Comparison of Standard and Physiologic Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure and the Assessment of Skeletal, Cardiovascular and Reproductive Parameters
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 42
- 试验地点
- 2
- 主要终点
- Change in 24 hour ambulatory blood pressure
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Premature Ovarian Failure
排除标准
- •Intercurrent illness
研究组 & 干预措施
1
Treatment with standard sex steroid replacement regimen
干预措施: Ethinylestradiol / Norethisterone (Drug)
2
Treatment with physiologic sex steroid regimen
干预措施: Estradiol / Progesterone (Drug)
结局指标
主要结局
Change in 24 hour ambulatory blood pressure
时间窗: Before each washout period, then at 0, 3, 6 and 12 months of each treatment
Bone mineral density measurements (DEXA)
时间窗: Baseline, 14 and 24 months
Uterine ultrasound scan to assess uterine volume, endometrial thickness, and uterine artery blood flow
时间窗: Before each washout period, then at 0, 3, 6 and 12 months of each treatment
次要结局
- 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)