Amount, Distribution and Dysfunction of Body Fat as Determinants of Female Gonadal Dysfunction: From Functional Hypothalamic Amenorrhea to the Polycystic Ovary Syndrome
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 2
- 主要终点
- Adipokine and myokine signaling identification
研究概览
简要总结
Reproduction requires from women enough energy depots to warrant an adequate nutritional supply to the fetus. Hence, adipose tissue is able to communicate with female hypothalamic-pituitary-ovary axis. The hypothesis of the project is that abnormalities in the quantity (absolute and relative to lean body mass), distribution and/or function of adipose tissue are associated with functional forms of female gonadal dysfunction in predisposed women, in a spectrum of anomalies that go from hypothalamic amenorrhea to the polycystic ovary syndrome (PCOS). To challenge this hypothesis, the investigators will study 5 groups of 10 women each: women with exercise-associated hypothalamic amenorrhea, women without ovulatory dysfunction that exercise equally, non-hyperandrogenic patients with PCOS, hyperandrogenic patients with PCOS, and healthy control women comparable to those with PCOS. The aims of the study will be:
Primary objective: To identify novel signalling factors originating from adipose tissue and muscle using targeted and nontargeted evaluation of the proteome and of gene expression of superficial subcutaneous fat, deep subcutaneous fat (which mimics visceral adipose tissue) and skeletal muscle.
Secondary objectives:
- To study the serum adipokine profile - including those identified by the primary objective - and circulating gut hormones during fasting and after a glucose load in the 5 groups of women, and their associations with sexual hormones and body fat distribution.
- To study body composition and body fat distribution in these women and their relationships with:
2.1, Sex steroid profiles.
2.2. Classic cardiovascular risk factors: carbohydrate metabolism, lipid profiles and blood pressure.
2.3 Markers of low-grade chronic inflammation.
2.4. Oxidative stress markers.
2.5. Cardiovascular autonomic function.
2.6. Surrogate markers of subclinical atherosclerosis.
2.7. Circulating concentrations of endocrine disruptors.
2.8. Oral and gut microbiome.
The results will provide a better understanding of the mechanisms linking body energy depots with the female reproductive axis and, hopefully, the identification of potential biomarkers for the diagnosis and treatment of the disorders studied here.
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
- 18 Years 至 40 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Body mass index between 18.5 and 25.0 kg/m
- •Group 1 ovulatory dysfunction [World Health Organization (WHO) classification].
- •Normal/low gonadotrophin levels [follicle-stimulating hormone (FSH) and luteinizing (LH) < 10 IU/l] and low estradiol (< 50 pg/ml).
- •Moderate-vigorous intensity physical activity (> 5 hours per week) plus low energy availability (< 30 kcal/per kg of lean mass).
- •Exclusion of secondary etiologies
- •Informed consent signed.
- •Polycystic ovary syndrome phenotype I, II and III [National Institute of Health (NIH)-2012] with hyperandrogenemia (http://prevention.nih.gov/workshops/2012/resources.aspx).
- •Body mass index between 18.5 and 40.0 kg/m
- •Informed consent signed.
- •Polycystic ovary syndrome phenotype IV (NIH-2012) (http://prevention.nih.gov/workshops/2012/resources.aspx).
- •Body mass index between 18.5 and 40.0 kg/m
- •Informed consent signed.
- •Body mass index between 18.5 and 25.0 kg/m
- •Regular menses.
- •Normal gonadotropins and estradiol levels at follicular phase.
- •Moderate-vigorous intensity physical activity (> 5 hours per week) with normal energy availability (> 30 kcal/per kg of lean mass).
- •Informed consent signed.
- •No signs or symptoms of hyperandrogenism.
- •No exercise or mild intensity physical activity.
- •Regular menses.
- •Body mass index between 18.5 and 40.0 kg/m
- •Informed consent signed.
排除标准
- •(Groups I-V)
- •Oral drugs interfering with ovulation (glucocorticoids, antipsychotics, antidepressants, contraceptives, sex steroids and/or opioids) for the previous 6 months to study inclusion.
- •Current pregnancy or lactation, or during the previous 6 months to study inclusion.
- •Asherman's syndrome or outflow tract disorders.
- •Current smoking or alcohol intake > 40 g per day.
- •Previous diagnosis of glucose intolerance, hypertension, dyslipidemia, known heart or lung diseases, kidney disease, liver disease, celiac disease or any other malabsorptive condition, chronic inflammatory disease or malignancy.
