title: Age at menopause, reproductive history, and venous thromboembolism risk among postmenopausal women: the Women's Health Initiative Hormone Therapy clinical trials.
abstract: OBJECTIVE
  This study aims to investigate venous thromboembolism (VTE) risk in relation to age at menopause, age at menarche, parity, bilateral oophorectomy, and time since menopause, as well as any interaction with randomized hormone therapy (HT) assignment, among postmenopausal women.
  
  
  METHODS
  Using pooled data from the Women's Health Initiative HT clinical trials including 27,035 postmenopausal women aged 50 to 79 years who had no history of VTE, we assessed the risk of VTE in relation to age at menopause, age at menarche, parity, bilateral oophorectomy, and time since menopause by Cox proportional hazards models. Linear trends, quadratic relationships, and interactions of reproductive life characteristics with HT on VTE risk were systematically tested.
  
  
  RESULTS
  During follow-up, 426 women reported a first VTE, including 294 non-procedure-related events. No apparent interaction of reproductive life characteristics with HT assignment on VTE risk was detected, and there was not a significant association between VTE and age at menarche, age at menopause, parity, oophorectomy, or time since menopause. However, analyses restricted to non-procedure-related VTE showed a U-shaped relationship between age at menopause and thrombotic risk that persisted after multivariable analysis (P < 0.01). Compared with women aged 40 to 49 years at menopause, those who had early menopause (age <40 y) or late menopause (age >55 y) had a significantly increased VTE risk (hazard ratio [95% CI]: 1.8 [1.2-2.7] and 1.5 [1.0-2.4], respectively).
  
  
  CONCLUSIONS
  Reproductive life characteristics have little association with VTE and do not seem to influence the effect of HT on thrombotic risk among postmenopausal women. Nevertheless, early and late onset of menopause might be newly identified risk factors for non-procedure-related VTE.
authors.affiliation: From the 1Hormones and Cardiovascular Disease, Center for Research in Epidemiology and Population Health, Villejuif, France; 2Université Paris Sud, UMRS 1018, Villejuif, France; 3Paris Descartes University and Cochin-Port Royal Hospital, Paris, France; 4Department of Obstetrics and Gynecology, Miller School of Medicine, University of Miami, Miami, FL; 5Stanford Prevention Research Center, Department of Medicine, Stanford University, Stanford, CA; 6University of Washington School of Nursing, Seattle, WA; and 7Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Marianne
authors.initials: M
authors.lastname: Canonico
authors.forename: Geneviève
authors.initials: G
authors.lastname: Plu-Bureau
authors.forename: Mary Jo
authors.initials: MJ
authors.lastname: O'Sullivan
authors.forename: Marcia L
authors.initials: ML
authors.lastname: Stefanick
authors.forename: Barbara
authors.initials: B
authors.lastname: Cochrane
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Scarabin
authors.forename: Joann E
authors.initials: JE
authors.lastname: Manson
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D002648:Child; D002986:Clinical Trials as Topic; D015914:Estrogen Replacement Therapy / Q000009:adverse effects; D005260:Female; D006801:Humans; D008572:Menarche; D008593:Menopause; D008875:Middle Aged; D010052:Ovariectomy; D010298:Parity; D017698:Postmenopause; D011247:Pregnancy; D017584:Reproductive History; D012307:Risk Factors; D054556:Venous Thromboembolism / Q000453:epidemiology*; D016387:Women's Health