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

Phase 4
Completed
Conditions
Premature Ovarian Failure
Interventions
Registration Number
NCT00732693
Lead Sponsor
University of Edinburgh
Brief Summary

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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
42
Inclusion Criteria
  • Premature Ovarian Failure
Exclusion Criteria
  • Intercurrent illness

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
2Estradiol / ProgesteroneTreatment with physiologic sex steroid regimen
1Ethinylestradiol / NorethisteroneTreatment with standard sex steroid replacement regimen
Primary Outcome Measures
NameTimeMethod
Change in 24 hour ambulatory blood pressureBefore each washout period, then at 0, 3, 6 and 12 months of each treatment
Bone mineral density measurements (DEXA)Baseline, 14 and 24 months
Uterine ultrasound scan to assess uterine volume, endometrial thickness, and uterine artery blood flowBefore each washout period, then at 0, 3, 6 and 12 months of each treatment
Secondary Outcome Measures
NameTimeMethod
Central arterial blood pressure and arterial stiffness measured using peripheral arterial tonometryBefore 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.Before each washout period, then at 0, 3, 6 and 12 months of each treatment phase
Serum markers of collagen turnover and bone matrix formationBefore 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 progesteroneBefore each washout period, then at 0, 3, 6 and 12 months of each treatment phase

Trial Locations

Locations (2)

Royal Infirmary of Edinburgh

🇬🇧

Edinburgh, United Kingdom

Royal Hospital for Sick Children

🇬🇧

Edinburgh, United Kingdom

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