研究组 & 干预措施
III- Non-hyperandrogenic polycystic ovary syndrome
5 lean women with non-hyperandrogenic polycystic ovary syndrome 5 women with weight excess and non-hyperandrogenic polycystic ovary syndrome
干预措施: Anthropometric and physical examination (Diagnostic Test)
III- Non-hyperandrogenic polycystic ovary syndrome
5 lean women with non-hyperandrogenic polycystic ovary syndrome 5 women with weight excess and non-hyperandrogenic polycystic ovary syndrome
干预措施: Indirect calorimetry, accelerometer and seven-day dietary recall (Diagnostic Test)
III- Non-hyperandrogenic polycystic ovary syndrome
5 lean women with non-hyperandrogenic polycystic ovary syndrome 5 women with weight excess and non-hyperandrogenic polycystic ovary syndrome
干预措施: Biochemical, hormonal and metabolic phenotyping (Diagnostic Test)
III- Non-hyperandrogenic polycystic ovary syndrome
5 lean women with non-hyperandrogenic polycystic ovary syndrome 5 women with weight excess and non-hyperandrogenic polycystic ovary syndrome
干预措施: Sonographic studies (Diagnostic Test)
III- Non-hyperandrogenic polycystic ovary syndrome
5 lean women with non-hyperandrogenic polycystic ovary syndrome 5 women with weight excess and non-hyperandrogenic polycystic ovary syndrome
干预措施: 24-hour Ambulatory blood pressure monitoring (Diagnostic Test)
III- Non-hyperandrogenic polycystic ovary syndrome
5 lean women with non-hyperandrogenic polycystic ovary syndrome 5 women with weight excess and non-hyperandrogenic polycystic ovary syndrome
干预措施: Percutaneous biopsy (Procedure)
III- Non-hyperandrogenic polycystic ovary syndrome
5 lean women with non-hyperandrogenic polycystic ovary syndrome 5 women with weight excess and non-hyperandrogenic polycystic ovary syndrome
干预措施: Cardiovascular autonomic function studies (Diagnostic Test)
III- Non-hyperandrogenic polycystic ovary syndrome
5 lean women with non-hyperandrogenic polycystic ovary syndrome 5 women with weight excess and non-hyperandrogenic polycystic ovary syndrome
干预措施: Oral smear and feces specimen (Diagnostic Test)
IV- Trained women without ovulatory dysfunction
10 women who exercise as intensively as women with exercise-associated hypothalamic amenorrhea but with normal ovulatory cycles.
干预措施: Anthropometric and physical examination (Diagnostic Test)
IV- Trained women without ovulatory dysfunction
10 women who exercise as intensively as women with exercise-associated hypothalamic amenorrhea but with normal ovulatory cycles.
干预措施: Indirect calorimetry, accelerometer and seven-day dietary recall (Diagnostic Test)
IV- Trained women without ovulatory dysfunction
10 women who exercise as intensively as women with exercise-associated hypothalamic amenorrhea but with normal ovulatory cycles.
干预措施: Biochemical, hormonal and metabolic phenotyping (Diagnostic Test)
IV- Trained women without ovulatory dysfunction
10 women who exercise as intensively as women with exercise-associated hypothalamic amenorrhea but with normal ovulatory cycles.
干预措施: Sonographic studies (Diagnostic Test)
IV- Trained women without ovulatory dysfunction
10 women who exercise as intensively as women with exercise-associated hypothalamic amenorrhea but with normal ovulatory cycles.
干预措施: 24-hour Ambulatory blood pressure monitoring (Diagnostic Test)
IV- Trained women without ovulatory dysfunction
10 women who exercise as intensively as women with exercise-associated hypothalamic amenorrhea but with normal ovulatory cycles.
干预措施: Percutaneous biopsy (Procedure)
IV- Trained women without ovulatory dysfunction
10 women who exercise as intensively as women with exercise-associated hypothalamic amenorrhea but with normal ovulatory cycles.
干预措施: Cardiovascular autonomic function studies (Diagnostic Test)
IV- Trained women without ovulatory dysfunction
10 women who exercise as intensively as women with exercise-associated hypothalamic amenorrhea but with normal ovulatory cycles.
干预措施: Oral smear and feces specimen (Diagnostic Test)
V- Non-hyperandrogenic healthy women
10 women matched by age and body mass index with women with polycystic ovary syndrome who do not perform physical activity on a regular basis
干预措施: Anthropometric and physical examination (Diagnostic Test)
V- Non-hyperandrogenic healthy women
10 women matched by age and body mass index with women with polycystic ovary syndrome who do not perform physical activity on a regular basis
干预措施: Indirect calorimetry, accelerometer and seven-day dietary recall (Diagnostic Test)
V- Non-hyperandrogenic healthy women
10 women matched by age and body mass index with women with polycystic ovary syndrome who do not perform physical activity on a regular basis
干预措施: Biochemical, hormonal and metabolic phenotyping (Diagnostic Test)
V- Non-hyperandrogenic healthy women
10 women matched by age and body mass index with women with polycystic ovary syndrome who do not perform physical activity on a regular basis
干预措施: Sonographic studies (Diagnostic Test)
V- Non-hyperandrogenic healthy women
10 women matched by age and body mass index with women with polycystic ovary syndrome who do not perform physical activity on a regular basis
干预措施: 24-hour Ambulatory blood pressure monitoring (Diagnostic Test)
V- Non-hyperandrogenic healthy women
10 women matched by age and body mass index with women with polycystic ovary syndrome who do not perform physical activity on a regular basis
干预措施: Percutaneous biopsy (Procedure)
V- Non-hyperandrogenic healthy women
10 women matched by age and body mass index with women with polycystic ovary syndrome who do not perform physical activity on a regular basis
干预措施: Cardiovascular autonomic function studies (Diagnostic Test)
V- Non-hyperandrogenic healthy women
10 women matched by age and body mass index with women with polycystic ovary syndrome who do not perform physical activity on a regular basis
干预措施: Oral smear and feces specimen (Diagnostic Test)
II- Hyperandrogenic polycystic ovary syndrome
5 lean women with hyperandrogenic polycystic ovary syndrome. 5 women with weight excess and hyperandrogenic polycystic ovary syndrome.
