Progestagen Type in Postmenopausal Hormone Therapy and Blood Gene Expression Profile

Study Overview
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Brief Summary
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The purpose of this study is to compare combined postmenopausal hormone therapy natural progesterone to the one containing synthetic progestagen (i.e. chlormadinone acetate) at the blood transcriptome level.

Official Title
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Progestagen Type in Postmenopausal Hormone Therapy and Blood Gene Expression

Conditions
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Pharmacogenomics, Systems Biology

Intervention / Treatment
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* Drug: Progesterone
* Drug: Chlormadinone acetate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Postmenopausal women defined as: 45 years< age < 65 years Amenorrhoeic for ≥ 1 year Amenorrhoeic for < 1 year either without any withdrawal vaginal bleeding for 3 consecutive months in spite of a cyclic progestagen treatment and/or blood estradiol levels ≤ 20 pg/mL and blood FSH levels ≥ 40 UI/mL Women with bilateral ovariectomy Women suffering of at least 1 postmenopausal symptoms listed: Hot flashes, Memory and Concentration Problems, Mood Swings, Insomnia, Urinary Incontinence, Night sweating, Join pains, Asthenia. No use of hormone therapy (HT) Previous HT user: HT use < 3 months - stop for 6 months HT use <= 1 year - stop for > 12 months If previous use of soya derivatives in dietary supplements: washout period = 3 months Signed informed consent, after having received both oral- and written- information regarding the study goals, its risks and benefits and its constraints, including the 12 month follow-up. A delay should be respected between information and the signature of the written consent. Exclusion Criteria: Past HT users who have used treatment for more than 1 year Hysterectomized women Women without health insurance (only in French centre) History of cardio-vascular accident either arterial or venous Untreated high blood pressure Liver disease Diabetes History of cancer except basal-cell skin cancer and colon cancer Severe history of familial breast cancer defined as at least 2 women first degree- relatives with breast cancer diagnosis before 50 years History of severe mastalgia History of breast biopsy showing hyperplasia (with or without atypia) Undiagnosed vaginal bleeding Diagnosed endometrial hyperplasia Auto-immune disease (e.g. lupus) Women with kidney transplant

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Natural progesterone<br>Combined menopausal treatment containing natural progesterone | Drug: Progesterone<br>* 200 mg/day oral micronized natural progesterone (e.g. Utrogestan® 100mg) + 0.05 mg/day transdermal (i.e. plaster) 17β-estradiol (e.g. Estraderm® 50µg) during a year<br>|
| Active Comparator: Chlormadinone acetate<br>Combined menopausal treatment containing chlormadinone acetate | Drug: Chlormadinone acetate<br>* 5 mg/day oral chlormadinone acetate (e.g. Luteran® 5mg)+ 0.05 mg/day transdermal (i.e. plaster) 17β-estradiol (e.g. Estraderm® 50µg)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Whole blood and white blood cells gene expression profiling after 3 months of HT treatment |  | 0 and 3 months after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life, proteome, plasma haemostatic variable measurements |  | 0,3,6 and 12 months | 
| Whole blood and white blood cells gene expression profiling after 12 months of HT treatment |  | 0 and 12 months after treatment |