Atherosclerosis, Immune Mediated Inflammation and Hypoestrogenemia in Young Women
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 29
- 试验地点
- 1
- 主要终点
- Rate of Change of Reactive Hyperemia Index (RHI) by Peripheral Arterial Tonometry
研究概览
简要总结
The purpose of this study is to determine whether young women with functional hypothalamic amenorrhea (premenopausal HypoE) is associated with risk factors for pre-clinical cardiovascular disease (CVD).
For this study, the investigators will measuring vascular function and inflammatory markers on:
- young women with functional hypothalamic amenorrhea (>3 months of no menstrual cycle due to low estrogen)
- young women with regular menstrual cycles not on hormone therapy.
- recently menopausal women (<3 years from final menstrual period) not on hormone therapy.
Premenopausal HypoE participants (women with functional hypothalamic amenorrhea) will be randomized to use either an estrogen patch or a placebo patch (no active medicine) for 12 weeks, followed by estrogen or placebo patch plus progesterone or placebo pills for 2 additional weeks. The investigators are looking to see if estrogen improves vascular and inflammation.
详细描述
Study Aims:
- To test the hypothesis premenopausal HypoE (women with FHA) is associated with pre-clinical CVD as determined by reductions in vascular endothelial function.
- To test the hypothesis premenopausal HypoE (women with FHA) is associated with increased immune-mediated inflammation.
- To test the hypothesis whether estrogen replacement can reduce inflammation and improve vascular endothelial function in premenopausal HypoE women (women with FHA).
In a randomized, double-blind placebo-controlled trial in premenopausal HypoE women (women with FHA) the investigators will test 12 weeks of transdermal estradiol 0.1 mg/day patch or placebo followed by 2 weeks of estradiol plus progesterone 200mg (for endometrial safety) on vascular endothelial function and immune-mediated inflammation versus placebo. Patches will be applied by the participant to the lower abdomen twice weekly, alternating sides.
The investigators will be using non-invasive tests to measure vascular function to measures reactive hyperemic index (RHI) using peripheral arterial tonometry (PAT)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •For premenopausal Hypo E and normal control women, inclusions include:
- •Premenopausal currently not on hormone therapy,
- •English speaking (for the purposes of complete psychosocial assessment)
- •able to give informed consent
- •a gynecological age (age since menarche) > 10 and < 25 years, and chronological age > 18 years
- •Within 90-110% of ideal body weight as determined by the 1983 Metropolitan Height and weight table for women
- •All participants with hypothalamic amenorrhea will be diagnosed based on exclusion of other etiologies for their amenorrhea, including pregnancy, thyroid dysfunction, hyperprolactinemia, premature ovarian insufficiency, and polycystic ovary disease
- •For recently menopausal women inclusions include:
- •Follicle stimulating hormones (FSH) >30 and 12 months of amenorrhea, within 3 years of final menstrual period with natural menopausal not on hormone therapy
- •English speaking
- •Able to give informed consent
- •Within 90-110% of ideal body weight
排除标准
- •For premenopausal Hypo E and normal control women exclusions include:
- •Hypertension
- •Hyperlipidemia
- •Medications including psychotropic or illicit drugs, medical, neurological
- •Ophthalmologic disease except acuity problems
- •Major Axis I disorder other than depression
- •Pregnancy in the last 12 months and/or lactating in the last 6 months
- •Current use of hormone contraceptive or any estrogen or progestin therapy
- •For HypoE women, exclusion criteria include:
- •Allergy to adhesive or tape
- •For recently menopausal women exclusions also include:
- •Previous or current use of hormone therapy, estrogen or progestin
- •Surgical or chemotherapy induced menopause
- •Premature ovarian failure
研究组 & 干预措施
Transdermal Placebo Patch, Placebo Pill
Placebo Transdermal Patch, Placebo Pill
干预措施: Placebo Pill (Drug)
17Beta Estradiol, Progesterone
17Beta Estradiol (0.1mg/day) , Progesterone (100mg) or Medroxyprogesterone (10mg) for patient with a peanut allergy because progesterone 100mg is a peanut based product
干预措施: 17beta Estradiol (Drug)
17Beta Estradiol, Progesterone
17Beta Estradiol (0.1mg/day) , Progesterone (100mg) or Medroxyprogesterone (10mg) for patient with a peanut allergy because progesterone 100mg is a peanut based product
干预措施: Progesterone (Drug)
Transdermal Placebo Patch, Placebo Pill
Placebo Transdermal Patch, Placebo Pill
干预措施: Transdermal placebo patch (Drug)
结局指标
主要结局
Rate of Change of Reactive Hyperemia Index (RHI) by Peripheral Arterial Tonometry
时间窗: Baseline, week 12 on trial
Change in PAT measured as reactive hyperemia index (RHI) from baseline to week 12 on treatment or placebo. Reactive hyperemia index (RHI) is the post-to-pre occlusion PAT signal ratio in the occluded arm, relative to the same ratio in the control arm, corrected for baseline vascular tone of the occluded arm calculated by taking the ratio of the pulse amplitude during the hyperemic phase (after a period of blood flow occlusion) to the baseline pulse amplitude. The values below \<1.67 are abnormal and suggest impaired endothelial function or endothelial dysfunction.
次要结局
- Serum Inflammatory Markers(Change in serum hsCRP from baseline to week 12 on treatment or placebo)
- Serum Estradiol Levels(Serum estradiol levels after 12 week of treatment vs placebo)
- Quality of Life (Questionnaire)(Change in quality of life scores after 12 week of treatment vs placebo)
- Depression(Change in PHQ-9 Scores after 12 week of treatment vs placebo)
- Change in Insomnia Severity Index After 12 Week of Treatment vs Placebo(Insomnia score after 12 week of treatment vs placebo)
- Anxiety(Change in Anxiety Scores after 12 week of treatment vs placebo)
- Stress(Change in stress scores after 12 week of treatment vs placebo)
- Change in Serum Estradiol Levels(change in estradiol after 12 week of treatment vs placebo)
研究者
Chrisandra Shufelt
Professor and Chair, Division of General Internal Medicine
Mayo Clinic