Journal of Adolescent Health 58 (2016) 284e289
www.jahonline.org Original article
Etonogestrel Implants in Adolescents: Experience, Satisfaction, and Continuation Laura Obijuru, M.D. a, *, Suzanne Bumpus, FNP-C a,1, Peggy Auinger, M.S. b, and Constance D. Baldwin, Ph.D. c a
Division of Adolescent Medicine, Department of Pediatrics, University of Rochester Medical Center, Rochester, New York Department of Neurology, Center for Human Experimental Therapeutics, University of Rochester Medical Center, Rochester, New York c Department of General Academic Pediatrics, University of Rochester Medical Center, Rochester, New York b
Article history: Received June 29, 2015; Accepted October 26, 2015 Keywords: Long-acting reversible contraception; Etonogestrel implant; Intrauterine device; Irregular bleeding; Nuisance bleeding; Adolescents; Unintended pregnancy
A B S T R A C T
Purpose: Few studies have evaluated the use of etonogestrel subdermal implants (ESI) by U.S. adolescents. We assessed several factors, including continuation rates, the association of implant removal with postimplant management of nuisance bleeding, and the relation between bleeding and body mass index. Methods: We reviewed 116 charts from all adolescent females with ESI placement in our adolescent medicine clinic from January 2010 to August 2013. Data were obtained from follow-up encounters up to 36 months after insertion. Results: Of the 116 adolescents, 94% were nulliparous. Follow-up data were available for 81% (n ¼ 94). Early ESI removal was defined as removal <32 months. ESI continuation rates at 12, 24, and 32 months were 78%, 50%, and 40%, respectively; this represents an early removal rate of 35% (33 of 94). Nuisance bleeding occurred in 48% (45 of 94). Of those complaining of bleeding, 63% (25 of 40) received medication management. Resolution of bleeding occurred in 25% of those in the early removal group versus 15% in the full retention group. Early implant removal due to nuisance bleeding occurred in 18% (17 of 94). There was no significant association between body mass index, nuisance bleeding, and early ESI removal. Conclusions: Implant continuation rates were quite high at 12 and 24 months, with 40% of patients reaching 32 months retention, providing a significant period of pregnancy prevention. Treatments for nuisance bleeding were often not prescribed and when they were, medication regimens varied among providers. An evidence-based protocol for medication management, combined with more routine use of appropriate medications and preventive or long-term therapies, may help improve continuation of ESI. Ó 2016 Society for Adolescent Health and Medicine. All rights reserved.
Conflicts of Interest: The authors do not have any conflict of interest to report. * Address correspondence to: Laura Obijuru, M.D., University Health Service, Box 270617, 738 Library Road, Rochester, NY 14627. E-mail address:
[email protected] (L. Obijuru). 1 Present Address: University of Rochester Health Service, University of Rochester, Rochester, New York.
[email protected] 1054-139X/Ó 2016 Society for Adolescent Health and Medicine. All rights reserved. http://dx.doi.org/10.1016/j.jadohealth.2015.10.254
IMPLICATIONS AND CONTRIBUTION
Adolescents with etonogestrel subdermal implants had good continuation rates: 78% at 12 months, 50% at 24 months, and 40% at 32 months. Half of patients with early removals discontinued because of nuisance bleeding. Only 63% of patients with early removals received medication management; among these, persistent bleeding occurred in 67%.
