpret. contraceptives were developed in response to Most studies were small, did not differentiate increased cardiovascular events associated between hemorrhagic and thromboembolic with higher-dose oral contraceptives. Studies stroke, and did not control for major risk fac- of oral contraceptives with less than 50 µg tors. Most evidence suggests that there is no estrogen have found no increased risk of increased risk in oral contraceptive users, myocardial infarction (MI) among healthy, except in those who smoke.27,28 nonsmoking women.22 The risk of stroke from use of these agents

688 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 70 • NUMBER 8 AUGUST 2003 Downloaded from www.ccjm.org on September 30, 2021. For personal use only. All other uses require permission. in migraine patients also is controversial. ■ NEW CONTRACEPTIVE OPTIONS Studies of older, high-dose oral contracep- tives showed an increased risk of stroke, The Yasmin pill: Ethinyl estradiol whereas studies of low-dose formulations have plus a spironolactone analogue not.29 Yasmin is a low-dose, monophasic oral contra- . Evidence of a possible link ceptive containing ethinyl estradiol and between breast cancer and hormone exposure drospirenone, a progestin analogue of spirono- has been inconsistent. lactone.34 Drospirenone is the only progestin A meta-analysis30 of 54 studies that with both antimineralocorticoid and antian- included a total of 53,000 women with breast drogenic properties that is approved by the US cancer and 100,000 controls found that the Food and Drug Administration (FDA). relative risk of breast cancer in current users of Effectiveness. Yasmin is 99% effective, oral contraceptives was 1.24. After the oral which is similar to other oral contraceptives.35 contraceptive was stopped, this risk decreased Advantages. Due to its antiandrogenic and was absent after 10 years. Breast cancers diuretic properties, Yasmin has the added ben- that were diagnosed while the patient was tak- efit of improving acne, seborrhea, and hir- ing an oral contraceptive tended to be less sutism as well as providing good weight stabil- advanced. ity—or even slight weight loss—from On the other hand, a recent case-control decreased water retention. study31 found that, in women aged 35 to 64 An 8-month study36 compared weight years, current or former oral contraceptive use gain in 80 women taking either Yasmin or was not associated with a significantly ethinyl estradiol and levonorgestrel (0.15 mg). increased risk of breast cancer. Women taking Yasmin lost an average of 1.8 In women with a family history of breast lb (0.8 kg), while women taking ethinyl estra- cancer in a first-degree relative, high-dose for- diol and levonorgestrel gained an average of mulations (used before 1975) may further 1.5 lb (0.7 kg). increase this risk, although the newer low- Yasmin may benefit women with premen- dose formulations have not been shown to strual symptoms such as bloating.37,38 Women with carry this increased risk.32 Practical considerations. The 3 mg of a history of In patients with a BRCA1 or BRCA2 drospirenone in each pill is equivalent to 25 mutation, the potential increased risk of breast mg of spironolactone, a potassium-sparing venous cancer needs to be weighed against the diuretic. Therefore, the serum potassium level thrombo- decreased risk of ovarian cancer. These should be checked during the first month of patients should consider discussing the safety therapy. embolism of oral contraceptives with a consultant, such Yasmin should be used with caution in should avoid as a geneticist or a specialist in women’s health women taking medications that can lead to or breast health. hyperkalemia, such as other potassium-sparing oral Cervical cancer. For every 100,000 diuretics, angiotensin-converting enzyme contraceptives women who use oral contraceptives for longer inhibitors, aldosterone antagonists, and non- than 8 years, 30 to 125 additional cases of cer- steroidal anti-inflammatory drugs. It is con- vical cancer may occur. However, oral contra- traindicated in women with renal, hepatic, or ceptive users may have more unprotected sex- adrenal insufficiency. ual encounters and an increased exposure to the human papillomavirus, a known risk fac- Ortho Evra: ‘The patch’ tor for cervical cancer. In 2001, the FDA approved the first transder- The slightly increased risk of cervical can- mal contraceptive patch, Ortho Evra (20 µg cer needs to be weighed against the roughly ethinyl estradiol and 150 µg norlegestromin 50% reduction in the risks of ovarian and per 24 hours).39 is a metabo- endometrial cancers. One model estimated lite of norgestimate, the progestin in the third- that for every 100,000 women, 44 fewer repro- generation pills Ortho-Cyclen and Ortho Tri- ductive cancers would occur in users than in Cyclen. nonusers.33 Effectiveness and advantages. Three

