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Effect of 17ß-estradiol on Inflammatory-immune Responses in Post-menopausal Women According to Administration Route

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00701337
Recruitment Status : Completed
First Posted : June 19, 2008
Last Update Posted : May 11, 2017
Information provided by (Responsible Party):
University Hospital, Toulouse

Brief 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

Condition or disease Intervention/treatment Phase
Postmenopausal Drug: oestradiol Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Effect of 17ß-estradiol on Inflammatory-immune Responses in Post-menopausal Women According to Administration Route: Pilot Study
Study Start Date : September 2006
Actual Primary Completion Date : January 2010
Actual Study Completion Date : January 2010

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Menopause

Arm Intervention/treatment
Experimental: 1 Oral
oestradiol by oral administration - Estrofem 2 mg
Drug: oestradiol
oestradiol 2 mg oral route 30 days
Other Name: Estrofem

Experimental: 2 patch
oestradiol par patch - Estrapatch 60microg/24h
Drug: oestradiol
oestradio transdermal patch 60ug by 24 hours 30 days
Other Name: Oestrapatch

Primary Outcome Measures :
  1. To determine the feasibility of a future multicentric randomized trial : estimation of the number of subjects required [ Time Frame: 1 month ]

Secondary Outcome Measures :
  1. variability and repeatability of the biological parameters studied [ Time Frame: 1 month ]
    number of circulating immune cells, expression of surface molecules by monocytes, secretion of cytokines following TLR activation

  2. Feasibility of the recruitment, enrollment and follow-up of menopausal women [ Time Frame: End of study ]

Information from the National Library of Medicine

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Ages Eligible for Study:   45 Years to 60 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Women with confirmed menopause (duration : 1 to 5 years)
  • No contra-indication of hormonal replacement therapy due to medical history
  • Mammogram without significant abnormality (< 12 months)
  • Normal body mass index (BMI) (19 ≤ IMC ≤ 25 kg/m2)
  • No treatment with estrogens and/or progestatives and/or SERM (specific moduator of estrogen receptor) and/or phytoestrogènes ongoing or stopped for less than 3 months
  • No clinical or biological abnormality or treatment indicating the presence of an infectious or inflammatory disease.
  • No participation to another clinical study during the 3 months before the inclusion
  • Ability to sign the consent form.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00701337

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University Hospital Toulouse
Toulouse, France, 31059
Sponsors and Collaborators
University Hospital, Toulouse
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Principal Investigator: Pierre GOURDY Hospital University Toulouse

Publications of Results:
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Responsible Party: University Hospital, Toulouse Identifier: NCT00701337     History of Changes
Other Study ID Numbers: 0507402
First Posted: June 19, 2008    Key Record Dates
Last Update Posted: May 11, 2017
Last Verified: May 2017
Keywords provided by University Hospital, Toulouse:
Estrogen Replacement Therapy
menopausal women
Additional relevant MeSH terms:
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Estradiol 3-benzoate
Estradiol 17 beta-cypionate
Polyestradiol phosphate
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Contraceptive Agents
Reproductive Control Agents
Contraceptive Agents, Female