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ORIGINAL RESEARCH |
From private practice clinics in Nashville, Tennessee; Bend, Oregon; Tacoma, Washington; and the R.W. Johnson Pharmaceutical Research Institute, Raritan, New Jersey.
Address reprint requests to: George W. Creasy, MD, The R.W. Johnson Pharmaceutical Research Institute, 920 Route 202, PO Box 300, Raritan, NJ 08869; E-mail: gcreasy{at}prius.jnj.com.
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ABSTRACT |
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 ABSTRACT MATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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METHODS: In this open-label, 73-center study, 1672 healthy, ovulatory, sexually active women received ORTHO EVRA/EVRA for six (n = 1171) or 13 cycles (n = 501). The treatment regimen for each cycle was three consecutive 7-day patches (21 days) followed by 1 patch-free week.
RESULTS: The overall and method-failure probabilities of pregnancy through 13 cycles were 0.7% and 0.4%, respectively. The incidence of breakthrough bleeding was low throughout the study. Perfect compliance (21 consecutive days of dosing, followed by a 7-day drug-free interval; no patch could be worn for more than 7 days) was achieved in 90% of subject cycles; only 1.9% of patches detached completely. Adverse events were typical of hormonal contraception, and most were mild-to-moderate in severity and not treatment limiting. The most common adverse events resulting in discontinuation were application site reactions (1.9%), nausea (1.8%), emotional lability (1.5%), headache (1.1%), and breast discomfort (1.0%).
CONCLUSIONS: The transdermal contraceptive patch provides effective contraception and cycle control, and is well tolerated. The weekly change schedule for the contraceptive patch is associated with excellent compliance and wearability characteristics.
Hormonal contraception is used by over 100 million women worldwide,1 and by over 12 million women in the United States.2,3 The introduction of lower-dose combination oral contraceptives (OCs) (<50 µg ethinyl estradiol) has provided many women a highly effective, safe, and tolerable method of contraception. However, the 1995 National Survey of Family Growth (NSFG) (US data) estimated that the failure rates of OCs were as high as 8.3% during the first year of typical use.4 This rate of failure is quite different from failure rates of 0.1% observed in clinical trials in which OCs were used correctly and consistently.5 Noncompliance is the primary reason cited for the difference between these rates.6–8 Although OCs provide effective birth control when used correctly, there is a need for effective, readily reversible hormonal contraception that will enhance user compliance by providing a simpler dosing schedule.
Transdermal systems for the delivery of estrogens and estrogen–progestin combinations have been developed for hormone replacement therapy.9,10 Until recently, the transdermal delivery of sufficient amounts of progestin and estrogen for effective contraception had not been possible. A new transdermal contraceptive patch (OR-THO EVRA (US trademark)/EVRA (worldwide trademark) containing norelgestromin (formerly known as 17-deacetyl norgestimate), the active metabolite of norgestimate, and ethinyl estradiol has been developed by The R.W. Johnson Pharmaceutical Research Institute, Raritan, NJ. The combination of norgestimate and ethinyl estradiol has been used effectively in leading OCs worldwide for nearly 10 years and has a favorable tolerability and safety profile.11–14
A weekly transdermally delivered hormonal contraceptive has the advantage of providing greater user convenience and the potential for superior user compliance compared with daily OC regimens. Unlike longer-acting injectable and implantable methods, the use of a contraceptive patch does not require administration by a health care provider, and the method is readily reversible. In addition, the contraceptive patch delivers continuous levels of progestin and estrogen directly to the peripheral circulation, avoiding the interference of absorption due to gastrointestinal disturbances, and eliminating the daily peaks and troughs that result from oral dosing.( Abrams LS, Skee D, Natarajan J, Lasseter KC, Wong F. Dose proportionality study of a contraceptive patch [abstract]. Clin Pharmacol Ther 2000;67:105. Abrams LS, Skee D, Bridson WE, Wong F. Pharmacokinetics of a contraceptive patch [abstract]. Clin Pharmacol Ther 2000;67:106. Abrams LS, Skee DM, Natarajan J, Wong FA, Anderson GD. Pharmacokinetics of a contraceptive patch (EvraTM/Ortho EvraTM) containing norelgestromin and ethinyl estradiol at four application sites [abstract]. Brit J Clin Pharmacol (in press). Abrams LS, Skee DM, Wong FA, Anderson NJ, Leese PT. Pharmacokinetics of norelgestromin and ethinyl estradiol from two consecutive contraceptive patches. J Clin Pharmacol (in press).)