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clinical trials have been conducted worldwide If a patch is detached for more than 1 day involving 4,578 women, 3,319 of whom used or if the woman is unsure how long it has been Ortho Evra. Compared with daily oral contra- detached, she may not be protected from preg- ceptives, the patch offered similar safety, con- nancy. She should stop the current contracep- traceptive efficacy, and menstrual cycle con- tive cycle and start a new cycle immediately trol and had the added benefit of improved by applying a new patch. compliance.40 It is hoped that improved com- Packages of single replacement patches pliance will lead to decreased failure rates. are available. Used patches still contain active Practical considerations. In clinical tri- hormones, so they should be folded in half als, most unintended pregnancies were in before they are discarded. women weighing more than 198 lb (90 kg), suggesting that Ortho Evra may be less effec- Lunelle: The ‘once-a-month shot’ tive in women heavier than this weight. Lunelle, the first monthly, injectable combina- Therefore, Ortho Evra should be used with tion hormone, contains and caution in these women. medroxyprogesterone acetate. The other The most common adverse effects in clin- injectable method, Depo-Provera, ical trials were, in decreasing order, breast ten- contains medroxyprogesterone acetate only and derness, headache, skin irritation, and nausea. is given intramuscularly every 3 months. It is unknown if the risk of VTE with Ortho Effectiveness. The efficacy rates of Depo- Evra is different than with oral contracep- Provera and Lunelle are comparable. Lunelle tives. is effective for contraception during the first The patient should start Ortho Evra on cycle of use. the first day of her menstrual period (or first Unexpected pregnancies occurring in day of withdrawal bleeding in oral contracep- women receiving Lunelle are uncommon and tive users). A new patch is applied weekly, on so far have not shown congenital malforma- the same day each week, for 3 weeks. Week 4 tions. is patch-free, and withdrawal bleeding is Compared with Ortho-Novum 7/7/7, Hypertensive expected during this time. As with the oral Lunelle had similar efficacy, although women women over contraceptives, there should not be more than using Lunelle were more likely to experience a 7-day hormone-free interval between dosing irregular bleeding at the end of the first year.41 age 35 who cycles. Weight gain was the most common smoke should The patch should be applied to clean, dry that led to discontinuation of skin on the buttocks, upper outer arm, lower Lunelle (5.7% compared with 0.9% in the not use oral abdomen, or upper torso (excluding breasts). Ortho-Novum 7/7/7 group). Women gained contraceptives Ortho Evra should not be placed on skin that an average of 4 lb during the first year and an is red or irritated or where it will be rubbed by additional 2 lb during the second year. Other tight clothing. Oils, creams, or cosmetics side effects are similar to those of oral contra- should not be applied near the patch. The ceptives, including irregular menstrual cycles, patient should be encouraged to participate in nausea, bloating, and breast tenderness. her usual physical activities (eg, sauna, Advantages. This agent is a good option whirlpool, swimming). for women in whom there are concerns about If the patch comes off. Of more than compliance. 70,000 Ortho Evra patches worn, 4.7% were Practical considerations. The first injec- replaced because they either fell off (1.8%) or tion should be given within the first 5 days of were partly detached (2.9%). menses, and subsequent injections are given If the patch is detached, a new one should within 28 to 30 days of the previous injection. be applied immediately. Supplemental adhe- If more than 33 days have passed since the last sives or wraps should not be used. injection, pregnancy must be ruled out before If a patch is partially or completely another injection is given. Patients switching detached for less than 1 day, the patient to Lunelle from oral contraceptives should get should replace it with a new patch immedi- their first injection within 7 days of their last ately. No back-up contraception is needed. active pill.

