Biological Mechanisms of Arterial Stiffening With Age and Estrogen Deficiency
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 155
- 试验地点
- 1
- 主要终点
- Arterial Stiffness (Carotid Artery Compliance) During Saline
研究概览
简要总结
The purpose of this study is to find out why women's arteries stiffen as they go through menopause, and how this is affected by estrogen loss. We believe that arteries stiffen with the loss of estrogen because of "oxidative stress," the production of molecules that can damage cells and tissues in the body, and because the arteries lose their ability to expand, or dilate.
详细描述
As women get older and go through menopause, estradiol levels decrease. Also with aging, the arteries that are located around the heart get stiffer. Over time this increase in arterial stiffness can lead to a number of health problems such as high blood pressure and heart disease. In this study we want to find out if a short-term drop in estrogen levels in premenopausal and perimenopausal women can cause arteries to become stiffer, and why this happens. Additionally, in postmenopausal women, we want to find out if a short-term increase in estrogen levels causes their arteries to become more flexible (less stiff).
Arterial health (i.e., stiffness) will be examined in premenopausal, perimenopausal and postmenopausal women before and after they are given a drug called Ganirelix™ (for 7 days), which will markedly lower their reproductive hormones. After the first 4 days of taking Ganirelix™, the women will be randomly placed into 1 of 2 treatment groups to take either estrogen (0.075 mg/d skin patch) replacement or placebo for the rest of the Ganirelix treatment. This is to increase estrogen levels back to the normal level. After having the patch on for 4 days, arterial health will be examined again.
Pre-specified Outcome Measures were divided into unit-of-measurement specific Outcome Measure tables for the purposes of results reporting to ClinicalTrials.gov
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Healthy women of all races and ethnic backgrounds in one of the following groups:
- •Premenopausal: 18-49 years, regular menstrual cycles with no change in observed cycle length (21-35 days)
- •Perimenopausal: 40-55 years, categorized as either early (at least 2 cycles with cycle length changes of at least 7 days) or late (more than 3 months of amenorrhea) transition
- •Postmenopausal: 45-70 years, more than 12 months of amenorrhea as defined by the menopausal staging system (STRAW); additionally, postmenopausal women will be categorized into early and late stages as defined by the STRAW definition, specifically, women who are less than 5 years postmenopause will be considered early, and women more than 6 years will be categorized as late
- •All postmenopausal women will have undergone natural menopause
- •No oral contraceptive or Hormone Replacement Therapy (HRT) use for at least 6 months
- •Resting blood pressure less than 140/90 mmHg
- •Plasma glucose concentrations less than 110 mg/dl under fasting conditions
- •Sedentary or recreationally active (less than 3 days of vigorous aerobic exercise)
- •No use of medications that might influence cardiovascular function
- •Nonsmokers
- •No use of vitamin supplements or willing to stop use for duration of the study
排除标准
- •History of or active estrogen-dependent neoplasms, acute liver or gallbladder disease, vaginal bleeding, venous thromboembolism, hypertriglyceridemia, and cardiovascular disease
- •Known allergy to transdermal patch or GnRHant
- •Other contraindications to HRT and GnRHant
研究组 & 干预措施
Pre1
Premenopausal - GnRHant plus estradiol
干预措施: GnRHant - Ganirelix acetate (Drug)
Pre1
Premenopausal - GnRHant plus estradiol
干预措施: Transdermal estradiol patch (Drug)
Pre2
Premenopausal - GnRHant plus placebo
干预措施: GnRHant - Ganirelix acetate (Drug)
Pre2
Premenopausal - GnRHant plus placebo
干预措施: Transdermal placebo patch (Drug)
Peri1
Perimenopausal (early) - GnRHant plus estradiol
干预措施: GnRHant - Ganirelix acetate (Drug)
Peri1
Perimenopausal (early) - GnRHant plus estradiol
干预措施: Transdermal estradiol patch (Drug)
Peri2
Perimenopausal (early) - GnRHant plus placebo
干预措施: GnRHant - Ganirelix acetate (Drug)
Peri2
Perimenopausal (early) - GnRHant plus placebo
干预措施: Transdermal placebo patch (Drug)
Peri3
Perimenopausal (late) - GnRHant plus estradiol
干预措施: GnRHant - Ganirelix acetate (Drug)
Peri3
Perimenopausal (late) - GnRHant plus estradiol
干预措施: Transdermal estradiol patch (Drug)
Peri4
Perimenopausal (late) - GnRHant plus placebo
干预措施: GnRHant - Ganirelix acetate (Drug)
Peri4
Perimenopausal (late) - GnRHant plus placebo
干预措施: Transdermal placebo patch (Drug)
Post1
Postmenopausal - GnRHant plus estradiol
干预措施: GnRHant - Ganirelix acetate (Drug)
Post1
Postmenopausal - GnRHant plus estradiol
干预措施: Transdermal estradiol patch (Drug)
Post2
Postmenopausal - GnRHant plus placebo
干预措施: GnRHant - Ganirelix acetate (Drug)
Post2
Postmenopausal - GnRHant plus placebo
干预措施: Transdermal placebo patch (Drug)
结局指标
主要结局
Arterial Stiffness (Carotid Artery Compliance) During Saline
时间窗: Baseline, day 4 of GnRHant and day 7 of GnRHant and estradiol or placebo treatment
Carotid artery compliance measured by carotid artery ultrasound and brachial artery blood pressure
Endothelial Function
时间窗: Baseline, day 4 of GnRHant and Day 7 of GnRHant and estradiol or placebo treatment
Brachial artery flow-mediated dilation (FMD) assessed by ultrasound. This other outcome measure was originally specified as "Secondary" in error and has been updated to "Primary" to be consistent with the protocol.
次要结局
未报告次要终点