title: Combination injectable contraceptives for contraception.
abstract: BACKGROUND
  Combination injectable contraceptives provide a highly effective, reversible method of preventing pregnancy, and they do not require daily administration or use at the time of coitus. Although they are used in many countries, their acceptability could be limited by method characteristics, such as the need to obtain a monthly injection or bleeding pattern changes.
  
  
  OBJECTIVE
  To assess the contraceptive efficacy, bleeding patterns, discontinuation, user preferences, and side effects of combination injectable contraceptives.
  
  
  METHODS
  We searched computerized databases for randomized controlled trials of combination injectable contraceptives.
  
  
  METHODS
  Randomized controlled trials reported in any language were eligible if they compared a combination injectable with any other contraceptive method (e.g., a second combination injectable contraceptive, progestin-only injectable contraceptive, other hormonal contraceptive or barrier method) or placebo. We limited the review to currently marketed combination injectable contraceptives.
  
  
  METHODS
  The primary reviewer evaluated all titles and abstracts from the literature searches to determine their eligibility. Two reviewers independently extracted data from the eligible trials. Data on contraceptive efficacy, bleeding patterns, continuation, and side effects were entered and analyzed with RevMan 4.2.
  
  
  RESULTS
  Combination injectable contraceptives include depot medroxyprogesterone acetate (DMPA) 25 mg plus estradiol cypionate (E(2)C) 5 mg, as well as norethisterone enanthate (NET-EN) 50 mg plus estradiol valerate (E(2)V) 5 mg. These combination injectable contraceptives resulted in lower rates of early study discontinuation due to amenorrhea or other bleeding problems, but had higher rates of discontinuation due to other reasons than the progestin-only comparison contraceptives. Studies comparing two combination injectable contraceptives found that NET-EN 50 mg plus E(2)V 5 mg resulted in less overall early discontinuation and less discontinuation due to amenorrhea or prolonged bleeding than DMPA 25 mg plus E(2)C 5 mg. However, these differences were not detected in all trials making this comparison. The NET-EN plus E(2)V group also had more cyclical (regular) bleeding and fewer prolonged bleeding reference periods than the DMPA plus E(2)C group. The groups did not differ in their amenorrhea rates.
  
  
  CONCLUSIONS
  While discontinuation rates can be viewed as a measure of method acceptability, the findings should be interpreted with caution since discontinuation rates are dependent on many other factors. Future research should be directed toward interventions to improve the acceptability of combination injectable contraceptives, such as providing injections in settings more convenient than clinical sites, methods for women to administer their own injections, and counseling about possible bleeding pattern changes.
authors: IPAS, 300 Market Street, suite 200, Chapel Hill, North Carolina 27516, USA. gallom@ipas.org
authors: M F
authors: MF
authors: Gallo
authors: D A
authors: DA
authors: Grimes
authors: K F
authors: KF
authors: Schulz
authors: C
authors: C
authors: d'Arcangues
authors: L M
authors: LM
authors: Lopez
mesh_terms: D000523:Algestone / Q000008:administration & dosage; D003267:Contraception / Q000379:methods*; D003271:Contraceptive Agents, Female / Q000008:administration & dosage*; D004338:Drug Combinations; D004958:Estradiol / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007267:Injections; D008525:Medroxyprogesterone / Q000008:administration & dosage; D019290:Megestrol Acetate / Q000008:administration & dosage; D009640:Norethindrone / Q000008:administration & dosage
chemical_list: D003271:Contraceptive Agents, Female; D004338:Drug Combinations; D000523:Algestone; D004958:Estradiol; D008525:Medroxyprogesterone; D009640:Norethindrone; D019290:Megestrol Acetate