Skip to main content
SpringerLink
Log in

Risks and Benefits, Advantages and Disadvantages of Levonorgestrel-Releasing Contraceptive Implants

  • Review Article
  • Published:
Drug Safety Aims and scope Submit manuscript

Abstract

Levonorgestrel-releasing implants are long acting contraceptives, approved for 5 years of continuous use. Two marketed systems, the six capsule Norplant®1 and the two rod Jadelle®, have essentially equal rates of drug release, pregnancy and adverse events over 5 years of use. Randomised clinical trials and controlled cohort observations indicate that for the first 3 years, when pregnancy rates are at or almost zero, no other contraceptive system is more effective, although etonogestrel implants provide equal effectiveness. Annual pregnancy rates rise in the fifth year of continuous use but remain below 1 per 100 women. Annual pregnancy rates of Norplant® users remain below 1 per 100 throughout 7 years of continuous use.

Levonorgestrel implants provide low progestogen doses; 40–50 μg/day at 1 year of use, decreasing to 25–30 μg/day in the fifth year. Serum levels of levonorgestrel at 5 years are 60–65% of those levels measured at 1 month of use.

Adverse effects with levonorgestrel implants are similar to those observed with progestogen only and combined oral contraceptives. Risks of ectopic pregnancy, other pregnancy complications and pelvic inflammatory disease are reduced in comparison with those of women using copper or non-medicated intrauterine devices. Risks of developing gallbladder disease and hypertension or borderline hypertension, although small, are about 1.5 and 1.8 times greater, respectively, in women using levonorgestrel implants than in women not using hormonal contraception. Other serious diseases have not been found to occur significantly more frequently in levonorgestrel implant users than in women not using hormonal contraception.

The great majority of levonorgestrel implant users experience menstrual problems, but serious bleeding problems are not more frequent than in controls. Other health problems reported more frequently by levonogestrel implant users than by women not using hormonal contraception in a study of 16 000 women included skin conditions, headache, upper limb neuropathies, dizziness, nervousness, malaise, minor visual disturbances, respiratory conditions, arthropathies, weight change, anxiety and non-clinical depression. Clinical depression is not more frequent in women using implants compared with those not using hormonal contraception (i.e. using intrauterine devices, sterilisation).

Removal problems occur less frequently with Jadelle® than with Norplant®. The mean removal time for Jadelle® is half that of Norplant®.

Levonorgestrel implants in nationally representative scientific samples, in randomised trials, and in controlled cohort studies have continuation rates as high as or higher than any other reversible contraceptive over a duration of 5 years. This would imply that the satisfaction women derive from the contraceptive effectiveness of levonorgestrel implants greatly outweighs the dissatisfaction that may accompany menstrual disturbances and other adverse effects associated with implants.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Table I
Table II
Table III
Table IV
Table V
Table VI
Fig. 1
Fig. 2
Table VII

Similar content being viewed by others

References

  1. Harrison PF, Rosenfield A. Effect of media coverage and litigation on Norplant® use. In: Harrison PF, Rosenfield A, editors. Contraceptive research, introduction and use: lessons from Norplant®. Washington, DC: National Academy Press, 1998: 21–2

    Google Scholar 

  2. Kalmuss D, Davidson AR. Utilization data: Norplant® discontinuation among low-income women. In: Harrison PF, Rosenfield A, editors. Contraceptive research, introduction and use; lessons from Norplant®. Washington, DC: National Academy Press, 1998: 79–82

    Google Scholar 

  3. Meirik O. Implantable contraceptives for women. Contraception 2002; 65(1): 1–2

    Article  PubMed  Google Scholar 

  4. Meirik O, Farley TM, Sivin I. Safety and efficacy of levonorgestrel implant, intrauterine device, and sterilization. Obstet Gynecol 2001; 97(4): 539–47

    Article  PubMed  CAS  Google Scholar 

  5. Sivin I. International experience with Norplant® and Norplant ®-2 contraceptives. Stud Fam Plann 1988; 19(2): 81–94

    Article  PubMed  CAS  Google Scholar 

  6. Sivin I. Norplant® contraceptive implants. In: Shoupe D, Haseltine FP, editors. Contraception. New York (NY): Springer-Verlag, 1993: 131–43

    Chapter  Google Scholar 

  7. Fraser IS, Tiitinen A, Affandi B, et al. Norplant® consensus statement and background review. Contraception 1998; 57(1): 1–9

    Article  PubMed  CAS  Google Scholar 

  8. Coukell AJ, Balfour JA. Levonorgestrel subdermal implants: a review of contraceptive efficacy and acceptability. Drugs 1998; 55(6): 861–87

    Article  PubMed  CAS  Google Scholar 

  9. Darney PD. Implantable contraception. Eur J Contracept Reprod Health Care 2000; 5Suppl. 2: 2–11

    PubMed  CAS  Google Scholar 

  10. Meckstroth KR, Darney PD. Implantable contraception. Obstet Gynecol Clin North Am 2000; 27(4): 781–815

    Article  PubMed  CAS  Google Scholar 

  11. Meckstroth KR, Darney PD. Implant contraception. Semin Reprod Med 2001; 19(4): 339–54

    Article  PubMed  CAS  Google Scholar 

  12. French RS, Cowan FM, Mansour DJ, et al. Implantable contraceptives (subdermal implants and hormonally impregnated intrauterine systems) versus other forms of reversible contraceptives: two systematic reviews to assess relative effectiveness, acceptability, tolerability and cost-effectiveness. Health Technol Assess 2000; 4(7): i–vi, 1-107

