Long Term Effects of Oral Versus Transdermal Estrogen Replacement Therapy in Turner Syndrome - A Randomized Trial
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Blood test values
研究概览
简要总结
This 14-month, phase IV, randomized controlled crossover trial aims to compare the effects of oral versus transdermal estrogen replacement therapy (ERT) in women with Turner syndrome (TS). The study's objectives are to clarify endocrine, metabolic, cardiovascular, and thromboembolic risk factors in TS after a wash-out period without estrogen (E2) treatment; compare the effects of oral versus transdermal (TD) ERT regimens; and examine the long-term effects of E2 administration via these two routes. The study involves 50 TS women aged 18-50 years and 50 control participants. TS participants are randomized to receive either oral or TD ERT for six months, followed by crossover to the alternate treatment for another six months. Prior to randomization, any existing ERT will be discontinued for a 1-month washout period. A second 1-month washout period will occur between the two 6-month treatment phases. Laboratory analyses and clinical investigations are performed after the first wash-out period, after the first six months of treatment, and after the last six months of treatment. We anticipate that this study may provide a basis for new and improved recommendations for sex hormone replacement therapy in TS.
详细描述
OBJECTIVES
- Clarify endocrine, metabolic, cardiovascular and thromboembolic risk factors in Turner syndrome (TS) after a wash out period
- Compare the effects of oral versus transdermal (TD) estrogen replacement therapy (ERT) in women with Turner syndrome
- Examine long term effects of ERT via the two routes on endocrine, metabolic, cardiovascular, physiologic and thromboembolic risk endpoints
BACKGROUND Turner syndrome (TS) is a rare genetic condition affecting approximately 1 in 2,000 female births. A hallmark of TS is ovarian dysgenesis, leading to hypogonadism, premature ovarian failure, and infertility. Consequently, estrogen replacement therapy (ERT) is typically initiated around age 11-12 to induce puberty and continued until the average age of menopause (50-55 years), aiming for at least 42 years of adequate estrogen exposure.
Hypogonadism in TS is associated with various health complications. Importantly, estradiol (E2) replacement may mitigate these risks. Estrogen deficiency in TS affects cardiovascular health (hypertension, congenital cardiac disease, altered lipid profiles), metabolic function (diabetes, thyroid dysfunction, hepatic disorders, kidney disease, skeletal abnormalities), and is linked to neurocognitive and social challenges.
E2 can be administered orally or transdermally (TD), but it remains unclear whether either route offers specific advantages. There is ongoing debate regarding a potential increased thromboembolic risk in TS patients treated with oral E2. Epidemiological studies in postmenopausal women have reported an elevated thromboembolic risk associated with oral estrogen treatment, but to a lesser extent with TD administration. However, extrapolating data from postmenopausal women to TS patients is inappropriate, as women with TS receive estrogen as replacement therapy due to inadequate endogenous production. Furthermore, limited knowledge exists regarding the side effects of oral versus TD estrogen replacement therapy for TS patients.
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
盲法说明
The patients with TS will be randomized to receive either oral (tablet) or transdermal (gel) estrogen replacement therapy. The study is not blinded, as both investigator and study participants know which medication, they are receiving.
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Oral estrogen treatment
Turner syndrome patients receiving oral estrogen treatment (Estrofem®)
干预措施: 17-beta estradiol (Drug)
Transdermal estrogen treatment
Turner syndrome patients receiving transdermal estrogen treatment (Divigel)
干预措施: 17-beta estradiol (Drug)
结局指标
主要结局
Blood test values
时间窗: After 1 month of wash-out, 6 months of oral and six months of transdermal treatment
Changes in blood test values of estradiol from baseline
Dual energy X-ray absorptiometry
时间窗: After 6 months of oral and six months of transdermal treatment
Changes in body composition and bone mineral density
Cardiovascular status
时间窗: After 6 months of oral and six months of transdermal treatment
Changes in arterial stiffness measured by SphygmoCor
Muscle quality (quadriceps femoris)
时间窗: After 6 months of oral and six months of transdermal treatment
MR scan of both quadriceps measuring muscle cross-sectional area (CSA) and fat content of the muscle. Maximal isometric muscle strength of both quadriceps (functional muscle tests). Muscle quality = maximum quadriceps strength measured in nM/muscle CSA.
Functional muscle tests
时间窗: After 6 months of oral and six months of transdermal treatment
Changes in maximal jumping height
Isometric muscle tests
时间窗: After 6 months of oral and six months of transdermal treatment
Changes in maximal isometric hand strength
Maximal oxygen uptake test (VO2 max)
时间窗: After 6 months of oral and six months of transdermal treatment
Changes in maximal oxygen uptake
次要结局
- Self-reported health-related quality of life and functioning (SF-36)(After 6 months of oral and six months of transdermal treatment)
- Self-reported quality of life (WHOQoL-Bref)(After 6 months of oral and six months of transdermal treatment)
- Subjective medication assesment(After 6 months of oral and six months of transdermal treatment)