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Lunelle is comparable in cost to other oral Mirena: The progestin IUD contraceptives, but patients must go to a nurse Mirena, an intrauterine device (IUD), has or pharmacist every month to get the injec- been used since the early 1980s in other coun- tion, which may add to the cost. tries for contraceptive and noncontraceptive Due to concerns about subpotency, pre- purposes. It recently was approved for contra- filled syringes of Lunelle were recalled in ceptive use in the United States. October 2002. Lunelle packaged in standard Mirena is a levonorgestrel-releasing sys- vials was not affected by this recall and is still tem that is effective for up to 5 years. It acts available. locally on the endometrium with progesto- genic effects and may also thicken cervical NuvaRing: A once-a-month vaginal ring mucus and inhibit sperm capacitation and sur- NuvaRing is a contraceptive vaginal ring that vival. releases 120 µg of and 15 µg of Effectiveness. Mirena is 99% effective. ethinyl estradiol daily. It is colorless and odor- A study in 1,169 women44 found that preg- less and measures 2 inches in diameter, with a nancy rates over 1 year and 5 years were less cross-sectional diameter of 4 mm. than 1%. Of the unwanted pregnancies, half The ring is easy for patients to insert and were ectopic. This translates into an annual is left in place for 3 weeks. Withdrawal incidence of one ectopic pregnancy per 1,000 bleeding occurs during the fourth, ring-free users, which is not significantly different week. than the rate of ectopic pregnancies in sexu- Efficacy. NuvaRing is comparable to oral ally active women not using any contracep- contraceptives in efficacy. tion. Advantages. NuvaRing is an excellent Advantages. Mirena’s delivery of proges- choice for most women, although it is not rec- terone to the endometrium results in less ommended if a cystocele, rectocele, or uterine bleeding than with IUDs.45 Some prolapse is present.42 One of its main advan- women, however, may have irregular bleeding tages is convenience. during the first 3 to 6 months. After that, Drosperinone A recent study of 247 women43 com- bleeding usually declines, and 20% of women may benefit pared cycle control and tolerability of have amenorrhea by the end of the first year. NuvaRing vs a standard combined oral con- The decreased bleeding profile and 5-year women with traceptive containing ethinyl estradiol 30 µg efficacy of Mirena make it an attractive µ premenstrual and levonorgestrel 150 g. Both groups expe- option, especially for women with menorrha- rienced withdrawal bleeding; however, the gia or those who desire long-term contracep- symptoms such incidence of irregular bleeding in the tion. as bloating NuvaRing group was significantly less than in the oral contraceptive group. In addition, ■ NuvaRing users had a higher incidence of normal intended bleeding patterns compared Postcoital (emergency) contraception is with the oral contraceptive group. The toler- defined as the prevention of pregnancy within ability of both contraceptives was good, 72 hours of unprotected intercourse or failure although the NuvaRing users had a higher of a contraceptive method (eg, a broken con- incidence of vaginal discomfort and vagini- dom). tis. Even though emergency contraception is Practical considerations. If the ring is out known to be effective and has a low potential of the vagina for more than 3 hours during the for adverse effects, many patients are not pre- first 3 weeks of the cycle, effective contracep- scribed it because their physicians either do tion cannot be guaranteed. The ring should be not know about it or are not comfortable with rinsed with warm water and reinserted within its use. Until recently, the most commonly 3 hours to maintain efficacy. prescribed regimens included: If a woman forgets to remove the ring after • Ethinyl estradiol 2.5 mg twice a day for 5 3 weeks, it will continue to inhibit ovulation days for up to 5 weeks. • Ethinyl estradiol 100 µg and levonorgestrel