The U.S. teen birth rate remains a significant problem, despite a reduction by 32% between the peak year of 1991 and 2008 [1]. Unintended pregnancies occur in 82% of pregnant adolescents aged 15e19 years and 60% of pregnant young women aged 20e24 years [2,3]. The 2006e2008 National Survey of Family Growth found that teenagers’ use of contraceptives has remained largely unchanged since 2002. Among sexually experienced
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females, the condom is still the most commonly used method of contraception (95%), followed by withdrawal (58%) and the pill (55%) [4]. These user-dependent and shorter term reversible contraception methods pose a challenge to adolescents because of the proven risk of inconsistent or incorrect use [5]. Studies have shown that most pregnancies result from user-related method failure, not failure of the method itself [5]. Therefore, recent recommendations call for long-acting, reversible contraception (LARC) methodsdwhich include intrauterine devices (IUDs) and contraceptive implants such as the etonogestrel subdermal implant (ESI)dto be used as the first-line contraceptive methods for both nulliparous and parous adolescents [6,7]. Despite the proven safety, effectiveness, and costeffectiveness of LARC, only 4.5% of 15- to 19-year-old females and 8.3% of 20- to 24-year-olds used LARC from 2002 to 2010 [8]. This LARC use represents primarily insertion of IUDs; in 2009, implant use was estimated to be only 1% [8]. Few studies have assessed the continuation and satisfaction rates of adolescents using LARC methods. An exception is the Contraceptive CHOICE study, which showed that 81% of females aged 14e19 years using LARC methods free of cost continued at 1 year, compared to 80%e85% of older women [9]. Females aged 14e19 years had higher discontinuation rates at 1 year for nonLARC methods compared to women aged >25 years (53% vs. 44%) [9]. Adolescents and older women were equally satisfied with LARC methods [9]. The CHOICE study found that 10% of all implant users of all ages reported discontinuing the method because of unpredictable bleeding [10]. In an open-label clinical trial of Implanon, comparable discontinuation rates for implant users were reported: 13% of women aged 18e40 years discontinued their implant because of bleeding irregularities [11]. Casey et al. [12] found that obese women were 2.6 times less likely to have ESI removal for bleeding versus normal-weight or overweight women, after adjusting for age and parity. On the other hand, Mansour et al. [13] found that lower-weight women had less bleeding/spotting than heavier women. However, no studies have investigated the relationship of body mass index (BMI) with early ESI removal in adolescents. ESI has been demonstrated to be the most effective LARC method [14], yet only 1% of adolescents use it. More needs to be learned about why the method is not more widely used by nulliparous adolescents, reasons for early discontinuation, and effectiveness of management of nuisance bleeding. To address these gaps, we conducted a retrospective chart review of all adolescent females who had ESIs placed in our outpatient adolescent medicine clinic over 3 years. We investigated demographic factors, BMI, contraceptive and reproductive history, discontinuation rates, reasons for implant removal, and side effects and their management. We aimed to identify factors associated with implant removal that might be modified to increase length of ESI retention, particularly medical management of side effects. Methods Design This retrospective study was approved by the University of Rochester Research Subjects Review Board. We used current procedural terminology codes through the electronic medical
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record to identify all 119 charts with codes for an ESI placement at the Outpatient Adolescent Medicine Subspecialty Clinic at Strong Memorial Hospital between January 1, 2010, and August 1, 2013. We reviewed records of follow-up clinic and telephone encounters made to Adolescent Medicine (AM) and General Pediatrics (GP) clinics and an affiliated school-based health center, from time of implant placement through 36 months after insertion (approved length of retention). Because data were analyzed in February 2015, 25% of patients had not yet reached 32 months postinsertion, but all had been in the study for at least 18 months. Exclusion criteria were age <13 years and no documentation of ESI insertion or contraception or reproductive history. Three charts were excluded; two had no documentation of ESI placement and the third was a duplicate chart. Contraception was provided at usual cost, and ESIs were covered by all patients’ insurance.