干预措施: Anthropometric and physical examination (Diagnostic Test)
II- Hyperandrogenic polycystic ovary syndrome
5 lean women with hyperandrogenic polycystic ovary syndrome. 5 women with weight excess and hyperandrogenic polycystic ovary syndrome.
干预措施: Indirect calorimetry, accelerometer and seven-day dietary recall (Diagnostic Test)
II- Hyperandrogenic polycystic ovary syndrome
5 lean women with hyperandrogenic polycystic ovary syndrome. 5 women with weight excess and hyperandrogenic polycystic ovary syndrome.
干预措施: Biochemical, hormonal and metabolic phenotyping (Diagnostic Test)
II- Hyperandrogenic polycystic ovary syndrome
5 lean women with hyperandrogenic polycystic ovary syndrome. 5 women with weight excess and hyperandrogenic polycystic ovary syndrome.
干预措施: Sonographic studies (Diagnostic Test)
II- Hyperandrogenic polycystic ovary syndrome
5 lean women with hyperandrogenic polycystic ovary syndrome. 5 women with weight excess and hyperandrogenic polycystic ovary syndrome.
干预措施: 24-hour Ambulatory blood pressure monitoring (Diagnostic Test)
II- Hyperandrogenic polycystic ovary syndrome
5 lean women with hyperandrogenic polycystic ovary syndrome. 5 women with weight excess and hyperandrogenic polycystic ovary syndrome.
干预措施: Percutaneous biopsy (Procedure)
II- Hyperandrogenic polycystic ovary syndrome
5 lean women with hyperandrogenic polycystic ovary syndrome. 5 women with weight excess and hyperandrogenic polycystic ovary syndrome.
干预措施: Cardiovascular autonomic function studies (Diagnostic Test)
II- Hyperandrogenic polycystic ovary syndrome
5 lean women with hyperandrogenic polycystic ovary syndrome. 5 women with weight excess and hyperandrogenic polycystic ovary syndrome.
干预措施: Oral smear and feces specimen (Diagnostic Test)
I- Hypothalamic amenorrhea
10 women with exercise-associated hypothalamic amenorrhea
干预措施: Anthropometric and physical examination (Diagnostic Test)
I- Hypothalamic amenorrhea
10 women with exercise-associated hypothalamic amenorrhea
干预措施: Indirect calorimetry, accelerometer and seven-day dietary recall (Diagnostic Test)
I- Hypothalamic amenorrhea
10 women with exercise-associated hypothalamic amenorrhea
干预措施: Biochemical, hormonal and metabolic phenotyping (Diagnostic Test)
I- Hypothalamic amenorrhea
10 women with exercise-associated hypothalamic amenorrhea
干预措施: Sonographic studies (Diagnostic Test)
I- Hypothalamic amenorrhea
10 women with exercise-associated hypothalamic amenorrhea
干预措施: 24-hour Ambulatory blood pressure monitoring (Diagnostic Test)
I- Hypothalamic amenorrhea
10 women with exercise-associated hypothalamic amenorrhea
干预措施: Percutaneous biopsy (Procedure)
I- Hypothalamic amenorrhea
10 women with exercise-associated hypothalamic amenorrhea
干预措施: Cardiovascular autonomic function studies (Diagnostic Test)
I- Hypothalamic amenorrhea
10 women with exercise-associated hypothalamic amenorrhea
干预措施: Oral smear and feces specimen (Diagnostic Test)
结局指标
主要结局
Adipokine and myokine signaling identification
时间窗: Up to 5 years
次要结局
- Circulating adipokine profile(Up to 5 years)
- Association between body fat depots and sex steroids(Up to 5 years)
- Appetite regulation hormonal profile(Up to 5 years)
- Association between body mass index and sex steroids(Up to 5 years)
- Association between percentage of fat mass with respect to total body weight and sex steroids(Up to 5 years)
- Association between percentage of lean mass with respect to total body weight and sex steroids(Up to 5 years)
- Association between body composition, sex steroids, and insulin resistance.(Up to 5 years)
- Association between body composition, sex steroids, and lipids.(Up to 5 years)
- Association between body composition, sex steroids, and office blood pressure.(Up to 5 years)
- Association between body composition, sex steroids, and ambulatory blood pressure monitoring parameters.(Up to 5 years)
- Association between body composition, sex steroids, and cardiovascular autonomic function tests.(Up to 5 years)
- Association between body composition, sex steroids, and carotid intima-media thickness.(Up to 5 years)
- Association between body composition, sex steroids, and oxidative stress.(Up to 5 years)
- Association between body composition, sex steroids, and microbiome(Up to 5 years)