The objectives of this large, open-label, international, noncomparative study were to evaluate the contraceptive efficacy, cycle control, compliance, and safety profile of the contraceptive patch in a large number of healthy, ovulatory, sexually active women.
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MATERIALS AND METHODS |
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ABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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A total of 1754 healthy women aged 18–45 years were enrolled and were to receive the contraceptive patch; 1672 subjects had available data and were evaluable for safety. Of these 1672 subjects, 1171 were to receive six cycles of treatment, and 501 were to receive 13 cycles of treatment. Contraceptive method at the time of enrollment was recorded. The women had to be sexually active and at risk of pregnancy, have regular menstrual cycles, have at least one normal menstrual cycle since their last pregnancy or since the removal of an intrauterine device or Norplant (if applicable), have a negative serum ß-human chorionic gonadotropin (ß-hCG) pregnancy test at screening and a negative urine pregnancy test at admission, have seated systolic/diastolic blood pressure less than 140/90 mmHg, be within 35% of ideal body weight,16 agree to use only the assigned study drug as contraception and not to use any other steroid hormonal therapy other than topical corticosteroids, and provide written informed consent. Exclusion criteria included lactation or pregnancy within 42 days of study admission, any disorders that were contraindications to steroid hormone therapy, uncontrolled thyroid disorder, Papanicolaou smear evidence of squamous intraepithelial lesions or adenocarcinoma or other malignancy, history or presence of dermal hypersensitivity in response to topical application, smoking in subjects over 35 years of age, alcohol or substance abuse within the previous 12 months, receipt of Depo-Provera within 6 months of screening, and receipt of any experimental drug, device, or hepatic enzyme–inducing drugs within 30 days of screening.
The matrix patch is thin, and consists of three layers: an outer protective layer of polyester; a medicated, adhesive middle layer; and a clear, polyester release liner that is removed before patch application. Subjects applied the patch on any of four anatomic sites (buttocks, upper outer arm, lower abdomen, or upper torso excluding breast). New patches could be applied to sites near the patch that was removed, but not to the same site as the preceding patch. Subjects could maintain their normal daily activities such as bathing, swimming, and exercising while wearing the patch, but were instructed not to apply oils, creams, or cosmetics on or around the area of patch placement. Subjects were instructed to apply the patch on the same day of each week (one patch per week) for 3 consecutive weeks, followed by 1 patch-free week. The patch has been shown to deliver norelgestromin and ethinyl estradiol within a defined reference range through 2 full days days beyond the recommended 7 days of wear. (Abrams LS, Skee DM, Wong FA, Anderson NJ, Leese PT. Pharmacokinetics of norelgestromin and ethinyl estradiol from two consecutive contraceptive patches. J Clin Pharmacol (in press).) Therefore, it was not necessary for subjects to change their patch at the exact same hour each week. In the event of an accidental patch detachment, a replacement patch was to be applied immediately and worn for the remainder of that week.
The sample size was chosen to provide more than 10,000 cycles (ie, approximately 850 women-years of observation) on the contraceptive patch. This was achieved among subjects who were enrolled for either 13 cycles or six cycles. Current regulatory guidance17 specifies that studies should be at least large enough to give the overall Pearl Index with a 95% confidence interval such that the difference between the upper limit of the confidence interval and the point estimate does not exceed one pregnancy per 100 woman-years. For methods with Pearl Indices of less than 2.2, this is achieved with 850 women-years.