    PubMed  CAS  Google Scholar 

  13. Sivin I, Lahteenmaki P, Ranta S, et al. Levonorgestrel concentrations during use of levonorgestrel rod (LNG ROD) implants. Contraception 1997; 55(2): 81–5

    Article  PubMed  CAS  Google Scholar 

  14. Olsson SE, Odlind V, Johansson ED, et al. Plasma levels of levonorgestrel and free levonorgestrel index in women using Norplant® implants or two covered rods (Norplant®-2). Contraception 1987; 35(3): 215–28

    Article  PubMed  CAS  Google Scholar 

  15. Fan H, Han L. A multicenter clinical comparative study of domestically produced implant contraceptives no. 1 and no. II with Norplant®. J Reprod Med 1999; 8Suppl. 1: 47–53

    Google Scholar 

  16. Population Council, Jadelle,® New Drug Approval (NDA) 20–544, with supplements, 2002

  17. Population Council, Norplant® New Drug Approval (NDA) 19–897, with supplements, 2002

  18. Sivin I, Wan L, Ranta S, et al. Levonorgestrel concentrations during 7 years of continuous use of Jadelle® contraceptive implants. Contraception 2001; 64(1): 43–9

    Article  PubMed  CAS  Google Scholar 

  19. Du M, Shao Q, Zhou X. Serum levels of levonorgestrel during long-term use of Norplant® [in Chinese]. Zhonghua Fu Chan Ke Za Zhi 1999; 34(6): 363–5

    PubMed  CAS  Google Scholar 

  20. Sivin I, Campodonico I, Kiriwat O, et al. The performance of levonorgestrel rod and Norplant® contraceptive implants: a 5-year randomized study. Hum Reprod 1998; 13(12): 3371–8

    Article  PubMed  CAS  Google Scholar 

  21. Sivin I, Viegas O, Campodonico I, et al. Clinical performance of a new two-rod levonorgestrel contraceptive implant: a three-year randomized study with Norplant® implants as controls. Contraception 1997; 55(2): 73–80

    Article  PubMed  CAS  Google Scholar 

  22. Sivin I, Alvarez F, Mishell Jr DR, et al. Contraception with two levonorgestrel rod implants: a 5-year study in the United States and Dominican Republic. Contraception 1998; 58(5): 275–82

    Article  PubMed  CAS  Google Scholar 

  23. Sivin I, Nash H, Waldman S. Jadelle® levonorgestrel rod implants: a summary of scientific data and lessons learned from programmatic experience. New York: Population Council, 2002: 1–64

    Google Scholar 

  24. Sivin I, Mishell Jr DR, Diaz S, et al. Prolonged effectiveness of Norplant® capsule implants: a 7-year study. Contraception 2000; 61(3): 187–94

    Article  PubMed  CAS  Google Scholar 

  25. Sivin I, Mishell Jr DR, Darney P, et al. Levonorgestrel capsule implants in the United States: a 5-year study. Obstet Gynecol 1998; 92(3): 337–44

    Article  PubMed  CAS  Google Scholar 

  26. Peterson HB, Xia Z, Hughes JM, et al. The risk of pregnancy after tubal sterilization: findings from the US Collaborative Review of Sterilization. Am J Obstet Gynecol 1996; 174(4): 1161–8

    Article  PubMed  CAS  Google Scholar 

  27. Affandi B, Hoesni HM, Barus RP, et al. A multicentered phase III comparative study between single-implant containing 3 ketodesogestrel (Implanon®) and implants containing levonorgestrel (Norplant®): I. efficacy and, acceptability and safety (three year results). Med J Indonesia 1999; 8(1): 49–55

    Google Scholar 

  28. Zheng SR, Zheng HM, Qian SZ, et al. A randomized multicenter study comparing the efficacy and bleeding pattern of asingle-rod (Implanon) and a six-capsule (Norplant®) hormonal contraceptive implant. Contraception 1999; 60(1): 1–8

    Article  PubMed  CAS  Google Scholar 

  29. Wang SL, Wu SC, Xin XM, et al. Three years’ experience with levonorgestrel-releasing intrauterine device and Norplant®-2 implants: a randomized comparative study. Adv Contracept 1992; 8(2): 105–14

    Article  PubMed  CAS  Google Scholar 

  30. Croxatto HB, Makarainen L. The pharmacodynamics and efficacy of Implanon: an overview of the data. Contraception 1998 Dec; 58(6 Suppl.): 91S–7S

    Article  PubMed  CAS  Google Scholar 

  31. Croxatto HB, Urbancsek J, Massai R, et al. A multicentre efficacy and safety study of the single contraceptive implant Implanon. Implanon Study Group. Hum Reprod 1999 Apr; 14(4): 976–81

    Article  PubMed  CAS  Google Scholar 

  32. Han L. A 5-year multicenre comparative study of domestically produced implant contraceptives no. I and no. II with Norplant®. Presentation at WHO, 2001 May

    Google Scholar 

  33. Glasier A. Implantable contraceptives for women: effectiveness, discontinuation rates, return of fertility, and outcome of pregnancies. Contraception 2002; 65: 29–37

