title: Estrogen alone and joint symptoms in the Women's Health Initiative randomized trial.
abstract: OBJECTIVE
  Although joint symptoms are commonly reported after menopause, observational studies examining exogenous estrogen's influence on joint symptoms provide mixed results. Against this background, estrogen-alone effects on joint symptoms were examined in post hoc analyses in the Women's Health Initiative randomized, placebo-controlled, clinical trial.
  
  
  METHODS
  A total of 10,739 postmenopausal women who have had a hysterectomy were randomized to receive daily oral conjugated equine estrogens (0.625 mg/d) or a matching placebo. The frequency and severity of joint pain and joint swelling were assessed by questionnaire in all participants at entry and on year 1, and in a 9.9% random subsample (n = 1,062) after years 3 and 6. Logistic regression models were used to compare the frequency and severity of symptoms by randomization group. Sensitivity analyses evaluated adherence influence on symptoms.
  
  
  RESULTS
  At baseline, joint pain and joint swelling were closely comparable in the randomization groups (about 77% with joint pain and 40% with joint swelling). After 1 year, joint pain frequency was significantly lower in the estrogen-alone group compared with the placebo group (76.3% vs 79.2%, P = 0.001), as was joint pain severity, and the difference in pain between randomization groups persisted through year 3. However, joint swelling frequency was higher in the estrogen-alone group (42.1% vs 39.7%, P = 0.02). Adherence-adjusted analyses strengthen estrogen's association with reduced joint pain but attenuate estrogen's association with increased joint swelling.
  
  
  CONCLUSIONS
  The current findings suggest that estrogen-alone use in postmenopausal women results in a modest but sustained reduction in the frequency of joint pain.
authors.affiliation: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA. rowanchlebowski@gmail.com
authors.forename: Rowan T
authors.initials: RT
authors.lastname: Chlebowski
authors.forename: Dominic J
authors.initials: DJ
authors.lastname: Cirillo
authors.forename: Charles B
authors.initials: CB
authors.lastname: Eaton
authors.forename: Marcia L
authors.initials: ML
authors.lastname: Stefanick
authors.forename: Mary
authors.initials: M
authors.lastname: Pettinger
authors.forename: Laura D
authors.initials: LD
authors.lastname: Carbone
authors.forename: Karen C
authors.initials: KC
authors.lastname: Johnson
authors.forename: Michael S
authors.initials: MS
authors.lastname: Simon
authors.forename: Nancy F
authors.initials: NF
authors.lastname: Woods
authors.forename: Jean
authors.initials: J
authors.lastname: Wactawski-Wende
mesh_terms: D000368:Aged; D018771:Arthralgia / Q000188:drug therapy / Q000453:epidemiology*; D002118:Calcium / Q000008:administration & dosage; D004311:Double-Blind Method; D015914:Estrogen Replacement Therapy / Q000379:methods*; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007044:Hysterectomy; D008875:Middle Aged; D010919:Placebos; D017698:Postmenopause; D011795:Surveys and Questionnaires; D014807:Vitamin D / Q000008:administration & dosage; D016387:Women's Health
chemical_list: D004966:Estrogens, Conjugated (USP); D010919:Placebos; D014807:Vitamin D; D002118:Calcium