Hormonal Contraception Update
2006; Elsevier BV; Volume: 81; Issue: 7 Linguagem: Inglês
10.4065/81.7.949
ISSN1942-5546
AutoresParu S. David, Elizabeth A. Boatwright, Beverly S. Tozer, Deepa P. Verma, Janis E. Blair, Anita P. Mayer, Julia A. Files,
Tópico(s)Maternal and fetal healthcare
ResumoUnintended pregnancy continues to be a serious public health issue in the United States. Of the 3 million unplanned pregnancies per year, 60% occur in women using some form of contraception. Educating and helping women choose a contraceptive agent that best suits their needs will improve compliance and contraceptive efficacy. A multitude of new contraceptive agents are now available. We review new hormonal contraceptive options and discuss newer oral agents, extended-cycle contraception, and innovative delivery methods. Unintended pregnancy continues to be a serious public health issue in the United States. Of the 3 million unplanned pregnancies per year, 60% occur in women using some form of contraception. Educating and helping women choose a contraceptive agent that best suits their needs will improve compliance and contraceptive efficacy. A multitude of new contraceptive agents are now available. We review new hormonal contraceptive options and discuss newer oral agents, extended-cycle contraception, and innovative delivery methods. Despite considerable advances in contraceptive technologies in the 20th century, unintended pregnancies remain a substantial public health issue in the United States. Among industrialized nations, the United States has the largest proportion of unplanned pregnancies. Of 6 million pregnancies each year, half are unintended, and 60% of these unintended pregnancies occur in women using contraception.1Henshaw SK Unintended pregnancy in the United States.Fam Plann Perspect. 1998; 30 (46.): 24-29Crossref PubMed Scopus (1078) Google Scholar, 2Piccinino LJ Mosher WD Trends in contraceptive use in the United States: 1982-1995.Fam Plann Perspect. 1998; 30 (46.): 4-10Crossref PubMed Scopus (356) Google Scholar The unplanned pregnancies have a bimodal distribution, with 78% occurring in teenagers and 51% in perimenopausal women.3Burkman R The evolution of oral contraceptives: 40 years of continuous improvement.Clinician. 2002; 20: 3-30Google Scholar Nearly 1 of every 2 unplanned pregnancies results in elective abortion.1Henshaw SK Unintended pregnancy in the United States.Fam Plann Perspect. 1998; 30 (46.): 24-29Crossref PubMed Scopus (1078) Google Scholar These statistics clearly highlight the need to improve contraceptive efficacy and compliance. With the advent of the 21st century, women have gained access to a multitude of contraceptive options (Table 1). The goal of this update is to review newer hormonal contraceptive methods to aid the clinician in selecting an appropriate contraceptive method, taking into account the patient's particular preferences.TABLE 1Types of Hormonal Contraception by Type of Delivery Method*EE = ethinyl estradiol.ProgestinTypeProgestin dose (mg)†Efficacy is reduced when used in combination with certain antibiotics and most antiepileptics.4EE dose (μg)†Efficacy is reduced when used in combination with certain antibiotics and most antiepileptics.4Proprietary nameOral contraceptives Norethindrone acetateMonophasic120Junel 21 1/20; Junel Fe 1/20; Loestrin 1/20; Loestrin Fe 1/20Monophasic1.530Junel 21 1.5/30; Junel Fe 1.5/30; Loestrin 1.5/30; Loestrin Fe 1.5/30Estrophasic120Estrostep Fe3035 NorethindroneMonophasic0.435Ovcon 35; Ovcon 35 chewableMonophasic0.535Brevicon; Nortrel 0.5/35Monophasic135Norinyl 1+35; Nortrel 1/35; Ortho-Novum 1/35Monophasic150Ovcon 50Biphasic0.535Ortho-Novum 10/11135Triphasic0.535Aranelle; Tri-Norinyl1350.535Triphasic0.535Ortho-Novum 7/7/70.7535135Progestin only0.35NoneMicronor; Nor-QD LevonorgestrelMonophasic0.120Alesse; Aviane; Lessina; LevliteMonophasic0.1530Levlen; Nordette; PortiaExtended cycle0.1530SeasonaleTriphasic0.0530Enpresse; Tri-Levlen; Triphasil0.075400.12530 NorgestrelMonophasic0.330Cryselle; Lo/OvralMonophasic0.550OvralProgestin only0.075NoneOvrette Ethynodiol diacetateMonophasic135Demulen 1/35Monophasic150Demulen 1/50 DesogestrelMonophasic0.1530Apri; Desogen; Ortho-CeptBiphasic0.1520Kariva; MircetteNone10Triphasic0.125Cyclessa; Velivet0.125250.1525 DrospirenoneMonophasic330YasminMonophasic320Yaz NorgestimateMonophasic0.2535Ortho Cyclen; SprintecTriphasic0.1825Ortho Tri-Cyclen Lo0.215250.2525Triphasic0.1835Ortho Tri-Cyclen; Tri-Sprintec0.215350.2535New delivery methods Medroxyprogesterone acetateInjectable agent104NoneDepo-subQ Provera 104 LevonorgestrelIntrauterine system20 μg‡Represents daily delivered doses. to 10 μg‡Represents daily delivered doses.