    Article  PubMed  Google Scholar 

  34. Gao J, Wang SL, Wu SC, et al. Comparison of the clinical performance, contraceptive efficacy and acceptability of levonorgestrel-releasing IUD and Norplant®-2 implants in China. Contraception 1990; 41(5): 485–94

    Article  PubMed  CAS  Google Scholar 

  35. Gu SJ, Du MK, Zhang LD, et al. A 5-year evaluation of NORPLANT® contraceptive implants in China. Obstet Gynecol 1994; 83(5 Pt 1): 673–8

    PubMed  CAS  Google Scholar 

  36. Gu S, Sivin I, Du M, et al. Effectiveness of Norplant® implants through seven years: a large-scale study in China. Contraception 1995; 52(2): 99–103

    Article  PubMed  CAS  Google Scholar 

  37. Gu S, Du M, Zhang L, et al. A five-year evaluation of NORPLANT ® II implants in China. Contraception 1994; 50(1): 27–34

    Article  PubMed  CAS  Google Scholar 

  38. Meirik O, Farley TMM, Diaz S, et al. Post-marketing surveillance of Norplant® contraceptive implants: I. contraceptive efficacy and reproductive health. Contraception 2001; 63(4): 167–86

    Article  Google Scholar 

  39. Fu H, Darroch JE, Haas T, et al. Contraceptive failure rates: new estimates from the 1995 National Survey of Family Growth. Fam Plann Perspect 1999; 31(2): 56–63

    Article  PubMed  CAS  Google Scholar 

  40. 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(2): 64–72, 93

    Article  PubMed  CAS  Google Scholar 

  41. Fisher AA, Prihartono J, Tuladhar J, et al. An assessment of Norplant® removal in Indonesia. Stud Fam Plann 1997; 28(4): 308–16

    Article  PubMed  CAS  Google Scholar 

  42. Sivin I. Fertility decline and contraceptive use in the International Postpartum family Planning Program. Stud Fam Plann 1971; 2: 248–56

    Article  PubMed  CAS  Google Scholar 

  43. Meirik O, Farley TMM, Collins J, et al. Post-marketing surveillance of Norplant® contraceptive implants: II. non-reproductive health. Contraception 2001; 63(4): 187–209

    Article  Google Scholar 

  44. Vessey M, Doll R, Peto R, et al. A long term follow-up study of women using different methods of contraception-an interim report. J Biosoc Sci 1976; 8(4): 373–427

    Article  PubMed  CAS  Google Scholar 

  45. Ramcharan S, Pellegrin FA, Ray RM, et al. The Walnut Creek Contraceptive Drug Study: a prospective study of the side effects of oral contraceptives. J Reprod Med 1980; 25: 346–72

    Google Scholar 

  46. Royal College of General Practitioners. Oral contraceptives and Health. London: Pitman Medical, 1974

  47. Curtis KM. Safety of implantable contraceptives for women: data from observational studies. Contraception 2002; 645: 85–96

    Article  Google Scholar 

  48. Wysowski DK, Green L, Serious adverse events in Norplant® users reported to the Food and Drug Administrations’s MedWatch spontaneous reporting system. Obstet Gynecol 1995; 85: 538–542

    Article  PubMed  CAS  Google Scholar 

  49. Sivin I. Serious adverse events in Norplant® users reported to the Food and Drug Administration’s MedWatch spontaneous reporting system. Obstet Gynecol 1995 Aug; 86(2): 318–20

    PubMed  CAS  Google Scholar 

  50. Petitti DB, Siscovick DS, Sidney S, et al. Norplant® implants and cardiovascular disease. Contraception 1998; 57: 361–2

    Article  PubMed  CAS  Google Scholar 

  51. World Health Organization. Collaborative study of cardiovascular disease and steroid hormone contraception: cardiovascular disease and use of oral and injectable progestogen-only contraceptives and combined injectable contraceptives. Contraception 1998; 57: 315–24

    Google Scholar 

  52. Poulter NR, Chang CL, Farley TM, et al. Effect on stroke of different progestagens in low oestrogen dose oral contraceptives: WHO Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Lancet 1999; 354(9175): 301–2

    Article  PubMed  CAS  Google Scholar 

  53. Chang CL, Donaghy M, Poulter N. Migraine and stroke in young women: case-control study. The World Health Organisation: Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. BMJ 1999; 318(7175): 13–8

    Article  PubMed  CAS  Google Scholar 

  54. Sivin I. Clinical effects of NORPLANT® subdermal implants for contraception. In: Mishell Jr DR, editor. Long-acting steroid contraception. New York: Raven Press, 1983: 89–116

    Google Scholar 

  55. Liu X, Mao J, Chen X, et al. The safety of Sino-implant- 3-year clinical observation. Shengzhi Yu Biyun 1999; 10(4): 234–41

    CAS  Google Scholar 

  56. Alder JB, Fraunfelder FT, Edwards R. Levonorgestrel implants and intracranial hypertension. N Engl J Med 1995 Jun 22; 332(25): 1720–1

    Article  PubMed  CAS  Google Scholar 

  57. Thijs C, Knipschild P. Oral contraceptives and the risk of gallbladder disease: a meta-analysis. Am J Public Health 1993; 83: 1113–20