Data collection Data collected at time of ESI insertion included demographic data, insurance type, BMI, history of sexually transmitted infections (STIs), prior and current methods of contraception, and parity. We reviewed office visit and phone call records from AM or GP clinics up to 36 months after ESI placement. We collected data regarding BMI, complications immediately after insertion, reported side effects and their management, and pregnancy and satisfaction with the implant and ESI outcome (continuation or removal). For those with implant removal, we recorded reason(s) for discontinuation and new method of contraception selected. In patients who had an ESI inserted, removed, and replaced around 36 months, only the initial insertion and removal were considered in the analysis. Statistical analysis. To evaluate interrater reliability, two investigators (L.O. and S.B.) each independently reviewed the same 10 records. There were no remarkable differences in data interpretation, and subsequent records were divided between both investigators and reviewed. Results were summarized using standard descriptive statistics, including frequency and percentages for categorical variables and mean, median, and standard deviation for continuous variables. ESI continuation rates were calculated using a KaplaneMeier survival curve. A power calculation was not performed as we planned to enroll all potentially eligible adolescents for this descriptive study.
Results Demographics A total of 116 patients were included in the study: 46% white, 40% black, and 12% Hispanic (Table 1). Mean age was 17 years, and most patients were nulliparous (94%). About 52% of patients had public insurance, whereas 39% had private insurance. Contraception was subsidized by insurance for all patients. Mean BMI was 26 kg/m2; 15% of patients were overweight and 19% were in the obese range. About 11% of patients had a history of an eating disorder.
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Table 1 Demographics of the initial study sample (n ¼ 116), based on self-reported questionnaire data Category
N
Percenta
Age, mean (standard deviation), range Race Black/African-American White Unknown/other Ethnicity Hispanic or Latino Marital status Single Married Unknown Insurance type Private Public None Unknown Body mass index (BMI), mean (standard deviation), range BMI categories <25 25e29.9 30
116
17 (1.8), 13e22
a
46 53 17
40 46 15
14
12
111 2 3
96 2 3
45 60 2 9 106
39 52 2 8 26 (8.3), 17e62
67 17 22
Figure 1. KaplaneMeier survival curve estimating continuation rates for etonogestrel subdermal implant (ESI) in adolescents. Data show continuation rates (arrows) of 78% at 12 months and 50% at 24 months. Recommended time for removal of ESI implants is 36 months. We defined the cutoff for “early removal” to be 32 months.
Etonogestrel subdermal implant satisfaction and continuation About 60%e70% of the 94 patients reported being satisfied with their ESI over 12e36 months. Time of implant retention was a median of 23.5 months (95% confidence interval [CI], 18.9e35.3). ESI continuation at 12, 24, and 32 months was 78%, 50%, and 40%, respectively (Figure 1 for KaplaneMeier curve estimating continuation rates over time). Seven of the 38 patients who continued to 36 months had another implant placed at time of ESI removal.
58 15 19
Results are % unless otherwise indicated (age and BMI).
Contraceptive use at time of placement As provided in Table 2, although 39% of participants reported previous use of oral contraceptives and 27% had received Depo-Provera, only 14% were using these methods at time of placement; 35% reported currently using condoms and 42% no contraception. Only 3% were using IUDs and 3% had a current ESI.
Follow-up Follow-up data were available for 81% of the 116 patients, yielding a total study group of 94. Time to first follow-up visit typically occurred 4e6 weeks after insertion. Because implants are approved for 36 months of use, we defined early ESI removal as removal before 32 months. Of the 94 patients with at least one implant-related follow-up visit, 79% had their first visit in the AM clinic versus 21% in the GP clinic. After implant placement, patients who received >50% of their follow-up care primarily at the AM versus GP clinics had very similar rates of early removal (39% vs. 40%, respectively, p ¼ .5).
