Hormones and Cardiovascular Disease
Director: Pierre-Yves Scarabin

Hormones and Cardiovascular Disease
Director: Pierre-Yves Scarabin

Hormones and Cardiovascular Disease
Director: Pierre-Yves Scarabin

 

Why the ESTHER study ?

Many women are prescribed estrogen therapy to treat postmenopausal climacteric symptoms. Hormone therapy is also effective for preventing osteoporotic fractures. By contrast, harmful effects of hormone therapy include breast cancer and venous thromboembolism. Most studies assessing the risk/benefit ratio of hormone therapy were done among postmenopausal women using oral estrogens. These results cannot be generalized to other regimens of hormones, especially those used in some European countries. In France, transdermal estrogens combined with progesterone are the most used. 

 

Oral oestrogen administration results in a hepatic first-pass effect and may impair the balance between procoagulant factors and antithrombotic mechanisms. A randomized trial coordinated by our group showed in 1997 the importance of the route of estrogens administration in the blood coagulation activation. Oral estrogens induce an hypercoagulability whereas transdermal estrogens appear to have little or no effect on haemostasis. The lack of data on the risk of venous thromboembolism according to the route of estrogens administration prompted us to undertake in 1998 the ESTHER study.

 

Study Design

 

The ESTHER (EStrogen and THromboEmbolism Risk) study is a multicenter case-control study promoted by Inserm. It was done in France in eight hospitals and in the general population between 1999 and 2006. The study was designed and coordinated by our team. Eligible cases were postmenopausal women, aged 45-70 years, and  admitted to hospital with a first documented episode of idiopathic venous thromboembolism. Controls had to have been admitted to the same hospital with a diagnosis a priori unrelated to estrogen use. In addition, we included consecutively outpatient cases from 3 haematology centers matched with community controls selected at random from electoral rolls.  Cases and controls were matched for center, 2-year age band, admission date and area of residence. Each case was matched with 1 to 3 controls. Both hospital and outpatient cases were excluded if they reported a personal history of VTE, had a contra-indication for hormone therapy (breast cancer, endometrial cancer and cardiovascular disease) or had a predisposing factor for VTE. Controls were subject to the same exclusion criteria as were cases.

 

Clinical events (deep venous thrombosis and/or pulmonary embolism) had to be diagnosed by using an imaging procedure. Events were adjudicated within each center but also centrally for outpatient cases. Events were validated by investigators blinded to estrogen use. Cases and controls were identified without knowledge of estrogen use and they were interviewed at hospital in a standard way with the same questionnaire. Identification of hormone therapy was assisted by showing pictures of both available estrogens and progestogens. Examination included a blood collection for DNA extraction. A total of 271 cases and 610 controls were recruited.

 

Participants to the ESTHER study

 

Clinical centers : Département de Médecine interne, Hôpital de la Cavale Blanche, Brest (E Oger, D Mottier), Service d'Exploration Fonctionnelle, Centre Hospitalier de Caen (MT Barrellier), Unité Hémostase-Thrombose, Hôtel-Dieu, Paris (J Conard, G Plu-Bureau), Service de Médecine Interne et Médecine Générale, Service d'Hématologie Biologique, Centre Hospitalier et Universitaire de Nancy (D Wahl, T Lecompte, E de Maistre, MC Laprevote-Heully), Département de Pneumologie, Hôpital Européen Georges Pompidou, Paris (G Meyer, MT Guillanneuf), Laboratoire d'Hématologie, Hôpital Cardiologique, Département de Médecine Interne, Centre Hospitalier de Rouen (H Lévesque, N Cailleux), Département de Médecine Vasculaire, Hôpital Purpan, Toulouse (P Léger, A Elias).

 

DNA bank : Hopital Européen Georges Pompidou- Laboratoire d’Hématologie- (M Alhenc-Gélas)

 

Coordinating center : Inserm U780 (E Oger, G Plu-Bureau, L Carcaillon, M Canonico and PY Scarabin).

 

Funding

 

The study is supported by the Fondation de France, by the Fondation pour la Recherche Médicale (FRM) and Institut National de la Santé et de la Recherche Médicale (Inserm), and by grants from Aventis, Besins International, Sanofi, and Servier Institute.

© Esther 2019