The Effect and Mechanism Of Weight Cycling on Hyperandrogenemia And Insulin Resistance in Polycystic Ovary Syndrome
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 425
- 试验地点
- 1
- 主要终点
- Weight loss rate
研究概览
简要总结
This study prospectively includes PCOS patients with normal weight and overweight/obesity, closely follows up and intensively manages them, and observes the level and distribution of weight reduction achieved by patients after lifestyle intervention (high-protein diet for weight loss). Additionally, it aims to provide reference for setting weight loss targets for future PCOS patients by comparing the differences in clinical improvement among patients achieving different degrees of weight reduction (<2% [equivalent to no weight loss], 2-5%, 5-10%, ≥10%) at different time points (3 months, 6 months) following dietary intervention. Furthermore, this study will compare the differences in reproductive and metabolic marker improvements between baseline PCOS patients experiencing weight rebound, those who successfully lost weight, and those who experienced weight rebound. This will help explore the impact of weight cycling on PCOS-related manifestations. Finally, at a genetic level, the study will analyze potential mechanisms underlying different outcome indicators by comparing differences in metagenomics, transcriptomics, and metabolomics among patient groups.
Ancillary/Nested Sub-study (12-week Precision Nutrition Trial):
Within the WHIP cohort, we will conduct a nested, prospective interventional sub-study to evaluate the efficacy of an insulin-resistance-phenotype-guided precision dietary prescription versus a standard guideline-based energy-restricted diet. Eligible participants are women with PCOS and insulin resistance enrolled in the cohort. The sub-study lasts 12 weeks with assessments at baseline and week 12. Primary endpoints include change in HOMA-IR and change in the core11 metabolic risk composite. Secondary endpoints include changes in gonadotropins (FSH, LH), sex steroid hormones (e.g., estradiol, progesterone), and patient-reported symptom scores.
详细描述
This study is a single-center, prospective cohort study that enrolled PCOS patients after screening. The patients were categorized into two groups based on their BMI: a normal weight group (18.5 kg/m2 ≤ BMI < 24 kg/m2) with a sample size of 45 and an overweight/obese group (BMI ≥ 24 kg/m2) with a sample size of 380, totaling 425 cases.
For the normal weight PCOS patients, interventions included control of total energy intake, adjustment of dietary structure, exercise, and behavioral intervention to prevent weight gain over a follow-up period of three months. If weight gain occurred during the follow-up period, these patients were transferred to the overweight/obese group for intensified intervention.
The overweight/obese PCOS patients received intensive intervention in accordance with high-protein diet adaptation criteria. This involved high-protein diets combined with exercise and behavioral intervention for weight reduction. After three months of follow-up, if they achieved their weight-loss goal, they transitioned to a low-energy diet and exercise intervention program to maintain their weight. If the goal was not met after three months, they continued with the high-protein weight-loss program.
The study compared differences in improvement in indicators such as insulin resistance (IR), blood androgen levels, inflammatory factors among different degrees of weight loss (<2%, 2% ≤weight loss <5%, 5%≤weight loss<10%, ≥10%), analyzing potential mechanisms.
For individuals experiencing weight cycling, differences in IR levels before and after rebounding from body mass were compared alongside changes in androgen levels and other metabolic indicators. This aimed to explore the impact of body mass cycling on clinical indicators while analyzing potential causes.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
盲法说明
ancillary randomized substudy nested in WHIP cohort
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Women aged 18-45 years in the reproductive period;
- •Women who have previously met the Rotterdam diagnostic criteria (at least 2 of the following 3 criteria have been confirmed, and have been diagnosed with PCOS): 1) Oligomenorrhea and/or anovulation; 2) clinical and/or biochemical evidence of hyperandrogenism; 3) ultrasound showing the presence of unilateral or bilateral polycystic ovaries;
- •Inclusion of 50 women in the normal weight group: 18.5 kg/m² ≤ BMI < 24 kg/m²; Inclusion of 400 women in the overweight/obese group: BMI ≥ 24 kg/m²;
- •Voluntarily participate in the intervention and sign an informed consent form.
排除标准
- •Currently pregnant or lactating, or have had a recent (within 6 months) plan for pregnancy;
- •Currently using known prescription weight loss medications (such as GLP-1RA, orlistat, topiramate, etc.);
- •History of weight loss surgery;
- •History of severe cardiovascular or cerebrovascular diseases; severe liver or kidney dysfunction (ALT > 3 times the upper limit of normal, or creatinine > 1.5 times the upper limit of normal); chronic or active gastrointestinal inflammatory diseases; severe systemic diseases; active malignant tumors;
- •Secondary obesity: including hypothalamic or pituitary obesity, obesity secondary to glucocorticoid use, hypogonadism-induced obesity, etc.;
- •Known history of serious endocrine system diseases;
- •Poor compliance with planned dietary interventions (psychiatric disorders such as binge eating disorder, anorexia nervosa, severe anxiety/depression);
- •Unable to follow up on time or deemed non-cooperative by the investigator.
研究组 & 干预措施
Normal weight group
18.5 kg/m2 ≤ BMI < 24 kg/m2
干预措施: Adjusting dietary structure + exercise + behavioral intervention (Other)
Obese/Overweight Group
BMI ≥24 kg/m²
干预措施: Adjusting dietary structure + exercise + behavioral intervention (Other)
Precision dietary prescription (nested substudy)
Within the WHIP cohort, participants with PCOS and insulin resistance who enroll in the ancillary 12-week pragmatic intervention will receive a precision dietary prescription tailored to their baseline insulin-resistance metabolic subphenotype. The prescription includes an individualized daily energy deficit according to the Chinese guideline for medical nutrition therapy in overweight/obesity, personalized macronutrient distribution, and food-based meal plans. Participants receive dietitian counseling at baseline and scheduled follow-ups throughout the 12-week period, in addition to standard lifestyle advice provided in the parent cohort.
干预措施: Precision dietary prescription (Behavioral)
Standard guideline-based low-energy diet (nested substudy control)
Within the WHIP cohort, participants with PCOS and insulin resistance who enroll in the ancillary 12-week pragmatic intervention will receive a uniform low-energy diet based on standard guideline recommendations. The daily energy deficit is set according to the Chinese guideline for medical nutrition therapy in overweight/obesity, without tailoring to metabolic subphenotype. Contact frequency and follow-up intensity are comparable to the precision-diet arm, and standard lifestyle advice is provided throughout the 12-week period.
干预措施: Standard guideline-based low-energy diet (Behavioral)
结局指标
主要结局
Weight loss rate
时间窗: 6 month
Percentage of weight loss: (Weight after reduction - Baseline weight before reduction) / Baseline weight before reduction (%)
Levels of insulin resistance
时间窗: 6 month
Measuring the level of insulin resistance in patients after the intervention.
次要结局
- Blood levels of androgen hormones (total testosterone, free testosterone index)(6 month)
- Levels of inflammatory factors (CRP, IL-6, TAC, GSH)(6 month)
- BMI(6 month)
- Waist(6 month)
- waist-to-hip ratio(6 month)
- Fasting blood sugar（FBG）(6 month)
- Blood lipid levels (LDL-C, HDL-C, total cholesterol)(6 month)
- Fasting insulin level（FINS）(6 month)
- Body fat percentage and distribution(6 month)
- Weight rebound rate(6 month)
研究者
Wei Chen
Professor
Peking Union Medical College Hospital