Effect of 17ß-estradiol on Inflammatory-immune Responses in Post-menopausal Women According to Administration Route
Condition: Postmenopausal
Study type: Interventional
Phase: Phase 4

Summary: 
      The aim of this pilot study conducted in post-menopausal women is to evaluate the effect of
      17ß-estradiol administration on inflammatory-immune cells, namely antigen-presenting cells
      (monocytes/dendritic cells), and more precisely on their activation by inflammatory stimuli.
      This study will allow us to determine our ability to recruit menopausal women and to
      characterize the optimal primary end-point among the numerous criteria tested
    

Detailed description: 
      Although the beneficial effects of hormonal replacement therapy (HRT) against osteoporosis
      and climacteric symptoms have been clearly established, randomized studies recently revealed
      that the combined administration of oral estrogens and medroxyprogesterone acetate increases
      the incidence of coronary events and strokes during the first months of treatment.
      Furthermore, oral estrogens significantly enhance IL-6 and CRP secretion. This increase in
      the plasma concentration of inflammatory markers probably results from a direct effect of
      oral administration on the liver, since i twas not observed with estrogens administered by
      transdermal route.

      Our experimental data in ovariectomized mice demonstrated that the chronic subcutaneous
      administration of17ß-estradiol (E2) enhances the expression of pro-inflammatory cytokines by
      Th1 lymphocytes, Natural Killer T cells and monocytes/macrophages. This pro-inflammatory
      effect of E2 could play a role in the deleterious vascular effects observed in randomized
      studies, especially by favoring plaque instability.

      Our aim is to determine whether E2 administration in menopausal women leads to an
      inflammatory phenotype of circulating antigen-presenting cells, especially monocytes. Indeed,
      evaluating the inflammatory status at the cellular level probably gives more precise
      informations than plasma cytokine concentrations to predict the ability of estrogens to
      enhance inflammatory processes. We first propose a pilot study in order to determine
      enrollment feasibility, as well as the optimal biological endpoints to assess monocyte
      activation status. These latter criteria will be then used in a future randomized study
      comparing two routes of E2 administration (oral vs transdermal).

      The present study will include 34 menopausal women. After the inclusion visit, three visits
      will be performed with the collection of a 50 ml blood sample and the isolation of
      circulating immune cells (monocytes).

      The following criteria will be studied before (V1 and V2) and after 30 ± 3 days of E2
      treatment (V3:

        1. expression of surface activation molecules.

        2. Secretion of cytokines in response to several Toll-like receptor stimuli.

        3. IL-6 and CRP-US plasma concentrations.

      We will first assess the intra-individual variability (V1 and V2). At visit 2 (V2), the
      subjects will be randomized to receive E2 either by oral (n= 17) or transdermal (n= 17)
      route.
    

Intervention name(s): oestradiol; oestradiol
Intervention type(s): Drug; Drug
Intervention description(s): oestradiol 2 mg oral route 30 days; oestradio transdermal patch 60ug by 24 hours 30 days
Other intervention name(s): Estrofem; Oestrapatch
Intervention MeSH terms: Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Estradiol; Polyestradiol phosphate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Estrogen Replacement Therapy; menopausal women