    Article  PubMed  CAS  Google Scholar 

  58. Farley TMM, Rosenberg MJ, Rowe, et al. Intrauterine devices and pelvic inflammatory disease: an international perspective. Lancet 1992; 339: 785–8

    Article  PubMed  CAS  Google Scholar 

  59. Wagner K, Berenson A. Norplant® associated-major depression and panic disorder. J Clin Psych 1994; 55: 478–80

    CAS  Google Scholar 

  60. Wagner K. Major depression and anxiety disorders associated with Norplant®. J Clin Psych 1996; 57: 152–7

    CAS  Google Scholar 

  61. Stevens-Simon C, Kelly L, Wallis J. The timing of Norplant® insertion and postpartum depression in teenagers. J Adolesc Health 2000; 26(6): 408–13

    Article  PubMed  CAS  Google Scholar 

  62. Westhoff C, Truman C, Kalmuss D, et al. Depressive symptoms and Norplant® contraceptive implants. Contraception 1998; 57(4): 241–5

    Article  PubMed  CAS  Google Scholar 

  63. Janowsky EC, Kupper LL, Hulka BS. Meta-analyses of the relation between silicone breast implants and the risk of connective tissue disease. N Engl J Med 2000; 342: 781–90

    Article  PubMed  CAS  Google Scholar 

  64. Dorflinger LJ. Metabolic effects of steroids used in implantable contraceptives for women. Contraception 2002; 65: 47–62

    Article  PubMed  CAS  Google Scholar 

  65. Harper MA, Meis PJ, Steele L. A prospective study of insulin sensitivity and glucose metabolism in women using a continuous subdermal levonorgestrel implant system. J Soc Gynecol Investig 1997; 4(2): 86–9

    Article  PubMed  CAS  Google Scholar 

  66. Koopersmith TB, Lobo RA. Insulin sensitivity is unaltered by the use of the Norplant® subdermal implant contraceptive. Contraception 1995; 51(3): 197–200

    Article  PubMed  CAS  Google Scholar 

  67. Singh K, Viegas OA, Loke DF, et al. Effect of Norplant® implants on liver, lipid and carbohydrate metabolism. Contraception 1992 Feb; 45(2): 141–53

    Article  PubMed  CAS  Google Scholar 

  68. Singh K, Viegas OA, Loke D, et al. Effect of Norplant® 2 rods on liver, lipid and carbohydrate metabolism. Contraception 1992; 45(5): 463–72

    Article  PubMed  CAS  Google Scholar 

  69. Konje JC, Odukoya OA, Otolorin EO, et al. Carbohydrate metabolism before and after Norplant® removal. Contraception 1992; 46: 61–9

    Article  PubMed  CAS  Google Scholar 

  70. Konje JC, Otolorin EO, Ladipo OA The effect of continuous subdermal levonorgestrel (Norplant®) on carbohydrate metabolism. Am J Obstet Gynecol 1992; 166(1 Pt 1): 15–9

    PubMed  CAS  Google Scholar 

  71. Konje JC, Otolorin EO, Ladipo OA. Changes in carbohydrate metabolism during 30 months on Norplant®. Contraception 1991; 44: 163–72

    Article  PubMed  CAS  Google Scholar 

  72. Lithell H, Weiner E, Vessby B, et al. Effects of continuous levonorgestrel treatment (subcutaneous capsules) on the lipoprotein and carbohydrate metabolism in fertile women. Ups J Med Sci 1983; 88(2): 103–8

    Article  PubMed  CAS  Google Scholar 

  73. Diab KM, Zaki MM. Contraception in diabetic women: comparative metabolic study of Norplant® depot medroxyprogesterone acetate, low dose oral contraceptive pill and CuT380A. J Obstet Gynaecol Res 2000 Feb; 26(1): 17–26

    Article  PubMed  CAS  Google Scholar 

  74. United Nations Development Programme (UNDP)/United Nations Population Fund (UNFPA)/World Health Organization (WHO)/World Bank (WB), Special Programme of Research development and Research Training in Human Reproduction, Task Force on long-acting systemic agents for fertility regulation. Study of the effects of the implantable contraceptive Norplant® on lipid and lipoprotein metabolism. Contraception 1999; 59 (1): 31–45

    Google Scholar 

  75. Rabe T, Thuro HC, Goebel K, et al. Lipid metabolism in Norplant®-2 users: a two-year follow-up study. Total cholesterol, triglycerides, lipoproteins and apolipoproteins. Contraception 1992; 45(1): 21–37

    Article  PubMed  CAS  Google Scholar 

  76. Singh K, Ratnam SS. A study on the effects of Norplant® implantable contraceptive on lipid, lipoprotein, and apolipoprotein metabolism in Singaporean women. Contraception 1997; 56(2): 77–83

    Article  PubMed  CAS  Google Scholar 

  77. Anwar M, Soejono SK, Maruo T, et al. Comparative assessment of the effects of subdermal levonorgestrel implant system and long acting progestogen injection method on lipid metabolism. Asia Oceania J Obstet Gynaecol 1994; 20(1): 53–8

    Article  PubMed  CAS  Google Scholar 

  78. Otubu JA, Towobola OA, Aisien AO, et al. Effects of Norplant® contraceptive subdermal implants on serum lipids and lipoproteins. Contraception 1993; 47(2): 149–59