The criteria for evaluating contraceptive efficacy included calculation of the life table estimates of the probability of pregnancy and the Pearl Index (number of pregnancies per 100 woman-years of use). Each subject was to have a urine pregnancy test performed 10 days after the scheduled final treatment cycle or upon early withdrawal. All pregnant subjects were to have an ultrasound. Pregnancies were classified into the following four categories based on available data from the investigators (ultrasound, diary cards, and narratives): 1) pretherapy, in which the estimated date of conception preceded study drug start; 2) posttherapy, in which the estimated date of conception was after the last cycle of therapy; 3) on-therapy method failure, in which the estimated date of conception was during the cycles of therapy and there was information that the subject complied with dosing; and 4) on-therapy user failure, defined as in on-therapy method failure, except that available information indicated that the subject failed to comply with dosing on, or the day immediately contiguous with, the date of conception. Follow-up information regarding the pregnancy outcome and any postnatal sequelae in the infant were to be obtained in all cases.
Cycle control was evaluated from information recorded on diary cards, which were to be completed daily by subjects. Breakthrough bleeding and spotting was any bleeding and spotting occurring on days 1 through 21, excluding bleeding contiguous with menses. Breakthrough bleeding was defined as that which required sanitary protection of more than one pad or tampon on any day during the intermenstrual period. Breakthrough spotting was defined as that which required sanitary protection of less than or equal to one pad or tampon on any day during the intermenstrual period. Amenorrhea was defined as two continuous cycles without any bleeding or spotting. The bleeding analyses included data from cycles in which data on dosing and bleeding were provided and for which the dosing instructions were followed except for minor variations.
Compliance was determined by patch application recorded on diary cards.
Patch replacement information was used to assess patch adhesion. Patches replaced for the reason of "fell off" were summarized as patches that completely detached due to lack of adhesion.
Adverse events, both those reported by subjects and those observed by study center personnel, were collected throughout the study. Clinical laboratory tests (hematology and serum chemistry), vital signs (blood pressure, pulse rate, and temperature), and physical and gynecologic examinations were performed before the study and at the final visit.
Pregnancy rates were estimated by Pearl Index and life table analyses and were based on all on-therapy pregnancies and the total number of on-therapy cycles through cycle 13, with the exception of cycles after the cycle of conception. The Pearl Index was calculated [(number of pregnancies x 1300)/number of on-therapy cycles] with the standard error computed by the Delta method.18 All subjects who received the study drug for at least 1 day and were not pregnant at the start of cycle 1 were included in the evaluation of efficacy. The method-failure Pearl Index was also calculated. The life table analyses evaluated overall and method-failure pregnancy rates using a Kaplan-Meier procedure with Proc LIFETEST of SAS (SAS Institute Inc., Cary, NC).19 For both Pearl Indices and life table estimates of the probability of pregnancy, 95% confidence intervals were calculated.
A key endpoint for the evaluation of cycle control was the incidence of breakthrough bleeding or spotting during cycle 3. Cycle control data included an evaluation of the incidence of breakthrough bleeding and/or spotting at each cycle, breakthrough bleeding at each cycle, and amenorrhea over all cycles.
The mean percentage of each subject’s cycles that demonstrated perfect compliance was calculated. Perfect compliance was defined as 21 consecutive days of dosing, followed by a 7-day drug-free interval; no patch could be worn for more than 7 days.
All subjects who applied a patch were evaluable for safety. Safety was assessed by adverse events, changes from baseline in hematology and serum chemistry parameters and vital signs, and changes in physical and gynecologic examinations.
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RESULTS |
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ABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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. Subjects who participated at US centers had a lower mean age and height and a greater mean weight than subjects participating at non-US centers (Table 1). In addition, more black subjects participated at US centers than non-US centers. Overall, approximately 24% of the subjects had not used OCs within the past 2 months, and approximately 48% switched directly from OCs to treatment with the contraceptive patch; the remaining subjects switched indirectly from OCs or data were not provided.