Table 2 Self-reported contraceptive method by the initial sample at time of ESI placement Current contraceptive method
Number (n ¼ 116)
Percent
“The Patch” “The Ring” “The Shot” “The Pill” Implanon/Nexplanon Mirena/Paraguard (intrauterine devices) Condoms None Unknown/not noted
2 0 15 2 3 3
2 0 13 2 3 3
40 49 5
35 42 4
Etonogestrel subdermal implant removal and reasons for early discontinuation Thirty-five percent of patients had their implant removed before 32 months. Early ESI removal was most frequent in the first 12 months: 18 of 33 between 0 and 12 months. The remaining 15 of 33 patients had their ESI removed between 13 and 32 months. Of the total group, 18% (17 of 94) had early removal for nuisance bleeding. Among the 33 patients with early ESI removal, the most common reason for removal was nuisance bleeding (52%). This complaint could potentially have been addressed at follow-up encounters before removal. Among patients with early removals, 21% had no such visits, whereas 57% had 3 follow-up encounters before removal. Of note, providers made the diagnosis of nuisance bleeding after an investigation of potential underlying causes of intermenstrual bleeding, namely STIs and pregnancy, as appropriate to each patient. Other reasons for early discontinuation were disliking the feel of the implant (15%), amenorrhea, alopecia, weight gain, breast changes, and anxiety about pregnancy (3%e6% each). Of the 15% (5 of 33) of patients who cited disliking the feel of the implant, two patients cited this plus a second reason for removal: one did not like that she had inconsistent pregnancy tests on the ESI and the other cited irregular bleeding as the other reason for early removal. Contraceptive method at time of etonogestrel subdermal implant insertion and nuisance bleeding on the etonogestrel subdermal implant Of the 15 patients who were currently on Depo-Provera at the time of ESI insertion, 6 (40%) went on to have irregular bleeding;
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of the 6 with irregular bleeding, 4 (67%) went on to have early ESI removal for persistent bleeding. Among this group of 15 patients, one had early ESI removal for unknown reasons, a second had early removal secondary to weight gain and a third disliked the feel of the implant. One patient in this group of 15 went on to have amenorrhea. None of the patients who were currently on the patch, oral contraceptive pills (OCPs), or ESI at the time of ESI insertion went on to have irregular bleeding or early ESI removal for nuisance bleeding. Only one patient who had an IUD at time of ESI placement went on to have irregular bleeding and then amenorrhea after her irregular bleeding was managed with medication. Another patient with an IUD at the time of ESI placement went on to have amenorrhea.
ESI removal (some reported irregular bleeding but did not complain that it was a nuisance), yet 36% (5 of 14) of these patients went on to have early ESI removal for persistent nuisance bleeding.
Medication management of nuisance bleeding on the etonogestrel subdermal implant
Irregular bleeding was reported by about 32% of obese, 47% of overweight, and 34% of normal-weight patients (p ¼ .56). The relation between BMI and ESI removal was also not significant (p ¼ .51).
Mean time to the first complaint of nuisance bleeding was 8 months after insertion of ESI, after which most patients received medication management that included nonsteroidal anti-inflammatory drugs, doxycycline, or OCPs. Figure 2 shows the history of complaint of nuisance bleeding and medication management in the full retention group (labeled A, N ¼ 61 of 94) and the early removal group (labeled B, N ¼ 33 of 94). These data show that in the full retention group, 13 of 21 (62%) of those who complained of nuisance bleeding received medication. Of those who received medication, only 2 of 13 (15%) had resolution after 2e4 courses of medication. In the early ESI removal group (Figure 2), 58% complained of nuisance bleeding, but only 63% (12 of 19) received medications. Of these, 8 of 12 went on to have early ESI removal for persistent bleeding after 1 course of medication. Forty-two percent of patients (14 of 33) did not complain of nuisance bleeding before
Amenorrhea on the etonogestrel subdermal implant Sixteen patients (17% of the total group) became amenorrheic. Only one of these patients had been treated for nuisance bleeding. Average time to documentation of amenorrhea was 8 months. Body mass index, nuisance bleeding, and early etonogestrel subdermal implant removal
Contraceptive method chosen after early etonogestrel subdermal implant removal Of the 33 patients in the early removal group, postremoval contraceptive method was known for 32 patients: condoms only (n ¼ 8); OCPs (n ¼ 8); patch (n ¼ 4); Depo Provera and Mirena IUD (n ¼ 4 each); vaginal ring (n ¼ 2); and no method (n ¼ 2). Pregnancies after early etonogestrel subdermal implant removal In the early removal group, 13 of 33 patients (39%) became pregnant after early ESI removal (at 1 week to 31 months; mean 9 months). Only 1 of these patients became pregnant intentionally. Over half of these patients had chosen a combined
Figure 2. Differences in nuisance bleeding, medication management, and early ESI removal between full retention (labeled A) and early ESI removal (labeled B) groups. Boxes are shaded to simplify comparison of data across the groups. The chart shows the percent of patients who complained of and received medication management for nuisance bleeding and the percent in each group whose bleeding resolved. Rounded black boxes at bottom show the variety of treatments received by those in both groups. NSAIDs ¼ nonsteroidal anti-inflammatory drugs; Doxy ¼ doxycycline; OCPs ¼ oral contraceptive pills.
