title: Combined oral contraceptives in women with systemic lupus erythematosus.
abstract: BACKGROUND
  Oral contraceptives are rarely prescribed for women with systemic lupus erythematosus, because of concern about potential negative side effects. In this double-blind, randomized, noninferiority trial, we prospectively evaluated the effect of oral contraceptives on lupus activity in premenopausal women with systemic lupus erythematosus.
  
  
  METHODS
  A total of 183 women with inactive (76 percent) or stable active (24 percent) systemic lupus erythematosus at 15 U.S. sites were randomly assigned to receive either oral contraceptives (triphasic ethinyl estradiol at a dose of 35 microg plus norethindrone at a dose of 0.5 to 1 mg for 12 cycles of 28 days each; 91 women) or placebo (92 women) and were evaluated at months 1, 2, 3, 6, 9, and 12. Subjects were excluded if they had moderate or high levels of anticardiolipin antibodies, lupus anticoagulant, or a history of thrombosis.
  
  
  RESULTS
  The primary end point, a severe lupus flare, occurred in 7 of 91 subjects receiving oral contraceptives (7.7 percent) as compared with 7 of 92 subjects receiving placebo (7.6 percent). The 12-month rates of severe flare were similar: 0.084 for the group receiving oral contraceptives and 0.087 for the placebo group (P=0.95; upper limit of the one-sided 95 percent confidence interval for this difference, 0.069, which is within the prespecified 9 percent margin for noninferiority). Rates of mild or moderate flares were 1.40 flares per person-year for subjects receiving oral contraceptives and 1.44 flares per person-year for subjects receiving placebo (relative risk, 0.98; P=0.86). In the group that was randomized to receive oral contraceptives, there was one deep venous thrombosis and one clotted graft; in the placebo group, there was one deep venous thrombosis, one ocular thrombosis, one superficial thrombophlebitis, and one death (after cessation of the trial).
  
  
  CONCLUSIONS
  Our study indicates that oral contraceptives do not increase the risk of flare among women with systemic lupus erythematosus whose disease is stable.
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Petri
authors.forename: Mimi Y
authors.initials: MY
authors.lastname: Kim
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Kalunian
authors.forename: Jennifer
authors.initials: J
authors.lastname: Grossman
authors.forename: Bevra H
authors.initials: BH
authors.lastname: Hahn
authors.forename: Lisa R
authors.initials: LR
authors.lastname: Sammaritano
authors.forename: Michael
authors.initials: M
authors.lastname: Lockshin
authors.forename: Joan T
authors.initials: JT
authors.lastname: Merrill
authors.forename: H Michael
authors.initials: HM
authors.lastname: Belmont
authors.forename: Anca D
authors.initials: AD
authors.lastname: Askanase
authors.forename: W Joseph
authors.initials: WJ
authors.lastname: McCune
authors.forename: Michelene
authors.initials: M
authors.lastname: Hearth-Holmes
authors.forename: Mary Anne
authors.initials: MA
authors.lastname: Dooley
authors.forename: Joan
authors.initials: J
authors.lastname: Von Feldt
authors.forename: Alan
authors.initials: A
authors.lastname: Friedman
authors.forename: Mark
authors.initials: M
authors.lastname: Tan
authors.forename: John
authors.initials: J
authors.lastname: Davis
authors.forename: Mary
authors.initials: M
authors.lastname: Cronin
authors.forename: Betty
authors.initials: B
authors.lastname: Diamond
authors.forename: Meggan
authors.initials: M
authors.lastname: Mackay
authors.forename: Lisa
authors.initials: L
authors.lastname: Sigler
authors.forename: Michael
authors.initials: M
authors.lastname: Fillius
authors.forename: Ann
authors.initials: A
authors.lastname: Rupel
authors.forename: Frederick
authors.initials: F
authors.lastname: Licciardi
authors.forename: Jill P
authors.initials: JP
authors.lastname: Buyon
mesh_terms: D000293:Adolescent; D000328:Adult; D003277:Contraceptives, Oral, Combined / Q000009:adverse effects*; D004311:Double-Blind Method; D004997:Ethinyl Estradiol / Q000009:adverse effects; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000145:classification; D009640:Norethindrone / Q000009:adverse effects; D011247:Pregnancy; D012720:Severity of Illness Index
chemical_list: D003277:Contraceptives, Oral, Combined; D004997:Ethinyl Estradiol; D009640:Norethindrone