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.
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.
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;
Parallel
Adjusting dietary structure + exercise + behavioral intervention
Other interventionAdjusting to a healthy diet involves consuming low GI and low-fat foods, avoiding sugary drinks, increasing dietary fiber intake, reducing saturated fat while increasing omega-3 unsaturated fat intake, and limiting trans fat consumption. A weight loss program includes a high-protein diet, exercise, and behavioral intervention with daily total energy needs calculated based on ideal body weight (kg) x 15-20 kcal/kg/d; developing a daily meal plan with regular protein supplementation; limiting salt intake to ≤5 g/d; ensuring adequate water consumption at 2-3L/d; aiming for a dietary fiber intake of 25-30g/d; recommending micronutrient supplementation as needed; maintaining daily aerobic exercise (40 minutes at 70-80% HRmax) along with resistance training (20 minutes); establishing an early bedtime before 11pm and an early wake-up time.
Precision dietary prescription
BehavioralA 12-week precision diet program individualized to baseline insulin-resistance metabolic subphenotype, including personalized macronutrient targets, food-based meal plans, and dietitian-led counseling with regular follow-ups.
Standard guideline-based low-energy diet
BehavioralA 12-week standardized low-energy diet based on national guideline recommendations for overweight/obesity, with the same counseling frequency as the precision-diet arm but without metabolic tailoring.
Weight loss rate
Percentage of weight loss: (Weight after reduction - Baseline weight before reduction) / Baseline weight before reduction (%)
Levels of insulin resistance
Measuring the level of insulin resistance in patients after the intervention.
Fasting insulin level（FINS）
Measure the fasting insulin levels of patients after the intervention.
Fasting blood sugar（FBG）
Measure the fasting blood glucose level of the patient after the intervention.
Blood levels of androgen hormones (total testosterone, free testosterone index)
Measure the blood testosterone levels of the patients after the intervention.
Blood lipid levels (LDL-C, HDL-C, total cholesterol)
Measure lipid levels in patients after the intervention.
Change in insulin resistance (HOMA-IR)
Change from baseline to week 12 in HOMA-IR among participants enrolled in the ancillary precision-diet substudy.
Change in core metabolic risk profile
Change from baseline to week 12 in the composite Z-score of the 11 predefined metabolic indicators (BMI, waist, FINS, FPG, TG, HDL, LDL, ALT, SBP, UA, SHBG) in the ancillary substudy.
Click on the lead sponsor to view all of their trials.
