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

Sponsor

University of Edinburgh (Other)

Overall Status

Completed

CT.gov ID

NCT00732693

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Premature Ovarian Failure	Drug: Ethinylestradiol / Norethisterone Drug: Estradiol / Progesterone	Phase 4

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

42 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Feb 1, 2002

Actual Primary Completion Date :

Nov 1, 2006

Actual Study Completion Date :

Nov 1, 2006

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Change in 24 hour ambulatory blood pressure [Before 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 flow [Before each washout period, then at 0, 3, 6 and 12 months of each treatment]

Secondary Outcome Measures

Central arterial blood pressure and arterial stiffness measured using peripheral arterial tonometry [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. [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 [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 [Before each washout period, then at 0, 3, 6 and 12 months of each treatment phase]