Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure

August 11, 2008 updated by: University of Edinburgh

Comparison of Standard and Physiologic Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure and the Assessment of Skeletal, Cardiovascular and Reproductive Parameters

The aim of the study is to determine whether physiological sex steroid replacement improves parameters of skeletal, cardiovascular and reproductive health of women treated with current sex steroid replacement regimens.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Premature ovarian failure, defined as the onset of the menopause before the age of 40 years, is a relatively common problem that affects 1% of women. There are a variety of aetiologies underlying premature ovarian failure including Turner syndrome and those with idiopathic onset, however with the increasing success of intensive treatment for childhood cancer, there are increasing numbers of young survivors, with a variety of late effects of treatment, including premature ovarian failure.

Evidence is required for the optimal management of young women with premature ovarian failure, either as a result of childhood cancer treatment or for other reasons. These women are currently offered combined sex steroid replacement in the convenient form of the oral contraceptive pill, or hormone replacement therapy, designed for older women after the menopause. These preparations are not designed to achieve physiological replacement of oestrogen or progesterone, either in dosage or in biochemical structure - many preparations using synthetic derivatives. These younger women who have differing metabolic and psychological requirements are looking to a future of 30 or more years of replacement. The optimal mode of SSR is not known for young women with premature ovarian failure, however there is concern that current regimens may be inadequate for optimal skeletal and cardiovascular health.

Current preliminary data demonstrates that use of physiological sex steroid replacement improves uterine parameters. Evidence is required to determine whether optimising sex steroid replacement can also significantly improve parameters of skeletal and cardiovascular health. Young women with ovarian failure face several decades of hormone replacement, so small improvements in management may make large differences to later morbidity and mortality.

The aim of the study is to determine whether physiological sex steroid replacement improves parameters of skeletal, cardiovascular and reproductive health of women treated with current sex steroid replacement regimens.

Study Type

Interventional

Enrollment (Actual)

42

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • Edinburgh, United Kingdom, EH9 1LF
        • Royal Hospital for Sick Children
      • Edinburgh, United Kingdom, EH16 4SA
        • Royal Infirmary of Edinburgh

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Premature Ovarian Failure

Exclusion Criteria:

  • Intercurrent illness

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1
Treatment with standard sex steroid replacement regimen
Drug: Ethinylestradiol / Norethisterone
Oral ethinylestradiol 30mcg and norethisterone 1.5mg daily for weeks 1-3, followed by 7 "pill free" days
Other Names:
  • Loestrin 30, Galen Ltd, UK
Experimental: 2
Treatment with physiologic sex steroid regimen
Drug: Estradiol / Progesterone
Transdermal estradiol 100mcg daily for week 1, then 150mcg daily for weeks 2-4; and vaginal progesterone pessaries 200mg twice daily for weeks 3-4
Other Names:
  • Estraderm TTS, Novartis Pharmaceuticals UK Ltd
  • Cyclogest, Activis UK Ltd

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Change in 24 hour ambulatory blood pressure
Time Frame: Before each washout period, then at 0, 3, 6 and 12 months of each treatment
Before each washout period, then at 0, 3, 6 and 12 months of each treatment
Bone mineral density measurements (DEXA)
Time Frame: Baseline, 14 and 24 months
Baseline, 14 and 24 months
Uterine ultrasound scan to assess uterine volume, endometrial thickness, and uterine artery blood flow
Time Frame: Before each washout period, then at 0, 3, 6 and 12 months of each treatment
Before each washout period, then at 0, 3, 6 and 12 months of each treatment

Secondary Outcome Measures

Outcome Measure
Time Frame
Central arterial blood pressure and arterial stiffness measured using peripheral arterial tonometry
Time Frame: Before each washout period, then at 0, 3, 6 and 12 months of each treatment phase
Before each washout period, then at 0, 3, 6 and 12 months of each treatment phase
Biochemical evidence of activity on the renin-angiotensin system, including plasma renin activity, angiotensin II, aldosterone, creatinine, urea and electrolyte concentrations.
Time Frame: Before each washout period, then at 0, 3, 6 and 12 months of each treatment phase
Before each washout period, then at 0, 3, 6 and 12 months of each treatment phase
Serum markers of collagen turnover and bone matrix formation
Time Frame: Before each washout period, then at 0, 3, 6 and 12 months of each treatment phase
Before each washout period, then at 0, 3, 6 and 12 months of each treatment phase
Hormonal assays for gonadotrophins, FSH, LH and sex steroids estrogen and progesterone
Time Frame: Before each washout period, then at 0, 3, 6 and 12 months of each treatment phase
Before each washout period, then at 0, 3, 6 and 12 months of each treatment phase

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Edinburgh

Investigators

  • Principal Investigator: W Hamish B Wallace, MD, NHS Lothian / University of Edinburgh

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2002

Primary Completion (Actual)

November 1, 2006

Study Completion (Actual)

November 1, 2006

Study Registration Dates

First Submitted

August 11, 2008

First Submitted That Met QC Criteria

August 11, 2008

First Posted (Estimate)

August 12, 2008

Study Record Updates

Last Update Posted (Estimate)

August 12, 2008

Last Update Submitted That Met QC Criteria

August 11, 2008

Last Verified

August 1, 2008

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CLIC/Sargent-178000-R35464

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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