§Decreases to 10 μg by 5 y.NoneMirena NorelgestrominTransdermal patch150 μg‡Represents daily delivered doses.20 μg‡Represents daily delivered doses.Ortho Evra EtonogestrelVaginal ring120 μg‡Represents daily delivered doses.15 μg‡Represents daily delivered doses.NuvaRing EtonogestrelImplantable device30 μlg‡Represents daily delivered doses.NoneImplanon* EE = ethinyl estradiol.† Efficacy is reduced when used in combination with certain antibiotics and most antiepileptics.4Brunton LL Lazo JS Parker K Goodman & Gilman's The Pharmacological Basis of Therapeutics. 11th ed. McGraw-Hill, New York2006Google Scholar‡ Represents daily delivered doses.§ Decreases to 10 μg by 5 y. Open table in a new tab In 1960, the first oral contraceptive (OC) was approved by the US Food and Drug Administration (FDA).3Burkman R The evolution of oral contraceptives: 40 years of continuous improvement.Clinician. 2002; 20: 3-30Google Scholar It contained 150-μg mestranol and 9.5-mg norethynodrel. Although it provided effective cycle control and contraception, women experienced many adverse effects, including weight gain, breast tenderness, bloating, and acne. By 1968, the high incidence of serious adverse health effects (eg, deep venous thrombosis, pulmonary embolism, and hypertension) led to a reduction in the estrogen dose to 50 μg.3Burkman R The evolution of oral contraceptives: 40 years of continuous improvement.Clinician. 2002; 20: 3-30Google Scholar By 1970, formulations with ethinyl estradiol (EE) doses as low as 20 μg were introduced. Although they reduced estrogen-related adverse effects, they also led to increased rates of breakthrough bleeding (BTB), as the dose of estrogen is directly related to the degree of endometrial support. The challenge is to balance the tendency toward BTB with the dose-dependent adverse effects of estrogen. In the past 2 decades, OCs with lower EE doses have been developed. Formulations can be found with EE doses as high as 50 μg and as low as 20 μg, but most are in the 30- to 35-μg dose range. Two newer OCs contain a unique dose of 25-μg EE using either triphasic norgestimate (NGM) or triphasic desogestrel (DSG). They provide both the reduced estrogenic effects of the 20-μg EE formulations and the better bleeding profiles of the 30- to 35-μg EE formulations. 5Hampton RM Short M Bieber E et al.Comparison of a novel norgestimate/ethinyl estradiol oral contraceptive (Ortho Tri-Cyclen Lo) with the oral contraceptive Loestrin Fe 1/20.Contraception. 2001; 63: 289-295Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar, 6Kaunitz AM Efficacy, cycle control, and safety of two triphasic oral contraceptives: Cyclessa (desogestrel/ethinyl estradiol) and ortho-Novum 7/7/7 (norethindrone/ethinyl estradiol): a randomized clinical trial.Contraception. 2000; 61: 295-302Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar Both NGM and DSG have comparable safety and contraceptive efficacy, acceptable bleeding profiles, superior cycle control, and acceptable tolerability. The more potent and selective progestins used in these 2 formulations in a cyclic fashion allow further reductions in estrogen without sacrificing cycle control.5Hampton RM Short M Bieber E et al.Comparison of a novel norgestimate/ethinyl estradiol oral contraceptive (Ortho Tri-Cyclen Lo) with the oral contraceptive Loestrin Fe 1/20.Contraception. 2001; 63: 289-295Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar, 6Kaunitz AM Efficacy, cycle control, and safety of two triphasic oral contraceptives: Cyclessa (desogestrel/ethinyl estradiol) and ortho-Novum 7/7/7 (norethindrone/ethinyl estradiol): a randomized clinical trial.Contraception. 2000; 61: 295-302Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar Unlike estrogens, progestins alone are sufficient for contraception.7Marshall J Progestins in oral contraceptives: a comparative review.Female Patient. 2003; 28: 32-38Google Scholar They suppress ovulation, thicken cervical mucus, and render the endometrium unsuitable for implantation of fertilized ovum. In conjunction with estrogen, they contribute to cycle control, changing proliferative endometrium to secretory endometrium. However, progestins are associated with androgenic sequelae, including acne, hirsutism, weight gain, and deleterious effects on lipid and carbohydrate metabolism.7Marshall J Progestins in oral contraceptives: a comparative review.Female Patient. 