title: Progestogens in combined oral contraceptives for contraception.
abstract: BACKGROUND
  The progestogen component of oral contraceptives (OC) has undergone changes since it was first recognised that their chemical structures could influence the spectrum of minor adverse and beneficial effects. The major determinants of OCs are effectiveness, cycle control and common side effects. The rationale of this review is to provide a systematic comparison of OCs containing the progestogens currently in use worldwide.
  
  
  OBJECTIVE
  The objective of this review is to compare currently available low-dose OCs containing ethinyl estradiol and different progestogens in terms of contraceptive effectiveness, cycle control, side effects and continuation rates.
  
  
  METHODS
  The Cochrane Controlled Trials Register, MEDLINE and EMBASE databases have been searched systematically. Relevant pharmaceutical companies and the authors of articles included in this review have been contacted for clarification.
  
  
  METHODS
  Randomised trials reporting clinical outcomes were considered for inclusion. We excluded studies comparing mono- with multiphasic pills, and crossover trials with trials in which the difference in total content of ethinyl estradiol between preparations exceeded 105 micro g.
  
  
  METHODS
  The methodological quality and validity of studies were assessed based on the above-mentioned inclusion criteria. Both application of inclusion criteria and data extraction were performed independently by the reviewers. Results are expressed as relative risk (RR) with 95% confidence interval (CI) using a random-effects model.
  
  
  RESULTS
  Twenty-two trials have been included in this review, thus generating 14 comparisons. Eighteen trials were sponsored by pharmaceutical companies and in only 5 cases had a blind trial been attempted. Most comparisons between different interventions included 1-3 trials. There was less discontinuation with second- compared to first-generation progestogens (RR: 0.79, 95% CI: 0.69-0.91). Cycle control appears to be better when using second- compared to first-generation progestogens for both mono- (RR: 0.69; 95% CI: 0.52-0.91) and triphasic (RR: 0.61; 95% CI: 0.43-0.85) preparations.Contraceptive effectiveness, spotting, breakthrough bleeding and the absence of withdrawal bleeding was similar when using GSD compared to LNG, although there was less intermenstrual bleeding in the GSD group (RR: 0.71, 95% CI: 0.55, 0.91). Drospirenone (DRSP) appeared to be similar to DSG.
  
  
  CONCLUSIONS
  Based on data from one trial, compared to pills containing LNG, those containing GSD may be associated with less intermenstrual bleeding although they show similar patterns of spotting, breakthrough bleeding and the absence of withdrawal bleeds. GSD is also comparable to DSG. Regarding acceptability, all the indices show that third- and second-generation progestogens are preferred over first-generation preparations. Future research should focus on independently conducted, well-designed randomised trials that compare third- and second-generation progestogens in particular.
authors.forename: N
authors.initials: N
authors.lastname: Maitra
authors.forename: R
authors.initials: R
authors.lastname: Kulier
authors.forename: K W M
authors.initials: KW
authors.lastname: Bloemenkamp
authors.forename: F M
authors.initials: FM
authors.lastname: Helmerhorst
authors.forename: A M
authors.initials: AM
authors.lastname: Gülmezoglu
mesh_terms: D003267:Contraception / Q000379:methods*; D003277:Contraceptives, Oral, Combined / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D011372:Progestins / Q000008:administration & dosage*; D016032:Randomized Controlled Trials as Topic
chemical_list: D003277:Contraceptives, Oral, Combined; D011372:Progestins