Weight Cycling on Hyperandrogenemia and Insulin Resistance in Polycystic Ovary Syndrome (WHIP)

November 25, 2025 updated by: Wei Chen, Peking Union Medical College Hospital

The Effect and Mechanism Of Weight Cycling on Hyperandrogenemia And Insulin Resistance in Polycystic Ovary Syndrome

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Ancillary/Nested Sub-study (12-week Precision Nutrition Trial):

A subset of cohort participants meeting criteria for PCOS with insulin resistance will enter a 12-week dietary intervention sub-study. Participants will be allocated in a 1:1 ratio to: (1) a phenotype-guided precision dietary prescription tailored to the individual's insulin-resistance metabolic subtype; or (2) a standard low-energy diet based on current Chinese clinical guidelines for overweight/obesity medical nutrition therapy. Both groups receive standardized lifestyle counseling and follow-up. Study visits occur at baseline and week 12. This nested sub-study is designed to test whether subtype-matched dietary prescriptions yield greater improvements in insulin resistance and metabolic risk than a uniform guideline diet, while remaining integrated within the parent WHIP cohort.

Study Type

Interventional

Enrollment (Estimated)

425

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Beijing Municipality
      • Beijing, Beijing Municipality, China, 100730
        • Recruiting
        • Peking Union Medical College Hospital
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Women aged 18-45 years in the reproductive period;
  2. 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;
  3. 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;
  4. Voluntarily participate in the intervention and sign an informed consent form.

Exclusion Criteria:

  1. Currently pregnant or lactating, or have had a recent (within 6 months) plan for pregnancy;
  2. Currently using known prescription weight loss medications (such as GLP-1RA, orlistat, topiramate, etc.);
  3. History of weight loss surgery;
  4. 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;
  5. Secondary obesity: including hypothalamic or pituitary obesity, obesity secondary to glucocorticoid use, hypogonadism-induced obesity, etc.;
  6. Known history of serious endocrine system diseases;
  7. Poor compliance with planned dietary interventions (psychiatric disorders such as binge eating disorder, anorexia nervosa, severe anxiety/depression);
  8. Unable to follow up on time or deemed non-cooperative by the investigator.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Normal weight group
18.5 kg/m2 ≤ BMI < 24 kg/m2
Other: Adjusting dietary structure + exercise + behavioral intervention
Adjusting 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.
Experimental: Obese/Overweight Group
BMI ≥24 kg/m²
Other: Adjusting dietary structure + exercise + behavioral intervention
Adjusting 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.
Experimental: 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.
Behavioral: Precision dietary prescription
A 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.
Active Comparator: 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.
Behavioral: Standard guideline-based low-energy diet
A 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Weight loss rate
Time Frame: 6 month
Percentage of weight loss: (Weight after reduction - Baseline weight before reduction) / Baseline weight before reduction (%)
6 month
Levels of insulin resistance
Time Frame: 6 month
Measuring the level of insulin resistance in patients after the intervention.
6 month

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Fasting insulin level（FINS）
Time Frame: 6 month
Measure the fasting insulin levels of patients after the intervention.
6 month
Fasting blood sugar（FBG）
Time Frame: 6 month
Measure the fasting blood glucose level of the patient after the intervention.
6 month
Blood levels of androgen hormones (total testosterone, free testosterone index)
Time Frame: 6 month
Measure the blood testosterone levels of the patients after the intervention.
6 month
Blood lipid levels (LDL-C, HDL-C, total cholesterol)
Time Frame: 6 month
Measure lipid levels in patients after the intervention.
6 month
Levels of inflammatory factors (CRP, IL-6, TAC, GSH)
Time Frame: 6 month
Detect the level of inflammatory factors in patients after intervention.
6 month
BMI
Time Frame: 6 month
Measuring the BMI of patients after the intervention.
6 month
Waist
Time Frame: 6 month
Measure the waist of the patients after the intervention.
6 month
waist-to-hip ratio
Time Frame: 6 month
Measure the waist-to-hip ratio of the patients after the intervention.
6 month
Body fat percentage and distribution
Time Frame: 6 month
Measure the Body Fat Content and Proportion in Patients after Intervention
6 month
Weight rebound rate
Time Frame: 6 month
Determine the rate of weight rebound in patients after intervention. Weight rebound is defined as a rebound in weight (≥5kg or 5% above baseline weight) after weight loss.
6 month

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in insulin resistance (HOMA-IR)
Time Frame: 12 weeks
Change from baseline to week 12 in HOMA-IR among participants enrolled in the ancillary precision-diet substudy.
12 weeks
Change in core metabolic risk profile
Time Frame: 12 weeks
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.
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peking Union Medical College Hospital

Investigators

  • Principal Investigator: Wei Chen, PhD, Peking Union Medical College Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 13, 2024

Primary Completion (Estimated)

March 1, 2026

Study Completion (Estimated)

April 1, 2026

Study Registration Dates

First Submitted

July 22, 2024

First Submitted That Met QC Criteria

August 7, 2024

First Posted (Actual)

August 9, 2024

Study Record Updates

Last Update Posted (Estimated)

December 3, 2025

Last Update Submitted That Met QC Criteria

November 25, 2025

Last Verified

November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • K5204

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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