2003; 28: 32-38Google Scholar These adverse effects led to the development of newer, more selective, and less androgenic progestins that could be used in lower doses. Initially, the progestins in OCs included norethindrone and its derivatives (eg, norethindrone acetate), levonorgestrel (LNG) and its derivatives, and medroxyprogesterone acetate. They have relatively low progesterone-receptor selectivity and therefore greater systemic androgenic activity. Dose reductions ameliorated unwanted androgenic adverse effects but also affected cycle control. This has led to the development of more selective, less androgenic progestins (eg, NGM, DSG, and drospirenone [DRSP]). Norgestimate is a 19-nortestosterone derivative with relatively high progesterone-receptor selectivity that suppresses ovulation at doses lower than natural progesterone.7Marshall J Progestins in oral contraceptives: a comparative review.Female Patient. 2003; 28: 32-38Google Scholar It has minimal androgenicity, thus having little impact on carbohydrate metabolism. In addition, NGM does not reduce the favorable effects of estrogen on lipids; OCs containing NGM increase high-density lipoprotein cholesterol, reduce low-density lipoprotein cholesterol, and minimally increase triglycerides.7Marshall J Progestins in oral contraceptives: a comparative review.Female Patient. 2003; 28: 32-38Google Scholar The primary active metabolite of oral NGM is norelgestromin, which is currently used transdermally. It has clinical effects similar to those of NGM.7Marshall J Progestins in oral contraceptives: a comparative review.Female Patient. 2003; 28: 32-38Google Scholar Desogestrel is a 19-nortestosterone derivative, and it has minimal androgenicity. Its active metabolite, etonogestrel, is contained in a contraceptive vaginal ring. Compared with NGM, DSG has slightly higher affinity for androgen receptors and slightly less affinity for progesterone receptors; overall, it is less androgenic than LNG.7Marshall J Progestins in oral contraceptives: a comparative review.Female Patient. 2003; 28: 32-38Google Scholar It provides good cycle control and has minimal effects on carbohydrate metabolism. Like NGM, DSG provides minimal attenuation of estrogen's beneficial effects on lipids. However, DSG increases triglycerides slightly more than NGM.7Marshall J Progestins in oral contraceptives: a comparative review.Female Patient. 2003; 28: 32-38Google Scholar There may be increased risk of venous thrombotic events in patients who use DSG-containing OCs. Data from epidemiological studies suggest an approximate 2-fold increased risk of venous thrombotic events in users of OCs that contain DSG vs other second- and third-generation progestins.8Jick H Kaye JA Vasilakis-Scaramozza C Jick SS Risk of venous thromboembolism among users of third generation oral contraceptives compared with users of oral contraceptives with levonorgestrel before and after 1995: cohort and case-control analysis.BMJ. 2000; 32: 1190-1195Crossref Scopus (183) Google Scholar However, it is not known whether the formulation of 25-μg EE with DSG is associated with an increased number of venous thrombotic events.8Jick H Kaye JA Vasilakis-Scaramozza C Jick SS Risk of venous thromboembolism among users of third generation oral contraceptives compared with users of oral contraceptives with levonorgestrel before and after 1995: cohort and case-control analysis.BMJ. 2000; 32: 1190-1195Crossref Scopus (183) Google Scholar Drospirenone is a novel progestin that has been available for clinical use in the United States since June 2001. An analogue of 17-α-spironolactone, DRSP has antimineralocorticoid activity comparable with that of natural progesterone. Drospirenone is less androgenic than older progestins because it counteracts estrogen-induced stimulation of the renin-angiotensin-aldosterone system and blocks testosterone from binding to androgen receptors.9Muhn P Fuhrmann U Fritzemeier KH Krattenmacher R Schillinger E Drospirenone: a novel progestogen with antimineralocorticoid and antiandrogenic activity.Ann N Y Acad Sci. 1995; 761: 311-335Crossref PubMed Scopus (131) Google Scholar Because DRSP is a spironolactone analogue, it may have natriuretic properties and may increase serum potassium levels. Thus, patients with concomitant medical problems who receive pharmacologic therapy may require additional monitoring. Contraindications include renal insufficiency, hepatic dysfunction, and adrenal insufficiency. Women should avoid this progestin if they are taking medications that can increase serum potassium levels (eg, nonsteroidal anti-inflammatory agents, potassium-sparing diuretics, potassium, angiotensin-converting enzyme inhibitors, and angiotensin-II receptor antagonists).3Burkman R The evolution of oral contraceptives: 40 years of continuous improvement.Clinician. 