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Update on Contraception: Benefits and Risks of the New Formulations

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Update on Contraception: Benefits and Risks of the New Formulations 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 pregnancies in the dose oral contraceptives as well as injectable, vaginal, and United States each year; half end in abortion.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 vaginal ring, the Mirena intrauterine device, 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 estrogen pregnancy 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 sterilization. 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 contraceptive patch 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 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 70 • NUMBER 8 AUGUST 2003 681 Downloaded from www.ccjm.org on September 30, 2021. For personal use only. All other uses require permission. CONTRACEPTION BATUR AND COLLEAGUES T ABLE 1 Monophasic oral contraceptives PRODUCTS ESTROGEN PROGESTIN Necon 1/50, Nelova 1/50 M, Mestranol 50 µg Norethindrone 1.0 mg Norinyl 1+50, Ortho-Novum 1/50 Demulen 1/50, Zovia 1/50 Ethinyl estradiol 50 µg Ethynodiol diacetate 1.0 mg Ovral, Ogestrel Ethinyl estradiol 50 µg Norgestrel 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 Norgestimate 0.25 mg Apri, Desogen, Ortho-Cept Ethinyl estradiol 30 µg Desogestrel 0.15 mg Yasmin Ethinyl estradiol 30 µg Drospirenone 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 Levonorgestrel 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 androgen 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 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 70 • NUMBER 8 AUGUST 2003 685 Downloaded from www.ccjm.org on September 30, 2021. For personal use only. All other uses require permission. CONTRACEPTION BATUR AND COLLEAGUES 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.
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