Hormone therapy and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration and progestogens: the ESTHER study.
BACKGROUND
Oral estrogen therapy increases the risk of venous thromboembolism (VTE) in postmenopausal women. Transdermal estrogen may be safer. However, currently available data have limited the ability to investigate the wide variety of types of progestogen.


RESULTS
We performed a multicenter case-control study of VTE among postmenopausal women 45 to 70 years of age between 1999 and 2005 in France. We recruited 271 consecutive cases with a first documented episode of idiopathic VTE (208 hospital cases, 63 outpatient cases) and 610 controls (426 hospital controls, 184 community controls) matched for center, age, and admission date. After adjustment for potential confounding factors, odds ratios (ORs) for VTE in current users of oral and transdermal estrogen compared with nonusers were 4.2 (95% CI, 1.5 to 11.6) and 0.9 (95% CI, 0.4 to 2.1), respectively. There was no significant association of VTE with micronized progesterone and pregnane derivatives (OR, 0.7; 95% CI, 0.3 to 1.9 and OR, 0.9; 95% CI, 0.4 to 2.3, respectively). In contrast, norpregnane derivatives were associated with a 4-fold-increased VTE risk (OR, 3.9; 95% CI, 1.5 to 10.0).


CONCLUSIONS
Oral but not transdermal estrogen is associated with an increased VTE risk. In addition, our data suggest that norpregnane derivatives may be thrombogenic, whereas micronized progesterone and pregnane derivatives appear safe with respect to thrombotic risk. If confirmed, these findings could benefit women in the management of their menopausal symptoms with respect to the VTE risk associated with oral estrogen and use of progestogens.
Canonico
Marianne
M
Inserm Unit 780, Cardiovascular Epidemiology Section, 16 Avenue Paul Vaillant Couturier, 94807 Villejuif Cedex, France.
Oger
Emmanuel
E
Plu-Bureau
Geneviève
G
Conard
Jacqueline
J
Meyer
Guy
G
Lévesque
Hervé
H
Trillot
Nathalie
N
Barrellier
Marie-Thérèse
MT
Wahl
Denis
D
Emmerich
Joseph
J
Scarabin
Pierre-Yves
PY
D000279:Administration, Cutaneous; D000284:Administration, Oral; D000368:Aged; D016022:Case-Control Studies; D004333:Drug Administration Routes; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D004967:Estrogens / Q000008:administration & dosage; D005260:Female; D006728:Hormones / Q000008:administration & dosage; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause; D011372:Progestins / Q000008:administration & dosage; D013923:Thromboembolism / Q000139:chemically induced*; D020246:Venous Thrombosis / Q000139:chemically induced*
D004967:Estrogens; D006728:Hormones; D011372:Progestins