    Article  PubMed  CAS  Google Scholar 

  79. Affandi B, Suherman SK, Djajalelana, et al. Serum lipids in Norplant® implants users: a cross-sectional study. Contraception 1987; 36(4): 429–34

    Article  PubMed  CAS  Google Scholar 

  80. Holma P, Robertson DN. Cholesterol and HDL-cholesterol values in women during use of subdermal implants releasing levonorgestrel. Contraception 1985; 32(2): 163–71

    Article  PubMed  CAS  Google Scholar 

  81. Shaaban MM, Elwan SI, Abdalla SA, et al. Effect of subdermal levonorgestrel contraceptive implants, Norplant® on serum lipids. Contraception 1984; 30(5): 413–9

    Article  PubMed  CAS  Google Scholar 

  82. Roy S, Mishell Jr DR, Robertson DN, et al. Long-term reversible contraception with levonorgestrel-releasing Silastic rods. Am J Obstet Gynecol 1984; 148(7): 1006–13

    PubMed  CAS  Google Scholar 

  83. Yang P, Wu X, Yang Q, et al. The effects of Sino-implant containing LNG on lipoprotein metabolism and changes in blood HDL2-C levels. Shengzhi Yu Biyun 1999; 10(2): 84–90

    Google Scholar 

  84. Egberg N, van Beek A, Gunnervik C, et al. Effects on the hemostatic system and liver function in relation to Implanon and Norplant® a prospective randomized clinical trial. Contraception 1998; 58(2): 93–8

    Article  PubMed  CAS  Google Scholar 

  85. Viegas OA, Koh SC, Ratnam SS. The effects of reformulated 2-rod Norplant® implant on hemostasis after three years. Contraception 1996; 54(4): 219–28

    Article  PubMed  CAS  Google Scholar 

  86. Singh K, Viegas OA, Koh SL, et al. Effect of Norplant®-2 rods on haemostatic function. Contraception 1992; 46(1): 71–81

    Article  CAS  Google Scholar 

  87. Singh K, Viegas OA, Koh SC, et al. Effect of long-term use of Norplant® implants on haemostatic function. Contraception 1992; 45(3): 203–19

    Article  PubMed  CAS  Google Scholar 

  88. Singh K, Viegas OA, Ratnam SS. A three-year evaluation of hemostatic function in Singaporean Norplant®-2 rod acceptors. Adv Contracept 1990; 6(2): 81–9

    Article  PubMed  CAS  Google Scholar 

  89. Singh K, Viegas OA, Ratnam SS. A three-year evaluation of hemostatic function in Singaporean Norplant® acceptors. Adv Contracept 1990; 6(1): 23–32

    Article  PubMed  CAS  Google Scholar 

  90. Singh K, Viegas OA, Koh S, et al. The effects of Norplant®-2 rods on clinical chemistry in Singaporean acceptors after 1 year of use: haemostatic changes. Contraception 1988; 38(4): 441–51

    Article  PubMed  CAS  Google Scholar 

  91. Gu SJ, Du MG, Yuan DY, et al. A two-year study of acceptability, side effects, and effectiveness of Norplant® and Norplant®-2 implants in the People’s Republic of China. Contraception 1988; 38(6): 641–57

    Article  PubMed  CAS  Google Scholar 

  92. Du MK, Zheng HM, Chen HC, et al. Study of Norplant® implants in Shanghai: three-year experience. Int J Gynecol Obstet 1990; 33: 45–57

    Article  Google Scholar 

  93. Fraser JL, Millenson M, Malynn ER, et al. Possible association between the Norplant® contraceptive system and thrombotic thrombocytopenic purpura. Obstet Gynecol 1996; 87(5 Pt 2): 860–3

    PubMed  CAS  Google Scholar 

  94. Shaaban MM, Elwan SI, el-Sharkawy MM, et al. Effect of subdermal levonorgestrel contraceptive implants, Norplant®, on liver functions. Contraception 1984; 30: 407–12

    Article  PubMed  CAS  Google Scholar 

  95. McCann MF, Potter LS. Progestin-only contraception; a comprehensive review. Contraception 1994; 50Suppl. 1: S1–195

    PubMed  CAS  Google Scholar 

  96. Cromer BA. Effects of hormonal contraceptives on bone mineral density. Drug Saf 1999; 20(3): 213–22

    Article  PubMed  CAS  Google Scholar 

  97. Cromer BA, Berg-Kelly KS, Van Groningen JP, et al. Depot medroxyprogesterone acetate (Depo-Provera) and levonorgestrel (Norplant®) use in adolescents among clinicians in Northern Europe and the United States. J Adolesc Health 1998; 23(2): 74–80

    Article  PubMed  CAS  Google Scholar 

  98. Cromer BA, Smith RD, Blair JM, et al. 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(5): 687–94

    PubMed  CAS  Google Scholar 

  99. Cromer BA, Blair JM, Mahan JD, et al. A prospective comparison of bone density in adolescent girls receiving depot medroxyprogesterone acetate (Depo-Provera), levonorgestrel (Norplant®) or oral contraceptives. J Pediatr 1996; 129(5): 671–6

    Article  PubMed  CAS  Google Scholar 

  100. Naessen T, Olsson S-E, Gudmundson J. Differential effect on bone density of progestogen: only methods for contraception in premenopausal women. Contraception 1995; 52: 35–9