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hormonal method, and about a third had chosen condoms only. Six percent used no contraception. Pregnancies during etonogestrel subdermal implant retention There were no method failures. However, four patients were found to be pregnant soon after placement. Patient 1 was found to be 7-weeks pregnant at the time of her first follow-up visit. She had a negative pregnancy test at ESI insertion but reported having had multiple episodes of unprotected intercourse within the first week of ESI insertion (a period when patients are instructed to use a backup method). Patient 2, who had a documented negative pregnancy test at ESI insertion, was found to be pregnant a few weeks later but had reported unprotected sex 8 days before ESI placement, before testing would be positive. Patient 3 also had a negative pregnancy test before ESI insertion but had sex the day before placement and failed to follow instructions to use emergency contraception. Patient 4 was known to have been previously pregnant but falsely stated that she had terminated the pregnancy. Discussion Sixty to seventy percent of our patients reported satisfaction with their ESI. Continuation rates are more meaningful, however, because a number who initially reported satisfaction went on to have early ESI removal. Our study demonstrated continuation rates of 78% at 12 months and 50% at 24 months. These results are comparable to the 12- and 24-month continuation rates reported by the CHOICE study (81% and 67%, respectively) [15]. At the time of our data analysis, 40% of our patients had reached at least 32 months of implant retention. This 40% may be an underestimate because 25% of our original sample had reached only 18 month postinsertion at the time of data analysis. Nuisance bleeding was the most common reason for discontinuation in our sample. Our 18% rate of removal for bleeding was comparable, though slightly higher than the 10%e16.5% reported in previous studies of a mixed sample of adolescents and adults [10e13,16]. We found that the first 12 months after insertion was a crucial time to address nuisance bleeding. This time frame is comparable to the finding by Funk et al. [11] that the number of patients who discontinued ESI because of menstrual irregularities was highest in the first 8 months. The highly variable treatment of nuisance bleeding by the providers in our study is a direct reflection of the lack of a standard, evidenced-based guideline on the type and duration of medication management for nuisance bleeding. In our study, some patients received only 1 course of medication, whereas others received two to four courses. The most common treatments were doxycycline, nonsteroidal anti-inflammatory drugs, and OCPs, sometimes prescribed sequentially (in any order) if a previously used medication was ineffective. Our study showed that the lack of effective methods for treatment of nuisance bleeding was a major factor in early removal. Among those who reported nuisance bleeding, some complained and some did not. Regardless of treatment, among the “complainers,” 63% went on to have early removals, but even among the “noncomplainers” (who had no treatment), 36% had early ESI removal. A literature search yielded only one article that offered recommendations for medication management of nuisance bleeding associated with ESI [16], and these
authors based their approach largely on studies of adult women. It is unknown whether the mechanisms for unpredictable vaginal bleeding in adolescent and young adult women on the ESI are similar to those in older adult women or whether the effects of medications are the same in both the age groups. In fact, little is known about the underlying mechanisms causing unpredictable vaginal bleeding on progestin-only contraceptives in women of any age. Unpredictable vaginal bleeding may be caused by disturbed endometrial angiogenesis, increased spontaneous endometrial tissue breakdown, or defective endometrial epithelial repair mechanisms [16]. Studies to clarify the causes of this common side effect of contraceptive implants should facilitate the development of more effective therapies. Our data on patients’ contraceptive method at time of ESI insertion and their development of nuisance bleeding