Postmenopausal hormone therapy and risk of idiopathic venous thromboembolism: results from the E3N cohort study.
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.
Canonico
Marianne
M
Inserm Unit 780, Cardiovascular Epidemiology Section, Cedex, France. marianne.canonico@inserm.fr
Fournier
Agnès
A
Carcaillon
Laure
L
Olié
Valérie
V
Plu-Bureau
Geneviève
G
Oger
Emmanuel
E
Mesrine
Sylvie
S
Boutron-Ruault
Marie-Christine
MC
Clavel-Chapelon
Françoise
F
Scarabin
Pierre-Yves
PY
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*
D004967:Estrogens; D011372:Progestins