Endothelial Dysfunction in Adolescents and Women With Polycystic Ovary Syndrome (PCOS)
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Peripheral vascular imaging via ultrasonography during brachial artery flow-mediated vasodilation (FMD)
研究概览
简要总结
The purpose of this study is to determine if changes in blood vessel health lead to the menstrual irregularities that women with PCOS experience. This research study will help determine if women with PCOS have early changes in their blood vessels called "endothelial dysfunction," and if the number of progenitor cells (cells that in a healthy person repair blood vessel damage) are related to these blood vessel changes. To do so, we will compare ultrasound (soundwave) pictures of a large blood vessel in the arm and the results of blood tests between women with PCOS and other healthy women with normal menstrual periods.
详细描述
Overview:
Although adult women with PCOS demonstrate evidence of endothelial dysfunction, little is known regarding alterations in the number of pro-inflammatory monocytes, CEC, CPC, and ECFC (endothelial injury/repair profile) among affected women. For many women, the clinical manifestations of PCOS emerge during adolescence. Based on studies documenting the increased prevalence of MetS and inflammatory markers in adolescent girls with PCOS, and non-invasive studies documenting the presence of endothelial dysfunction in children with traditional cardiovascular risk factors, it is likely adolescent girls with PCOS already manifest evidence of early vascular dysfunction, which may in turn impair follicular development and contribute to the development of infertility.
Consequently, we hypothesize that perturbations in the balance between circulating inflammatory and progenitor cells contribute to the endothelial dysfunction observed in adult women with PCOS. Specifically, we anticipate that PCOS women will manifest greater evidence of vascular injury (increased numbers of inflammatory monocytes, CEC, and ECFC) and impaired endothelial repair (decreased levels of CPC) compared with control women. Moreover, we propose that, in adolescent girls with PCOS, endothelial dysfunction and corresponding alterations in the endothelial injury/repair profile are already present.
Specific Aim 1: Determine if the endothelial injury/repair profile (inflammatory monocytes, CEC, CPC, and ECFC) assessed by flow cytometry (PFC) and endothelial function (assessed by flow-mediated vasodilation (FMD) of the brachial artery) are altered in treatment-naïve adult (18-40 years of age) women with PCOS (n=15) compared with age and body mass index (BMI)-matched control women (n=15).
Specific Aim 2: Determine if the endothelial injury/repair profile assessed by PFC, AGE levels, and endothelial function (assessed by FMD of the brachial artery) are altered in treatment-naïve adolescents (14-17 years of age) with PCOS (n=15) compared with age and BMI-Z-score-matched control girls (n=15).
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 14 Years 至 40 Years（Child, Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •PCOS as defined by NIH/NICHD criteria: 1) oligo- or amenorrhea (≤8 menstrual periods annually, persisting 2 years post menarche); 2) biochemical hyperandrogenism(HA), i.e.,elevated total or free testosterone concentration and/or clinical evidence of HA (defined as the presence of hirsutism); and 3) exclusion of secondary causes of ovulatory dysfunction and HA (including hyperprolactinemia, thyroid dysfunction, non-classical congenital adrenal hyperplasia (NCAH) due to 21-hydroxylase deficiency, Cushing syndrome, androgen secreting neoplasms, and androgenic/anabolic drug use).
- •Inclusion criteria for adolescent and adult control subjects will include 1) normal menstrual periods (defined as regular cycles between 22-36 days in length); 2) normal serum androgens (total/free testosterone and dehydroepiandrosterone-sulfate [DHEA-S]); and 3) absence of clinical evidence of hyperandrogenism. Additionally, adolescent controls must be 2 years post menarche.
排除标准
- •Diabetes mellitus
- •Underlying endocrine, neurologic, and/or genetic syndromes leading to obesity
- •Congenital heart disease or abnormal resting ECG
- •Renal or hepatic disease
- •History of rheumatologic disorders or malignancy
- •Use of medications or dietary supplements known to affect insulin sensitivity (i.e. metformin, corticosteroids, and oral contraceptive pills), blood pressure, or cholesterol within 3 months of study participation
- •Investigation drug use within 3 months of study participation
- •Pregnancy
- •Current tobacco use
结局指标
主要结局
Peripheral vascular imaging via ultrasonography during brachial artery flow-mediated vasodilation (FMD)
时间窗: ~ 30 minutes
A blood pressure cuff is placed on right forearm. A 7-12MHz linear array ultrasound transducer is placed on upper arm. 2-D and Doppler images are acquired. Forearm cuff is inflated to \~ 50 mmHg above resting systolic blood pressure (max 300 mmHg) for 4.5 minutes, then deflated. Blood flow velocity via Doppler is recorded for 15 seconds; 2D-images of the brachial artery are collected for 3 minutes. Brachial artery diameter is measured at end diastole (R-wave on ECG).FMD is determined: %FMD=(LDp-LDb)/LDbx100, where LDp=luminal diameter after inflation and LDb=luminal diameter at baseline
次要结局
- FMD with non-endothelial dependent (NED) vessel dilation(~30 minutes)