title: The effect of multivitamin supplements on continuation rate and side effects of combined oral contraceptives: A randomised controlled trial.
abstract: OBJECTIVE
  This study aimed to assess the effect of multivitamin use during the pill-free interval on the continuation rate and side effects of combined oral contraceptives (COCs) within the first few cycles of use.
  
  
  METHODS
  In this trial, 332 women presenting to public health centres in an Iranian city each received a COC pack containing 21 pills and were randomised to one of three groups: two of the groups also received 42 multivitamin pills or 42 placebo pills to be taken once a day for 7 days before starting COCs and again during the 7-day pill-free interval for five cycles, while the third group received no multivitamin or placebo pills with their COCs. The groups were compared using Cox regression and χ(2) tests.
  
  
  RESULTS
  There were no losses to follow-up. Continuation rates at the sixth cycle were 88% for the multivitamin group, 75% for the placebo group and 67% for the no intervention group. Compared with the multivitamin group, the six-cycle discontinuation rate was significantly higher in the placebo group (hazard ratio [HR] 2.26, 95% confidence interval [CI] 1.15-4.45; p = 0.019) and no intervention group (HR 3.15, 95% CI 1.66-5.99; p < 0.001). Nausea, mood changes, weight gain and breast tenderness were significantly less common in the multivitamin group than in the other groups in all cycles, and spotting/irregular bleeding and dizziness were significantly less common in most of the second, third and sixth cycle follow-up.
  
  
  CONCLUSIONS
  Multivitamin supplements could significantly reduce the side effects of COCs in the initial cycles and improve continuation rates. However, the study limitations do not allow for any definite conclusion for their use in clinical practice, especially in communities rich in nutrients.
authors: a * Social Determinants of Health Research Center, Tabriz University of Medical Sciences , Tabriz , Iran.
authors: Sakineh
authors: S
authors: Mohammad-Alizadeh-Charandabi
authors: b Department of Midwifery , Faculty of Nursing and Midwifery, Tabriz University of Medical Sciences , Tabriz , Iran.
authors: Mojgan
authors: M
authors: Mirghafourvand
authors: c Students' Research Committee, International Branch of Aras, Tabriz University of Medical Sciences , Tabriz , Iran.
authors: Laya
authors: L
authors: Froghy
authors: d Pharmaceutics Department, Faculty of Pharmacy, Tabriz University of Medical Sciences , Tabriz , Iran.
authors: Yousef
authors: Y
authors: Javadzadeh
authors: e Drug Applied Research Centre, Students' Research Committee, Tabriz University of Medical Sciences , Tabriz , Iran.
authors: Nasser
authors: N
authors: Razmaraii
mesh_terms: D000328:Adult; D003268:Contraception Behavior / Q000523:psychology*; D003277:Contraceptives, Oral, Combined / Q000008:administration & dosage* / Q000009:adverse effects; D019587:Dietary Supplements; D004311:Double-Blind Method; D004338:Drug Combinations; D004359:Drug Therapy, Combination / Q000379:methods / Q000523:psychology; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000209:etiology; D005260:Female; D006801:Humans; D007492:Iran; D010349:Patient Compliance; D016016:Proportional Hazards Models; D014815:Vitamins / Q000008:administration & dosage*
chemical_list: D003277:Contraceptives, Oral, Combined; D004338:Drug Combinations; D014815:Vitamins
keywords: Adverse effects; Combined oral contraceptives; Continuation rate; Vitamins