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The life table estimates of the probability of overall and method-failure pregnancy are summarized in Table 2. The overall and method-failure probabilities of pregnancy through 13 cycles of treatment were 0.7% and 0.4%, respectively. Five method-failure pregnancies and one user-failure pregnancy occurred among 1664 women treated for 10,994 cycles. Table 3 provides a profile of each of the six on-therapy pregnancies. The overall Pearl Index was 0.71, and the method-failure Pearl Index was 0.59.
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. No subjects reported amenorrhea. Cycle control was evaluable in 95% of all cycles.
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Only 1.9% of patches were replaced due to complete detachment.
Adverse events were generally consistent with the use of hormonal contraceptives,20 with the exception of mild-to-moderate application-site reactions, which are expected with topically applied products.10 Adverse events that occurred in 10% or more of subjects included headache, application-site reactions, nausea, breast discomfort, upper respiratory infection, and dysmenorrhea. For those subjects with breast discomfort, 80% rated the discomfort as mild to moderate in severity. For cycles 3 to 13, the by-cycle incidence of breast discomfort was less than 3%. Other studies have shown that although breast discomfort is somewhat more frequent with the contraceptive patch than OC comparators in the first two cycles of treatment, by cycle 3 the incidence of breast discomfort is comparable to that observed with the OC comparators.21 (Hedon B, Helmerhorst FM, Cronje HS, Shangold G, Fisher A, Creasy G. Comparison of efficacy, cycle control, compliance, and safety in users of a contraceptive patch vs an oral contraceptive [abstract]. Int J Gynaecol Obstet 2000;70(Suppl 1):78.) The most common adverse events resulting in discontinuation of therapy were application-site reactions (1.9%), nausea (1.8%), emotional lability (1.5%), headache (1.1%), and breast discomfort (1.0%). Three serious adverse events were considered possibly related to the study drug, and they included one case of adenocarcinoma in situ of the cervix, one case of menorrhagia, and one case of pulmonary embolism (resolved with treatment). The pulmonary embolism followed a protocol violation (the patch was worn until the day of surgery) and occurred 3 weeks after patch removal during recovery.
There were no clinically meaningful changes in laboratory parameters, vital signs, or physical or gynecologic examination findings. The mean change in body weight from baseline to the end of the study was an increase of less than 1 pound (0.4 kg).
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DISCUSSION |
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ABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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In the study reported here, of the 1664 subjects evaluable for efficacy, there were six on-therapy pregnancies, including five method-failure pregnancies and one user-failure pregnancy. The "overall" probability of pregnancy through 13 cycles was low (0.7% [95% confidence interval (CI) 0, 1.4]). The low overall failure rate with the contraceptive patch may be due in part to the high level of perfect compliance (90%) with the once-weekly dosing schedule. Among the six observed pregnancies, there was a single user-failure at cycle 13. The MTO ratio for the contraceptive patch in this study is, therefore, 0.83. It is worth noting that in this study, for cycles 1 through 6, a duration of treatment that all study participants were to complete, there were no user failures. A similar level of compliance has been reported in two other randomized clinical trials comparing the contraceptive patch with OCs; in these trials the contraceptive patch showed significantly higher levels of compliance than the comparator OCs.21 (Hedon B, et al. Int J Gynaecol Obstet 2000;70(Suppl 1):78.)
It has been noted that of the six pregnancies in this study, four occurred among women with a body weight of at least 90 kg, a group that constituted approximately 3% (52 of 1672) of the study population. Although this suggests that the occurrence of pregnancy is associated with increased body weight, these results are not conclusive. A meta-analysis of all contraceptive patch studies is being performed and will be the subject of another article.
