title: Headaches and oral contraceptives: impact of eliminating the standard 7-day placebo interval.
abstract: OBJECTIVE
  The aim was to assess the timing and severity of self-reported headaches in patients utilizing a standard 28-day oral contraceptive (OC) cycle consisting of 21 hormone (estrogen + progestin)-containing pills and 7 placebo pills (ie, 21/7-day cycle) converted to a placebo-free extended OC regimen.
  
  
  METHODS
  An open label single-center prospective analysis of headaches recorded daily on a severity scale of 0 to 10, along with the headache item of the Penn Daily Symptom Rating (DSR17) and a weekly modified Migraine Disability Assessment (MIDAS) headache questionnaire, during standard 21/7-day cycles followed by a 168-day extended placebo-free regimen of an OC containing 3 mg of drosperinone and 30 mcg of ethinyl estradiol (DRSP/EE).
  
  
  RESULTS
  Of the 114 patients who began the trial, 111 completed the 21/7-day cycle portion of the study. Based on the headaches scales, there were significant differences in headache severity among the 28 days of the standard 21/7 cycles (P < .001). Greater headache severity occurred on days 25 through 28 during the 7-day placebo interval of the 21/7 cycles (P < .05). Of the 111 patients who completed the 21/7 phase of the study, 102 (92%) completed the 168-day extended placebo-free OC regimen. During the first 28 days of the extended placebo-free regimen, daily headache scores decreased (P < .0001) compared to those of the previous 21 active/7 placebo day cycle. The difference on a daily basis was first detected on extended cycle days 25 through 28 (P < .0001) and persisted throughout the remainder of the 168-day regimen. Subjects were divided into 2 groups (severe and mild) based on the median of the total headache score during the 21/7 OC cycle. The group with higher total headache scores demonstrated a significant (P < .0001) reduction in daily headaches beginning in the first 28-day interval of the extended placebo-free regimen, persisting throughout the entire 168-day extended regimen. In contrast, the group with the lower total headache score remained unchanged (P= .79) throughout the extended regimen. Impact of headaches on work, family, and social functions also improved on the extended placebo-free regimen in 6 of 8 measures (P < .05) assessed by weekly headache questionnaires.
  
  
  CONCLUSIONS
  Compared to a 21/7-day OC regimen, a 168-day extended placebo-free regimen of DRSP/EE led to a decrease in headache severity along with improvement in work productivity and involvement in activities. This is a preliminary study and results may not be widely generalizable.
authors.affiliation: Scott and White Memorial Hospital--Obstetrics and Gynecology, 2401 South 31st Street, Temple, TX 76508, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Sulak
authors.forename: Sherilyn
authors.initials: S
authors.lastname: Willis
authors.forename: Thomas
authors.initials: T
authors.lastname: Kuehl
authors.forename: Andrea
authors.initials: A
authors.lastname: Coffee
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Clark
mesh_terms: D000328:Adult; D015331:Cohort Studies; D003278:Contraceptives, Oral, Hormonal / Q000009:adverse effects* / Q000627:therapeutic use*; D004185:Disability Evaluation; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004967:Estrogens / Q000627:therapeutic use; D005260:Female; D006261:Headache / Q000139:chemically induced* / Q000503:physiopathology; D006801:Humans; D008875:Middle Aged; D010919:Placebos / Q000009:adverse effects*; D011372:Progestins / Q000627:therapeutic use; D011446:Prospective Studies; D012720:Severity of Illness Index; D013375:Substance Withdrawal Syndrome / Q000517:prevention & control*; D011795:Surveys and Questionnaires
chemical_list: D003278:Contraceptives, Oral, Hormonal; D004967:Estrogens; D010919:Placebos; D011372:Progestins