2002; 20: 3-30Google Scholar A 3-mg DRSP and 30-μg EE formulation has been in clinical use since 2001. A recently approved 3-mg DRSP and 20-μg EE has the unique feature of a 24/4-day format in contrast to the standard 21/7-day format. Rationale for this format stems from emerging evidence that using OCs containing 20-μg EE combined with the newer progestins results in a greater chance of ovulation and pregnancy if the active pills are not restarted within exactly 7 days after the last active pill was taken. Decreasing the duration of the hormone-free interval may also lessen the adverse symptoms some women experience during this time.10Mishell Jr, DR Rationale for decreasing the number of days of the hormone-free interval with use of low-dose oral contraceptive formulations.Contraception. 2005; 71: 304-305Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar Triphasic OCs were developed to reduce the overall progestin dose while still providing effective cycle control and avoiding endometrial proliferation. The per-cycle dose of progestin for the triphasic formulation is generally 0.6 to 0.9 times that of the monophasic product. The4Brunton LL Lazo JS Parker K Goodman & Gilman's The Pharmacological Basis of Therapeutics. 11th ed. McGraw-Hill, New York2006Google Scholar triphasic formulations available in the United States all contain EE and 1 of 4 progestins (norethindrone, NGM, LNG, or DSG). In the limited studies available, there appears to be no significant difference between monophasic and triphasic regimens with regard to BTB, side effects profile, and lipid and carbohydrate metabolism.11Cedars MI Triphasic oral contraceptives: review and comparison of various regimens.Fertil Steril. 2002; 77: 1-14Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar One study identified increased libido and sexual arousal in women using triphasic OCs compared with women using monophasic OCs.12McCoy NL Matyas JR Oral contraceptives and sexuality in university women.Arch Sex Behav. 1996; 25: 73-90Crossref PubMed Scopus (77) Google Scholar Oral contraceptives were originally designed to mimic the menstrual cycle by producing a monthly withdrawal bleed, and the traditional “Sunday start” allowed women to avoid menstruating on weekends. As early as the 1970s, researchers established that women wanted to control the timing of their menstrual cycles.13Louden NB Foxwell M Potts DM Guild AL Short RV Acceptability of an oral contraceptive that reduces the frequency of menstruation: the tri-cycle pill regimen.BMJ. 1977; 2: 487-490Crossref PubMed Scopus (125) Google Scholar More recent studies have echoed these findings. A Dutch telephone survey of 1279 women found that most women would choose to menstruate less than once a month.14den Tonkelaar I Oddens BJ Preferred frequency and characteristics of menstrual bleeding in relation to reproductive status, oral contraceptive use, and hormone replacement therapy use.Contraception. 1999; 59: 357-362Abstract Full Text Full Text PDF PubMed Scopus (169) Google Scholar A Harris poll conducted in 2002 found that 1 in 4 respondents considered menstruation to have a negative impact on important aspects of their lives and that 44% preferred to never menstruate.15Association of Reproductive Health Professionals Extended and Continuous Use of Contraceptives to Reduce Menstruation. ARHP Clinical Proceedings.Available at: www.arhp.org/healthcareproviders/cme/onlinecme/ReduceMensesCP/TOC.cfmDate: September 2004Google Scholar Overall, many women expressed interest in having less frequent periods. Women who use OCs also may experience unpleasant symptoms or exacerbation of underlying medical conditions during the hormone-free interval of the OC cycle.16Sulak PJ Scow RD Preece C Riggs MW Kuehl TJ Hormone withdrawl symptoms in oral contraceptive users.Obstet Gynecol. 