The incidence of unexpected vaginal bleeding with a hormonal contraceptive may contribute to a woman’s decision to discontinue a particular method; 33% of women who discontinue OCs do so because of unexpected vaginal bleeding.7 Currently, the vast majority of available hormonal methods that require less frequent dosing than OCs contain only progestin, and progestin-only methods are associated with frequent episodes of unexpected bleeding when compared with combination estrogen–progestin methods.24,25 In this trial, the contraceptive patch had a low incidence of breakthrough bleeding (Table 4
), and in 2 separate comparative trials, the incidence of breakthrough bleeding with the patch was similar to the OC comparators. (Triphasil21 [Wyeth-Ayerst, Philadelphia, PA] and Mercilon [Organon, OSS, The Netherlands]) (Hedon B, et al. Int J Gynaecol Obstet 2000;70(Suppl 1):78.)
The high rate of adhesion of the contraceptive patch may also contribute to contraceptive efficacy, cycle control, and patient satisfaction. The percentage of patch replacement for complete detachment was 1.9% in this study.
The adverse events reported in this study were typical of hormonal contraceptives and most were of mild-to-moderate severity, not serious, and not treatment limiting; no single type of adverse event led to discontinuation in more than 2% of subjects.
In summary, the contraceptive patch provides combination hormonal contraception with convenient weekly dosing for a 21-day regimen. The excellent compliance seen with the contraceptive patch in this study and other studies comparing once-weekly dosing with daily OC dosing may reflect the convenience of weekly dosing with the patch.
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Footnotes |
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This study was supported by The R.W. Johnson Pharmaceutical Research Institute. Principal investigators: B.M. Sibai, V.L. Odlind, T. Lefton, Marilyn Short, J.S. Brigham, F.D. Fingerhut, E. Weisberg, B. Satterfield, D.A. Sundwall, U. Gaspard, B.R. Kurtz, S.A. Funk, A. Bigrigg, L. Hopkins, K.K. Leonhardt, M. Weerasinghe, D.-M. Gruber, J. Adelglass, R.L. Holly, M. McCartney, T. Bäckström, E.G. Garner, G. Berg, G.M. Bouw, A. Van Zanten, H. Resnick, F. Sargos, S. Craft, M.-C. Jourdan, B.-M. Landgren, J.F. Peipert, P. Farrington, R. Kroll, S. Randall, D. Stucki, A. Youssoupov-Labatut, I. Zordan, A. Glasier, M.A. Macsalka, B. Soltes, M. Birkhäuser, D.H. Bogchelman, R. de Boer, A.L. Troostwijk, F.J.M. Broekmans, D. Hochner-Celnikier, G.S. Merki, J. Bitzer, J. Itzkovitz, D.F. Archer, A. Kubba, P.H.M. van de Weijer, E. Weisberg, R.W. Ke, R. Kirkman, M. Boyce, A. Brzezinski, F. Dargacha-Sablé, J. Guillebaud, M. Walling, H.A. Zacur, S. Jones, D. Man-sour, Y. Rabinovici, R.D. Crist, Dr. Eberhard, C. Wilkinson, and M. Kishen.
Received January 30, 2001. Received in revised form May 4, 2001. Accepted May 31, 2001.
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REFERENCES |
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2. Piccinino LJ, Mosher WD. Trends in contraceptive use in the United States: 1982–1995. Fam Plann Perspect 1998; 30:4–10, 46.[Medline]
3. Alan Guttmacher Institute. Facts in brief: Contraceptive use. Available at: http://www.agi-usa.org/pubs/fb_contr_use.html. Accessed August 21, 2001.