    Article  PubMed  CAS  Google Scholar 

  101. Di X, Li Y, Zhang C, et al. Effects of Levonorgestrel-releasing subdermal contraceptive implants on bone density and bone metabolism. Contraception 1999; 60(3): 161–6

    Article  PubMed  CAS  Google Scholar 

  102. Taneepanichskul S, Intaraprasert S, Theppisai U, et al. Bone mineral density during long-term treatment with Norplant® implants and depot medroxyprogesterone acetate: a cross-sectional study of Thai women. Contraception 1997; 56(3): 153–5

    Article  PubMed  CAS  Google Scholar 

  103. Petitti DB, Piaggio G, Mehta S, et al. Steroid hormone contraception and bone mineral density: a cross-sectional study in an international population. The WHO Study of Hormonal Contraception and Bone Health. Obstet Gynecol 2000; 95: 736–44

    Article  PubMed  CAS  Google Scholar 

  104. Banks E, Berrington A, Casabonne D. Overview of the relationship between use of progestogen only contraceptives and bone mineral density. BJOG 2001; 108(12): 1214–21

    PubMed  CAS  Google Scholar 

  105. Diaz S, Reyes MV, Zepeda A, et al. Norplant® implants and progesterone vaginal rings do not affect maternal bone turnover and density during lactation and after weaning. Hum Reprod 1999; 14(10): 2499–505

    Article  PubMed  CAS  Google Scholar 

  106. Brache V, Faundes A, Alvarez F, et al. Nonmenstrual adverse events during use of implantable contraceptives for women: data from clinical trials. Contraception 2002; 65: 63–74

    Article  PubMed  CAS  Google Scholar 

  107. Mitra SN, Ali MN, Islam S, et al. The Bangladesh demographic and health survey, 1993-1994. Calverton (MD): Macro International Inc, 1994

    Google Scholar 

  108. Li HQ, Goldberg JM, Go H. A 4-year follow-up study of women with Norplant®-2 contraceptive implants. Contraception 2001; 64: 301–3

    Article  Google Scholar 

  109. Affandi B, Hoesni HM, Barus RP, et al. A multicentered phase III comparative study between single implant containing 3-ketodesogestrel (Implanon®) and implants containing levonorgestrel (Norplant®): II. vaginal bleeding patterns. Med J Indonesia 1999; 8(1): 56–64

    Google Scholar 

  110. Biswas A, Leong WP, Ratnam SS, et al. Menstrual bleeding patterns in Norplant®-2 implant users. Contraception 1996; 54(2): 91–5

    Article  PubMed  CAS  Google Scholar 

  111. Meng F, Fan H, Han L. Vaginal bleeding patterns and the regularity in use of Norplant® [in Chinese]. Zhonghua Yi Xue Za Zhi 1996 May; 76(5): 331–4

    PubMed  CAS  Google Scholar 

  112. Meng F, Gu S. Menstrual bleeding patterns in Chinese women using the Norplant® subdermal implant. Hum Reprod 1996; 11Suppl. 2: 14–9

    Google Scholar 

  113. Datey S, Gaur LN, Saxena BN. Vaginal bleeding patterns of women using different contraceptive methods (implants, injectables, IUDs, oral pills): an Indian experience. An ICMR Task Force Study. Indian Council of Medical Research. Contraception 1995; 51(3): 155–65

    Article  PubMed  CAS  Google Scholar 

  114. Cheng L, Zhu H, Wang A, et al. Once a month administration of mifepristone improves bleeding patterns in women using sub-dermal contraceptive implants releasing levonorgestrel. Hum Reprod 2000; 15(9): 1969–72

    Article  PubMed  CAS  Google Scholar 

  115. Nutley T, Dunson TR. Treatment of bleeding problems associated with progestin-only contraceptives: survey results. Adv Contracept 1997; 13(4): 419–28

    Article  PubMed  CAS  Google Scholar 

  116. Alvarez-Sanchez F, Brache V, Thevenin F, et al. Hormonal treatment for bleeding irregularities in Norplant® implant users. Am J Obstet Gynecol 1996; 174(3): 919–22

    Article  PubMed  CAS  Google Scholar 

  117. Diaz S, Croxatto HB, Pavez M, et al. Clinical assessment of treatments for prolonged bleeding in users of Norplant® implants. Contraception 1990; 42(1): 97–109

    Article  PubMed  CAS  Google Scholar 

  118. Fraser IS, Weisberg E, Minehan E, et al. A detailed analysis of menstrual blood loss in women using Norplant® and Nestorone progestogen-only contraceptive implants or vaginal rings. Contraception 2000; 61(4): 241–51

    Article  PubMed  CAS  Google Scholar 

  119. Han L, Fan H, Gong Q, et al. Effects of three types of long acting contraceptive implants on menstrual blood loss in 89 women. Shengzhi Yu Biyun 1999; 10(2): 91–7

    CAS  Google Scholar 

  120. Task Force for Epidemiological Research on Reproductive Health, United Nations Development Programme/United Nations Population Fund/World Health Organization/World Bank Special Programme of Research, Development and Research Training in Human Reproduction, et al. Effects of contraceptives on hemoglobin and ferritin. Contraception 1998; 58 (5): 262–73