2000; 95: 261-266Crossref PubMed Scopus (273) Google Scholar For this reason, investigators evaluated the safety and efficacy of extending the active pill cycle to decrease the number of withdrawal bleeds. A 2002 study demonstrated that extending the active-pill cycle to 6 to 12 weeks, followed by a 7-day pill-free interval, led to substantial alleviation of menstrual-related complaints and fewer reported adverse effects. Minor adverse effects included mastalgia, bloating, and headache.17Sulak PJ Kuehl TJ Ortiz M Shull BL Acceptance of altering the standard 21-day/7-day oral contraceptive regimen to delay menses and reduce hormone withdrawal symptoms.Am J Obstet Gynecol. 2002; 186: 1142-1149Abstract Full Text Full Text PDF PubMed Scopus (147) Google Scholar In clinical practice, the most common way to provide extended-cycle contraception is to modify the standard use of monophasic OCs. Patients use active pills continuously for 84 days followed by 1 week of inactive pills, which induces a withdrawal bleed approximately 4 times a year. This strategy has been effective with monophasic OCs. Until recently, the use of extended-cycle contraception presented challenges related to packaging issues and insurance reimbursement constraints. In 2003, the FDA approved a prepackaged extended-cycle monophasic OC regimen (84/7 days) containing 30-μg EE and 0.15-mg LNG.18US Food and Drug Administration FDA Approves Seasonale Oral Contraceptive.Available at: www.fda.gov/bbs/topics/ANSWERS/2003/ANS01251.htmlDate: September 5, 2003Google Scholar The largest trial of extended-cycle oral contraception was conducted with this product.19Anderson FD Hait H A multicenter, randomized study of an extended cycle oral contraceptive [published correction appears in Contraception. 2004; 69:175.Contraception. 2003; 68: 89-96Abstract Full Text Full Text PDF PubMed Scopus (253) Google Scholar That study showed that this product was as effective in pregnancy prevention as the conventional therapy (21/7 days), with no difference in duration of withdrawal bleeding. In some patients, unscheduled bleeding with extended-cycle use declined with successive cycles.19Anderson FD Hait H A multicenter, randomized study of an extended cycle oral contraceptive [published correction appears in Contraception. 2004; 69:175.Contraception. 2003; 68: 89-96Abstract Full Text Full Text PDF PubMed Scopus (253) Google Scholar Extended-cycle contraception now offers women fewer menstrual cycles, ease of administration, and convenient packaging. The active ingredient in a new subcutaneous contraceptive is 104-mg medroxyprogesterone acetate (DMPA-104) available in an injectable suspension. It was approved by the FDA in 2004. In contrast to the original intramuscular version, which contained 150-mg medroxyprogesterone acetate, DMPA-104 comes in prefilled syringes that can be clinician- or self-administered subcutaneously in the thigh or abdomen every 12 to 14 weeks. No dosage adjustment is needed for body weight. DMPA-104 prevents pituitary gonadotropin secretion to inhibit maturation of follicles, thereby inhibiting ovulation. Many women using DMPA-104 will experience altered menstrual bleeding, including heavy bleeding, irregular spotting, irregular menses, and amenorrhea. In contraception trials, 39% of women using DMPA-104 had amenorrhea in the sixth month, and 56.5% had amenorrhea at 1 year.20Pfizer Physician information: depo-subQ provera 104™ medroxyprogesterone acetate injectable suspension.Available at: www.pfizer.com/pfizer/download/uspi_depo_subq_provera.pdfGoogle Scholar By suppressing gonadotropins, DMPA-104 also suppresses estrogen concentration, making it an effective treatment of endometriosis. A serious consequence of the estrogen suppression observed with DMPA-104 is loss of bone mineral density. For this reason, long-term use (>2 years) of DMPA-104 also requires calcium and vitamin D supplementation and may require monitoring of bone mineral density. Bone mineral density seems to improve in women 17 to 39 years of age after discontinuation of DMPA-104; however, bone loss may not be entirely reversible. The long-term effect of DMPA-104 on bone density in young adolescents (ages 14-16) is less clear and requires further study.21Scholes D LaCroix AZ Ichikawa LE Barlow WE Ott SM Injectable hormone contraception and bone density: results from a prospective study [published correction appears in Epidemiology. 2002;13:749].Epidemiology. 