692 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 70 • NUMBER 8 AUGUST 2003 Downloaded from www.ccjm.org on September 30, 2021. For personal use only. All other uses require permission. 0.5 mg, repeated in 12 hours ■ : AN EXPERIMENTAL DEVICE • Levonorgestrel 0.75 mg, repeated in 12 FOR SURGERY-FREE STERILIZATION hours Recently, the FDA approved two emer- Currently, the only option for women who gency contraceptive kits. The Preven kit con- want permanent birth control is tubal liga- tains a pregnancy test to exclude pregnancy tion, a surgical procedure that requires anes- before taking the pills, which each contain thesia and several days of recovery. ethinyl estradiol 50 µg and levonorgestrel The Essure device is a mesh embedded in 0.25 mg. The patient takes two pills and coils that causes scar tissue and stricture of the another two in 12 hours. fallopian tubes. It is inserted through a hys- The Plan B kit is similar, but contains teroscope and requires no incision and mini- progestin only, thus causing less nausea and mal anesthesia. This device is awaiting FDA vomiting than regimens that also contain approval and may be available this year. Long- estrogen.46 One tablet of Plan B should be fol- term data are unavailable. lowed by a second dose within 12 hours. These regimens have similar efficacy, ■ THE WOMAN SHOULD CHOOSE THE reducing the number of pregnancies by 89%; RIGHT OPTION FOR HER LIFESTYLE however, if Plan B is taken in the first 24 hours, it can prevent 95% of expected preg- Many effective contraceptive methods offer nancies. both contraceptive and noncontraceptive The most significant side effect of these benefits. Low-dose oral contraceptives are regimens is nausea; therefore, an antiemetic safe, effective, and popular. Injectable, can be prescribed concomitantly. implantable, and transdermal formulations are (Mifeprex; RU-486) in a available for women who have difficulties single 600-mg dose, has higher efficacy than with compliance. Progestin-only contracep- the previously mentioned regimens, as well tive options are alternatives, especially for as a lower incidence of adverse effects.47 women who cannot take or tolerate . However, it is not FDA-approved for emer- The best contraceptive choice for each gency contraceptive use in the United woman is the method that she feels the most States. comfortable with and that suits her lifestyle. A copper IUD also can be used as emer- Women should be educated about the various gency contraception if placed within 120 forms of contraception and encouraged to hours of unprotected intercourse, although choose one that best meets their needs and this is not commonly done in the clinical set- desires. This, in turn, will improve patient sat- ting. isfaction and compliance.

■ REFERENCES

1. Rosenberg MJ, Waugh MS, Long S. Unintended pregnancies and eral density in women using depot medroxyprogesterone acetate use, misuse and discontinuation of oral contraceptives. J Reprod for contraception. Obstet Gynecol 1999; 93:233–238. Med 1995; 40:355–360. 9. Cromer BA, Blair JM, Mahan JD, et al. A prospective comparison of 2. Piccinino LJ, Mosher WD. Trends in contraceptive use in the United bone density in adolescent girls receiving depot medroxyproges- States: 1982–1995. Fam Plann Perspect 1998; 30:4–10,46. terone acetate (Depo-Provera), levonorgestrel (Norplant), or oral 3. Forrest JD, Singh S. The sexual and reproductive behavior of contraceptives. J Pediatr 1996; 129:671–676. American women, 1982–1988. Fam Plann Perspect 1990; 10. Yue QY, Bergquist C, Gerden B. Safety of St John’s wort (Hypericum 22:206–214. perforatum). Lancet 2000; 355:576–577. 