    Google Scholar 

  121. Nilsson CG, Holma P. Menstrual blood loss with contraceptive subdermal levonorgestrel implants. Fertil Steril 1981; 35(3): 304–6

    PubMed  CAS  Google Scholar 

  122. Frank ML, Poindexter III AN, Cornin LM, et al. One-year experience with subdermal contraceptive implants in the United States. Contraception 1993; 48(3): 229–43

    Article  PubMed  CAS  Google Scholar 

  123. Crosby UD, Schwarz BE, Gluck KL, et al. A preliminary report of Norplant® implant insertions in a large urban family planning program. Contraception 1993; 48(4): 359–66

    Article  PubMed  CAS  Google Scholar 

  124. Berenson AB, Wiemann CM. Patient satisfaction and side effects with levonorgestrel implant (Norplant®) use in adolescents 18 years of age or younger. Pediatrics 1993; 92(2): 257–60

    PubMed  CAS  Google Scholar 

  125. Klavon SL, Grubb GS. Insertion site complications during the first year of NORPLANT® use. Contraception 1990; 41(1): 27–37

    Article  PubMed  CAS  Google Scholar 

  126. Nuovo J, Sweha A. Keloid formation from levonorgestrel implant (Norplant® System) insertion. J Am Board Fam Pract 1994; 7(2): 152–4

    PubMed  CAS  Google Scholar 

  127. Sarma SP, Hatcher RP. Neurovascular injury during removal of levonorgestrel implants. Am J Obstet Gynecol 1995; 172(1 Pt 1): 120–1

    Article  PubMed  CAS  Google Scholar 

  128. Sarma SP, Silverstein M, Lewis C. Removal of a Norplant® implant located near a major nerve using interventional radiology-digital subtraction fluoroscopy. Contraception 1998; 58(6): 387–9

    Article  PubMed  CAS  Google Scholar 

  129. Smith JM, Conwit RA, Blumenthal PD. Ulnar nerve injury associated with removal of Norplant® implants. Contraception 1998; 57(2): 99–101

    Article  PubMed  CAS  Google Scholar 

  130. Hueston WJ, Locke KT. Norplant® neuropathy: peripheral neurologic symptoms associated with subdermal contraceptive implants. J Fam Pract 1995; 40(2): 184–6

    PubMed  CAS  Google Scholar 

  131. Marin R, McMillian D. Ulnar neuropathy associated with subdermal contraceptive implant. South Med J 1998; 91(9): 875–8

    Article  PubMed  CAS  Google Scholar 

  132. Creinin MD, Klaisle CM. Removal of levonorgestrel capsules from the biceps muscle. Int J Gynaecol Obstet 1995; 50(2): 189–91

    Article  PubMed  CAS  Google Scholar 

  133. Sarma SP, Wamsher JG, Whitlock SW. Removal of deeply inserted, nonpalpable levonorgestrel (Norplant® implants. Contraception 1996; 53(3): 159–61

    Article  PubMed  CAS  Google Scholar 

  134. Crist T, Barnes MR, Whitehurst WC. Difficulty finding and removing a Norplant® system capsule [letter]. N C Med J 1994; 55(2): 76

    PubMed  CAS  Google Scholar 

  135. Weiner HM, DiMarcangelo MT, Heim JA, et al. Use of computed tomography guidance and mammographic hook wires to remove displaced, embedded contraceptive rods. J Am Osteopath Assoc 1996; 96(7): 422–3

    PubMed  CAS  Google Scholar 

  136. Dunson TR, Amatya RN, Krueger SL. Complications and risk factors associated with the removal of Norplant® implants. Obstet Gynecol 1995; 85(4): 543–8

    Article  PubMed  CAS  Google Scholar 

  137. Wehrle KE. The Norplant® System: easy to insert, easy to remove. Nurse Pract 1994; 19(4): 47–54

    Article  PubMed  CAS  Google Scholar 

  138. Shaaban MM, Odlind V, Salem HT, et al. Levonorgestrel concentrations in maternal and infant serum during use of subdermal levonorgestrel contraceptive implants, Norplant® by nursing mothers. Contraception 1986; 33(4): 357–63

    Article  PubMed  CAS  Google Scholar 

  139. Diaz S, Herreros C, Juez G, et al. Fertility regulation in nursing women: VII. influence of NORPLANT® levonorgestrel implants upon lactation and infant growth. Contraception 1985; 32(1): 53–74

    Article  PubMed  CAS  Google Scholar 

  140. Shaaban MM, Salem HT, Abdullah KA. Influence of levonorgestrel contraceptive implants, NORPLANT®, initiated early postpartum upon lactation and infant growth. Contraception 1985; 32(6): 623–35

    Article  PubMed  CAS  Google Scholar 

  141. Diaz S. Contraceptive implants and lactation. Contraception 2002; 65(1): 39–46

    Article  PubMed  CAS  Google Scholar 

  142. Shaaban MM. Contraception with progestogens and progesterone during lactation. J Steroid Biochem Mol Biol 1991; 40(4-6): 705–10

    Article  PubMed  CAS  Google Scholar 

  143. Taneepanichskul S, Tanprasertkul C. Use of Norplant® implants in the immediate postpartum period among asymptomatic HIV-1-positive mothers. Contraception 2001; 64(1): 39–41