2002; 13: 581-587Crossref PubMed Scopus (150) Google Scholar, 22Bonny AE Harkness LS Cromer BA Depot medroxyprogesterone acetate: implications for weight status and bone mineral density in the adolescent female.Adolesc Med Clin. 2005; 16: 569-584Crossref PubMed Scopus (12) Google Scholar Additional factors to consider when prescribing DMPA-104 are mood disorders and fertility issues. Patients with a history of depression who take DMPA-104 should be monitored for recurrence. There is also a delay of fertility after injections are stopped: median time to ovulation is 10 months, earliest time to ovulation is 6 months, with 80% of women treated with DMPA-104 ovulating by 1 year.20Pfizer Physician information: depo-subQ provera 104™ medroxyprogesterone acetate injectable suspension.Available at: www.pfizer.com/pfizer/download/uspi_depo_subq_provera.pdfGoogle Scholar Long-term use of DMPA-104 should be considered only after a risk-benefit analysis and only when other methods are inadequate.20Pfizer Physician information: depo-subQ provera 104™ medroxyprogesterone acetate injectable suspension.Available at: www.pfizer.com/pfizer/download/uspi_depo_subq_provera.pdfGoogle Scholar Worldwide, intrauterine contraception is a widely accepted contraceptive method,23Rivera R Best K Current opinion: consensus statement on intrauterine contraception.Contraception. 2002; 65: 385-388Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar but it has never attained great popularity in the United States. Although intrauterine devices have been available for 50 years, fewer than 1% of US women use intrauterine contraception.23Rivera R Best K Current opinion: consensus statement on intrauterine contraception.Contraception. 2002; 65: 385-388Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar In 2000, the FDA approved an LNG-releasing intrauterine system (LNG IUS), the only hormonal intrauterine device available. The LNG IUS releases 20-μg LNG per day, decreasing to approximately 10 μg by 5 years. The LNG IUS is inserted by a clinician and remains effective for 5 years.24Mirena [package insert]. Berlex Laboratories, Montville, NJ2000Google Scholar This contraceptive method has an efficacy rate of 99.7% and has the additional benefit of suppressing the endometrial lining, thus decreasing menstrual flow.25Hidalgo M Bahamondes L Perrotti M Diaz J Danatas-Monteiro C Petta C Bleeding patterns and clinical performance of the levonorgestrel-releasing intrauterine system (Mirena) up to two years.Contraception. 2002; 65: 129-132Abstract Full Text Full Text PDF PubMed Scopus (193) Google Scholar Endometrial atrophy occurs as a consequence of the high endometrial levels of LNG and results in a high rate of amenorrhea. Twenty percent of women have cessation of menses after 1 year.25Hidalgo M Bahamondes L Perrotti M Diaz J Danatas-Monteiro C Petta C Bleeding patterns and clinical performance of the levonorgestrel-releasing intrauterine system (Mirena) up to two years.Contraception. 2002; 65: 129-132Abstract Full Text Full Text PDF PubMed Scopus (193) Google Scholar The LNG IUS is an excellent contraceptive option for women experiencing menorrhagia, including those in the perimenopausal transition.26Association of Reproductive Health Professionals New Developments in Intrauterine Contraception. ARHP Clinical Proceedings.Available at: http://www.arhp.org/healthcareproviders/cme/onlinecme/IUDCP/TOC.cfmDate: September 2004Google Scholar The transdermal contraceptive patch, approved for use in the United States in 2001, delivers continuous daily doses of 150-μg norelgestromin and 20-μg EE. One patch is applied weekly for 3 weeks, followed by a patch-free week.27Audet MC Moreau M Koltun WD ORTHO EVRA/EVRA 004 Study Group et al.Evaluation of contraceptive efficacy and cycle control of a transdermal contraceptive patch vs an oral contraceptive: a randomized controlled trial.JAMA. 2001; 285: 2347-2354Crossref PubMed Scopus (305) Google Scholar Compliance with the patch is superior to that for OCs; however, the adverse effects profiles of both agents are similar.27Audet MC Moreau M Koltun WD ORTHO EVRA/EVRA 004 Study Group et al.Evaluation of contraceptive efficacy and cycle control of a transdermal contraceptive patch vs an oral contraceptive: a randomized controlled trial.JAMA. 2001; 285: 2347-2354Crossref PubMed Scopus (305) Google Scholar In November 2005, the FDA updated labeling of the patch with a boldfaced warning to alert clinicians and patients that this product exposes women to higher levels of estrogen than most OCs. Currently, the clinical implications of this increased estrogen exposure are unknown.28US Food and Drug Administration FDA Updates Labeling for Ortho Evra Contraceptive Patch.Available at: www.fda.gov/bbs/topics/news/2005/NEW01262.htmlGoogle Scholar The transdermal patch is highly efficacious in women weighing less than 90 kg, whereas there is an increased risk of pregnancy in women exceeding that weight. The patch has been reported to have no effect on body weight29Sibai BM Odlind V Meador ML Shangold GA Fisher AC Creasy GW A comparative and pooled analysis of the safety and tolerability of the contraceptive patch (Ortho Evra/Evra).Fertil Steril. 