Oral Verses Patch Trial In Menopausal Women - Individualisation of Oestrogen Therapy

Study Overview
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Brief Summary
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Ultra-low-dose oral E2/D will have more beneficial effects than trans-dermal HRT on lipids and insulin resistance in postmenopausal women, whilst adverse effects on coagulation will be avoided.

Detailed Description
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Following screening for eligibility, women will be studied at baseline and then randomized to one of two groups: Group A administered Femoston Conti - oral oestradiol 17β 0.5 mg/dydrogesterone 2.5 mg daily for the duration of the treatment phase (24 weeks) Group B administered ½ Evorel Conti patches - trans-dermal Estradiol 25 mcg/norethisterone acetate 85 mcg (½ Evorel Conti patches) daily for the duration of the treatment phase (24 weeks). Studies will be repeated after 6 months of therapy at the follow up visit.

Official Title
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Comparison of Ultra-low-dose Oral Versus Trans-dermal Hormone Therapy on Coagulation Activation and Metabolic Risk Factors for Cardiovascular Disease

Conditions
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Venous Thrombosis, Insulin Resistance

Intervention / Treatment
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* Drug: Femoston Conti
* Drug: EVOREL® CONTI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy and postmenopausal woman who have had a normal ultrasound result Aged 40 - 60 years At least 1 year post last menstrual period (per participant report) BMI 18 - 32 Normal mammogram within 2 years of study commencement Continue on any concomitant medications without any change during the study give informed consent Exclusion Criteria: Estrogen or androgen therapy during preceding 3 months Use of hormone implants during the preceding 12 months Have received any medications which may interfere with the study (SSRI, antiandrogens, PDE5 inhibitors, DHEA, SERMS) Have a significant psychiatric disorder Have a history of breast or oestrogen dependent cancer Have diabetes, thrombo-embolic disorders (recent MI angina DVT varicose veins or recurrent DVT), cardiovascular disease, liver disease any condition affecting carbohydrate metabolism, uncontrolled hypertension and uncontrolled hyperlipidaemia Untreated endometrial hyperplasia Dubin-Johnson syndrome and Rotor syndrome Undiagnosed vaginal bleeding Women who have had a hysterectomy

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 60 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

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Femoston Conti 0.5mg/2.5mg<br>Ultra low dose, film-coated 17β-estradiol (as hemihydrate) 0.5mg & dydrogesterone 2.5 mg Once a day The duration is six months. Drug intervention: Estradiol&DydrogesteronevsOestradiol&Norethisterone acetate | Drug: Femoston Conti<br>* Ultra-low-dose oral E2/D [Oestradiol 17β 0.5mg/dydrogesterone 2.5 mg] oral Femoston Conti 0.5mg Estradiol&Dydrogesterone vs Oestradiol&Norethisterone acetate<br>* Other names: Femoston Conti 0.5mg/2.5mg film-coated tablets versus;|
| Active Comparator: EVOREL® CONTI transdermal patches<br>EVOREL CONTI is a transdermal self adhesive patch which is 0.1 mm in thickness and each patch releases 50mcg of oestradiol and 170mcg of norethisterone acetate over 24 hours . The Evorel Conti patch is cut in half and applied to the lower part of the body for 3.5 days (delivering approx 25mcg of oestradiol over 24 hours ) this is replaced every 3.5 days . The duration is six months. Drug intervention: Estradiol&DydrogesteronevsOestradiol&Norethisterone acetate | Drug: EVOREL® CONTI<br>* Trans-dermal Estradiol 25mcg/norethisterone acetate 85 mcg 1/2 an Evorel Conti patch<br>* Other names: Evorel Conti transdermal patch 25 mcg transdermal dose;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Thrombin Generation IU/DL |  | Six months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| triglycerides | mmol/L | 6 months | 
| HDL | mmol/L | 6 months | 
| Total cholesterol | mmol/L | 6 months | 
| LDL | mmol/L | 6 months | 
| D-Dimers | ng/ml | 6 months | 
| APC resistance | >2 or <2 | 6 months | 
| fibrinogen | g/L | 6 months | 
| Factor V11 | U/ml | 6 months | 
| PAI-1 protein | nq/ml | 6 months | 
| fasting insulin | pmol/L | 6 months | 
| fasting glucose | mmol/L | 6 months |