4. Fu H, Darroch JE, Haas T, Ranjit N. Contraceptive failure rates; new estimates from the 1995 National Survey of Family Growth. Fam Plann Perspect 1999;31:56–63.[Medline]
5. Trussell J, Vaughan B. Contraceptive failure, method-related discontinuation and resumption of use: results from the 1995 National Survey of Family Growth. Fam Plann Perspect 1999;31:64–72, 93.[Medline]
6. Rosenberg MJ, Waugh MS, Burnhill MS. Compliance, counseling and satisfaction with oral contraceptives: A prospective evaluation. Fam Plann Perspect 1998;30: 89–92, 104.[Medline]
7. Rosenberg MJ, Waugh MS, Meehan TE. Use and misuse of oral contraceptives: Risk indicators for poor pill taking and discontinuation. Contraception 1995;51:283–8.[Medline]
8. Potter L, Oakley D, de Leon-Wong E, Canamar R. Measuring compliance among oral contraceptive users. Fam Plann Perspect 1996;28:154–8.[Medline]
9. Whitehead MI, Fraser D, Schenkel L, Crook D, Stevenson JC. Transdermal administration of oestrogen/progestagen hormone replacement therapy. Lancet 1990;335:310–2.[Medline]
10. Utian WH, Burry KA, Archer DF, Gallagher JC, Boyett RL, Guy MP, et al. Efficacy and safety of low, standard, and high dosages of an estradiol transdermal system (Esclim) compared with placebo on vasomotor symptoms in highly symptomatic menopausal patients. Am J Obstet Gynecol 1999;181:71–9.[Medline]
11. Kafrissen ME. A norgestimate-containing oral contraceptive: review of clinical studies. Am J Obstet Gynecol 1992; 167:1196–202.[Medline]
12. Corson SL. Efficacy and clinical profile of a new oral contraceptive containing norgestimate. U.S. clinical trials. Acta Obstet Gynecol Scand 1990;152(Suppl):25–31.
13. Speroff L, DeCherney A, The Advisory Board for the New Progestins. Evaluation of a new generation of oral contraceptives. Obstet Gynecol 1993;81:1034–47.
14. Anderson FD. Selectivity and minimal androgenicity of norgestimate in monophasic and triphasic oral contraceptives. Acta Obstet Gynecol Scand 1992;156(Suppl):15–21.
15. The European Agency for the Evaluation of Medicinal Products. Note for Guidance on Good Clinical Practice. January 17, 1997. Available at: http://www.emea.eu.int/pdfs/human/ich/013595en.pdf. Accessed August 2001.
16. Thomas AE, McKay DA, Cutlip MB. A nomograph method for assessing body weight. Am J Clin Nutr 1976. 29:302–4.
17. Committee for Proprietary Medicinal Products (CPMP). Note for guidance on clinical investigation of steroid contraceptives in women. February 17, 2000. Available at: http://www.emea.eu.int/pdfs/human/ewp/051998en.pdf. Accessed August 2001.
18. Bishop YMM, Fienberg, SE, Holland PW, Light RJ, Mosteller F. Discrete multivariate analysis: Theory and practice. Cambridge, MA: MIT Press, 1975:486–500.
19. Kalfbfleisch JD, Prentice RL. The statistical analysis of failure time data. New York: John Wiley & Sons Inc., 1980:9–16.
20. Food and Drug Administration. Guidance for industry. Combined oral contraceptives—labeling for healthcare providers and patients. June 2000. Available at: http://www.fda.gov/cder/guidance/2448dft.pdf. Accessed August 2001.
21. Audet M-C, Moreau M, Koltun WD, Waldbaum AS, Shangold G, Fisher AC, et al. Evaluation of contraceptive efficacy and cycle control of a transdermal contraceptive patch vs an oral contraceptive: A randomized controlled trial. JAMA 2001;285:2347–54.
22. Rosenberg MJ, Waugh MS, Long S. Unintended pregnancies and use, misuse and discontinuation of oral contraceptives. J Reprod Med 1995;40:355–60.[Medline]
23. Trussell J. Contraceptive efficacy. In: Hatcher RA, Trussell J, Stewart F, Cates W, Stewart GK, Guest F, et al, eds. Contraceptive technology. 17th ed. New York: Ardent Media Inc., 1998:779–844.
24. Cromer BA, Smith RD, Blair JM, Dwyer J, Brown RT. A prospective study of adolescents who choose among levonorgestrel implant (Norplant), medroxyprogesterone acetate (Depo-Provera), or the combined oral contraceptive pill as contraception. Pediatrics 1994;94:687–94.
25. Kaunitz AM, Illions EH, Jones JL, Sang LA. Contraception. A clinical review for the internist. Med Clin North Am 1995;79:1377–409.[Medline]
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