2002; 77: S19-S26Abstract Full Text Full Text PDF PubMed Google Scholar or lipid profiles.30Creasy G Fisher A Hall N Shangold G Effect of a contraceptive patch vs. placebo (PBO) on serum lipid profile [abstract].Fertil Steril. 2000; 74: S185Abstract Full Text Full Text PDF Google Scholar The adhesiveness of the patch is excellent; the need for early replacement is less than 3% and is usually related to environmental factors or exercise.31Zacur HA Hedon B Mansour D Shangold GA Fisher AC Creasy GW Integrated summary of Ortho Evra/Evra contraceptive patch adhesion in varied climates and conditions.Fertil Steril. 2002; 77: S32-S35Abstract Full Text Full Text PDF PubMed Google Scholar Reactions at the site of application occur in as many as 20% of users, but only 2.6% subsequently discontinue use.29Sibai BM Odlind V Meador ML Shangold GA Fisher AC Creasy GW A comparative and pooled analysis of the safety and tolerability of the contraceptive patch (Ortho Evra/Evra).Fertil Steril. 2002; 77: S19-S26Abstract Full Text Full Text PDF PubMed Google Scholar Within the first few months, BTB is higher than that observed with OCs but decreases over time to a similar rate.27Audet MC Moreau M Koltun WD ORTHO EVRA/EVRA 004 Study Group et al.Evaluation of contraceptive efficacy and cycle control of a transdermal contraceptive patch vs an oral contraceptive: a randomized controlled trial.JAMA. 2001; 285: 2347-2354Crossref PubMed Scopus (305) Google Scholar The patch is an excellent option for women who find it difficult to comply with a daily pill-taking regimen. The vaginal ring, approved in 2001 by the FDA, is a novel technology designed to release daily doses of 120-μg etonogestrel, the active metabolite of DSG, and 15-μg EE through a flexible ring inserted vaginally. The hormones are absorbed through the vaginal epithelium, bypassing the first-pass effect on the liver. Serum concentrations of hormones are lower for women using a vaginal ring than those observed with OCs. The ring is flexible and transparent, with an outer diameter of 54 mm. It can be easily inserted and removed by the patient and is well tolerated by patients and their partners. Efficacy does not depend on exact placement of the ring. It is inserted once per cycle and remains in place for 3 weeks. It is then removed for the last 7 days of the cycle, at which point menses occurs. After 7 days, a new ring is inserted to initiate the next cycle. The vaginal ring provides good cycle control, with BTB reported in less than 1.1% of cycles.32Roumen FJ Apter D Mulders TM Dieben TO Efficacy, tolerability and acceptability of a novel contraceptive vaginal ring releasing etonogestrel and ethinyl oestradiol.Hum Reprod. 2001; 16: 469-475Crossref PubMed Scopus (255) Google Scholar Cost should be considered when prescribing this form of contraception because it may cost twice as much as an OC.33Association of Reproductive Health Professionals Periodic WellWoman Visit: Individualized Contraceptive Care. ARHP Clinical Proceedings.Available at: www.arhp.org/healthcareproviders/cme/onlinecme/wellwoman/TOC.cfm?ID=336Date: May 2004Google Scholar The most common reasons for discontinuation are menstrual irregularities and device expulsion.32Roumen FJ Apter D Mulders TM Dieben TO Efficacy, tolerability and acceptability of a novel contraceptive vaginal ring releasing etonogestrel and ethinyl oestradiol.Hum Reprod. 