Identifying Neurophysiological Mechanisms of Susceptibility to Estradiol Fluctuation and Irritability Symptoms in the Menopause Transition: An Experimental Approach
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Mean IDAS Ill Temper Scale Score Over Time
研究概览
简要总结
Women in the menopause transition (perimenopause) experience substantial day-to-day variability in estradiol and have a 2-4-fold increase in major depression risk. About 40% of perimenopausal women are susceptible to the emergence of affective symptoms tied to changes in estradiol. Among the perimenopausal women with affective impairment, most report irritability, not "depression," is their primary source of impairment and distress. The purpose of this research is to determine the neurophysiologic basis of susceptibility to estradiol fluctuations and irritability symptoms in perimenopausal women.
详细描述
Using a within-subjects, cross-over design and transdermal estradiol to stabilize estradiol fluctuations (and increase levels) the investigators will test if neural dynamics (oscillatory activity in the theta and beta frequencies assessed via EEG) associated with key constructs of irritability (attentional bias to threat and frustration to non-reward) represent a biomarker target of irritability symptom response to transdermal estradiol.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
There will be one unblinded Research Assistant administering interventions to preserve masking of research personnel and participants involved. Care provider may be unmasked for specific participants if there are adverse events requiring referral.
入排标准
- 年龄范围
- 45 Years 至 59 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Healthy women 45 - 59 years of age
- •In the early menopause transition (defined by variable menstrual cycle length that is 7+ days longer or shorter than usual)
- •Increase in irritability since the onset of menstrual cycle changes
- •Moderate to severe irritability symptoms, as defined by IDAS ill-temper scale score >10
- •Have experienced 1+ very stressful life event (e.g. divorce, death of family member) within the past 6 months
- •Negative mammogram within the past two years
- •BMI between 18 - 45 kg/m^2
排除标准
- •Use of psychotropic agents or hormonal preparations, or herbal supplements (other than multivitamins) believed to affect mood or menopausal symptoms
- •History of psychosis, bipolar disorder, or substance dependence
- •Active psychological symptoms severe enough to require treatment
- •Current suicidal intent or recent history of suicide attempts (within past 10 years)
- •Personal or family history of cancer indicative of more than average risk for breast, ovarian or endometrial cancers
- •Personal history of any cardiovascular disease including coronary artery disease, arteriosclerosis, heart attack, stroke
- •Personal history of thromboembolic disorders
- •History of E2-dependent neoplasia
- •History of gallbladder disease
- •Recent history of migraine with aura
- •Blood pressure classified as higher than stage 2 hypertension (≥160 mmHg systolic or ≥100 mmHg diastolic)
- •Liver dysfunction or disease
- •Undiagnosed abnormal genital bleeding
- •Type I diabetes
- •Known sensitivities to the matrix patch system in Climara® or allergy to peanut oil used in Prometrium®
研究组 & 干预措施
Estradiol, Then Placebo
Participants will first receive 0.1 mg/day of transdermal estradiol patch for 3 weeks. After a washout period of 3 weeks, participants will then receive transdermal placebo patch (matching transdermal estradiol 0.1 mg/day patch) for 3 weeks. Upon completion of the second intervention, all participants will receive 200 mg/day of progesterone for 10 days.
干预措施: Estradiol Patch, 0.1 mg/24 Hours Weekly Transdermal Film, Extended Release (Drug)
Estradiol, Then Placebo
Participants will first receive 0.1 mg/day of transdermal estradiol patch for 3 weeks. After a washout period of 3 weeks, participants will then receive transdermal placebo patch (matching transdermal estradiol 0.1 mg/day patch) for 3 weeks. Upon completion of the second intervention, all participants will receive 200 mg/day of progesterone for 10 days.
干预措施: Placebo (Drug)
Estradiol, Then Placebo
Participants will first receive 0.1 mg/day of transdermal estradiol patch for 3 weeks. After a washout period of 3 weeks, participants will then receive transdermal placebo patch (matching transdermal estradiol 0.1 mg/day patch) for 3 weeks. Upon completion of the second intervention, all participants will receive 200 mg/day of progesterone for 10 days.
干预措施: Progesterone 200 mg (Drug)
Placebo, Then Estradiol
Participants will first receive transdermal placebo patch (matching transdermal estradiol 0.1 mg/day patch) for 3 weeks. After a washout period of 3 weeks, participants will then receive 0.1 mg/day of transdermal estradiol patch for 3 weeks. Upon completion of the second intervention, all participants will receive 200 mg/day of progesterone for 10 days.
干预措施: Estradiol Patch, 0.1 mg/24 Hours Weekly Transdermal Film, Extended Release (Drug)
Placebo, Then Estradiol
Participants will first receive transdermal placebo patch (matching transdermal estradiol 0.1 mg/day patch) for 3 weeks. After a washout period of 3 weeks, participants will then receive 0.1 mg/day of transdermal estradiol patch for 3 weeks. Upon completion of the second intervention, all participants will receive 200 mg/day of progesterone for 10 days.
干预措施: Placebo (Drug)
Placebo, Then Estradiol
Participants will first receive transdermal placebo patch (matching transdermal estradiol 0.1 mg/day patch) for 3 weeks. After a washout period of 3 weeks, participants will then receive 0.1 mg/day of transdermal estradiol patch for 3 weeks. Upon completion of the second intervention, all participants will receive 200 mg/day of progesterone for 10 days.
干预措施: Progesterone 200 mg (Drug)
结局指标
主要结局
Mean IDAS Ill Temper Scale Score Over Time
时间窗: 3 weeks during each intervention
The 5-item ill temper scale of the Inventory of Depression and Anxiety Symptoms (IDAS) will be the primary measure of irritability symptom severity. Each symptom item is rated 1 (not at all) to 5 (extremely). The total IDAS ill temper scale score may range from 5-25. Higher scores indicate more severe irritability symptoms. The average daily irritability scores will be evaluated for each 3-week treatment condition (Active Estradiol vs. Placebo).
次要结局
- Reward Positivity (RewP) in Response to the Affective Posner Paradigm(At the end of each three-week treatment period.)
- Mean LPP Amplitude During Implicit Viewing Task Dysfunctional Threat Processing Was Indexed by Greater Late Positive Potential (LPP) Component for Emotional Face Stimuli, Elicited 400-900 Milliseconds After the Stimulus Presentation.(At the end of each 3-week treatment period)