on the ESI showed that about 40% of patients previously on DepoProvera (DMPA) went on to have irregular bleeding on the ESI and two thirds had early ESI removal for persistent bleeding. In contrast, none of the patients who were on the patch, OCPs, or ESI at time of ESI placement went on to have irregular bleeding or early ESI removal for nuisance bleeding. It has been argued that estrogen, in its role in the endometrial repair process that takes place after menstruation, helps to stabilize the endometrium [16]. Our data are consistent with this hypothesis. DMPA contains no estrogen, whereas the patch and OCPs do, and therefore, DMPA may have made bleeding after ESI placement more likely. Furthermore, DMPA contains higher progestin levels than the ESI, so patients with a previous ESI may have had more endometrial stability than those previously using DMPA. Although 35% of our patients had early ESI removal, their retention of the implant for even a year was an important benefit to their adolescent development. These adolescents not only avoided pregnancy for a crucial period of their maturation but also adopted improved contraceptive methods after ESI removal. Before implant, nearly 80% of patients used either condoms only or no contraceptive method, whereas after implant, 44% chose to use hormonal contraception. There is still room for improvement, but our study indicates that the time after early ESI removal offers a key opportunity to increase adolescents’ adoption of other reliable contraceptive methods. Although choosing and adhering to any hormonal method is good, studies have shown that most unintended pregnancies result from user-dependent or no contraceptive methods [5]. In our study, 39% of patients in the early removal group, of whom over half had chosen user-dependent methods after removal, became pregnant within the next 9 months, on average. Only one patient in this group intended a pregnancy. Given the significant rate of unplanned pregnancies that results from user-dependent methods [5], we believe that patients who have early ESI removal should be encouraged to choose another user-independent method, such as the IUD. This study had several strengths. We had an 81% follow-up rate over 36 months with medication tracking for the management of nuisance bleeding. Ninety-four percent of the sample was nulliparous, a group seldom included in contraceptive studies. The study also explored contraceptive methods chosen after early ESI removal. To our knowledge, this is the only study looking at pregnancies in adolescents and young women after early discontinuation of ESI.
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Ours is one of only a few studies to look at BMI, nuisance bleeding, and implant removal in adolescents and the only study that has attempted to evaluate the association between ESI removal and follow-up site in an adolescent or general pediatric clinic. Regrettably, our small sample size limited our ability to detect significant associations between ESI removal and either BMI or follow-up site. Because of the infrequency of ESI use in adolescents, we maximized our sample size by including patients who had ESI placement over a 3.7-year period, but at our deadline for data analysis, 25% had not yet reached 32 months of implant retention. This study did not attempt to use qualitative methods to explore psychosocial or attitudinal factors, such as responses to counselling about nuisance bleeding that could improve length of implant retention in adolescents. However, a recent study has shown that there are no significant differences between intensive and routine counseling on discontinuation rates due to unpredictable menstrual bleeding on LARCs [17]. Furthermore, in a recent study of patients with ESI and nuisance bleeding who were treated with reassurance plus medication management versus reassurance alone, early ESI discontinuation rates were reduced in the group receiving medication plus reassurance [18]. Our study presents the findings of an adolescent medicine practice that uses the strategy of routine counseling and reassurance in addition to the option of medication management of ESI-related bleeding. Another weakness is that our study, similar to all retrospective chart reviews, relied on chart