title: Postmenopausal hormone therapy and risk of idiopathic venous thromboembolism: results from the E3N cohort study.
abstract: OBJECTIVE
  Oral estrogen therapy increases venous thromboembolism risk among postmenopausal women. Although recent data showed transdermal estrogens may be safe with respect to thrombotic risk, the impact of the route of estrogen administration and concomitant progestogens is not fully established.
  
  
  RESULTS
  We used data from the E3N French prospective cohort of women born between 1925 and 1950 and biennially followed by questionnaires from 1990. Study population consisted of 80 308 postmenopausal women (average follow-up: 10.1 years) including 549 documented idiopathic first venous thromboembolism. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional models. Compared to never-users, past-users of hormone therapy had no increased thrombotic risk (HR=1.1; 95% CI: 0.8 to 1.5). Oral not transdermal estrogens were associated with increased thrombotic risk (HR=1.7; 95% CI: 1.1 to 2.8 and HR=1.1; 95% CI: 0.8 to 1.8; homogeneity: P=0.01). The thrombotic risk significantly differed by concomitant progestogens type (homogeneity: P<0.01): there was no significant association with progesterone, pregnanes, and nortestosterones (HR=0.9; 95% CI: 0.6 to 1.5, HR=1.3; 95% CI: 0.9 to 2.0 and HR=1.4; 95% CI: 0.7 to 2.4). However, norpregnanes were associated with increased thrombotic risk (HR=1.8; 95% CI: 1.2 to 2.7).
  
  
  CONCLUSIONS
  In this large study, we found that route of estrogen administration and concomitant progestogens type are 2 important determinants of thrombotic risk among postmenopausal women using hormone therapy. Transdermal estrogens alone or combined with progesterone might be safe with respect to thrombotic risk.
authors.affiliation: Inserm Unit 780, Cardiovascular Epidemiology Section, Cedex, France. marianne.canonico@inserm.fr
authors.forename: Marianne
authors.initials: M
authors.lastname: Canonico
authors.forename: Agnès
authors.initials: A
authors.lastname: Fournier
authors.forename: Laure
authors.initials: L
authors.lastname: Carcaillon
authors.forename: Valérie
authors.initials: V
authors.lastname: Olié
authors.forename: Geneviève
authors.initials: G
authors.lastname: Plu-Bureau
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Oger
authors.forename: Sylvie
authors.initials: S
authors.lastname: Mesrine
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Boutron-Ruault
authors.forename: Françoise
authors.initials: F
authors.lastname: Clavel-Chapelon
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Scarabin
mesh_terms: D000279:Administration, Cutaneous; D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D004359:Drug Therapy, Combination; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D004967:Estrogens / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D005602:France; D006801:Humans; D008875:Middle Aged; D011372:Progestins / Q000008:administration & dosage / Q000009:adverse effects*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D011795:Surveys and Questionnaires; D013997:Time Factors; D054556:Venous Thromboembolism / Q000139:chemically induced*
chemical_list: D004967:Estrogens; D011372:Progestins