Weight Cycling on Hyperandrogenemia and Insulin Resistance in Polycystic Ovary Syndrome

NCT06545721 | Recruiting

• 1 other identifier: K5204
• Study Type: interventional
• Target: 425
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Polycystic Ovary Syndrome

Keywords

Weight Cycling; Hyperandrogenemia; Insulin Resistance; High-protein diet; Transcriptome; Metabolome; Inflammatory status

Outcome Measures

Primary Outcomes (2)

• Weight loss rate

  Percentage of weight loss: (Weight after reduction - Baseline weight before reduction) / Baseline weight before reduction (%)

  6 month

• Levels of insulin resistance

  Measuring the level of insulin resistance in patients after the intervention.

  6 month

Secondary Outcomes (10)

• Fasting insulin level（FINS）

  6 month

• Fasting blood sugar（FBG）

  6 month

• Blood levels of androgen hormones (total testosterone, free testosterone index)

  6 month

• Blood lipid levels (LDL-C, HDL-C, total cholesterol)

  6 month

• Levels of inflammatory factors (CRP, IL-6, TAC, GSH)

  6 month

Other Outcomes (2)

• Change in insulin resistance (HOMA-IR)

  12 weeks

• Change in core metabolic risk profile

  12 weeks

Study Arms (4)

Normal weight group

EXPERIMENTAL

18.5 kg/m2 ≤ BMI \< 24 kg/m2

Other: Adjusting dietary structure + exercise + behavioral intervention

Obese/Overweight Group

EXPERIMENTAL

BMI ≥24 kg/m²

Other: Adjusting dietary structure + exercise + behavioral intervention

Precision dietary prescription (nested substudy)

EXPERIMENTAL

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

Standard guideline-based low-energy diet (nested substudy control)

ACTIVE COMPARATOR

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

Interventions

Standard guideline-based low-energy diet BEHAVIORAL

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.

Standard guideline-based low-energy diet (nested substudy control)

Adjusting dietary structure + exercise + behavioral intervention OTHER

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.

Normal weight group; Obese/Overweight Group

Precision dietary prescription BEHAVIORAL

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.

Precision dietary prescription (nested substudy)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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;
• Voluntarily participate in the intervention and sign an informed consent form.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead

Study Sites (1)

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

RECRUITING

Related Publications (27)

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• Pirotta S, Barillaro M, Brennan L, Grassi A, Jeanes YM, Joham AE, Kulkarni J, Couch LM, Lim SS, Moran LJ. Disordered Eating Behaviours and Eating Disorders in Women in Australia with and without Polycystic Ovary Syndrome: A Cross-Sectional Study. J Clin Med. 2019 Oct 14;8(10):1682. doi: 10.3390/jcm8101682.

  PMID: 31615157 RESULT

MeSH Terms

Conditions

Polycystic Ovary Syndrome; Weight Cycling; Insulin Resistance

Interventions

Exercise; Behavior Therapy

Condition Hierarchy (Ancestors)

Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases; Weight Gain; Body Weight Changes; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Weight Loss; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Psychotherapy; Behavioral Disciplines and Activities

Study Officials

• Wei Chen, PhD

  Peking Union Medical College Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wei Chen, PhD

CONTACT

13911006820; txchenwei@sina.com

Menglu Zhang, PhD

CONTACT

13051336015; 499527281@qq.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: ancillary randomized substudy nested in WHIP cohort
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: the sample size for the normal weight group is 45, and the sample size for the overweight/obese group is 380.

Study Record Dates

• First Submitted: July 22, 2024
• First Posted: August 9, 2024
• Study Start: August 13, 2024
• Primary Completion: March 1, 2026
• Study Completion: April 1, 2026
• Last Updated: December 3, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)