data that may have been inaccurate. However, the adolescent medicine providers at our institution routinely use a standard electronic template for clinic notes pertaining to contraceptive visits (at time of insertion, follow-up visits after insertion, and at time of removal of ESI), so this practice minimized variation among providers in the type of data recorded about each patient. On the basis of our findings, we conclude that more attention needs to be paid to early reports of nuisance bleeding, but we found that current medication management of nuisance bleeding is often ineffective. Current medications are not adequate and work, if at all, only in the short term [16]. Although some patients with ESI will choose early removal, the ESIdalong with the IUDdshould continue to be the first-line contraceptive method offered to adolescents and young women. As most patients who have early ESI removal cite nuisance bleeding as their reason for discontinuation, more research is needed to support evidenced-based practices regarding
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medications to manage unpredictable bleeding. Improved therapies that prevent or provide long-term control of nuisance bleeding will increase the use of this highly reliable method of birth control for adolescents who need protection against the serious consequences of unintended pregnancy. References [1] Hamilton BE, Martin JA, Ventura SJ. Births: Preliminary data for 2008. National Vital Statistics Reports, vol. 58 no 16. Hyattsville, Maryland: National Center for Health Statistics; 2010. [2] Finer L, Henshaw S. Disparities in rates of unintended pregnancy in the United States. 1994 and 2001. Perspect Sex Reprod Health 2006;38:90. [3] Finer L, Zolna M. Unintended pregnancy in the United States: Incidence and disparities, 2006. Contraception 2011;84:478e85. [4] Abma JC, Martinez GM, Copen CE. Teenagers in the United States: Sexual activity, contraceptive use, and childbearing, National Survey of Family Growth 2006e2008. Vital Health Stat 2010;23:1e47. [5] Frost JJ, Darroch JE. Factors associated with contraceptive choice and inconsistent method use, United States, 2004. Perspect Sex Reprod Health 2008;40:94e104. [6] Committee ACOG. Opinion No. 539, October 2012. Adolescents and longacting reversible contraception: Implants and intrauterine devices. [7] American Academy of Pediatrics. Committee on Adolescents. Pediatrics 2014;134:e1244e56. [8] Finer LB, Jerman J, Kavanaugh ML. Changes in use on long-acting contraceptive methods in the United States, 2007-2009. Fertil Steril 2012;98: 893e7. [9] Rosenstock JR, Peipert JF, Madden T, et al. Continuation of reversible contraception in teenagers and young women. Obstet Gynecol 2012;120: 1298e305. [10] Peipert JF, Zhao Q, Allsworth JE, et al. Continuation and satisfaction of reversible contraception. Obstet Gynecol 2011;117:1105e13. [11] Funk S, Miller MM, Mishell DR Jr, et al. Safety and efficacy of ImplanonTM, a single-rod implantable contraceptive containing etonogestrel. Contraception 2005;71:319e26. [12] Casey PM, Long ME, Marnach ML, et al. Association of body mass index with removal of etonogestrel subdermal implant. Contraception 2013;87: 370e4. [13] Mansour D, Korver T, Marintcheva-Petrova M, Fraser IS. The effects of Implanon on menstrual bleeding patterns. Eur J Contracept Reprod Health Care 2008;13(Suppl 1):13e28. [14] Graesslin O, Korver T. The contraceptive efficacy of implanon: A review of clinical trials and marketing experience. Eur J Contracept Reprod Health Care 2008;13(Suppl 1):4e12. [15] O’neil-Callahan M, Peipert JF, Zhao Q, et al. Twenty-four month continuation of reversible contraception. Obstet Gynecol 2013;122:1083e91. [16] Mansour D, Bahamondes L, Critchley H, et al. The management of unacceptable bleeding patterns in etonogestrel-releasing contraceptive implant users. Contraception 2011;83:202e10. [17] Modesto W, Bahamondes MV, Bahamondes L. A randomized clinical trial of the effect of intensive versus non-intensive counseling on discontinuation rates due to bleeding disturbances of three long-acting reversible contraceptives. Hum Reprod 2014;29:1393e9. [18] Casey PM, Long ME, Drozdowicz LB, et al. Management of etonogestrel subdermal implant-related bleeding. J Reprod Med 2014;59:306e12.