2001; 16: 469-475Crossref PubMed Scopus (255) Google Scholar Ongoing research is evaluating the ring in extended use for 6 weeks, 12 weeks, or 12 months of continuous use.34Reape KZ Current contraceptive research and development.Adolesc Med Clin. 2005; 16: 617-633Crossref PubMed Scopus (10) Google Scholar The vaginal ring offers an excellent option for women who are concerned about compliance with a daily pill-taking regimen and want to avoid barrier contraception or a visible transdermal patch. A new implantable form of contraception containing 68-mg etonogestrel is currently available in most countries and is expected to be available in the United States soon. The implant, which lasts for 3 years, prevents pregnancy by inhibiting ovulation and altering cervical mucus, which impedes the passage of sperm. Within 1 day of insertion, the implant produces a concentration of etonogestrel adequate enough to inhibit ovulation. In clinical trials, women had no ovulations during the first 2 years and only rarely in the third year.35Implanon. NV Organon; c2004.Available at: www.implanon.comGoogle Scholar Lower concentrations of etonogestrel have been found in obese patients; therefore, heavier women may need a new implant every 2 years. The implant has no significant effect on bone mineral density or lipid metabolism. Since the etonogestrel implant is not biodegradable, it must be removed before insertion of a new one. It can be inserted subdermally on days 1 to 5 of the cycle but cannot be inserted after day 5. If the patient is currently taking OCs, the etonogestrel implant can be inserted on the first day of placebo pills but no later than the last day. A 3-month follow-up is recommended to evaluate blood pressure and address any questions from the patient. Frequent or prolonged irregular bleeding is a common reason for discontinuation. However, in one study, 29% to 51% of women using the etonogestrel implant experienced infrequent bleeding or amenorrhea.35Implanon. NV Organon; c2004.Available at: www.implanon.comGoogle Scholar Of those who initially experienced dysmenorrhea, 85% had improvement in symptoms after insertion of the implant. Of women who had acne at the beginning of the study, 59% reported that use of the etonogestrel implant improved or resolved the acne.35Implanon. NV Organon; c2004.Available at: www.implanon.comGoogle Scholar Cycles usually return to normal within 3 months of removal. Contraindications are similar to those for any progestin-only form of contraception: pregnancy, severe hepatic disease, undiagnosed uterine bleeding, or hypersensitivity to the formulation. This form of contraception should be considered in women who have a contraindication to estrogen.35Implanon. NV Organon; c2004.Available at: www.implanon.comGoogle Scholar Many of the new contraception technologies are highly accepted by patients and clinicians because of improved tolerability and adverse effects profiles, reversibility, ease of use, and the desire for less frequent dosing while maintaining high levels of efficacy. These factors have driven the trend for continued research in the field of contraception. Several products are either in phase 3 trials or in the new drug application stage with the FDA. An OC in the new drug application stage is a 91-day extended regimen of 84 days of 150-μg LNG and 30-μg EE followed by 7 days of 10-μg EE. Oral contraceptives in phase 3 trials include an 84/7 regimen of 100-μg LNG and 20-μg EE, a product with the progestin dienogest combined with estradiol targeted for perimenopausal women, and a continuous regimen for use up to 1 year with 100-μg LNG and 20-μg EE. A new weekly transdermal patch in phase 3 trials contains the progestin gestodene combined with EE.34Reape KZ Current contraceptive research and development.Adolesc Med Clin. 2005; 16: 617-633Crossref PubMed Scopus (10) Google Scholar Contraception is an important topic for women of reproductive age. An armamentarium of agents is available toprovide a menu of contraceptive options. With effective counseling, women can make informed decisions and select contraception that is safe, effective, and convenient and that has a low adverse effects profile (Table 2). Clinicians providing primary care to women must be well informed about the various hormonal contraceptive options and work with each patient to find her optimal regimen.TABLE 2Characteristics of Different Types of Hormonal Contraceptives*IUS = intrauterine system.CharacteristicMethodEfficaciousOffice visits requiredEasily reversibleDosing frequencyUser controlledDiscreetRapid return to fertilityOralYesPrescriptionYesDailyYesYesYesInjectableYesPrescription†Can be clinician- or self-administered every 3 mo.YesEvery 3 moNoYesSlight delayRingYesPrescriptionYesMonthlyYesYesYesPatchYesPrescriptionYesWeeklyYesSometimesYesIUSYesEvery 5 yYesEvery 5 yNoYesYesImplantYesEvery 3 yYesEvery 3 yNoSometimesYes* IUS = intrauterine system.† Can be clinician- or self-administered every 3 mo. Open table in a new tab
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