title: Menopausal symptom experience before and after stopping estrogen therapy in the Women's Health Initiative randomized, placebo-controlled trial.
abstract: OBJECTIVE
  The aim of this study was to assess vasomotor and other menopausal symptoms before starting estrogens or placebo, 1 year later, again at trial closure, and after stopping estrogens or placebo. The role of baseline symptoms and age was examined, as was the frequency and determinants of hormone use and symptom management strategies after discontinuing conjugated equine estrogens (CEE) or placebo.
  
  
  METHODS
  Intent-to-treat analyses of 10,739 postmenopausal women before and 1 year after randomization to CEE or placebo at 40 clinical centers and a cohort analysis of participants (n = 3,496) who continued taking assigned study pills up to trial closure and completed symptom surveys shortly before (mean, 7.4 +/- 1.1 y from baseline) and after (mean, 306 +/- 55 d after trial closure) stopping pills were performed. Generalized linear regression modeled vasomotor symptoms, vaginal dryness, breast tenderness, pain/stiffness, and mood swings as a function of treatment assignment and baseline symptoms, before and after stopping study pills.
  
  
  RESULTS
  Approximately one third of participants reported at least one moderate to severe symptom at baseline. Fewer symptoms were reported with increasing age, except joint pain/stiffness, which was similar among age groups. At 1 year, hot flashes, night sweats, and vaginal dryness were reduced by CEE, whereas breast tenderness was increased. Breast tenderness was also significantly higher in the CEE group at trial closure. After stopping, vasomotor symptoms were reported by significantly more women who had reported symptoms at baseline, compared with those who had not, and by significantly more participants assigned to CEE (9.8%) versus placebo (3.2%); however, among women with no moderate or severe symptoms at baseline, more than five times as many reported hot flashes after stopping CEE (7.2%) versus placebo (1.5%).
  
  
  CONCLUSIONS
  CEE significantly reduced vasomotor symptoms and vaginal dryness in women with baseline symptoms but increased breast tenderness. The likelihood of experiencing symptoms was significantly higher after stopping CEE than placebo regardless of baseline symptom status. These potential effects should be considered before initiating CEE to relieve menopausal symptoms.
authors.affiliation: Department of Family and Community Medicine, University of Nevada School of Medicine, Reno, NV 89511, USA. bbrunner@medicine.nevada.edu
authors.forename: Robert L
authors.initials: RL
authors.lastname: Brunner
authors.forename: Aaron
authors.initials: A
authors.lastname: Aragaki
authors.forename: Vanessa
authors.initials: V
authors.lastname: Barnabei
authors.forename: Barbara B
authors.initials: BB
authors.lastname: Cochrane
authors.forename: Margery
authors.initials: M
authors.lastname: Gass
authors.forename: Susan
authors.initials: S
authors.lastname: Hendrix
authors.forename: Dorothy
authors.initials: D
authors.lastname: Lane
authors.forename: Judith
authors.initials: J
authors.lastname: Ockene
authors.forename: Nancy F
authors.initials: NF
authors.lastname: Woods
authors.forename: Shagufta
authors.initials: S
authors.lastname: Yasmeen
authors.forename: Marcia
authors.initials: M
authors.lastname: Stefanick
mesh_terms: D004334:Drug Administration Schedule; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D019584:Hot Flashes / Q000188:drug therapy*; D006801:Humans; D008593:Menopause; D010919:Placebos
chemical_list: D004966:Estrogens, Conjugated (USP); D010919:Placebos