    Article  PubMed  CAS  Google Scholar 

  144. Taneepanichskul S, Intaraprasert S, Phuapradit W, et al. Use of Norplant® implants in asymptomatic HIV-1 infected women. Contraception 1997; 55(4): 205–7

    Article  PubMed  CAS  Google Scholar 

  145. Polaneczky M, Slap G, Forke C, et al. The use of levonorgestrel implants (Norplant® for contraception in adolescent mothers. N Engl J Med 1994; 331(18): 1201–6

    Article  PubMed  CAS  Google Scholar 

  146. Ricketts SA. Repeat fertility and contraceptive implant use among Medicaid recipients in Colorado. Fam Plann Perspect 1996; 28(6): 278–80, 284

    Article  PubMed  CAS  Google Scholar 

  147. Blumenthal PD, Wilson LE, Remsburg RE, et al. Contraceptive outcomes among post-partum and post-abortal adolescents. Contraception 1994; 50(5): 451–60

    Article  PubMed  CAS  Google Scholar 

  148. Samil RS, Kramadibrata S, Affandi B. Levonorgestrel implant contraceptive during lactation: effect on infant’s growth in one-year. Presented at the Sixth Annual Meeting of the Society for the Advancement of Contraception; 1988 May 23-26; Tokyo, Japan

  149. Kalmuss D, Davidson A, Cushman L, et al. Potential barriers to the removal of Norplant® among family planning clinic patients. Am J Public Health 1998; 88(12): 1846–50

    Article  PubMed  CAS  Google Scholar 

  150. Cullins VE, Remsburg RE, Blumenthal PD, et al. Comparison of adolescent and adult experiences with Norplant® levonorgestrel contraceptive implants. Obstet Gynecol 1994 Jun; 83(6): 1026–32

    Article  PubMed  CAS  Google Scholar 

  151. Vekemans M, Delvigne A, Paesmans M. Continuation rates with a levonorgestrel-releasing contraceptive implant (Norplant®): a prospective study in Belgium. Contraception 1997 Nov; 56(5): 291–9

    Article  PubMed  CAS  Google Scholar 

  152. Glantz S, Schaff E, Campbell-Heider N, et al. Contraceptive implant use among inner city teens. J Adolesc Health 1995; 16(5): 389–95

    Article  PubMed  CAS  Google Scholar 

  153. Glantz S, Glantz JC, Campbell-Heider N, et al. Norplant® use among urban minority women in the United States. Contraception 2000; 61(2): 83–90

    Article  PubMed  CAS  Google Scholar 

  154. Taneepanichskul S, Intharasakda P. Efficacy and side effects of Norplant® use in Thai women above the age of 35 years. Contraception 2001; 64(5): 305–7

    Article  PubMed  CAS  Google Scholar 

  155. Ortayli N, Bulut A, Sahin T, et al. Immediate postabortal contraception with the levonorgestrel intrauterine device, Norplant ® and traditional methods. Contraception 2001; 63(6): 309–14

    Article  PubMed  CAS  Google Scholar 

  156. Kurunmaki H. Contraception with levonorgestrel-releasing subdermal capsules, Norplant® after pregnancy termination. Contraception 1983; 27: 473–82

    Article  PubMed  CAS  Google Scholar 

  157. Ashraf T, Arnold SB, Maxfield Jr M. Cost-effectiveness of levonorgestrel subdermal implants: comparison with other contraceptive methods available in the United States. J Reprod Med 1994; 39(10): 791–8

    PubMed  CAS  Google Scholar 

  158. Trussell J, Leveque JA, Koening JD, et al. The economic value of contraception: a comparison of 14 methods. Am J Public Health 1995; 58: 494–503

    Article  Google Scholar 

  159. Westfall JM, Main DS. The contraceptive implant and the injectable: a comparison of costs. Fam Plann Perspect 1995; 27(1): 34–6

    Article  PubMed  CAS  Google Scholar 

  160. Ortmeier BG, Sauer KA, Langley PC, et al. A cost-benefit analysis of four hormonal contraceptive methods. Clin Ther 1994; 16(4): 707–13

    PubMed  CAS  Google Scholar 

  161. Janowitz B, Kanchanasinith K, Auamkul N, et al. Introducing the contraceptive implant in Thailand: impact on method use and costs. Int Fam Plann Perspect 1994 Dec; 20(4): 131–6

    Article  Google Scholar 

  162. Hannaford P. Postmarketing surveillance study of Norplant® in developing countries. Lancet 2001; 357(9271): 1815–6

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Preparation of this manuscript was assisted by a cooperative agreement between the US Agency for International Development (USAID) and the Population Council. The author has written some of the registration documents for levonorgestrel implants.

Author information

Authors and Affiliations

  1. Population Council, Center for Biomedical Research, 1230 York Avenue, New York, New York, 10021, USA

    Irving Sivin

Authors
  1. Irving Sivin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Irving Sivin.

Additional information

1 Use of tradenames is for product identification purposes only and does not imply endorsement.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sivin, I. Risks and Benefits, Advantages and Disadvantages of Levonorgestrel-Releasing Contraceptive Implants. Drug-Safety 26, 303–335 (2003). https://doi.org/10.2165/00002018-200326050-00002

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00002018-200326050-00002

Keywords

Search

Navigation