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

Overview

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.

Full Title of Study: “Comparison of Ultra-low-dose Oral Versus Trans-dermal Hormone Therapy on Coagulation Activation and Metabolic Risk Factors for Cardiovascular Disease”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: November 2014

Detailed Description

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.

Interventions

  • Drug: Femoston Conti
    • 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
  • Drug: EVOREL® CONTI
    • Trans-dermal Estradiol 25mcg/norethisterone acetate 85 mcg 1/2 an Evorel Conti patch

Arms, Groups and Cohorts

  • Experimental: Femoston Conti 0.5mg/2.5mg
    • 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
  • Active Comparator: EVOREL® CONTI transdermal patches
    • 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

Clinical Trial Outcome Measures

Primary Measures

  • Thrombin Generation IU/DL
    • Time Frame: Six months

Secondary Measures

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

Participating in This Clinical Trial

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

Gender Eligibility: Female

Minimum Age: 40 Years

Maximum Age: 60 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Royal Brompton & Harefield NHS Foundation Trust
  • Collaborator
    • Chelsea and Westminster NHS Foundation Trust
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • John Stevenson, MBBS, Principal Investigator, Royal Brompton & Harefield NHS Foundation Trust
  • Overall Contact(s)
    • John Stevenson, MBBS, 0207 351 8112, j.stevenson@imperial.ac.uk

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