Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
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|ClinicalTrials.gov Identifier: NCT00732693|
Recruitment Status : Completed
First Posted : August 12, 2008
Last Update Posted : August 12, 2008
|Condition or disease||Intervention/treatment||Phase|
|Premature Ovarian Failure||Drug: Ethinylestradiol / Norethisterone Drug: Estradiol / Progesterone||Phase 4|
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 (Clinical Trial)|
|Actual Enrollment :||42 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||None (Open Label)|
|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 :||February 2002|
|Actual Primary Completion Date :||November 2006|
|Actual Study Completion Date :||November 2006|
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 Name: Loestrin 30, Galen Ltd, UK
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
- Change in 24 hour ambulatory blood pressure [ Time Frame: 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 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00732693
|Royal Infirmary of Edinburgh|
|Edinburgh, United Kingdom, EH16 4SA|
|Royal Hospital for Sick Children|
|Edinburgh, United Kingdom, EH9 1LF|
|Principal Investigator:||W Hamish B Wallace, MD||NHS Lothian / University of Edinburgh|