4. Forrest JD. Has she or hasn’t she? US women’s experience with con- 11. Dickinson BD, Altman RD, Nielsen NH, Sterling ML. Drug interac- traception. Fam Plann Perspect 1987; 19:133. tions between oral contraceptives and antibiotics. Obstet Gynecol 5. Phillips A, Hahn DW, McGuire JL. Preclinical evaluation of norgesti- 2001; 98:853–860. mate, a progestin with minimal androgenic activity. Am J Obstet 12. Hatcher RA, Guillebaud MA. The pill: combined oral contraceptives. Gynecol 1992; 167:1191–1196. In: Hatcher RA, Trussell J, Stewart F, et al, editors. Contraceptive 6. Vandenbroucke JP, Rosendaal FR. End of the line for “third-genera- Technology. New York: Ardent Media, 1998:405–466. tion-pill” controversy? Lancet 1997; 349:1113–1114. 13. Beral V, Hermon C, Kay C, Hannaford P, Darby S, Reeves G. 7. Van Vliet HA, Grimes DA, Helmerhorst FM, Schulz KF. Biphasic ver- Mortality associated with oral contraceptive use: 25-year followup sus monophasic oral contraceptives for contraception: a Cochrane of cohort of 46,000 women from Royal College of General review. Hum Reprod 2002; 17:870–873. Practitioners’ oral contraception study. BMJ 1999; 318:96–100. 8. Scholes D, Lacroix AZ, Ott SM, Ichikawa LE, Barlow WE. Bone min- 14. Speroff L, Glass RH, Kase NG. Steroid contraception. In: Clinical

CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 70 • NUMBER 8 AUGUST 2003 695 Downloaded from www.ccjm.org on September 30, 2021. For personal use only. All other uses require permission. CONTRACEPTION BATUR AND COLLEAGUES

Gynecologic Endocrinology and Infertility. Baltimore: Williams and and the risk of breast cancer. N Engl J Med 2002; 346:2025–2032. Wilkins, 1983. 32. Grabrick DM, Hartmann LC, Cerhan JR, et al. Risk of breast cancer 15. Narod SA, Risch H, Moslehi R, et al. Oral contraceptives and the risk with oral contraceptive use in women with a family history of of hereditary ovarian cancer. Hereditary Ovarian Cancer Clinical breast cancer. JAMA 2000; 284:1791–1798. Study Group. N Engl J Med 1998; 339:424–428. 33. Coker AL, Harlap S, Fortney JA. Oral contraceptives and reproduc- 16. Modan B, Hartge P, Hirsh-Yechezkel G, et al. Parity, oral contracep- tive cancers: weighing the risks and benefits. Fam Plann Perspect tives, and the risk of ovarian cancer among carriers and noncarriers 1993; 25:17–21,36. of a BRCA1 or BRCA2 mutation. N Engl J Med 2001; 345:235–240. 34. Krattenmacher R. Drospirenone: pharmacology and pharmacokinet- 17. Fernandez E, La Vecchia C, Balducci A, Chatenoud L, Franceschi S, ics of a unique . Contraception 2000; 62:29–38. Negri E. Oral contraceptives and colorectal cancer risk: a meta- 35. Yasmin: an oral contraceptive with a new progestin. Med Lett analysis. Br J Cancer 2001; 84:722–727. Drugs Ther 2002; 44:55–57. 18. Franceschi S, La Vecchia C. Oral contraceptives and colorectal 36. Oelkers W, Foidart JM, Dombrovicz N, Welter A, Heithecker R. tumors. A review of epidemiologic studies. Contraception 1998; Effects of a new oral contraceptive containing an antimineralocorti- 58:335–343. coid progestogen, drospirenone, on the renin-aldosterone system, 19. Pasco JA, Kotowicz MA, Henry MJ, Panahi S, Seeman E, Nicholson body weight, blood pressure, glucose tolerance, and lipid metabo- GC. Oral contraceptives and bone mineral density: a population- lism. J Clin Endocrinol Metab 1995; 80:1816–1821. based study. Am J Obstet Gynecol 2000; 182:265–269. 37. Ludicke F, Johannisson E, Helmerhorst FM, Campana A, Foidart J, 20. Michaelsson K, Baron JA, Farahmand BY, Persson I, Ljunghall S. Heithecker R. Effect of a combined oral contraceptive containing 3 Oral-contraceptive use and risk of hip fracture: a case-control study. mg of drospirenone and 30 microg of ethinyl estradiol on the Lancet 1999; 353:1481–1484. human endometrium. Fertil Steril 2001; 76:102–107. 21. Godsland IF, Crook D, Simpson R, et al. The effects of different for- 38. Mansour D. Yasmin—a new oral contraceptive, a new progestogen: mulations of oral contraceptive agents on lipid and carbohydrate the reasons why. Eur J Contracept Reprod Health Care 2000; 5(suppl metabolism. N Engl J Med 1990; 323:1375–1381. 