Bioenergetic and Metabolic Consequences of the Loss of Ovarian Function in Women - 2018
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 57
- 试验地点
- 1
- 主要终点
- Change in the Microdialysis Cortisone Challenge (MCC) Index
研究概览
简要总结
The menopause transition is associated with increased risk for weight gain and a shift toward storing fat in the belly region, which may increase risk for cardiovascular disease and diabetes. The study will determine whether the stress hormone cortisol contributes to this shift.
详细描述
The menopause transition is associated with increased risk for weight gain and a shift toward storing fat in the belly region, which may increase risk for cardiovascular disease and diabetes. The stress hormone cortisol is known to promote the accumulation of belly fat, and there is evidence that low estrogen is associated with higher cortisol levels. The first aim of the study is to determine whether low estrogen levels in premenopausal and early postmenopausal women increase cortisol levels in the blood and in fat tissue. When estrogen level decreases at the time of menopause, there is an increase in follicle-stimulating hormone, or FSH. Recent evidence in mice suggests that blocking FSH prevents the increase in belly fat. The second aim of the study is to determine whether decreasing the high FSH level in postmenopausal women causes a decrease in belly fat and changes other factors that are typically thought to be related to estrogen rather than FSH. Because estrogen and FSH levels fluctuate in premenopausal and early postmenopausal women, the investigators will use an approach that controls estrogen and FSH levels to address the aims. The investigators will use a drug that is typically used to treat endometriosis or uterine fibroids to reduce estrogen and FSH levels and an estrogen patch to increase estrogen in some women. The study will generate new knowledge on how menopause affects fat gain and disease risk.
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 65 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Volunteers will be healthy peri/postmenopausal women who are willing and able to undergo the proposed hormone manipulation and study procedures. Women will be at least 6 months but not more than 7 years past the last menstrual period (i.e., late perimenopausal or early postmenopausal) with FSH >30 IU/L. We will make a major effort to ensure that the women enrolled in this study come from all races and ethnicities and a wide range of socioeconomic and educational levels. Women will be excluded for the reasons listed below.
排除标准
- •abnormal vaginal bleeding
- •on hormonal contraceptive or menopausal therapy or intention to start during the period of study
- •positive pregnancy test or intention to become pregnant during the period of study
- •lactation
- •known hypersensitivity to degarelix acetate, estradiol, or medroxyprogesterone acetate
- •Center for Epidemiological Studies Depression Scale (CES-D) score <,16 (unless clinician follow-up and clinical judgement determine they are eligible (will be noted in study chart)
- •current tobacco and/or vape use more than 2 times/week
- •current marijuana or tetrahydrocannabinol (THC) use in any form more than 3 times/week
- •regular self-reported alcohol consumption >14 drinks/week
- •BMI >39 kg/m2
- •use of glucocorticoids or drugs that affect glucocorticoid metabolism (e.g., ketoconazole)
- •severe osteopenia or osteoporosis, defined as femoral neck or lumbar spine t-score <-2.0
- •thyroid dysfunction, defined as an ultrasensitive TSH <0.5 or >5.0 mU/L; volunteers with abnormal thyroid stimulating hormone (TSH) values will be re-considered for participation in the study after follow-up evaluation by the PCP with initiation or adjustment of thyroid hormone replacement
- •liver dysfunction, defined as liver function tests (AST, ALT) >1.5 times the upper limit of normal
- •uncontrolled hypertension defined as resting systolic BP >150 mmHg or diastolic BP>90 mmHg; participants who do not meet these criteria at first screening will be re-evaluated, including after follow-up evaluation by the primary care provider (PCP) with initiation or adjustment of anti-hypertensive medications
- •self-reported history of breast cancer or other estrogen-dependent neoplasms
- •self-reported history of venous thromboembolism, pulmonary embolism, or other thromboembolic disorder
- •self-reported history of cardiovascular disease
研究组 & 干预措施
Postmenopausal: GnRH antagonist + estradiol
GnRH antagonist is degarelix acetate, 80 mg, delivered twice as a subcutaneous injection (at baseline and after 12 weeks)
Estradiol is a transdermal patch 0.075 mg, applied weekly for 24 weeks
干预措施: GnRH antagonist (Drug)
Postmenopausal: GnRH antagonist + estradiol
GnRH antagonist is degarelix acetate, 80 mg, delivered twice as a subcutaneous injection (at baseline and after 12 weeks)
Estradiol is a transdermal patch 0.075 mg, applied weekly for 24 weeks
干预措施: Estrogen Product (Drug)
Postmenopausal: GnRH antagonist + placebo
GnRH antagonist is degarelix acetate, 80 mg, delivered twice as a subcutaneous injection (at baseline and after 12 weeks)
Placebo is a transdermal patch, applied weekly for 24 weeks
干预措施: GnRH antagonist (Drug)
Postmenopausal: GnRH antagonist + placebo
GnRH antagonist is degarelix acetate, 80 mg, delivered twice as a subcutaneous injection (at baseline and after 12 weeks)
Placebo is a transdermal patch, applied weekly for 24 weeks
干预措施: Placebo estradiol (Drug)
Postmenopausal: placebo + placebo
Placebo (1) is normal saline, delivered twice as a subcutaneous injection (at baseline and after 12 weeks)
Placebo (2) is a transdermal patch, applied weekly for 24 weeks
干预措施: Placebo estradiol (Drug)
Postmenopausal: placebo + placebo
Placebo (1) is normal saline, delivered twice as a subcutaneous injection (at baseline and after 12 weeks)
Placebo (2) is a transdermal patch, applied weekly for 24 weeks
干预措施: Placebo GnRH antagonist (Drug)
结局指标
主要结局
Change in the Microdialysis Cortisone Challenge (MCC) Index
时间窗: Baseline, week 12
The MCC Index is an in vivo measurement of local cortisol production in abdominal adipose tissue. A higher MCC Index is an indicator of more local cortisol production.
Change in the Oral Cortisone Challenge (OCC) Area Under the Curve (AUC)
时间窗: Baseline, week 12
The OCC AUC is a systemic measurement of peripheral glucocorticoid metabolism. A higher OCC AUC is an indicator of more production of cortisol.
次要结局
- Change in resting energy expenditure (REE)(Baseline, week 12, week 24)
- Change in proximal femur Bone Mineral Density (BMD)(Baseline, week 24)
- Change in flow-mediated dilation (FMD)(Baseline, week 12, week 24)
- Change in lumbar spine Bone Mineral Density (BMD)(Baseline, week 24)
- Change in visceral fat area (VFA)(Baseline, week 24)