3):9–16. 22. Chasan-Taber L, Stampfer MJ. Epidemiology of oral contraceptives 39. Ortho Evra: a contraceptive patch. Med Lett Drugs Ther 2002; 44:8. and cardiovascular disease. Ann Intern Med 1998; 128:467–477. 40. Audet MC, Moreau M, Koltun WD, et al. Evaluation of contracep- 23. Rosenberg L, Palmer JR, Lesko SM, Shapiro S. Oral contraceptive tive efficacy and cycle control of a transdermal contraceptive patch use and the risk of myocardial infarction. Am J Epidemiol 1990; vs an oral contraceptive: a randomized controlled trial. JAMA 2001; 131:1009–1016. 285:2347–2354. 24. Cardiovascular disease and steroid hormone contraception: report 41. Kaunitz AM, Garceau RJ, Cromie MA. Comparative safety, efficacy, of a scientific group. Geneva: Switzerland: World Health and cycle control of Lunelle monthly contraceptive injection Organization; 1998. www.who.int/hrp/progress/46/01.html. Accessed (medroxyprogesterone acetate and estradiol cypionate injectable July 9, 2003. suspension) and Ortho-Novum 7/7/7 oral contraceptive (norethin- 25. Spitzer WO, Lewis MA, Heinemann LA, Thorogood M, MacRae KD. drone/ethinyl estradiol triphasic). Lunelle Study Group. Third-generation oral contraceptives and risk of venous throm- Contraception 1999; 60:179–187. boembolic disorders: an international case-control study. 42. Mulders TM, Dieben TO. Use of the novel combined contraceptive Transnational Research Group on Oral Contraceptives and the vaginal ring NuvaRing for ovulation inhibition. Fertil Steril 2001; Health of Young Women. BMJ 1996; 312:83–88. 75:865–870. 26. Effect of different in low-oestrogen oral contracep- 43. Bjarnadottir R, Tuppurainen M, Killick SR. Comparison of cycle con- tives on venous thromboembolic disease. World Health trol with a combined contraceptive vaginal ring and oral levo- Organization Collaborative Study of Cardiovascular Disease and norgestrel/ethinyl estradiol. Am J Obstet Gynecol 2002; 186:389–395. Steroid Hormone Contraception. Lancet 1995; 346:1582–1588. 44. Trussell J. Contraceptive efficacy. In: Hatcher RA, Trussell J, et al, 27. Vandenbroucke JP, Rosing J, Bloemenkamp KW, et al. Oral contra- editors. Contraceptive Technology: 17th revised ed. New York: ceptives and the risk of venous thrombosis. N Engl J Med 2001; Irvington Publishers, 1998. 344:1527–1535. 45. Rogerson L, Duffy S, Crocombe W, Stead M, Dassu D. Management 28. Venous thromboembolic disease and combined oral contraceptives: of menorrhagia: the SMART (Satisfaction with Mirena and Ablation: results of international multicentre case-control study. World a Randomised Trial) study. BJOG 2000; 107:1325–1326. Health Organization Collaborative Study of Cardiovascular Disease 46. Task Force on Postovulatory Methods of Regulation. and Steroid Hormone Contraception. Lancet 1995; 346:1575–1582. Randomised controlled trial of levonorgestrel versus the Yuzpe reg- 29. ACOG Committee on Practice Bulletins-Gynecology. The use of hor- imen of combined oral contraceptives for emergency contraception. monal contraception in women with coexisting medical conditions. Lancet 1998; 352:428–433. Practice Bulletin: No. 18, July, 2000. 47. Webb AM, Russell J, Elstein M. Comparison of , 30. Collaborative Group on Hormonal Factors in Breast Cancer. Breast danazol, and mifepristone (RU486) in oral postcoital contraception. cancer and hormonal contraceptives: collaborative reanalysis of BMJ 1992; 305:927–931. individual data on 53,297 women with breast cancer and 100,239 women without breast cancer from 54 epidemiological studies. ADDRESS: Pelin Batur, MD, Women’s Health Center, A10, The Cleveland Lancet 1996; 347:1713–1727. Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195; e-mail 31. Marchbanks PA, McDonald JA, Wilson HG, et al. Oral contraceptives [email protected].

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